# Patent

## Title
Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto

## Abstract

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the following formula (“Formula One”).

## Background
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of, and priority from, U.S. Provisional Patent Application Ser. No. 62/041,685 filed 26 Aug. 2014, the entire disclosure of which is hereby expressly incorporated by reference.


FIELD OF THE DISCLOSURE
The invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.
BACKGROUND OF THE DISCLOSURE
Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year.
Termites cause damage to all kinds of private and public structures. The world-wide termite damage losses amount to billions of U.S. dollars each year.
Stored food pests eat and adulterate stored food. The world-wide stored food losses amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.
There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pesticides, for example, imidacloprid.
Therefore, for many reasons, including the above reasons, a need exists for new pesticides.
DEFINITIONS
The examples given in the definitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molecule to which it is attached.
“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.
“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.
“Alkoxy” means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy.
“Alkyl” means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (C3)alkyl which represents n-propyl and isopropyl, (C4)alkyl which represents n-butyl, sec-butyl, isobutyl, and tert-butyl.
“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.
“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.
“Aryl” means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.
“Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.
“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy.
“Halo” means fluoro, chloro, bromo, and iodo.
“Haloalkoxy” means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.
“Haloalkyl” means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.
“Heterocyclyl” means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, that atom can be in other oxidation states such as a sulfoxide and sulfone. Examples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl.


DETAILED DESCRIPTION OF THE DISCLOSURE
This document discloses molecules having the following formula (“Formula One”)




wherein:

(A) R1, R2, R3, R4, R5, R6, R7, and R9 are each independently selected from the group consisting of H, F, Cl, Br, I, CN, NO2, OH, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, and (C3-C6)cycloalkoxy,
wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, and cycloalkoxy is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo;
(B) R8 is H;
(C) L is a (C1-C4)alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo;
(D) R10 is selected from the group consisting of H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, ((C1-C4)alkyl)((C3-C6)cycloalkyl), (C1-C4)alkylphenyl, (C1-C4)alkylheterocyclyl, ((C1-C4)alkyl)O((C1-C4)alkyl), ((C1-C4)alkyl)OC(O)((C1-C4)alkyl), ((C1-C4)alkyl)OC(O)O((C1-C4)alkyl), C(O)((C1-C4)alkyl), and C(O)phenyl,
wherein each alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, phenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo;
(E) R11, R12, R13, R14, and R15 are each independently selected from the group consisting of H, F, Cl, Br, I, CN, NO2, OH, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, and (C3-C6)cycloalkoxy;
(F) R16 and R17 are each independently selected from the group consisting of (G), H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, ((C1-C4)alkyl)((C3-C6)cycloalkyl), (C1-C4)alkylphenyl, (C1-C4)alkylheterocyclyl, ((C1-C4)alkyl)C(O)((C1-C4)alkyl), and ((C1-C4)alkyl)C(O)O((C1-C4)alkyl),
wherein each alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, phenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo; and
(G) R16 and R17 together with (S)Cx(Nx) forms a 4 to 8 membered heterocyclyl ring,
wherein said heterocyclyl ring may optionally be substituted with one or more substituents independently selected from R18,
wherein R18 is selected from the group consisting of H, F, Cl, Br, I, CN, OH, (C1-C4)alkyl, oxo, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, ((C1-C4)alkyl)((C3-C6)cycloalkyl), (C1-C4)alkylphenyl, (C1-C4)alkylheterocyclyl, ((C1-C4)alkyl)C(O)((C1-C4)alkyl), ((C1-C4)alkyl)C(O)O((C1-C4)alkyl), phenyl, and heterocyclyl,
wherein each alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, phenyl, and heterocyclyl are optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, I, CN, OH, and oxo.
In another embodiment R1, R2, R3, R4, R6, R7, R8, R9, R10, and R14 are H. This embodiment may be used in combination with the other embodiments of R5, L, R11, R12, R13, R15, R16, R17, and R18.
In another embodiment R5 is (C1-C4)haloalkoxy. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, R16, R17, and R18.
In another embodiment R5 is OCF3 or OCF2CF3. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, R16, R17, and R18.
In another embodiment L is —CH2— or —CH2CH2—. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, and R18.
In another embodiment R11 is (C1-C4)alkyl. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R12, R13, R14, R15, R16, R17, and R18.
In another embodiment R11 is H or CH3. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R12, R13, R14, R15, R16, R17, and R18.
In another embodiment R12 is halo, (C1-C4)alkyl, or (C1-C4)alkoxy. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R13, R14, R15, R16, R17, and R18.
In another embodiment R12 is H, Cl, CH3, or OCH3. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R13, R14, R15, R16, R17, and R18.
In another embodiment R13 is halo, (C1-C4)alkyl, or (C1-C4)alkoxy. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R14, R15, R16, R17, and R18.
In another embodiment R13 is H, F, CH3, or OCH3. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R14, R15, R16, R17, and R18.
In another embodiment R15 is halo, (C1-C4)alkyl, (C3-C6)cycloalkyl, or (C1-C4)alkoxy. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R16, R17, and R18.
In another embodiment R15 is Cl, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, cyclopropyl, or OCH3. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R16, R17, and R18.
In another embodiment R16 is H. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, R17, and R18.
In another embodiment R16 and R17 together is —C(R18)—C(R18)—, —C(R18)—C(R18)—C(R18)—, or —C(R18)═C(CR18)—. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, and R15.
In another embodiment R17 is H. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R5, R16, and R18.
In another embodiment R18 is (C1-C4)alkyl. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, R16, and R17.
In another embodiment R18 is H, F, CH3, OH, or oxo. This embodiment may be used in combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, R16, and R17.
In another embodiment:
(A) R1, R2, R3, R4, R5, R6, R7, and R9 are each independently selected from the group consisting of H and (C1-C4)haloalkoxy;
(B) R8 is H;
(C) L is (C1-C4)alkyl;
(D) R10 is H;
(E) R11, R12, R13, R14, and R15 are each independently selected from the group consisting of H, F, Cl, Br, I, (C1-C4)alkyl, and (C3-C6)cycloalkyl;
(F) R16 and R17 are (G) or H; and
(G) R16 and R17 together with (S)Cx(Nx) forms a 4 to 8 membered heterocyclyl ring,
wherein said heterocyclyl ring may optionally be substituted with one or more substituents independently selected from R18,
wherein R18 is selected from the group consisting of H, CH3, and oxo.
Preparation of Molecules of Formula One
Many of the molecules of Formula One may be depicted in two or more tautomeric forms such as when R16 and R17 are H (Scheme TAU). For the sake of simplifying the schemes, all molecules have been depicted as existing as a single tautomer. Any and all energetically accessible tautomers are included within the scope of this Formula One, and no inference should be made as to whether the molecule exists as the tautomeric form in which it is drawn.




The molecules of Formula One will generally have a molecular mass of about 400 Daltons to about 1200 Daltons.
Preparation of Thiobiurets




Thiobiurets disclosed herein are prepared from corresponding isocyanates 1-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and L are as previously disclosed. Typically, isocyanates 1-2 are not isolated, but are instead generated in situ from a suitable precursor and used directly in the preparation of a thiobiuret. Suitable precursors are amines 1-1, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and L are as previously disclosed, which may be converted into isocyanates 1-2 by using one of several common reagents such as phosgene, diphosgene, or triphosgene (Scheme 1, step 1a), in a mixed solvent system such as dichloromethane and water or diethyl ether and water, in the presence of a base such as sodium bicarbonate or triethylamine, at temperatures from about −10° C. to about 50° C.




Isocyanates 1-2 may be treated directly with N-aryl thioureas 2-1, wherein R11, R12, R13, R14, and R15 are as previously disclosed, in the presence of about 0.1 equivalents to about 2 equivalents of an inorganic base, such as cesium carbonate or sodium hydride, resulting in the formation of thiobiurets 2-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14 and R15 are as previously disclosed (Scheme 2, step 2a). The reaction may be performed at temperatures from about 0° C. to about 100° C., preferably from about 20° C. to about 80° C., in an aprotic solvent or solvent mixture chosen from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane, or mixtures thereof, but use of acetonitrile is preferred.




Thiobiurets 2-2 generated in situ may be converted directly without purification into a variety of cyclized analogs (Scheme 3, step 3a), or they may be isolated from the reaction medium prior to cyclization. Cyclization may be achieved by treatment with an α-halo ester such as methyl bromoacetate to form 2-imino 1,3-thiazolin-4-ones 3-1, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14, R15, and R18 are as previously disclosed (step a); vicinal dihalides such as 1-bromo-2-chloroethane or 1,2-dichloroethane, to form 2-imino-1,3-thiazolines 3-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14, R15, and R18 are as previously disclosed (step 3b); α-halo ketones such as chloroacetone to form 2-imino-1,3-thiazolinols 3-2 (step 3c); or 2-imino-1,3-thiazoles 3-3, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14, R15, and R18 are as previously disclosed (step 3d). With step a, use of sodium acetate in a protic solvent such as ethanol or methanol, at temperatures ranging from about 20° C. to about 70° C. is preferred. With step b, use of an inorganic base such as potassium carbonate in a solvent such as acetonitrile or 2-butanone, at a temperature between about 0° C. and about 80° C., is preferred.




Cyclization may also be achieved by treatment of thioureas 2-2 with an α,β-unsaturated acid chlorides such as acryloyl chloride to form 2-imino-1,3-thiazinones 4-1, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14, R15, and R18 are as previously disclosed (Scheme 4, step 4a) or 1,3-dihalopropanes such as 1-bromo-3-chloro-propane to form 2-imino-1,3-thiazinanes 4-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14, R15, and R18 are as previously disclosed (step 4b).




An alternative method for preparing analogs having the general structure 3-1 is described in Scheme 5. 2-Iminothiazolidin-4-ones 5-1, wherein R11, R12, R13, R14, R15, and R18 are as previously disclosed, may be treated directly with isocyanates 1-2, either in the absence of base or in the presence of about 0.1 equivalents to about 2 equivalents of an inorganic base, such as cesium carbonate or sodium hydride, to form cyclized thiobiurets 3-1 (step 5a). The reaction may be performed at temperatures from about 0° C. to about 100° C., preferably from about 20° C. to about 80° C., in an aprotic solvent or solvent mixture chosen from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane, or mixtures thereof, but use of acetonitrile is preferred.
Alternatively, 2-iminothiazolidin-2-ones 5-1 may be reacted with 4-nitrophenyl chloroformate, forming 4-nitrophenyl carbamates 5-2, wherein R11, R12, R13, R14, R15, and R18 are as previously disclosed (step 5b). This reaction may be conducted with equimolar quantities of 2-iminothiazolidin-2-ones 5-1 and the chloroformate, in a polar aprotic solvent, such as tetrahydrofuran, dioxane, or acetonitrile, in the presence of from about 0.1 equivalents to about 2 equivalents of an inorganic base, such as cesium carbonate or potassium carbonate, preferably at about room temperature. 4-Nitrophenyl carbamates 5-2 may be isolated by filtration and concentration of the filtrate, or 4-nitrophenyl carbamates 5-2 may be used directly in step 5c. Treatment of 4-nitrophenyl carbamates 5-2 with triaryl amines 5-3, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, and R10 are as previously disclosed may generate cyclized thiobiurets 3-1. Step 5c may also be conducted in the presence of an inorganic base, such as cesium carbonate or potassium carbonate, from about 0.1 equivalents to about 2 equivalents, preferably about 1 equivalents to about 1.2 equivalents, at temperatures from about 0° C. to about 100° C., preferably about room temperature.




Thiobiurets 2-2 may be treated with R17-halo, wherein R17 is as previously disclosed, in a protic solvent, such as ethanol, in the presence of a base, such as sodium acetate, at temperatures from about 0° C. to about 60° C., to yield S-alkylated thiobiurets 6-1, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, R16, and R17 are as previously disclosed (Scheme 6, step 6a).
Preparation of Substituted Thiobiurets




2-Imino 1,3-thiazolin-4-ones 7-1, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, and R15 are as previously disclosed, may be treated with Selectfluor® and 9-fluorenone in anhydrous acetonitrile (JACS. 2013, 135, 17494) to provide mono-fluoro analogs 7-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, and R15 are as previously disclosed (Scheme 7, step 7a). Treatment temperatures ranging from about 0° C. to about 30° C. may provide the mono-bromo analog 7-3, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, and R15 are as previously disclosed (step 7b). Alkylation, using about 1 equivalent or about 2 equivalents of alkylating agent R18-halo, wherein R18 is as previously disclosed, and a strong base, such as sodium hydride or lithium diisopropylamide, in a polar aprotic solvent, such as dimethylformamide or tetrahydrofuran may lead to a mono or di-alkylated analogs 7-4, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R10, R11, R12, R13, R14, R15, and R18 are as previously disclosed (step 7c). 2-Imino 1,3-thiazolin-4-ones 7-1, wherein R10 is H may be treated with paraformaldehyde and trifluoroacetic acid in a solvent such as dichloromethane followed by treatment with an acid chloride to provide 2-imino 1,3-thiazolin-4-ones 7-5, wherein R10 is CH2OCO(C1-C4 alkyl) and R1, R2, R3, R4, R5, R6, R7, R8, R9, L, R11, R12, R13, R14, R15, and R18 are as previously disclosed (step 7d). Likewise, 2-Imino 1,3-thiazolin-4-ones 7-1, wherein R10 is H may be treated with acid chlorides in the presence of a base in a solvent such as dichloromethane to provide 2-imino 1,3-thiazolin-4-ones 7-5, wherein R10 is C(O)((C1-C4)alkyl) or C(O)phenyl (step 7d).
Preparation of Tricyclic Amine Precursors




Methods for preparation of the tricyclic amines required for preparation of molecules of Formula One are described in Scheme 8. The coupling of bromo-heterocycles 8-1, wherein R3, R4, R5, R6, R7, and R8 are as previously disclosed, with boronate esters 8-2, wherein PG is an amine protecting group such as tert-butoxycarbonyl (Boc) or benxyloxycarbonyl (Cbz) and R1, R2, R9, L, and R10 are as previously disclosed, may be accomplished using a palladium catalyst and phosphine ligand, in the presence of a base, such as sodium bicarbonate, potassium phosphate, or cesium fluoride, in a suitable solvent system, such as dioxane and water, at temperatures from about 50° C. to about 120° C., using conventional or microwave heating, to form N-protected aminoalkylphenyl intermediates (Scheme 7, step 7a). Deprotection of the tert-butoxycarbonyl group may be accomplished under acidic conditions with strong acids, such as hydrogen chloride or trifluoroacetic acid, followed by free basing with a base, such as sodium bicarbonate or sodium hydroxide, to furnish triaryl amines 5-3 (step b). Deprotection of the benzyloxycarbonyl group may be accomplished under standard conditions using hydrogen and a transition metal catalyst such as palladium(0). It is appreciated that this reaction sequence may be applied to the synthesis of amines 1-1.
Preparation of Boronate Esters




Protected aryl amines 9-2, wherein R1, R2, R9, L, R10, and PG are as previously disclosed, may be prepared by treating aryl amines 9-1, wherein R1, R2, R9, L, and R10 are as previously disclosed, with an activated nitrogen protecting group, such as di-tert-butoxydicarbonyl or benzyloxycarbonyl chloride, in the presence of a base, such as triethylamine, at temperatures from about −10° C. to about 50° C., in a solvent, such as dichloromethane (Scheme 9, step 9a). Boronate esters 8-2 may be prepared from aryl amines 9-1, using Miyaura conditions (step 9b). Standard nitrogen protecting groups known to be compatible under Miyaura coupling conditions may be employed.
EXAMPLES
These examples are for illustration purposes and are not to be construed as limiting the disclosure to only the embodiments disclosed in these examples.
Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/SealTM from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. Examples using “room temperature” were conducted in climate controlled laboratories with temperatures ranging from about 20° C. to about 24° C. Molecules are given their known names, named according to naming programs within ISIS Draw, ChemDraw or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using conventional naming rules. 1H NMR spectral data are in ppm (δ) and were recorded at 300, 400 or 600 MHz; 13C NMR spectral data are in ppm (δ) and were recorded at 75, 100 or 150 MHz, and 19F NMR spectral data are in ppm (δ) and were recorded at 376 MHz, unless otherwise stated.
Example 1
Preparation of tert-butyl (5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (C1)




To 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (2.75 g, 8.93 mmol), tert-butyl (5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (3.21 g, 8.93 mmol), sodium bicarbonate (1.50 g, 17.9 mmol), dioxane (45 mL) and water (15 mL) in a round-bottomed flask (100 mL) equipped with a stir bar and nitrogen was added tetrakis(triphenylphosphine)palladium(0) (1.03 g, 0.893 mmol). The reaction vessel was evacuated with vacuum and purged with nitrogen (2×). The reaction was heated to 80° C. overnight. The reaction was cooled, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with Brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-40% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent provided the title compound as a white solid (2.10 g, 51%): 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.05 (d, J=1.5 Hz, 1H), 8.01 (dd, J=7.8, 1.6 Hz, 1H), 7.83-7.77 (m, 2H), 7.39 (dt, J=7.9, 1.0 Hz, 2H), 7.32 (d, J=7.9 Hz, 1H), 4.78 (s, 1H), 4.53 (s, 1H), 3.43-3.22 (m, 2H), 2.85 (ddd, J=15.9, 10.1, 4.9 Hz, 2H), 1.45 (s, 9H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 461 ([M+H]+).
Example 2
Preparation of tert-butyl (5-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (C2)




3-Bromo-1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazole (0.409 g, 1.14 mmol), tert-butyl (5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (0.411 g, 1.14 mmol), sodium bicarbonate (0.0960 g, 1.14 mmol), tetrakis(triphenylphosphine)palladium(0) (0.132 g, 0.114 mmol), dioxane (6 mL), and water (2 mL) in a vial (20 mL) were capped and heated at 140° C. for 30 minutes in a Biotage Initiator® microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with Brine. The organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-20% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent followed by drying at 50° C. at about 25 in. Hg provided the title compound as a white solid (0.345 g, 59%): mp 161-165° C.; 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.05 (s, 1H), 8.02 (dd, J=7.7, 1.6 Hz, 1H), 7.84-7.78 (m, 2H), 7.39 (d, J=8.8 Hz, 2H), 7.32 (d, J=7.8 Hz, 1H), 4.87-4.70 (m, 1H), 4.60-4.45 (m, 1H), 3.34 (dt, J=16.2, 8.0 Hz, 2H), 2.86 (ddd, J=15.8, 10.1, 4.9 Hz, 2H), 1.45 (s, 9H); 19F NMR (376 MHz, CDCl3) δ −85.89, −87.85; ESIMS m/z 511 ([M+H]+).
Example 3
Preparation of 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine dihydrochloride (C3)




To tert-butyl (5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (C1) (0.484 g, 1.05 mmol) in a round-bottomed flask (100 mL) equipped with a stir bar and nitrogen was added dioxane (3 mL) and hydrogen chloride (4 M in dioxane, 3.02 mL, 12.1 mmol). The reaction was stirred overnight at room temperature. Additional hydrogen chloride (4 M in dioxane, 3.02 mL, 12.1 mmol) was added and the reaction was heated to 40° C. overnight. More hydrogen chloride (4 M in dioxane, 3.02 mL, 12.1 mmol) was added. After several hours, the reaction was cooled to room temperature and diluted with diethyl ether. The solid was filtered, washed with diethyl ether, and dried under house vacuum providing the title compound as a white solid (0.379 g, 83%): 1H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.36-8.17 (m, 3H), 8.11-8.04 (m, 2H), 8.02 (s, 1H), 7.98 (dd, J=7.8, 1.6 Hz, 1H), 7.65-7.60 (m, 2H), 7.43 (d, J=7.9 Hz, 1H), 4.11-4.00 (m, 2H), 3.36 (ddd, J=16.9, 13.8, 7.7 Hz, 2H), 3.04 (ddd, J=17.2, 12.3, 5.2 Hz, 2H); 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 361 ([M+H]+).
Example 4
Preparation of 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine 2,2,2-trifluoroacetate (C4)




To tert-butyl (5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (C1) (2.1 g, 4.6 mmol) in a round-bottomed flask (200 mL) equipped with a stir bar and nitrogen was added dichloromethane (30 mL). The reaction was cooled with an ice-water bath and trifluoroacetic acid (3.9 mL, 50 mmol) was added in one portion. The ice bath was removed and the reaction was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was slurried with diethyl ether and concentrated until a white solid was obtained. The solid was triturated with diethyl ether and hexanes, filtered, collected, and dried at 50° C. at about 25 in. Hg overnight providing the title compound as a white solid (1.9 g, 86%): 19F NMR (376 MHz, DMSO-d6) δ −56.96, −73.55; ESIMS m/z 361 ([M+H]+).
Example 5
Preparation of 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C5)




5-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine 2,2,2-trifluoroacetate (C4) (1.46 g, 3.08 mmol) in dichloromethane was washed in a separatory funnel with sodium hydroxide (1 N). The organic layer was poured through phase separator and concentrated. The solid was dried overnight at 50° C. at about 25 in. Hg providing the title compound as a tan solid (0.779 g, 70%): 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.05 (d, J=1.5 Hz, 1H), 8.02-7.97 (m, 1H), 7.86-7.75 (m, 2H), 7.43-7.34 (m, 2H), 7.32 (d, J=7.8 Hz, 1H), 3.90 (s, 1H), 3.25 (ddd, J=16.6, 10.2, 6.7 Hz, 2H), 2.75 (ddd, J=16.4, 9.4, 5.1 Hz, 2H) (NH2 not observed); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 361 ([M+H]+).
Example 6
Preparation of 5-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C6)




To tert-butyl (5-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)carbamate (C2) (0.305 g, 0.598 mmol) in a round-bottomed flask (100 mL) equipped with a stir bar and nitrogen was added dichloromethane (4 mL) followed by trifluoroacetic acid (0.506 mL, 6.57 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was cooled with an ice-water bath and made basic with sodium hydroxide (2 M, 3.29 mL, 6.57 mmol). The layers were separated and the aqueous layer was extracted with chloroform/isopropanol (3:1, 3×). The organic layers were poured through a phase separator and concentrated providing the title compound as a yellow oil used without further purification (0.290 g, 118%): 19F NMR (376 MHz, CDCl3) δ −85.90, −87.85; ESIMS m/z 411 ([M+H]+).
Example 7
Preparation of 4-methoxy-2-nitro-1-(prop-1-en-2-yl)benzene (C7)




To 1-chloro-4-methoxy-2-nitrobenzene (5.03 g, 26.8 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (5.41 g, 32.2 mmol), bis(triphenylphosphine)palladium(II) chloride (1.50 g, 2.15 mmol), and sodium carbonate (3.41 g, 32.2 mmol) was added dioxane/water (4:1, 100 mL:25 mL). The reaction was heated at 80° C. for 5 hours. The reaction was cooled to room temperature overnight. The reaction mixture was diluted with water, extracted with ethyl acetate (3×), dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-5% ethyl acetate/hexanes as eluent followed by drying in vacuum oven provided the title compound as an orange oil (2.74 g, 53%): 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J=2.7 Hz, 1H), 7.23 (d, J=8.6 Hz, 1H), 7.08 (dd, J=8.5, 2.6 Hz, 1H), 5.24-4.75 (m, 2H), 3.86 (s, 3H), 2.19-1.88 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 158.79, 148.61, 142.53, 131.41, 131.32, 119.24, 115.20, 108.64, 55.84, 23.38; EIMS m/z 193 ([M]+).
The following compounds were prepared in accordance to the procedure in Example 7.
4-Chloro-2-nitro-1-(prop-1-en-2-yl)benzene (C8)




The title compound was prepared as described in Example 7 using 1-bromo-4-chloro-2-nitrobenzene heated overnight and isolated as a light orange liquid (10.73 g, 84%): 1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J=2.2 Hz, 1H), 7.76 (dd, J=8.3, 2.2 Hz, 1H), 7.52 (d, J=8.3 Hz, 1H), 5.24 (p, J=1.5 Hz, 1H), 4.95 (p, J=1.0 Hz, 1H), 2.07 (dd, J=1.5, 0.9 Hz, 3H); 13C NMR (101 MHz, DMSO) δ 148.37, 140.83, 136.10, 132.62, 132.45, 131.63, 123.50, 115.98, 22.60; EIMS m/z 197 ([M]+).
Example 8
Preparation of 1-allyl-4-methyl-2-nitrobenzene (C9)




To 1-chloro-4-methyl-2-nitrobenzene (2.00 g, 11.7 mmol), allyltributylstannane (5.79 g, 17.5 mmol) and bis(triphenylphosphine)palladium(II) dichloride (0.818 g, 1.17 mmol) in two 25-mL reaction vials was added 1,2-dichloroethane (20 mL). The vials were capped and heated at 120° C. for 45 minutes in a Biotage Initiator® microwave reactor with an external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was loaded onto a Celite® cartridge. The crude material was purified by flash column chromatography using 0-50% ethyl acetate/hexanes as eluent followed by reverse-phase flash column chromatography using 0-100% acetonitrile/water as eluent. The combined acetonitrile/water fractions were concentrated, extracted with ethyl acetate, dried over sodium sulfate, filtered, concentrated, and dried in a vacuum oven to provide the title compound as a yellow liquid (1.76 g, 84%): 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J=0.9 Hz, 1H), 7.34 (dd, J=7.8, 1.2 Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 5.96 (ddt, J=16.6, 10.1, 6.4 Hz, 1H), 5.08 (ddq, J=18.5, 17.0, 1.5 Hz, 2H), 3.64 (d, J=6.4 Hz, 2H), 2.40 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 149.09, 137.62, 135.35, 133.81, 131.81, 131.72, 124.94, 116.81, 36.62, 20.72; EIMS m/z 176 ([M]+).
The following compounds were prepared in accordance to the procedure in Example 8:
4-Methyl-2-nitro-1-vinylbenzene (C10)




The title compound was prepared as described in Example 8 using 1-chloro-4-methyl-2-nitrobenzene and tributyl(vinyl)stannane, further purified by flash column chromatography and reverse phase chromatography and isolated as a yellow liquid (1.26 g, 65%): 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J=0.8 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.46-7.35 (m, 1H), 7.13 (dd, J=17.3, 11.0 Hz, 1H), 5.71 (dd, J=17.3, 0.9 Hz, 1H), 5.43 (dd, J=11.0, 0.9 Hz, 1H), 2.42 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 147.71, 138.91, 133.92, 132.31, 130.52, 128.22, 124.63, 118.10, 20.88; EIMS m/z 163 ([M]+).
Example 9
Preparation of 5-methyl-2-propylaniline (C11)




A round-bottomed flask containing 1-allyl-4-methyl-2-nitrobenzene (C9) (1.75 g, 9.87 mmol) and palladium on carbon (10%, 1.05 g, 0.990 mmol) in ethyl acetate (49 mL) was evacuated under vacuum and backfilled with nitrogen (2×), then evacuated under vacuum and filled with hydrogen by balloon. The reaction was stirred at room temperature for two nights. The reaction mixture was filtered through Celite® with ethyl acetate and concentrated. The liquid was dried in vacuum oven providing the title compound as a yellow liquid (1.39 g, 93%): 1H NMR (400 MHz, CDCl3) δ 6.92 (d, J=7.6 Hz, 1H), 6.55 (d, J=7.6 Hz, 1H), 6.51 (s, 1H), 3.55 (s, 2H), 2.47-2.37 (m, 2H), 2.24 (s, 3H), 1.69-1.53 (m, 2H), 0.99 (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 143.91, 136.52, 129.46, 123.83, 119.49, 116.29, 33.05, 22.10, 21.05, 14.19; EIMS m/z 149 ([M]+).
The following compounds were prepared in accordance to the procedure in Example 9:
2-Ethyl-5-methylaniline (C12)




The title compound was prepared as described in Example 9 using 4-methyl-2-nitro-1-vinylbenzene (C10) and isolated as a yellow liquid (0.926 g, 88%): 1H NMR (400 MHz, CDCl3) δ 6.95 (d, J=7.6 Hz, 1H), 6.57 (d, J=7.6 Hz, 1H), 6.52 (s, 1H), 3.56 (s, 2H), 2.48 (q, J=7.5 Hz, 2H), 2.25 (s, 3H), 1.23 (t, J=7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 143.80, 136.48, 128.32, 125.22, 119.59, 116.15, 23.67, 21.03, 13.24; EIMS m/z 135 ([M]+).
2-Isopropyl-5-methoxyaniline (C13)




The title compound was prepared as described in Example 9 using 4-methoxy-2-nitro-1-(prop-1-en-2-yl)benzene (C7) and isolated as a yellow liquid (2.23 g, 95%): 1H NMR (400 MHz, CDCl3) δ 7.03 (d, J=8.4 Hz, 1H), 6.35 (dd, J=8.5, 2.6 Hz, 1H), 6.25 (d, J=2.6 Hz, 1H), 3.75 (s, 3H), 3.65 (s, 2H), 2.83 (p, J=6.8 Hz, 1H), 1.24 (d, J=6.8 Hz, 6H); EIMS m/z 165 ([M]+).
5-Chloro-2-isopropylaniline (C14)




The title compound was prepared as described in Example 9 using 4-chloro-2-nitro-1-(prop-1-en-2-yl)benzene (C8) and isolated as a brown liquid (1.82 g, 84%): 1H NMR (400 MHz, CDCl3) δ 7.38-7.31 (m, 1H), 7.22-7.16 (m, 1H), 7.07 (d, J=8.1 Hz, 1H), 6.83-6.77 (m, 2H), 2.90 (p, J=6.8 Hz, 1H), 1.25 (d, J=6.8 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 126.91, 126.83, 126.51, 121.34, 120.07, 116.37, 27.44, 22.34; EIMS m/z 169 ([M]+).
Example 10
Preparation of N-((5-methyl-2-propylphenyl)carbamothioyl)benzamide (C15)




To 5-methyl-2-propylaniline (C11) (1.38 g, 9.22 mmol) and benzoyl isothiocyanate (1.24 mL, 9.22 mmol) was added acetone (13 mL). The reaction was heated at 60° C. for 4 hours. The reaction was cooled and concentrated. The resulting oil was dried in a vacuum oven overnight providing the title compound as a brown oil (3.26 g, 100%): 1H NMR (400 MHz, CDCl3) δ 12.20 (s, 1H), 9.15 (s, 1H), 7.92 (dt, J=8.5, 1.7 Hz, 2H), 7.71-7.60 (m, 1H), 7.55 (m, 3H), 7.18 (d, J=7.8 Hz, 1H), 7.09 (dd, J=7.8, 1.1 Hz, 1H), 2.66-2.55 (m, 2H), 2.36 (s, 3H), 1.72-1.57 (m, 2H), 0.97 (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 179.64, 166.90, 136.22, 135.72, 134.57, 133.74, 131.68, 129.79, 129.22, 128.64, 127.55, 127.24, 33.28, 23.58, 21.01, 13.98; ESIMS m/z 313 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 10:
N-((2-Ethyl-6-methylphenyl)carbamothioyl)benzamide (C16)




The title compound was prepared as described in Example 10 using 2-ethyl-6-methylaniline and isolated as a yellow liquid (6.41 g, 100%): 1H NMR (400 MHz, CDCl3) δ 11.88 (s, 1H), 9.21 (s, 1H), 8.02-7.85 (m, 2H), 7.73-7.63 (m, 1H), 7.62-7.50 (m, 2H), 7.29-7.23 (m, 1H), 7.20-7.14 (m, 2H), 2.75-2.57 (m, 2H), 2.33 (s, 3H), 1.25 (t, J=7.6 Hz, 3H); ESIMS m/z 299 ([M+H]+).
N-((2-Ethyl-5-methylphenyl)carbamothioyl)benzamide (C17)




The title compound was prepared as described in Example 10 using 2-ethyl-5-methylaniline (C12) and isolated as an orange solid (2.10 g, 97%): mp 105-107° C.; 1H NMR (400 MHz, CDCl3) δ 12.18 (s, 1H), 9.14 (s, 1H), 7.92 (dt, J=8.6, 1.7 Hz, 2H), 7.73-7.60 (m, 1H), 7.59-7.53 (m, 2H), 7.50 (s, 1H), 7.21 (d, J=7.8 Hz, 1H), 7.11 (dd, J=7.8, 1.1 Hz, 1H), 2.71-2.59 (m, 2H), 2.37 (s, 3H), 1.24 (t, J=7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 179.72, 166.94, 136.22, 136.13, 135.53, 133.75, 131.65, 129.23, 128.88, 128.86, 127.53, 127.23, 24.26, 20.98, 14.56; ESIMS m/z 299 ([M+H]+).
N-((2-Isopropyl-5-methoxyphenyl)carbamothioyl)benzamide (C18)




The title compound was prepared as described in Example 10 using 2-isopropyl-5-methoxyaniline (C13) and isolated as a yellow liquid (4.63 g, 100%): 1H NMR (400 MHz, CDCl3) δ 12.23 (s, 1H), 9.13 (s, 1H), 7.98-7.82 (m, 2H), 7.74-7.61 (m, 1H), 7.61-7.51 (m, 2H), 7.32-7.26 (m, 2H), 6.89 (dd, J=8.7, 2.7 Hz, 1H), 3.81 (s, 3H), 3.10 (p, J=6.9 Hz, 1H), 1.26 (d, J=6.8 Hz, 6H); ESIMS m/z 329 ([M+H]+).
N-((5-Chloro-2-isopropylphenyl)carbamothioyl)benzamide (C19)




The title compound was prepared as described in Example 10 using 5-chloro-2-isopropylaniline (C14) followed by purification by flash column chromatography and isolated as a light yellow solid (16.3 g, 98%): 1H NMR (400 MHz, DMSO-d6) δ 12.32 (s, 1H), 11.76 (s, 1H), 8.07-7.95 (m, 2H), 7.72-7.63 (m, 1H), 7.60-7.50 (m, 3H), 7.42 (d, J=8.5 Hz, 1H), 7.37 (dd, J=8.5, 2.2 Hz, 1H), 3.08 (hept, J=6.9 Hz, 1H), 1.19 (d, J=6.8 Hz, 6H); 13C NMR (101 MHz, DMSO) δ 181.12, 168.37, 142.95, 137.03, 133.18, 131.93, 129.67, 128.75, 128.40, 127.61, 127.55, 127.52, 27.63, 22.84; ESIMS m/z 333 ([M+H]+).
Example 11
Preparation of 1-(5-methyl-2-propylphenyl)thiourea (C20)




To N-((5-methyl-2-propylphenyl)carbamothioyl)benzamide (C15) (3.21 g, 10.3 mmol) in methanol (80 mL) was added sodium hydroxide (2 N, 10.3 mL, 20.5 mmol) and heated at 50° C. for 2 hours and then stirred at room temperature over the weekend. The reaction was concentrated, diluted with water, extracted with dichloromethane, filtered through a phase separator, concentrated, and dried in a vacuum oven to provide the title compound as a tan solid (1.80 g, 83%): mp 143-145° C.; 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.20 (d, J=7.8 Hz, 1H), 7.12 (dd, J=7.8, 1.2 Hz, 1H), 7.04 (s, 1H), 5.99 (d, J=254.5 Hz, 2H), 2.57 (d, J=7.5 Hz, 2H), 2.33 (s, 3H), 1.59 (dq, J=14.8, 7.4 Hz, 2H), 0.95 (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 181.96, 137.53, 136.74, 134.00, 130.69, 129.72, 127.85, 32.90, 23.66, 20.80, 13.93; ESIMS m/z 209 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 11:
1-(2-Ethyl-6-methylphenyl)thiourea (C21)




The title compound was prepared as described in Example 11 using N-((2-ethyl-6-methylphenyl)carbamothioyl)benzamide (C16), further purified by trituration with water and isolated as a white solid (3.46 g, 83%): 1H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.25 (d, J=7.9 Hz, 1H), 7.22-7.11 (m, 2H), 6.13 (bs, 1H), 5.33 (bs, 1H), 2.77-2.55 (m, 2H), 2.31 (s, 3H), 1.21 (t, J=7.6 Hz, 3H); ESIMS m/z 195 ([M+H]+).
1-(2-Ethyl-5-methylphenyl)thiourea (C22)




The title compound was prepared as described in Example 11 using N-((2-ethyl-5-methylphenyl)carbamothioyl)benzamide (C17) and isolated as a pale orange solid (1.26 g, 94%): mp 143-147° C.; 1H NMR (400 MHz, CDCl3) δ 7.48 (s, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.14 (d, J=8.0 Hz, 1H), 7.04 (s, 1H), 5.86 (s, 2H), 2.61 (q, J=7.5 Hz, 2H), 2.33 (s, 3H), 1.19 (t, J=7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 182.13, 138.27, 137.53, 133.74, 129.95, 129.93, 127.84, 24.00, 20.79, 14.77; ESIMS m/z 195 ([M+H]+).
1-(2-Isopropyl-5-methoxyphenyl)thiourea (C23)




The title compound was prepared as described in Example 11 using N-((2-isopropyl-5-methoxyphenyl)carbamothioyl)benzamide (C18) and isolated as an orange solid (2.65 g, 83%): mp 134-139° C.; 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.30 (d, J=8.7 Hz, 1H), 6.93 (dd, J=8.7, 2.7 Hz, 1H), 6.75 (d, J=2.7 Hz, 1H), 5.88 (s, 2H), 3.79 (s, 3H), 3.10 (p, J=6.9 Hz, 1H), 1.19 (d, J=6.9 Hz, 6H); ESIMS m/z 225 ([M+H]+).
1-(5-Chloro-2-isopropylphenyl)thiourea (C24)




The title compound was prepared as described in Example 69 using N-((5-chloro-2-isopropylphenyl)carbamothioyl)benzamide (C19) and isolated as a brown sticky gum (1.38 g, 93%): 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.34 (d, J=1.4 Hz, 2H), 7.24 (t, J=1.3 Hz, 1H), 5.97 (s, 2H), 3.27-3.10 (m, 1H), 1.21 (d, J=6.8 Hz, 6H); ESIMS m/z 229 ([M+H]+).
Example 12
Preparation of 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F1)




To 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine dihydrochloride (C3) (0.279 g, 0.645 mmol) in a vial (25 mL) equipped with a stir bar and nitrogen was added dichloromethane (4 mL), water (2 mL), and sodium bicarbonate (0.271 g, 3.22 mmol). The reaction mixture was cooled in an ice water bath. Triphosgene (0.0770 g, 0.258 mmol) was added in one portion and the reaction was stirred vigorously until the conversion of the starting material was observed by LCMS. The reaction mixture was poured into a separatory funnel and diluted with dichloromethane. The layers were separated and the aqueous layer was extracted with dichloromethane. The organic layers were poured through a phase separator and concentrated. The resultant solid was suspended in acetonitrile (6 mL) in a round-bottomed flask (100 mL) equipped with a stir bar and nitrogen. To this was added cesium carbonate (0.231 g, 0.709 mmol) and 1-(2-isopropyl-5-methylphenyl)thiourea (0.134 g, 0.645 mmol). The reaction was stirred overnight at room temperature. The mixture was diluted with ethyl acetate and washed with half saturated brine. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent provided the title compound as a white solid (0.148 g, 39%).
The following compounds were prepared according to the procedures disclosed in Example 12:
1-[(2-Ethyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F5)




Isolated as a white solid using 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine 2,2,2-trifluoroacetate (C4) and 1-(2-Ethyl-5-methylphenyl)thiourea (C22) (0.077 g, 32%).
1-[(2-Ethyl-6-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F6)




Isolated as a white solid using 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine 2,2,2-trifluoroacetate (C4) and 1-(2-Ethyl-6-methylphenyl)thiourea (C21) (0.110 g, 45%).
1-[(2-Ethylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F7)




Isolated as a white solid using 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C5) and 1-(2-ethylphenyl)thiourea (0.108 g, 44%).
1-[(5-Methyl-2-propyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F8)




Isolated as a white solid using 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C5) and 1-(5-methyl-2-propylphenyl)thiourea (C20) (0.103 g, 40%).
1-[(2-Cyclopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F11)




Isolated as a white solid using 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C5) and 1-(2-cyclopropylphenyl)thiourea (0.106 g, 42%).
1-[(2-Isopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F14)




Isolated as a white solid using 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C5) and 1-(2-isopropylphenyl)thiourea (0.106 g, 42%).
Example 13
Preparation of 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F3)




To 5-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C6) (0.245 g, 0.597 mmol) in a round-bottomed flask (100 mL) equipped with a stir bar and nitrogen was added sodium bicarbonate (0.150 g, 1.79 mmol) followed by dichloromethane (4 mL) and water (2 mL). Triphosgene (0.0710 g, 0.239 mmol) was added in one portion and the reaction was stirred vigorously. Following conversion to the isocyanate as observed by LCMS the reaction mixture was poured through a phase separator and concentrated in a round-bottomed flask (100 mL). A stir bar and nitrogen were added to the flask and the solid was taken up in acetonitrile (6 mL). Cesium carbonate (0.214 g, 0.657 mmol) followed by 1-(2-isopropyl-5-methylphenyl)thiourea (0.124 g, 0.597 mmol) was added and the reaction was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with Brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent followed by trituration of the resultant solid with diethyl ether provided the title compound as a yellow solid (0.141 g, 37%).
Example 14
Preparation of (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F2)




To 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F1) (0.100 g, 0.168 mmol) in a vial (25 mL) equipped with a stir bar and Vigreux column was added ethanol (3 mL) followed by sodium acetate (0.0550 g, 0.673 mmol) and methyl bromoacetate (0.0230 mL, 0.252 mmol). The reaction was heated to 70° C. overnight. The reaction was cooled to room temperature and diluted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent followed by drying at 50° C. at about 25 in. Hg overnight provided the title compound as a white solid (0.0839 g, 79%).
The following compounds were prepared according to the procedures disclosed in Example 14:
(Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F4)




Isolated as a white solid using 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F3) (0.078 g, 66%).
(Z)-1-(3-(2-Ethyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F9)




Isolated as a white solid using 1-[(2-ethyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F5) (0.050 g, 72%).
(Z)-1-(3-(2-Ethyl-6-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F10)




Isolated as a white solid using 1-[(2-ethyl-6-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F6) (0.047 g, 46%).
(Z)-1-(3-(2-Ethylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F12)




Isolated as a white solid using 1-[(2-ethylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F7) (0.083 g, 81%).
(Z)-1-(3-(5-Methyl-2-propylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F13)




Isolated as a white solid using 1-[(5-methyl-2-propyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F8) (0.079 g, 81%).
(Z)-1-(3-(2-Cyclopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F15)




Isolated as a white solid using 1-[(2-cyclopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F11) (0.097 g, 83%).
(Z)-1-(3-(2-Isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (F16)




Isolated as a white solid using 1-[(2-isopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F14) (0.079 g, 78%).
Example 15
Preparation of benzyl (6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (C25)




6-Bromo-1,2,3,4-tetrahydronaphthalen-2-amine (0.14 g, 0.62 mmol) and sodium hydroxide (0.099 g, 2.5 mmol) in tetrahydrofuran/water (2.4 mL, 1:1) was stirred at room temperature. Benzyl chloroformate (0.10 mL, 0.68 mmol) was added. The reaction was stirred for 1 hour. The reaction was quenched with brine and diluted with ethyl acetate. The organic layer was separated and concentrated providing the title compound as an orange solid which was used without further purification (0.28 g, 125%): ESIMS m/z 360, 362 ([M+H]+).
Example 16
Preparation of benzyl (6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (C26)




Benzyl (6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (C25) (0.28 g, 0.85 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.038 g, 0.052 mmol), bis(pinacolato)diboron (0.26 mg, 1.0 mmol), and potassium acetate (0.17 g, 1.7 mmol) in dioxane (3.4 mL) was heated at 75° C. overnight. The reaction was cooled, quenched with water, and extracted with ethyl acetate. The organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent provided the title compound as a clear oil (0.11 g, 35%): 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J=7.6 Hz, 2H), 7.40-7.29 (m, 5H), 7.07 (d, J=7.6 Hz, 1H), 5.10 (s, 2H), 4.78 (s, 1H), 4.06 (s, 1H), 3.15 (dd, J=16.5, 5.1 Hz, 1H), 2.89 (t, J=6.6 Hz, 2H), 2.67 (dd, J=16.7, 8.2 Hz, 1H), 2.09 (d, J=2.7 Hz, 1H), 1.79 (d, J=11.6 Hz, 1H), 1.33 (s, 12H); 13C NMR (126 MHz, CDCl3) δ 155.70, 137.44, 136.50, 135.36, 134.77, 132.18, 128.96, 128.53, 128.13, 126.99, 83.72, 66.63, 60.40, 46.68, 36.20, 25.03, 24.83; ESIMS m/z 408 ([M+H]+).
Example 17
Preparation of benzyl (6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (C27)




3-Bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (0.088 g, 0.29 mmol), benzyl (6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (C26) (0.12 g, 0.26 mmol), dichloro[1,1-bis(di-tert-butylphosphino)ferrocene]palladium(II) (0.015 g, 0.023 mmol), and potassium phosphate (0.16 g, 0.75 mmol) in dioxane (1.3 mL) and water (0.4 mL) was heated at 75° C. for 6 hours. The reaction was cooled and diluted with ethyl acetate and washed with brine. The brine layer was extracted with ethyl acetate. The organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-100% ethyl acetate/B, where B is 1:1 dichloromethane/hexanes as eluent provided the title compound as a white solid (0.088 g, 65%): mp 138-139° C.; 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 7.93 (d, J=6.0 Hz, 2H), 7.83-7.76 (m, 2H), 7.42-7.29 (m, 7H), 7.17 (d, J=8.4 Hz, 1H), 5.12 (s, 2H), 4.83 (d, J=8.0 Hz, 1H), 4.10 (s, 1H), 3.20 (d, J=18.6 Hz, 1H), 2.98 (t, J=6.7 Hz, 2H), 2.72 (dd, J=16.5, 8.2 Hz, 1H), 2.12 (s, 1H), 1.84 (d, J=12.7 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 509 ([M+H]+).
Example 18
Preparation of 6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-amine (C28)




Benzyl (6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (C27) (0.088 g, 0.17 mmol) and palladium on carbon (10 wt %, 0.018 g, 0.017 mmol) in ethyl acetate (1.7 mL) was stirred under hydrogen (balloon) for 6 hours. The reaction was filtered through Celite®, washed with ethyl acetate, and concentrated providing the title compound as a black solid. (0.060 g, 91%): mp 112-116° C.; 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 7.92 (d, J=7.7 Hz, 2H), 7.84-7.76 (m, 2H), 7.38 (dq, J=7.8, 1.0 Hz, 2H), 7.19 (d, J=7.9 Hz, 1H), 3.29-3.18 (m, 1H), 3.09-2.91 (m, 3H), 2.61 (dd, J=16.3, 9.3 Hz, 1H), 2.09-2.00 (m, 1H), 1.64 (dtd, J=12.8, 10.3, 6.0 Hz, 1H), 1.43 (s, 2H); 19F NMR (376 MHz, CDCl3) δ −58.04; EIMS m/z 373 ([M]+).
Alternative preparation of 6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-amine (C28)
To a solution of tert-butyl (6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (CA38) (15.0 g, 32.6 mmol) in dichloromethane (225 mL) was added 3,3,3-triflouroacetic acid (27.0 mL, 359 mmol) in one portion at 0° C. After addition, the ice bath was removed, and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and the residue was triturated with diethyl ether/hexanes. The resultant 3,3,3-trifluoroacetate salt was dissolved in dichloromethane and washed with sodium hydroxide (1 N). The organic layer was separated and concentrated to provide the title compound as an off-white solid (7.50 g, 64%): 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.91 (d, J=7.6 Hz, 2H), 7.79 (d, J=8.8 Hz, 2H), 7.37 (d, J=8.8 Hz, 2H), 7.18 (d, J=8 Hz, 1H), 3.26-3.19 (m, 1H), 3.08-2.93 (m, 3H), 2.64-2.57 (m, 1H), 2.06-2.02 (m, 1H), 1.68-1.59 (m, 1H); ESIMS m/z 375 ([M+H]+).
Example 19
Preparation of 2-imino-3-(2-isopropyl-5-methylphenyl)thiazolidin-4-one (C29)




Step 1.
2-Isopropyl-5-methylaniline (286 g, 1.91 mol) and sodium bicarbonate (270 g, 3.22 mol) were charged in to a round bottomed flask with stirring under nitrogen atmosphere and cooled to 0-5° C. 2-Chloroacetyl chloride (218 g, 1.93 mol) was added drop wise at 0-5° C. over a period of 1 hour. The reaction was stirred at 0-5° C. for 1 hour. After completion of the reaction, purified water (2.86 L) was added and stirred at 25-30° C. for 15 minutes. The layers were then separated. The organic layer was washed with water (2×2.86 L) and with brine (1.43 L). The aqueous layers were combined and extracted with ethyl acetate (1.43 L). The organic layers were dried with sodium sulphate, filtered, and concentrated at 50-55° C. under vacuum (500-600 mm Hg) to 2⁄5ths volume. Hexanes (2.86 L) were added and the mixture was stirred at 25-30° C. for 1 hour. The solid was filtered, washed with hexanes (1.43 L), and dried at 45-50° C. under vacuum (500-600 mm Hg) to give 2-chloro-N-(2-isopropyl-5-methylphenyl)acetamide as an off-white solid (270 g, 66%): mp 97-99° C.; 1H NMR (300 MHz, CDCl3) δ 8.27 (s, 1H), 7.60 (s, 1H), 7.20 (d, J=7.95 Hz, 1H), 7.04 (d, J=7.89 Hz, 1H), 4.25 (s, 2H), 2.99 (q, J=6.78 Hz, 1H), 2.34 (s, 3H), 1.26 (d, J=6.84 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 164.07, 137.28, 136.33, 132.95, 127.35, 125.62, 124.46, 43.21, 27.86, 22.98, 21.00; ESIMS m/z 226 ([M+H]+).
Step 2.
2-Chloro-N-(2-isopropyl-5-methylphenyl)acetamide (290 g, 1.28 mol) and acetone (1.60 L) were charged in to a round bottomed flask with stirring under a nitrogen atmosphere. Potassium thiocyanate (250 g, 2.57 mol) was added in portions over a period of 30 minutes maintaining the temperature at 15-20° C. The reaction was stirred at 15-20° C. for 10 minutes after which time the temperature was slowly raised 53-55° C. and maintained at 53-55° C. for 3 hours. The reaction was then cooled to 20-25° C., cesium carbonate (20.9 g, 0.0641 mol) was added, and the reaction mixture was stirred at 20-25° C. for 30 minutes. After completion, the reaction mixture was filtered through Celite®, washed with acetone (1.45 L), and the filtrate collected. The filtrate was concentrated at 40-45° C. under vacuum (500-600 mm Hg) providing a syrup. The syrup was dissolved in ethyl acetate (2.90 L), washed with water (2×2.90 L) and with brine (1.45 L). The organic layers were dried with sodium sulphate, filtered, and concentrated at 50-55° C. under vacuum (500-600 mm Hg) to provide the title compound as a dark brown syrup (345 g, 99%): 1H NMR (400 MHz, CDCl3) δ 7.64 (s, 1H), 7.44-7.38 (m, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.12-7.02 (m, 1H), 3.88 (s, 2H), 3.04 (tp, J=13.7, 6.9 Hz, 1H), 2.38-2.31 (m, 1H), 2.32 (s, 3H), 1.25 (d, J=6.8 Hz, 6H); ESIMS m/z 248 ([M]+).
Example 20
Preparation of (Z)-4-nitrophenyl (3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)carbamate (C30)




2-Imino-3-(2-isopropyl-5-methylphenyl)thiazolidin-4-one (C29) (0.97 g, 3.9 mmol), 4-nitrophenyl chloroformate (0.83 g, 4.1 mmol), and cesium carbonate (1.3 g, 4.1 mmol) in acetonitrile (9.8 mL) was stirred at room temperature 30 minutes. The reaction was diluted with dichloromethane and adsorbed onto silica gel. Purification by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent provided the title compound as an orange foam (1.4 g, 87%): 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J=9.2 Hz, 2H), 7.35 (d, J=8.1 Hz, 1H), 7.32-7.27 (m, 3H), 6.90-6.85 (m, 1H), 4.06 (d, J=1.8 Hz, 2H), 2.61 (p, J=6.8 Hz, 1H), 2.36 (d, J=0.8 Hz, 3H), 1.25-1.12 (m, 6H); ESIMS m/z 414 ([M+H]+).
Example 21
Preparation of (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (F17)




6-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-amine (C28) (0.060 g, 0.16 mmol), (Z)-4-nitrophenyl (3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)carbamate (C30) (0.080 g, 0.19 mmol), and cesium carbonate (0.026 g, 0.080 mmol) in acetonitrile (1.6 mL) was stirred at room temperature for 4 hours. The reaction was diluted with water and dichloromethane and filtered through phase separator. The solution concentrated and loaded onto Celite cartridge. Purification by flash column chromatography using 0-100% ethyl acetate/B, where B is 1:1 dichloromethane/hexanes as eluent provided the title compound as a tan solid (0.083 g, 79%).
Example 22
Preparation of 3-(2-isocyanato-2,3-dihydro-1H-inden-5-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (CA1)




To a solution of 5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-amine (C5) (3.00 g, 8.33 mmol) in dichloromethane and water (15:7.5 mL) under a nitrogen atmosphere was added sodium bicarbonate (2.10 g, 25.0 mmol). The reaction mixture was cooled in an ice water bath and triphosgene (1.20 g, 4.17 mmol) in dichloromethane was added slowly; the reaction mixture was stirred for 2 hours. The reaction mixture was diluted with dichloromethane, and the layers were separated; the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the title compound as a white solid which was used in the next step without further purification or characterization (2.60 g, 81%).
The following compounds were prepared in accordance to the procedure in Example 22:
3-(6-Isocyanato-5,6,7,8-tetrahydronaphthalen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (CA2)




The title compound was prepared as described in Example 22 using 6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-amine (C28) and isolated as a white solid (2.6 g, 78%): 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.56 (s, 1H), 7.95 (d, J=6.4 Hz, 2H), 7.81-7.78 (m, 2H), 7.38 (d, J=8.4 Hz, 2H), 7.18 (d, J=8.4 Hz, 1H), 4.02-3.94 (bs, 1H), 3.20-3.15 (m, 1H), 3.10-3.03 (m, 1H), 2.98-2.90 (m, 1H), 2.17-2.12 (m, 1H), 2.04-1.97 (m, 1H); ESIMS m/z 402 ([M+H]+).
Example 23
Preparation of 3-(2-isocyanato-2,3-dihydro-1H-inden-5-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (P1)




To a solution of 3-(2-isocyanato-2,3-dihydro-1H-inden-5-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (CA1) (0.40 g, 1.0 mmol) in acetonitrile (5.0 mL) was added cesium carbonate (0.37 g, 1.1 mmol) and 1-(4-methoxy-2-methylphenyl)thiourea (CA3) (0.203 g, 1.03 mmol) and the reaction mixture was stirred for 16 h at rt. The reaction mixture was diluted with ethyl acetate and washed with brine. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (100-200 mesh silica) eluting with, 40% of ethyl acetate in hexane to afford compound 10a (0.08 g, 13%) as a white solid. The following compounds were prepared in accordance to the procedure in Example 23:
1-[(4-Fluoro-2-isopropyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P2)




The title compound was prepared as described in Example 23 using 1-(4-fluoro-2-isopropylphenyl)thiourea (CA5) and isolated as an off-white solid (0.070 g, 13%).
1-[(5-Chloro-2-isopropyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P3)




The title compound was prepared as described in Example 23 using 1-(5-chloro-2-isopropylphenyl)thiourea (C24) and isolated as a white solid (0.110 g, 18%).
1-[(2-Isopropyl-5-methoxy-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P4)




The title compound was prepared as described in Example 23 using 1-(2-isopropyl-5-methoxyphenyl)thiourea (C23) and isolated as a white solid (0.050 g, 8%).
1-[(2-Isopropyl-4-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P5)




The title compound was prepared as described in Example 23 using 1-(2-isopropyl-4-methylphenyl)thiourea (CA4) and isolated as a pale green solid (0.040 g, 7%).
1-[(2-Isopropyl-5-methyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P21)




The title compound was prepared as described in Example 23 using 1-(2-isopropyl-5-methylphenyl)thiourea and isolated as an off-white solid (0.1 g, 26%).
1-[(2-Isopropylphenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P22)




The title compound was prepared as described in Example 23 using 1-(2-isopropylphenyl)thiourea and isolated as an off-white solid (0.090 g, 22%).
1-[(2,5-Dimethylphenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P25)




The title compound was prepared as described in Example 23 using 1-(2,5-dimethylphenyl)thiourea and isolated as an off-white solid (0.060 g, 17%).
1-[(5-Chloro-2-isopropyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P26)




The title compound was prepared as described in Example 23 using 1-(5-chloro-2-isopropylphenyl)thiourea (C24) and isolated as an off-white solid (0.090 g, 23%).
1-[(5-Methyl-2-propyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P27)




The title compound was prepared as described in Example 23 using 1-(5-methyl-2-propylphenyl)thiourea (C20) and isolated as an off-white solid (0.095 g, 25%).
1-[(4-Methoxy-2-methyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P28)




The title compound was prepared as described in Example 23 using 1-(4-methoxy-2-methylphenyl)thiourea (CA3) and isolated as a white solid (0.064 g, 10%).
1-[(2-Ethyl-6-methyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P29)




The title compound was prepared as described in Example 23 using 1-(2-ethyl-6-methylphenyl)thiourea (C21) and isolated as an off-white solid (0.120 g, 32%).
1-[(2-Chloro-5-methyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P30)




The title compound was prepared as described in Example 23 using 1-(2-chloro-5-methylphenyl)thiourea and isolated as an off-white solid (0.060 g, 16%).
1-[(2-Methoxy-5-methyl-phenyl)carbamothioyl]-3-[6-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]tetralin-2-yl]urea (P31)




The title compound was prepared as described in Example 23 using 1-(2-methoxy-5-methylphenyl)thiourea and isolated as an off-white solid (0.065 g, 18%).
Example 24
Preparation of 1-(4-methoxy-2-methylphenyl)thiourea (CA3)




To a solution of N-((4-methoxy-2-methylphenyl)carbamothioyl)benzamide (CA6) (4.0 g, 13 mmol) in methanol (40 mL) was added sodium hydroxide (2 N, 12 mL, 27 mmol), and the reaction mixture was stirred at 50° C. for 6 hours. The reaction mixture was cooled to room temperature and concentrated. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to provide the title compound as a gray solid (1.4 g, 54%): mp 198-200° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.06 (s, 1H), 7.50 (bs, 1H), 7.03 (d, J=8.7 Hz, 1H), 6.82 (d, J=2.7 Hz, 1H), 6.74 (dd, J=9.0, 8.4 Hz, 1H), 3.73 (s, 3H), 2.14 (s, 3H); ESIMS m/z 197 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 24:
1-(2-Isopropyl-4-methylphenyl)thiourea (CA4)




The title compound was prepared as described in Example 24 using N-((2-isopropyl-4-methylphenyl)carbamothioyl)benzamide (CA7) and isolated as a pale yellow solid (3.0 g, 91%): mp 142-145° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 7.50 (bs, 1H), 7.13 (s, 1H), 6.98 (s, 2H), 6.50 (bs, 1H), 3.04-2.99 (m, 1H), 2.29 (s, 3H), 1.13 (d, J=7.6 Hz, 6H); ESIMS m/z 209 ([M+H]+).
1-(4-Fluoro-2-isopropylphenyl)thiourea (CA5)




The title compound was prepared as described in Example 24 using N-((4-fluoro-2-isopropylphenyl)carbamothioyl)benzamide (CA8) and isolated as a white solid (2.8 g, 93%): mp 168-172° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 7.55 (bs, 1H), 7.15-7.11 (m, 2H), 7.05-6.97 (m, 1H), 6.50 (bs, 1H), 3.05-3.00 (m, 1H), 1.13 (d, J=6.8 Hz, 6H); ESIMS m/z 209 ([M+H]+).
Example 25
Preparation of N-((4-methoxy-2-methylphenyl)carbamothioyl)benzamide (CA6)




To a solution of 4-methoxy-2-methylaniline (2.0 g, 15 mmol) in acetone (70 mL) was added benzoyl isothiocyanate (2.0 mL, 15 mmol), and the reaction mixture was heated at 50° C. for 16 hours. The reaction mixture was concentrated to provide the title compounds as an off-white solid (4.0 g, 91%): 1H NMR (400 MHz, CDCl3) δ 12.1 (s, 1H), 9.13 (s, 1H), 7.92-7.89 (m, 2H), 7.68-7.64 (m, 1H), 7.57-7.50 (m, 3H), 6.82-6.80 (m, 2H), 3.82-3.80 (s, 3H), 2.33 (s, 3H).
The following compounds were prepared in accordance to the procedure in Example 25:
N-((2-Isopropyl-4-methylphenyl)carbamothioyl)benzamide (CA7)




The title compound was prepared as described in Example 25 using 2-isopropyl-4-methylaniline (CA9) and isolated as a pale yellow solid (5.0 g, 76%): 1H NMR (400 MHz, CDCl3) δ 12.1 (s, 1H), 9.15 (s, 1H), 7.92-7.90 (m, 2H), 7.68-7.64 (m, 1H), 7.58-7.53 (m, 2H), 7.45-7.43 (m, 1H), 7.17 (s, 1H), 7.08 (dd, J=8.4, 1.6 Hz, 1H), 3.15-3.08 (m, 1H), 2.38 (s, 3H), 1.27 (d, J=6.8 Hz, 6H); ESIMS m/z 313 ([M+H]+).
N-((4-Fluoro-2-isopropylphenyl)carbamothioyl)benzamide (CA8)




The title compound was prepared as described in Example 25 using 4-fluoro-2-isopropylaniline (CA10) and isolated as a pale yellow solid (4.5 g, 88%): 1H NMR (400 MHz, CDCl3) δ 12.1 (s, 1H), 9.18 (s, 1H), 7.93-7.90 (m, 2H), 7.69-7.64 (m, 1H), 7.58-7.52 (m, 3H), 7.06 (dd, J=8.4, 1.6 Hz, 1H), 6.99-6.94 (m, 1H), 3.15-3.11 (m, 1H), 1.26 (d, J=6.8 Hz, 6H); ESIMS m/z 317 ([M+H]+).
Example 26
Preparation of 2-isopropyl-4-methylaniline (CA9)




To a solution of 4-methyl-1-nitro-2-(prop-1-en-2-yl)benzene (CA11) (3.6 g, 20 mmol) in ethyl acetate (40 mL) was added palladium on carbon (10%, 0.50 g), and the reaction mixture was evacuated and purged with hydrogen. The reaction mixture was stirred under hydrogen (50 psi) for 24 hours. The reaction mixture was filtered over a pad of Celite®, washed with ethyl acetate, and concentrated. The crude product was triturated with diethyl ether to provide the title compound as a pale yellow liquid (2.8 g, 93%): 1H NMR (300 MHz, CDCl3) δ 6.95 (s, 1H), 6.83 (d, J=7.5 Hz, 1H), 6.60 (d, J=8.1 Hz, 1H), 3.50 (bs, 2H), 2.93-2.85 (m, 1H), 2.25 (s, 3H), 1.25 (d, J=6.9 Hz, 6H); ESIMS m/z 150 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 26:
4-Fluoro-2-isopropylaniline (CA10)




The title compound was prepared as described in Example 26 using 4-fluoro-1-nitro-2-(prop-1-en-2-yl)benzene (CA12) and isolated as an off-white solid (2.5 g, 90%): 1H NMR (400 MHz, CDCl3) δ 6.85 (dd, J=10.5, 2.4 Hz, 1H), 6.75-6.69 (m, 1H), 6.63-6.58 (m, 1H), 3.44 (bs, 2H), 2.93-2.84 (m, 1H), 1.24 (d, J=6.0 Hz, 6H); ESIMS m/z 154 ([M+H]+).
Example 27
Preparation of 4-methyl-1-nitro-2-(prop-1-en-2-yl)benzene (CA11)




To a stirred solution of 2-chloro-4-methyl-1-nitrobenzene (5.0 g, 29 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (5.9 g, 35 mmol) in 1,4-dioxane and water (30:10 mL) was added sodium carbonate (3.7 g, 35 mmol); the reaction mixture was degassed with argon for 10 minutes. Bis(triphenylphosphine)palladium(II) dichloride (1.6 g, 2.3 mmol) was added to the reaction mixture (degassed for 5 additional minutes), and the reaction mixture was heated to 100° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with water (30 mL), and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 20-80% ethyl acetate/hexanes as eluent provided the title compound as a pale yellow solid (3.6 g, 73%): 1H NMR (300 MHz, CDCl3) δ 7.81 (d, J=8.4 Hz, 1H), 7.16 (d, J=8.4 Hz, 1H), 7.10 (s, 1H), 5.15 (t, J=1.5 Hz, 1H), 4.90 (s, 1H), 2.42 (s, 3H), 2.07 (s, 3H); ESIMS m/z 178 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 27:
4-Fluoro-1-nitro-2-(prop-1-en-2-yl)benzene (CA12)




The title compound was prepared as described in Example 27 using 2-chloro-4-fluoro-1-nitrobenzene and isolated as a pale yellow liquid (2.6 g, 84%): 1H NMR (400 MHz, CDCl3) δ 7.97-7.93 (m, 1H), 7.10-7.06 (m, 1H), 7.01 (dd, J=8.8, 2.8 Hz 1H), 5.19 (t, J=1.6 Hz, 1H), 4.96 (s, 1H), 2.08 (s, 3H); ESIMS m/z 182 ([M+H]+).
Example 28
Preparation of (Z)-1-(3-(4-methoxy-2-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P6)




To a solution of 3-(2-isocyanato-2,3-dihydro-1H-inden-5-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (P1) (0.40 g, 0.69 mmol) in ethanol (5 mL) was added sodium acetate (0.12 g, 1.4 mmol) and methyl 2-bromoacetate (0.10 mL, 1.0 mmol). The reaction mixture was heated to 70° C. overnight, cooled to room temperature, and diluted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by reverse phase column chromatography using 70-80% acetonitrile/0.1% formic acid in water as eluent provided the title compound as a pale yellow solid (0.12 g, 28%).
The following compounds were prepared in accordance to the procedure in Example 28:
(Z)-1-(3-(2-Isopropyl-4-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P7)




The title compound was prepared as described in Example 28 using 1-[(2-isopropyl-4-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P5) and isolated as an off-white solid (0.090 g, 14%).
(Z)-1-(3-(5-Chloro-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P8)




The title compound was prepared as described in Example 28 using 1-[(5-chloro-2-isopropyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P3) and isolated as a pale yellow liquid (0.060 g, 23%).
(Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P9)




The title compound was prepared as described in Example 28 using 1-[(2-isopropyl-5-methoxy-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P4) and isolated as a pale yellow solid (0.095 g, 15%).
(Z)-1-(3-(4-Fluoro-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P10)




The title compound was prepared as described in Example 28 using 1-[(4-fluoro-2-isopropyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (P2) and isolated as an off-white solid (0.190 g, 35%).
Example 29
Preparation of (Z)-1-(3-(2-isopropylphenyl)-4-methylthiazol-2(3H)-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (FA1)




To a solution of 1-[(2-isopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F14) (0.30 g, 0.52 mmol) in 2-butanone (5 mL) was added triethylamine (0.080 mL, 0.57 mmol) followed by chloroacetone (0.047 mL, 0.57 mmol), and the reaction mixture was heated at 80° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with water. The aqueous layer was extracted with dichloromethane (2×25 mL) and separated. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by preparative high pressure liquid chromatography provided the title compound as a pale brown solid (0.055 g, 19%).
The following compounds were prepared in accordance to the procedure in Example 29:
(Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-methylthiazol-2(3H)-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P12)




The title compound was prepared as described in Example 29 using 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F1) and isolated as an off-white solid (0.030 g, 11%).
Example 30
Preparation of (Z)-1-(3-(2-isopropylphenyl)-5-methyl-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (FA2)




To a solution of 1-[(2-isopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F14) (0.25 g, 0.43 mmol) in ethanol (2 mL) was added sodium acetate (0.078 g, 0.83 mmol) and methyl 2-brompropanoate (0.072 mL, 0.65 mmol) and heated to 60° C. for 16 hours. The reaction mixture was cooled to rt and diluted with water. The aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by reverse phase column chromatography using 70-80% acetonitrile/0.1% formic acid in water as eluent provided the title compound as a pale yellow solid (0.11 g, 37%).
The following compounds were prepared in accordance to the procedure in Example 30:
(Z)-1-(3-(2-Isopropyl-5-methylphenyl)-5-methyl-4-oxothiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P13)




The title compound was prepared as described in Example 30 using 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F1) and isolated as an off-white solid (0.095 g, 35%).
Example 31
Preparation of (Z)-1-(3-(2-isopropylphenyl)-4-methylthiazolidin-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (FA3)




To a solution of 1-[(2-isopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F14) (0.20 g, 0.33 mmol) in 2-butanone (3 mL) was added potassium carbonate (0.096 g, 0.52 mmol), 1,2-dibromopropane (0.050 mL, 0.52 mmol), and the reaction mixture was heated to 80° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with water. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by reverse phase column chromatography using 70-80% acetonitrile/0.1% formic acid in water as eluent to provide the title compound as a pale yellow solid (0.030 g, 14%).
Example 32
Preparation of (Z)-1-(3-(2-isopropylphenyl)-4-oxo-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (FA4)




To a solution of 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F1) (0.30 g, 0.52 mmol) in 2-butanone (2 mL) was added acryloyl chloride (0.050 mL, 0.62 mmol) and heated at 40° C. for 4 hours. The reaction mixture was cooled to room temperature and concentrated. Purification by reverse phase column chromatography using 70-80% acetonitrile/0.1% formic acid in water as eluent provided the title compound as an off-white solid (0.016 g, 5%).
The following compounds were prepared in accordance to the procedure in Example 32:
(Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxo-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P17)




The title compound was prepared as described in Example 32 using 1-[(2-isopropylphenyl)carbamothioyl]-3-[5-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]indan-2-yl]urea (F14) and isolated as a yellow solid (0.015 g, 7%).
Example 33
Preparation of (Z)-1-(3-(2-isopropyl-5-methylphenyl)-5-methyl-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P18)




To a solution of 3-(2-isocyanato-2,3-dihydro-1H-inden-5-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (CA1) (0.35 g, 0.92 mmol) in acetonitrile (10 mL) was added cesium carbonate (0.60 g, 1.8 mmol) and 3-(2-isopropyl-5-methylphenyl)-5-methyl-1,3-thiazinan-2-imine (CA13) (0.24 g, 0.92 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with 50% saturated brine. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by reverse phase column chromatography 70-80% acetonitrile/0.1% formic acid in water as eluent provided the title compound as an off-white solid (0.10 g, 17%).
The following compounds were prepared in accordance to the procedure in Example 33:
(Z)-1-(3-(2-Isopropylphenyl)-5-methyl-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (FA5)




The title compound was prepared as described in Example 33 using 3-(2-isopropylphenyl)-5-methyl-1,3-thiazinan-2-imine (CA14) and isolated as an off-white solid (0.140 g, 28%).
(Z)-1-(3-(2-Isopropylphenyl)-4-methyl-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (FA6)




The title compound was prepared as described in Example 33 using 3-(2-isopropylphenyl)-4-methyl-1,3-thiazinan-2-imine (CA16) and isolated as a pale yellow solid (0.050 g, 10%).
(Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-methyl-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P16)




The title compound was prepared as described in Example 33 using 3-(2-isopropyl-5-methylphenyl)-4-methyl-1,3-thiazinan-2-imine (CA15) and isolated as a yellow green liquid (0.013 g, 3%).
(Z)-1-(3-(2-Isopropylphenyl)-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P19)




The title compound was prepared as described in Example 33 using 3-(2-isopropylphenyl)-1,3-thiazinan-2-imine (CA18) and isolated as a pale yellow solid (0.060 g, 15%).
(Z)-1-(3-(2-Isopropyl-5-methylphenyl)-1,3-thiazinan-2-ylidene)-3-(5-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2,3-dihydro-1H-inden-2-yl)urea (P20)




The title compound was prepared as described in Example 33 using 3-(2-isopropyl-5-methylphenyl)-1,3-thiazinan-2-imine (CA17) and isolated as an off-white solid (0.053 g, 6%).
Example 34
Preparation of 3-(2-isopropyl-5-methylphenyl)-5-methyl-1,3-thiazinan-2-imine (CA13)




To a solution of 1-(2-isopropyl-5-methylphenyl)thiourea (0.50 g, 2.6 mmol) in 2-butanone (13 mL) was added potassium (0.71 g, 5.1 mmol), 1,3-dibromobutane (0.46 mL, 3.9 mmol), and the reaction mixture was heated at 60° C. for 16 hours. The reaction mixture was cooled to room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to provide the title compound as a gummy oil which was used in the next step without purification (0.30 g, 74%): EIMS m/z 263 ([M]+).
The following compounds were prepared in accordance to the procedure in Example 34:
3-(2-Isopropylphenyl)-5-methyl-1,3-thiazinan-2-imine (CA14)




The title compound was prepared as described in Example 34 using 1-(2-isopropylphenyl)thiourea and isolated as gummy oil: ESIMS m/z 249 ([M+H]+).
3-(2-Isopropyl-5-methylphenyl)-4-methyl-1,3-thiazinan-2-imine (CA15)




The title compound was prepared as described in Example 34 using 1-bromo-3-chloro-2-methylpropane and isolated as a tan oil (0.24 g, 89%).
3-(2-Isopropylphenyl)-4-methyl-1,3-thiazinan-2-imine (CA16)




The title compound was prepared as described in Example 34 using 1-(2-isopropylphenyl)thiourea and 1-bromo-3-chloro-2-methylpropane and isolated as a gummy oil: ESIMS m/z 249 ([M+H]+).
3-(2-Isopropyl-5-methylphenyl)-1,3-thiazinan-2-imine (CA17)




The title compound was prepared as described in Example 34 using 1,3-dibromobutane: ESIMS m/z 249 ([M+H]+).
3-(2-Isopropylphenyl)-1,3-thiazinan-2-imine (CA18)




The title compound was prepared as described in Example 34 using 1-(2-isopropylphenyl)thiourea and 1,3-dibromobutane: ESIMS m/z 235 ([M+H]+).
Example 35
Preparation of (Z)-1-(3-(4-methoxy-2-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P35)




To a stirred solution of 6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-amine (C28) (0.25 g, 0.66 mmol) in acetonitrile was added 4-nitrophenylchloroformate (0.16 g, 0.80 mmol) was added at room temperature under argon atmosphere and stirred for 1 hour. 2-Imino-3-(4-methoxy-2-methylphenyl)thiazolidin-4-one (CA19) (0.17 g, 0.73 mmol) was added followed by cesium carbonate (0.43 g, 1.3 mmol) and diisopropylethylamine (0.28 g, 2.0 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered through Celite®, and the filtrate was concentrated. Purification by preparative high pressure liquid chromatography provided the title compound as an off-white solid (0.075 g, 19%).
The following compounds were prepared in accordance to the procedure in Example 35:
(Z)-1-(3-(2-Isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P24)




The title compound was prepared as described in Example 35 using 2-imino-3-(2-isopropylphenyl)thiazolidin-4-one (CA24) and isolated as an off-white solid (0.190 g, 28%).
(Z)-1-(3-(2,5-Dimethylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P32)




The title compound was prepared as described in Example 35 using 3-(2,5-dimethylphenyl)-2-iminothiazolidin-4-one (CA20) and isolated as an off-white solid (0.090 g, 20%).
(Z)-1-(3-(5-Chloro-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P33)




The title compound was prepared as described in Example 35 using 3-(5-chloro-2-isopropylphenyl)-2-iminothiazolidin-4-one (CA22) and isolated as an off-white solid (0.030 g, 8%).
(Z)-1-(3-(5-Methyl-2-propylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P34)




The title compound was prepared as described in Example 35 using 2-imino-3-(5-methyl-2-propylphenyl)thiazolidin-4-one (CA25) and isolated as an off-white solid (0.055 g, 14%).
(Z)-1-(3-(2-Ethyl-6-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P36)




The title compound was prepared as described in Example 35 using 3-(2-ethyl-6-methylphenyl)-2-iminothiazolidin-4-one (CA21) and isolated as an off-white solid (0.100 g, 25%).
(Z)-1-(3-(2-Chloro-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P37)




The title compound was prepared as described in Example 35 using 3-(2-chloro-5-methylphenyl)-2-iminothiazolidin-4-one (CA23) and isolated as an off-white solid (0.050 g, 10%).
(Z)-1-(3-(2-Methoxy-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)urea (P38)




The title compound was prepared as described in Example 35 using 2-imino-3-(2-methoxy-5-methylphenyl)thiazolidin-4-one (CA26) and isolated as an off-white solid (0.120 g, 30%).
Example 36
Preparation of 2-imino-3-(4-methoxy-2-methylphenyl)thiazolidin-4-one (CA19)




To a solution of N-carbamothioyl-2-chloro-N-(4-methoxy-2-methylphenyl)acetamide (CA27) (0.700 g, 3.27 mmol) in acetone (15 mL) and potassium thiocyanate (0.636 g, 6.55 mmol) was heated to reflux for 5 hours. The reaction mixture was cooled to room temperature followed by the addition of cesium carbonate (0.0550 g, 0.160 mmol), and the reaction mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated and the residue was purified by flash column chromatography to provide the title compound as an off-white solid which was used without further purification (0.650 g, 84%): ESIMS m/z 237 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 36:
3-(2,5-Dimethylphenyl)-2-iminothiazolidin-4-one (CA20)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(2,5-dimethylphenyl)acetamide (CA28) and isolated as a brown liquid (0.800 g, 44%): 1H NMR (300 MHz, CDCl3) δ 7.84 (br s, 1H), 7.23-7.19 (m, 2H), 6.94 (s, 1H), 4.08 (s, 2H), 2.34 (s, 3H), 2.12 (s, 3H); ESIMS m/z 221 ([M+H]+).
3-(2-Ethyl-6-methylphenyl)-2-iminothiazolidin-4-one (CA21)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (CA29) and isolated as a pale brown solid (1.3 g, 81%): mp 120-123° C.; 1H NMR (400 MHz, CDCl3) δ 7.83 (br s, 1H), 7.31-7.19 (m, 3H), 4.18-4.03 (m, 2H), 2.47 (q, J=7.2 Hz, 2H), 2.21-2.03 (s, 3H), 1.18 (t, J=6.8 Hz, 3H); ESIMS m/z 235 ([M+H]+).
3-(5-Chloro-2-isopropylphenyl)-2-iminothiazolidin-4-one (CA22)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(5-chloro-2-isopropylphenyl)acetamide (CA30) and isolated as a pale yellow liquid (0.450 g, 40%): 1H NMR (400 MHz, CDCl3) δ 7.89 (br s, 1H), 7.41 (br s, 1H), 7.11 (d, J=1.6 Hz, 1H), 4.10 (br s, 2H), 2.70 (m, 1H), 1.24-1.19 (m, 6H); ESIMS m/z 269 ([M+H]+).
3-(2-Chloro-5-methylphenyl)-2-iminothiazolidin-4-one (CA23)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(2-chloro-5-methylphenyl)acetamide (CA31) and isolated as a pale brown solid (0.700 g, 45%): mp 128-129° C.; 1H NMR (400 MHz, CDCl3) δ 7.87 (br s, 1H), 7.44 (br d, J=7.8 Hz, 1H), 7.24 (br s, 1H), 7.11 (s, 1H), 4.17-4.04 (m, 4H), 2.38 (s, 3H); ESIMS m/z 241 ([M+H]+).
2-Imino-3-(2-isopropylphenyl)thiazolidin-4-one (CA24)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(2-isopropylphenyl)acetamide (CA32) and isolated as a brown liquid (2.1 g, 63%): 1H NMR (300 MHz, CDCl3) δ 7.48 (m, 2H), 7.37-7.29 (m, 1H), 7.08 (d, J=7.7 Hz, 1H), 4.09 (s, 2H), 2.65-2.78 (m, 1H), 1.20 (dd, J=6.6, 2.2 Hz, 6H); ESIMS m/z 235 ([M+H]+).
2-Imino-3-(5-methyl-2-propylphenyl)thiazolidin-4-one (CA25)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(5-methyl-2-propylphenyl)acetamide (CA33) and isolated as a brown liquid (0.600 g, 34%): 1H NMR (300 MHz, CDCl3) δ 7.84 (br s, 1H), 7.29 (m, 2H), 6.92 (s, 1H), 4.10-4.08 (m, 2H), 2.40-2.35 (m, 3H), 1.60-1.53 (m, 2H), 0.95-0.89 (m, 3H); ESIMS m/z 249 ([M+H]+).
2-Imino-3-(2-methoxy-5-methylphenyl)thiazolidin-4-one (CA26)




The title compound was prepared as described in Example 36 using N-carbamothioyl-2-chloro-N-(2-methoxy-5-methylphenyl)acetamide (CA34) and isolated as a pale brown solid (0.650 g, 37%): mp 118-121° C.; 1H NMR (300 MHz, CDCl3) δ 7.22 (s, 1H), 7.00-6.92 (m, 2H), 4.15-3.94 (m, 2H), 3.79 (s, 3H), 2.32 (s, 3H); ESIMS m/z 237 ([M+H]+).
Example 37
Preparation of 2-chloro-N-(4-methoxy-2-methylphenyl)acetamide (CA27)




To a solution of 4-methoxy-2-methylaniline (0.500 g, 4.00 mmol) and sodium bicarbonate in (0.600 g, 7.21 mmol) in ethyl acetate (25 mL) was added 2-chloroacetyl chloride (0.490 g, 4.40 mmol) dropwise at room temperature. The reaction mixture was stirred for 6 hours. The reaction was concentrated and triturated with n-pentane, filtered, and dried to provide the title compound as an off-white solid (0.650 g, 76%): 1H NMR (300 MHz, CDCl3) δ 8.05 (s, 1H), 7.62-7.58 (m, 1H), 6.77-6.74 (dd, J=7.6, 4.2 Hz, 1H), 4.22 (s, 2H), 3.79 (s, 3H), 2.26 (s, 3H); ESIMS m/z 212 ([M+H]+).
The following compounds were prepared in accordance to the procedure in Example 37:
2-Chloro-N-(2,5-dimethylphenyl)acetamide (CA28)




The title compound was prepared as described in Example 37 using 2,5-dimethylaniline and isolated as an off-white solid (1.6 g, 98%): ESIMS m/z 198 ([M+H]+).
2-Chloro-N-(2-ethyl-6-methylphenyl)acetamide (CA29)




The title compound was prepared as described in Example 37 using 2-ethyl-6-methylaniline and isolated as an off-white solid (1.5 g, 96%): ESIMS m/z 212 ([M+H]+).
2-Chloro-N-(5-chloro-2-isopropylphenyl)acetamide (CA30)




The title compound was prepared as described in Example 37 using 5-chloro-2-isopropylaniline (C14) and isolated as an off-white solid (1.0 g, 40%): 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.94 (s, 1H), 7.26 (m, 1H), 7.13-7.16 (m, 1H), 4.24 (s, 2H), 3.02-2.95 (m, 1H), 1.27 (d, J=6.8 Hz, 6H); ESIMS m/z 246 ([M+H]+).
2-Chloro-N-(2-chloro-5-methylphenyl)acetamide (CA31)




The title compound was prepared as described in Example 37 using 2-chloro-5-methylaniline and isolated as an off-white solid (1.4 g, 90%): 1H NMR (400 MHz, CDCl3) δ 8.85 (bs, 1H), 8.85 (s, 1H), 7.88 (d, J=8.4 Hz, 1H), 6.91 (dd, J=8.4 Hz, 2 Hz, 1H), 4.22 (s, 2H), 2.35 (s, 3H); ESIMS m/z 218 ([M+H]+).
2-Chloro-N-(2-isopropylphenyl)acetamide (CA32)




The title compound was prepared as described in Example 37 using 2-isopropylaniline and isolated as an off-white solid (0.700 g, 88%): 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 7.79-7.76 (m, 1H), 7.33-7.29 (m, 1H), 7.25-7.19 (m, 2H), 4.25 (s, 2H), 3.07-3.00 (m, 1H), 1.27 (d, J=6.8 Hz, 6H); ESIMS m/z 212 ([M+H]+).
2-Chloro-N-(5-methyl-2-propylphenyl)acetamide (CA33)




The title compound was prepared as described in Example 37 using 5-methyl-2-propylaniline (C11) and isolated as an off-white solid (1.7 g, 75%): 1H NMR (400 MHz, CDCl3) δ 8.26 (bs, 1H), 7.72 (s, 1H), 7.08 (d, J=8.0 Hz, 1H), 6.95 (d, J=7.6 Hz, 1H), 4.23 (s, 2H), 2.54 (t, J=7.2 Hz, 2H) 1.66-1.57 (m, 2H), 0.97 (t, J=7.2 Hz, 3H); ESIMS m/z 226 ([M+H]+).
2-Chloro-N-(2-methoxy-5-methylphenyl)acetamide (CA34)




The title compound was prepared as described in Example 36 using 2-methoxy-5-methylaniline and isolated as an off-white solid (1.4 g, 90%): 1H NMR (300 MHz, CDCl3) δ 8.90 (s, 1H), 8.16 (d, J=1.5 Hz, 1H), 6.90-6.87 (m, 1H), 6.79 (d, J=7.8, Hz, 1H), 4.19 (s, 2H), 3.88 (s, 3H); ESIMS m/z 214 ([M+H]+).
Example 38
Preparation of 6-bromo-1,2,3,4-tetrahydronaphthalen-2-amine (CA35)




To a solution of 6-bromo-3,4-dihydronaphthalen-2(1H)-one (25.0 g, 111 mmol), ammonium acetate (5.58 g, 72.5 mmol) in methanol (450 mL) was added sodium cyanoborohydride (7.75 g, 123 mmol) in presence of 4 Å molecular sieves at room temperature. The reaction mixture was stirred overnight at room temperature. The reaction mixture was acidified with hydrochloric acid (2 N), stirred for 10 minutes, and concentrated. The residue was dissolved in water and washed with dichloromethane (2×200 mL). The aqueous layer was basified with sodium hydroxide (2 N) and extracted with dichloromethane (3×300 mL). The organic layers were dried over sodium sulfate, filtered, and concentrated providing the title compound as a brown solid (12.3 g, 49%): 1H NMR (300 MHz, CDCl3) δ 7.24 (d, J=10.8 Hz, 1H), 7.19 (d, J=2.4 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 3.19-3.13 (m, 1H), 2.96-2.80 (m, 3H), 2.51-2.43 (m, 1H), 2.02-1.93 (m, 1H), 1.62-1.44 (m, 2H); ESIMS m/z 228 ([M+H]+).
Example 39
Preparation of tert-butyl (6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (CA36)




To a solution of 6-bromo-1,2,3,4-tetrahydronaphthalen-2-amine (CA35) (10.0 g, 44.2 mmol), triethylamine (8.95 g, 88.5 mmol) in dichloromethane (90 mL) was added di-tert-butyl dicarbonate (11.6 g, 53.1 mmol) dropwise at room temperature. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was quenched with brine and diluted with dichloromethane. The separated organic layer was dried over sodium sulfate, filtered, and concentrated providing the title compound as a brown solid (11.3 g, 77%): 1H NMR (300 MHz, CDCl3) δ 7.26-7.21 (m, 2H), 6.92 (d, J=5.1 Hz, 1H), 4.54 (bs, 1H), 3.94 (bs, 1H), 3.08-3.01 (m, 1H), 2.87-2.82 (m, 2H), 2.59-2.51 (m, 1H), 2.07-2.02 (m, 1H), 1.77-1.67 (m, 1H), 1.45 (s, 9H); ESIMS m/z 326 ([M+H]+).
Example 40
Preparation of tert-butyl (6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (CA37)




tert-Butyl (6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (CA36) (11.2 g, 34.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.70 g, 2.05 mmol), bis(pinacolato)diboron (10.6 g, 41.2 mmol), and potassium acetate (6.73 g, 68.7 mmol) in dioxane (150 mL) was heated at 100° C. overnight. The reaction was cooled, quenched with water, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 30-100% ethyl acetate/hexanes as eluent provided the title compound as a pale brown solid (15.0 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.54 (d, J=7.5 Hz, 2H), 7.07 (d, J=7.2 Hz, 1H), 4.65 (s, 1H), 4.05 (s, 1H), 3.10 (s, 1H), 2.90-2.85 (m, 2H), 2.67-2.62 (m, 1H), 2.05 (br s, 1H), 1.44 (s, 9H), 1.33 (s, 12H); ESIMS m/z 375 ([M+H]+).
Example 41
Preparation of tert-butyl (6-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (CA38)




To a solution of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (12.0 g, 39.0 mmol) in dioxane:water (3:1, 420 mL) was added tert-butyl (6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (CA37) (16.0 g, 42.9 mmol), potassium phosphate (23.8 g, 112 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (2.80 g, 3.42 mmol). The reaction was evacuated and purged with nitrogen, and heated at 100° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. The separated aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 20-40% ethyl acetate/hexanes as eluent provided the title compound as a pale brown solid (15.0 g, 80%): 1H NMR (300 MHz, CDCl3) δ 8.54 (s, 1H), 7.92 (m, 2H), 7.80 (dd, J=6.9, 2.1 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 7.17 (d, J=8.4 Hz, 1H), 3.17 (dd, J=16.8 Hz, 5.1, 1H), 2.97 (t, J=7.2, 2H), 2.72-2.63 (m, 1H), 2.13-2.08 (bs, 1H), 1.92 (s, 1H), 1.82-1.75 (m, 1H), 1.48 (s, 9H); ESIMS m/z 476 ([M+H]+).
The following prophetic molecules may be prepared in accordance with the schemes or examples disclosed above:







TABLE 1







Structure and Preparation Method for P Series Compounds











May be




Prep.




according


No.
Structure
to





P1




Example 12


 


P2




Example 12


 


P3




Example 12


 


P4




Example 12


 


P5




Example 12


 


P6




Example 14


 


P7




Example 14


 


P8




Example 14


 


P9




Example 14


 


P10




Example 14


 


P11




Scheme 3


 


P12




Scheme 3


 


P13




Example 14


 


P14




Scheme 7


 


P15




Scheme 3


 


P16




Scheme 3


 


P17




Scheme 3


 


P18




Scheme 3


 


P19




Scheme 3


 


P20




Scheme 3


 


P21




Example 12


 


P22




Example 12


 


P23




Example 14


 


P24




Example 14


 


P25




Example 12


 


P26




Example 12


 


P27




Example 12


 


P28




Example 12


 


P29




Example 12


 


P30




Example 12


 


P31




Example 12


 


P32




Example 14


 


P33




Example 14


 


P34




Example 14


 


P35




Example 14


 


P36




Example 14


 


P37




Example 14


 


P38




Example 14









Example A
Bioassays on Beet Armyworm (“BAW”) and Cabbage Looper (“CL”)
BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CL feeds on a wide variety of cultivated plants and weeds. It feeds readily on crucifers, and has been reported damaging broccoli, cabbage, cauliflower, Chinese cabbage, collards, kale, mustard, radish, rutabaga, turnip, and watercress. Other vegetable crops injured include beet, cantaloupe, celery, cucumber, lima bean, lettuce, parsnip, pea, pepper, potato, snap bean, spinach, squash, sweet potato, tomato, and watermelon. CL is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.
Certain molecules disclosed in this document were tested against BAW and CL using procedures described in the following examples. In the reporting of the results, the “BAW & CL Rating Table” was used (See Table Section).
Bioassays on BAW (Spodoptera exigua)
Bioassays on BAW were conducted using a 128-well diet tray assay. one to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm2 of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the tables entitled “Table ABC: Assay Results” and “Table ABCD: Assay Results” (See Table Section).
Bioassays on CL (Trichoplusia ni)
Bioassays on CL were conducted using a 128-well diet tray assay. One to five second instar CL larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm2 of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table ABC: Assay Results” and “Table ABCD: Assay Results” (See Table Section).
Example B
Bioassays on Green Peach Aphid (“GPA”) (Myzus persicae)
GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.
Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the “GPA & YFM Rating Table” was used (See Table Section).
Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/MeOH (1:1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5× with 0.025% Tween 20 in water to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/MeOH (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25° C. and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W. S. Abbott, “A Method of Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp. 265-267) as follows. Corrected % Control=100*(X−Y)/X where X=No. of live aphids on solvent check plants and Y=No. of live aphids on treated plants. The results are indicated in the table entitled “Table ABC: Assay Results” and “Table ABCD: Assay Results” (See Table Section).
Example C
Bioassays on Yellow Fever Mosquito “YFM” (Aedes aegypti)
YFM prefers to feed on humans during the daytime and is most frequently found in or near human habitations. YFM is a vector for transmitting several diseases. It is a mosquito that can spread the dengue fever and yellow fever viruses. Yellow fever is the second most dangerous mosquito-borne disease after malaria. Yellow fever is an acute viral hemorrhagic disease and up to 50% of severely affected persons without treatment will die from yellow fever. There are an estimated 200,000 cases of yellow fever, causing 30,000 deaths, worldwide each year. Dengue fever is a nasty, viral disease; it is sometimes called “breakbone fever” or “break-heart fever” because of the intense pain it can produce. Dengue fever kills about 20,000 people annually. Consequently, because of the above factors control of this pest is important. Furthermore, molecules that control this pest (YFM), which is known as a sucking pest, are useful in controlling other pests that cause human and animal suffering.
Certain molecules disclosed in this document were tested against YFM using procedures described in the following paragraph. In the reporting of the results, the “GPA & YFM Rating Table” was used (See Table Section).
Master plates containing 400 μg of a molecule dissolved in 100 μL of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used. A master plate of assembled molecules contains 15 μL per well. To this plate, 135 μL of a 90:10 water:acetone mixture is added to each well. A robot (Biomek® NXP Laboratory Automation Workstation) is programmed to dispense 15 μL aspirations from the master plate into an empty 96-well shallow plate (“daughter” plate). There are 6 reps (“daughter” plates) created per master. The created daughter plates are then immediately infested with YFM larvae.
The day before plates are to be treated, mosquito eggs are placed in Millipore water containing liver powder to begin hatching (4 g. into 400 mL). After the daughter plates are created using the robot, they are infested with 220 μL of the liver powder/larval mosquito mixture (about 1 day-old larvae). After plates are infested with mosquito larvae, a non-evaporative lid is used to cover the plate to reduce drying. Plates are held at room temperature for 3 days prior to grading. After 3 days, each well is observed and scored based on mortality.
The results are indicated in the table entitled “Table ABC: Assay Results” and “Table ABCD: Assay Results” (See Table Section).
Agriculturally Acceptable Acid Addition Salts, Salt Derivatives, Solvates, Ester Derivatives, Polymorphs, Isotopes, and Radionuclides
Molecules of Formula One may be formulated into pesticidally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.
Molecules of Formula One may be formulated into salt derivatives. By way of a non-limiting example, a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt. A free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine salt.
Molecules of Formula One may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as “solvates.” However, it is particularly desirable to form stable hydrates with water as the solvent.
Molecules of Formula One may be made into ester derivatives. These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.
Molecules of Formula One may be made as various crystal polymorphs. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
Molecules of Formula One may be made with different isotopes. Of particular importance are molecules having 2H (also known as deuterium) in place of 1H.
Molecules of Formula One may be made with different radionuclides. Of particular importance are molecules having 14C.
Stereoisomers
Molecules of Formula One may exist as one or more stereoisomers. Thus, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules disclosed in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric forms of the molecule.
Combinations
In another embodiment, molecules of Formula One may be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds each having a mode of action that is the same as, similar to, or different from, the mode of action (“MoA”) of the molecules of Formula One. Modes of action include, for example the following: Acetylcholinesterase (AChE) inhibitors; GABA-gated chloride channel antagonists; Sodium channel modulators; Nicotinic acetylcholine (nAChR) agonists; Nicotinic acetylcholine receptor (nAChR) allosteric activators; Chloride channel activators; Juvenile hormone mimics; Miscellaneous non-specific (multi-site) inhibitors; Selective homopteran feeding blockers; Mite growth inhibitors; Microbial disruptors of insect midgut membranes; Inhibitors of mitochondrial ATP synthase; Uncouplers of oxidative phosphorylation via disruption of the proton gradient; Nicotinic acetylcholine receptor (nAChR) channel blockers; Inhibitors of chitin biosynthesis, type 0; Inhibitors of chitin biosynthesis, type 1; Moulting disruptor, Dipteran; Ecdysone receptor agonists; Octopamine receptor agonists; Mitochondrial complex III electron transport inhibitors; Mitochondrial complex I electron transport inhibitors; Voltage-dependent sodium channel blockers; Inhibitors of acetyl CoA carboxylase; Mitochondrial complex IV electron transport inhibitors; Mitochondrial complex II electron transport inhibitors; and Ryanodine receptor modulators.
In another embodiment, molecules of Formula One may be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, and/or virucidal properties.
In another embodiment, the molecules of Formula One may be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, and/or synergists.
In another embodiment, the molecules of Formula One may be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with “another compound”, such as one or more of the following compounds—(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-diolamine, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, afidopyropen, afoxolaner, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, anabasine sulfate, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzovindiflupyr, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, broflanilide, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloroprallethrin, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, cholecalciferol, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clacyfos, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclaniliprole, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclopyrimorate, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalodiamide, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dicloromezotiaz, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-P-potassium, dichlorprop-P-sodium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipymetitrone, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, enoxastrobin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, epsilon-metofluthrin, epsilon-momfluorothrin, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenaminstrobin, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenquinotrione, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazaindolizine, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenoxystrobin, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, fluhexafon, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, fluralaner, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halauxifen, halauxifen-methyl, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptafluthrin, heptenophos, heptopargil, herbimycin, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isofetamid, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, kappa-bifenthrin, kappa-tefluthrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, Ivdingjunzhi, Ivxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, mandestrobin, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, momfluorothrin, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, napropamide-M, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxathiapiprolin, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentachlorophenyl laurate, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picarbutrazox, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pydiflumetofen, pyflubumide, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyraziflumid, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyriminostrobin, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrisoxazole, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, rescalure, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetraniliprole, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiafenacil, tiaojiean, tiocarbazil, tioclorim, tioxazafen, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolprocarb, tolpyralate, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyricarb, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, trifludimoxazin, triflumezopyrim, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneacetic acid. For more information consult the “COMPENDIUM OF PESTICIDE COMMON NAMES” located at alanwood.net. Also consult “THE PESTICIDE MANUAL” 15th Edition, edited by C D S Tomlin, copyright 2009 by British Crop Production Council, or its prior, or more recent editions.
In another embodiment, molecules of Formula One may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with the following compound.




In another embodiment, molecules of Formula One may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more biopesticides. The term “biopesticide” is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on: entomopathogenic fungi (e.g. Metarhizium anisopliae); entomopathogenic nematodes (e.g. Steinernema feltiae); and entomopathogenic viruses (e.g. Cydia pomonella granulovirus).
Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism. In one embodiment, the molecules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology-based control) products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.
In another embodiment, the above possible combinations may be used in a wide variety of weight ratios. For example, a two component mixture, the weight ratio of a molecule of Formula One to another compound, can be from about 100:1 to about 1:100; in another example the weight ratio can be about 50:1 to about 1:50; in another example the weight ratio can be about 20:1 to about 1 to 20; in another example the weight ratio can be about 10:1 to about 1:10; in another example the weight ratio can be about 5:1 to 1:5; in another example the weight ratio can be about 3:1 to about 1:3; in another example the weight ratio can be about 2:1 to about 1:2; and in a final example the weight ratio can be about 1:1. However, preferably, weight ratios less than about 10:1 to about 1:10 are preferred. It is also preferred sometimes to use a three or four component mixture comprising one or more molecules of Formula One and one or more other compounds from the above possible combinations.










TABLE A








Range of the Weight Ratio of



No.
a molecule of the Formula One to another compound









1
100:1 to 1:100



2
50:1 to 1:50



3
20:1 to 1:20



4
10:1 to 1:10



5
5:1 to 1:5



6
3:1 to 1:3



7
2:1 to 1:2



8
1:1










Weight ratios of a molecule of the Formula One or any agriculturally acceptable salt thereof to another compound envisioned to be synergistic pesticidal compositions may be depicted as X:Y; wherein X is the parts by weight of a molecule of the Formula One or any agriculturally acceptable salt thereof, and Y is the parts by weight of another compound. The numerical range of the parts by weight for X is 0<X≦100 and the parts by weight for Y is 0<Y≦100 as shown graphically in TABLE B. By way of non-limiting example, the weight ratio of the pesticide to another compound may be about 20:1.


















TABLE B







Another Compound
100
X, Y

X, Y


X, Y





(Y) Parts by weight
50
X, Y
X, Y
X, Y


X, Y
X, Y





20
X, Y

X, Y
X, Y

X, Y

X, Y




15
X, Y
X, Y




X, Y
X, Y
X, Y



10
X, Y

X, Y









5
X, Y
X, Y
X, Y



X, Y





3
X, Y
X, Y

X, Y
X, Y

X, Y
X, Y
X, Y



2
X, Y

X, Y
X, Y

X, Y

X, Y




1
X, Y
X, Y
X, Y
X, Y
X, Y
X, Y
X, Y
X, Y
X, Y







1
2
3
5
10
15
20
50
100









Molecule of the Formula One



(X) Parts by weight









Ranges of weight ratios of a molecule of the Formula One or any agriculturally acceptable salt thereof to another compound envisioned to be synergistic pesticidal compositions may be depicted as X1:Y1 to X2:Y2, wherein X and Y are defined as above. In one particular embodiment, the range of weight ratios may be X1:Y1 to X2:Y2, wherein X1>Y1 and X2<Y2. By way of non-limiting example, the range of weight ratios of a molecule of the Formula One or any agriculturally acceptable salt thereof to another compound may be between about 3:1 and about 1:3. In some embodiments, the range of weight ratios may be X1:Y1 to X2:Y2, wherein X1>Y1 and X2>Y2. By way of non-limiting example, the range of a molecule of the Formula One or any agriculturally acceptable salt thereof to another compound may be between about 15:1 and about 3:1. In further embodiments, the range of weight ratios may be X1:Y1 to X2:Y2, wherein X1<Y1 and X2<Y2. By way of non-limiting example, the range of weight ratios of a molecule of the Formula One or any agriculturally acceptable salt thereof to another compound may be between about 1:3 and about 1:20.
Formulations
A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra-low volume solutions. For further information on formulation types see “Catalogue of Pesticide Formulation Types and International Coding System” Technical Monograph no 2, 5th Edition by CropLife International (2002).
Pesticides are applied most often as aqueous suspensions or emulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The carrier is usually selected from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.
Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.
Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.
Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine.
It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure-generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.
Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.
Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest's respiratory system or being absorbed through the pest's cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers.
Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.
Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.
Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non-ionic hydrophilic surface-active agent and (3) at least one ionic surface-active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published Feb. 1, 2007, having patent application Ser. No. 11/495,228. For ease of use, this embodiment will be referred to as “OIWE”.
For further information consult “Insect Pest Management” 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult “Handbook of Pest Control—The Behavior, Life History, and Control of Household Pests” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
Other Formulation Components
Generally, when the molecules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.
A wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the penetration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.
A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensates and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents. These have very long hydrophobic ‘backbones’ and a large number of ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrates because the hydrophobic backbones have many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.
An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB”) values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.
A solubilizing agent is a surfactant which will form micelles in water at concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.
Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.
A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water-dispersible granules.
Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil-in-water emulsions, suspoemulsions, and ultra-low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.
Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets. Thickening, gelling, and anti-settling agents generally fall into two categories, namely water-insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.
Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).
The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.
“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.
For further information, see “Chemistry and Technology of Agrochemical Formulations” edited by D. A. Knowles, copyright 1998 by Kluwer Academic Publishers. Also see “Insecticides in Agriculture and Environment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.
Pests
In general, the molecules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
In another embodiment, the molecules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.
In another embodiment, the molecules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.
In another embodiment, the molecules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Anoplura. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis. 
In another embodiment, the molecules of Formula One may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Dermaptera.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chilo suppressalis, Chilo polychrysus, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pyrina. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips tabaci. 
In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp.
In another embodiment, the molecules of Formula One may be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor. 
In another embodiment, the molecules of Formula One may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata. 
In another embodiment, the molecules of Formula One may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis. 
For additional information consult “HANDBOOK OF PEST CONTROL—THE BEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
Applications
Controlling pests of Phyla Nematoda, Arthropoda, and/or Mollusca generally means that pest populations, pest activity, or both, are reduced in an locus. This can come about when:
(a) pest populations are repulsed from a locus;
(b) pests are incapacitated in, or around, a locus; or
(c) pests are exterminated in, or around, a locus.
Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent, and most preferably more than 98 percent. Generally, the locus is not in, or on, a human; consequently, the locus is generally a non-human locus.
In another embodiment, the locus to which a molecule of Formula One is applied can be any locus that is inhabited, or that may become inhabited, or that may be traversed, by a pest of Phyla Nematoda, Arthropoda, and/or Mollusca. For example, the locus can be:
(a) where crops, trees, fruits, cereals, fodder species, vines, turf, and/or ornamental plants, are growing;
(b) where domesticated animals are residing;
(c) the interior or exterior surfaces of buildings (such as places where grains are stored);
(d) the materials of construction used in buildings (such as impregnated wood); and
(e) the soil around buildings.
Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use ammonium sulfate with a molecule of Formula One when growing various plants.
In another embodiment, molecules of Formula One are generally used in amounts from about 0.1 grams per hectare to about 5000 grams per hectare to provide control. In another embodiment, it is preferred that molecules of Formula One are used in amounts from about 0.1 grams per hectare to about 500 grams per hectare. In another embodiment, it is more preferred that molecules of Formula One are used in amounts from about 0.01 gram per hectare to about 50 grams per hectare.
The molecules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1-methylcyclopropene (also known as 1-MCP). Furthermore, such molecules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuable agricultural commodities. Such times include the early planting season when pest pressure is usually low.
The molecules of Formula One can be applied to the foliar and fruiting portions of plants to control pests. The molecules will either come in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The molecules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.
Generally, with baits, the baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can comprise a molecule of Formula One.
The molecules of Formula One can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).
Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the molecules of Formula One may be desirable to control newly emerged larvae.
Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molecules of Formula One to a different portion of the plant. For example, control of foliar-feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.
Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as “Roundup Ready” seed, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits. Furthermore, such seed treatments with the molecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the molecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.
It should be readily apparent that the molecules of Formula One may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, or any other beneficial traits.
The molecules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The molecules of Formula One are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.
The molecules of Formula One may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals. Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and formulations that are suitable depend on the species.
The molecules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.
The molecules of Formula One may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The molecules of Formula One may also be used on such new invasive species to control them in such new environment.
The molecules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molecules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.
Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy evaluation processes by various governmental authorities (local, regional, state, national, and international). Voluminous data requirements are specified by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.
A molecule according to Formula One can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.
The headings in this document are for convenience only and must not be used to interpret any portion hereof.
Table Section







TABLE 2







Structure and Preparation Method for F Series Compounds











Prep.




accord-




ing to


No.
Structure
example





F1




12


 


F2




14


 


F3




13


 


F4




14


 


F5




12


 


F6




12


 


F7




12


 


F8




12


 


F9




14


 


F10




14


 


F11




12


 


F12




12


 


F13




14


 


F14




12


 


F15




14


 


F16




14


 


F17




21
















TABLE 3







Structure and Preparation Method for C Series Compounds











Prep.




according




to


No.
Structure
Example












C1




1


 


C2




2


 


C3




3


 


C4




4


 


C5




5


 


C6




6


 


C8




7


 


C11




9


 


C15




10


 


C17




10


 


C18




10


 


C19




10


 


C20




11


 


C21




11


 


C22




11


 


C23




11


 


C24




11


 


C25




15


 


C26




16


 


C27




17


 


C28




18


 


C29




19


 


C30




20
















TABLE 4







Analytical Data for Compounds in Table 2

















13CNMR;


No.
Mp (° C.)
IR (cm−1)
Mass (m/z)
1H NMR
19F NMR





F1
134

ESIMS m/z 595
1H NMR (400 MHz,
19F NMR



(dec.)

([M + H]+)
CDCl3) δ 9.63 (s,
(376 MHz,






1H), 8.63 (s, 1H),
CDCl3) δ −58.02






7.99 (d, J = 8.7 Hz,






2H),






7.83-7.74 (m, 2H), 7.38 (d, J = 8.6 Hz,






2H),






7.26 (s, 5H), 7.14 (s,






1H),






4.65-4.60 (m, 1H), 3.36 (td, J = 18.5,






17.7, 7.3 Hz,






2H), 3.05 (d, J = 8.7 Hz,






1H),






2.84 (s, 2H), 2.31 (s,






3H), 1.22 (d, J = 6.8 Hz,






6H)


F2
171

ESIMS m/z 635
1H NMR (400 MHz,
19F NMR



(dec.)

([M + H]+)
DMSO-d6) δ
(376 MHz,






9.36 (s, 1H),
DMSO-d6)






8.11-8.02 (m, 2H), 7.93 (d, J = 7.1 Hz,
δ −56.96






1H),






7.88 (d, J = 7.8 Hz, 2H),






7.66-7.57 (m,






2H), 7.34 (d, J = 8.0 Hz,






1H),






7.29 (d, J = 7.7 Hz, 1H),






7.25-7.19 (m,






1H), 6.99 (dd, J = 1.8,






0.9 Hz, 1H),






4.41 (q, J = 7.4 Hz,






1H), 4.13 (d, J = 18.0 Hz,






1H),






4.01 (d, J = 18.0 Hz,






1H),






3.25-3.06 (m, 2H),






2.93-2.82 (m, 2H),






2.62 (hept, J = 6.8 Hz,






1H),






2.30-2.23 (m, 3H), 1.11 (dd,






J = 6.8, 1.4 Hz,






3H), 1.07 (d, J = 6.8 Hz,






3H)


F3


ESIMS m/z 645
1H NMR (400 MHz,
19F NMR





([M + H]+)
DMSO-d6) δ
(376 MHz,






11.87 (s, 1H), 9.83 (s,
DMSO-d6)






1H), 9.40 (s, 1H),
δ −85.19,






8.12-8.06 (m,
−86.91






2H), 8.02 (s, 1H),






7.96 (dd, J = 7.8,






1.6 Hz, 1H),






7.63 (d, J = 9.1 Hz, 2H),






7.43 (t, J = 6.9 Hz,






2H), 7.23 (d, J = 8.0 Hz,






1H),






7.21 (d, J = 1.8 Hz, 1H),






7.09 (d, J = 7.9 Hz,






1H), 4.50 (d, J = 6.4 Hz,






1H),






3.44-3.34 (m, 1H),






3.05-2.80 (m, 4H),






2.27 (s, 3H),






1.16 (d, J = 6.9 Hz, 6H)


F4
131-141

ESIMS m/z 685
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.55 (s,






1H),






8.04-7.96 (m, 2H),






7.85-7.76 (m, 2H),






7.45-7.37 (m, 2H),






7.30 (t, J = 7.6 Hz,






3H),






6.86-6.81 (m, 1H), 5.69 (d, J = 7.9 Hz,






1H),






4.74-4.59 (m, 1H),






4.04-3.83 (m,






2H),






3.46-3.27 (m, 2H),






3.00-2.76 (m, 2H),






2.62 (hept, J = 6.7 Hz,






1H), 2.32 (s, 3H),






1.21-1.08 (m, 6H)


F5


ESIMS m/z 581
1H NMR (400 MHz,
19F NMR





([M + H]+)
DMSO-d6) δ
(376 MHz,






11.94 (s, 1H), 9.82 (s,
DMSO-d6)






1H), 9.39 (d, J = 2.4 Hz,
δ −56.96






1H),






8.11-8.05 (m, 2H),






8.02 (d, J = 1.5 Hz, 1H),






7.96 (d, J = 8.1 Hz,






1H),






7.67-7.59 (m, 2H), 7.43 (t, J = 7.5 Hz,






2H),






7.40-7.32 (m, 1H),






7.17 (d, J = 7.8 Hz,






1H), 7.04 (d, J = 7.9 Hz,






1H),






4.50 (d, J = 6.6 Hz, 1H),






3.33 (s, 4H),






2.97-2.81 (m, 2H),






2.27 (s, 3H), 1.12 (t, J = 7.5 Hz,






3H)


F6


ESIMS m/z 579
1H NMR (400 MHz,
19F NMR





([M − H]−)
DMSO-d6) δ
(376 MHz,






11.56 (s, 1H), 9.84 (s,
DMSO-d6)






1H), 9.39 (s, 1H),
δ −56.96






8.13-8.05 (m,






2H), 8.02 (s, 1H),






8.00-7.93 (m,






1H), 7.63 (d, J = 8.4 Hz,






2H),






7.42 (d, J = 7.9 Hz, 2H),






7.17 (d, J = 7.4 Hz,






1H),






7.15-7.07 (m, 2H), 4.51 (d, J = 7.1 Hz,






1H),






3.33 (s, 4H),






2.97-2.77 (m, 2H), 2.18 (s,






3H), 1.14 (t, J = 7.6 Hz,






3H)


F7


ESIMS m/z 567
1H NMR (400 MHz,
19F NMR





([M + H]+)
DMSO-d6) δ
(376 MHz,






11.99 (s, 1H), 9.84 (s,
DMSO-d6)






1H), 9.39 (s, 1H),
δ −56.96






8.12-8.05 (m,






2H), 8.02 (d, J = 1.5 Hz,






1H),






7.96 (dd, J = 7.8, 1.6 Hz,






1H),






7.66-7.59 (m, 2H),






7.55 (dd, J = 5.6, 3.7 Hz,






1H), 7.44 (dd, J = 11.0,






7.5 Hz,






2H),






7.32-7.27 (m, 1H),






7.26-7.20 (m, 2H),






4.62-4.41 (m, 1H),






3.33 (s, 2H),






2.89 (ddd, J = 17.1,






13.2, 4.8 Hz, 2H),






2.67-2.51 (m,






2H), 1.15 (t, J = 7.6 Hz,






3H)


F8


ESIMS m/z 595
1H NMR (400 MHz,
19F NMR





([M + H]+)
DMSO-d6) δ
(376 MHz,






11.97 (s, 1H), 9.81 (s,
DMSO-d6)






1H), 9.39 (s, 1H),
δ −56.96






8.12-8.05 (m,






2H), 8.02 (d, J = 1.6 Hz,






1H),






7.96 (d, J = 7.7 Hz, 1H),






7.63 (d, J = 8.8 Hz,






2H), 7.43 (t, J = 7.1 Hz,






2H),






7.38 (s, 1H), 7.15 (d, J = 7.7 Hz,






1H),






7.03 (d, J = 7.9 Hz, 1H),






4.49 (d, J = 7.4 Hz,






1H), 3.33 (s, 2H),






3.00-2.78 (m,






2H), 2.50 (p, J = 1.9 Hz,






2H),






2.27 (s, 3H), 1.51 (dt, J = 14.9,






7.5 Hz,






2H), 0.89 (t, J = 7.3 Hz,






3H)


F9
125-131

ESIMS m/z 621
1H NMR (400 MHz,
19F NMR





([M + H]+)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






8.03-7.94 (m, 2H),






7.83-7.75 (m, 2H),






7.38 (dd, J = 8.9, 1.2 Hz,






2H), 7.26 (s,






3H), 6.87 (d, J = 1.7 Hz,






1H),






5.69 (d, J = 7.9 Hz, 1H),






4.76-4.53 (m,






1H),






4.00-3.81 (m, 2H), 3.35 (dt, J = 16.5,






8.0 Hz,






2H), 2.87 (dtd, J = 15.0,






10.0, 9.5, 4.6 Hz,






2H), 2.39 (q, J = 7.6 Hz,






2H),






2.33 (d, J = 1.3 Hz, 3H),






1.13 (td, J = 7.6,






0.6 Hz, 3H)


F10
152

ESIMS m/z 621
1H NMR (400 MHz,
19F NMR



(dec.)

([M + H]+)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






8.05-7.95 (m, 2H),






7.85-7.75 (m, 2H),






7.44-7.36 (m, 2H),






7.30 (t, J = 7.6 Hz,






2H),






7.23-7.11 (m, 2H), 5.68 (d, J = 7.9 Hz,






1H),






4.76-4.59 (m, 1H),






3.94 (s, 2H),






3.44-3.22 (m, 2H),






2.86 (ddt, J = 15.9, 9.9,






4.7 Hz, 2H),






2.41 (q, J = 7.6 Hz, 2H),






2.10 (s, 3H),






1.15 (td, J = 7.6, 0.7 Hz,






3H


F11


ESIMS m/z 579
1H NMR (400 MHz,
19F NMR





([M + H]+)
DMSO-d6) δ
(376 MHz,






12.27 (s, 1H), 9.83 (s,
DMSO-d6)






1H), 9.39 (s, 1H),
δ −56.96






8.11-8.04 (m,






2H), 8.02 (s, 1H),






7.99-7.93 (m,






1H),






7.81-7.76 (m, 1H),






7.66-7.59 (m, 2H),






7.49-7.39 (m, 2H),






7.25-7.13 (m,






2H), 7.05 (dd, J = 7.3,






1.9 Hz, 1H),






4.57-4.43 (m,






1H),






3.46-3.24 (m, 2H),






2.98-2.79 (m, 2H),






1.96-1.77 (m, 1H),






1.02-0.91 (m,






2H),






0.74-0.56 (m, 2H)


F12
146

ESIMS m/z 607
1H NMR (400 MHz,
19F NMR



(dec.)

([M + H]+)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






8.03-7.96 (m, 2H),






7.84-7.75 (m, 2H),






7.45-7.34 (m, 4H),






7.34-7.27 (m,






2H), 7.06 (dd, J = 7.8,






1.3 Hz, 1H),






5.66 (d, J = 7.9 Hz,






1H),






4.74-4.59 (m, 1H),






4.00-3.86 (m, 2H),






3.35 (dt, J = 16.6, 8.3 Hz,






2H), 2.87 (ddd,






J = 16.2, 10.8, 5.0 Hz,






2H), 2.44 (q, J = 7.6 Hz,






2H),






1.16 (dd, J = 7.8, 7.3 Hz,






3H)


F13
136

ESIMS m/z 633
1H NMR (400 MHz,
19F NMR



(dec.)

([M − H]−)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






8.05-7.95 (m, 2H),






7.83-7.75 (m, 2H),






7.42-7.35 (m, 2H),






7.29 (d, J = 7.8 Hz,






1H),






7.25-7.13 (m, 2H),






6.90-6.85 (m, 1H),






5.68 (d, J = 7.8 Hz, 1H),






4.74-4.57 (m,






1H),






4.03-3.78 (m, 2H), 3.35 (dt, J = 16.5,






8.1 Hz,






2H), 2.87 (dtd, J = 14.6,






10.3, 9.6, 4.6 Hz,






2H),






2.40-2.23 (m, 5H),






1.55 (s, 2H), 0.89 (t, J = 7.3 Hz,






3H)


F14


ESIMS m/z 581
1H NMR (400 MHz,
19F NMR





([M + H]+)
DMSO-d6) δ
(376 MHz,






11.93 (s, 1H), 9.85 (s,
DMSO-d6)






1H), 9.39 (s, 1H),
δ −56.96






8.12-8.05 (m,






2H), 8.02 (s, 1H),






7.96 (dd, J = 7.7,






1.6 Hz, 1H),






7.63 (dd, J = 9.2, 1.0 Hz,






2H),






7.49-7.39 (m, 3H),






7.36 (dd, J = 7.8, 1.6 Hz,






1H), 7.28 (td, J = 7.5,






1.5 Hz, 1H),






7.21 (td, J = 7.5,






1.7 Hz, 1H),






4.60-4.38 (m, 1H),






3.42-3.26 (m, 2H),






3.02 (hept, J = 6.9 Hz,






1H), 2.89 (ddd,






J = 17.1, 13.2, 4.8 Hz,






2H), 1.18 (d, J = 6.9 Hz,






6H)


F15
141

ESIMS m/z 619
1H NMR (400 MHz,
19F NMR



(dec.)

([M + H]+)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






8.04-7.97 (m, 2H),






7.82-7.76 (m, 2H),






7.43-7.33 (m, 3H),






7.29 (dd, J = 7.7,






1.3 Hz, 2H),






7.15 (dd, J = 7.7, 1.6 Hz,






1H), 7.09 (dd, J = 7.7,






1.4 Hz, 1H),






5.68 (d, J = 7.9 Hz,






1H), 4.66 (ddt, J = 11.8,






7.3, 3.6 Hz,






1H),






4.04-3.85 (m, 2H),






3.44-3.26 (m, 2H),






2.87 (ddt, J = 15.9, 9.7,






5.1 Hz, 2H),






1.68 (ddd, J = 13.9, 8.6,






5.4 Hz, 1H),






0.93-0.77 (m, 2H),






0.71-0.61 (m, 1H),






0.57 (ddt, J = 11.0,






6.8, 2.4 Hz, 1H)


F16
239-243

ESIMS m/z 621
1H NMR (400 MHz,
19F NMR





([M + H]+)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






8.04-7.96 (m, 2H),






7.82-7.75 (m, 2H),






7.46-7.41 (m, 2H),






7.41-7.35 (m,






2H),






7.33-7.27 (m, 2H), 7.03 (dt, J = 8.0,






0.9 Hz, 1H),






5.65 (d, J = 8.0 Hz,






1H),






4.71-4.60 (m, 1H),






4.01-3.86 (m, 2H),






3.43-3.23 (m, 2H),






2.95-2.76 (m,






2H), 2.67 (hept, J = 6.9 Hz,






1H),






1.16 (ddd, J = 10.1, 6.9,






1.1 Hz, 6H)


F17
169-175

ESIMS m/z 649
1H NMR (400 MHz,
19F NMR





([M + H]+)
CDCl3) δ 8.54 (s,
(376 MHz,






1H),
CDCl3) δ −58.03






7.93-7.88 (m, 2H),






7.81-7.77 (m, 2H),






7.41-7.35 (m, 2H),






7.33 (dd, J = 8.0,






1.9 Hz, 1H),






7.27 (s, 1H), 7.14 (d, J = 8.1 Hz,






1H),






6.87 (s, 1H),






5.57-5.47 (m, 1H), 4.18 (s,






1H), 3.92 (d, J = 2.2 Hz,






2H),






3.17 (dt, J = 16.6, 5.2 Hz,






1H), 2.93 (dd, J = 11.4,






5.9 Hz,






2H),






2.75-2.58 (m, 2H), 2.34 (t, J = 0.9 Hz,






3H),






2.18-2.01 (m, 1H),






1.79 (s, 1H),






1.19-1.09 (m, 6H)
















TABLE 5







Structure and Preparation Method for Exemplified P Series Compounds











Prep.




accord-




ing to


No.
Structure
example





P1




23


 


P2




23


 


P3




23


 


P4




23


 


P5




23


 


P6




28


 


P7




28


 


P8




28


 


P9




28


 


P10




28


 


P12




29


 


P13




30


 


P16




33


 


P17




32


 


P18




33


 


P19




33


 


P20




33


 


P21




23


 


P22




23


 


P24




35


 


P25




23


 


P26




23


 


P27




23


 


P28




23


 


P29




23


 


P30




23


 


P31




23


 


P32




35


 


P33




35


 


P34




35


 


P35




35


 


P36




35


 


P37




35


 


P38




35
















TABLE 6







Structure and Preparation Method for CA Series Compounds











Prep.




according




to


No.
Structure
Example





CA1 




22


 


CA2 




22


 


CA3 




24


 


CA4 




24


 


CA5 




24


 


CA6 




25


 


CA7 




25


 


CA8 




25


 


CA9 




26


 


CA10




26


 


CA11




27


 


CA12




27


 


CA13




34


 


CA14




34


 


CA15




34


 


CA16




34


 


CA17




34


 


CA18




34


 


CA19




36


 


CA20




36


 


CA21




36


 


CA22




36


 


CA23




36


 


CA24




36


 


CA25




36


 


CA26




36


 


CA27




37


 


CA28




37


 


CA29




37


 


CA30




37


 


CA31




37


 


CA32




37


 


CA33




37


 


CA34




37


 


CA35




38


 


CA36




39


 


CA37




40


 


CA38




41
















TABLE 7







Structure and Preparation Method for FA Series Compounds











Prep.




according




to


No.
Structure
example





FA1




29


 


FA2




30


 


FA3




31


 


FA4




32


 


FA5




33


 


FA6




33
















TABLE 8







Analytical Data for Compounds in Table 5

















13CNMR;


No.
Mp (° C.)
IR (cm−1)
Mass (m/z)
1H NMR
19F NMR














P1
166-168

ESIMS m/z 583
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 11.5 (bs,






1H), 9.38 (bs, 1H),






8.60 (s, 1H),






8.05-8.00 (m, 2H),






7.79 (d, J = 8.8 Hz, 2H),






7.37 (d, J = 8.8 Hz,






2H), 7.31 (d, J = 8.0 Hz,






2H),






6.76-6.74 (m, 2H),






4.63 (bs, 1H), 3.78 (s,






3H),






3.42-3.32 (m, 2H),






2.94-2.80 (m, 2H),






2.25 (s, 3H)


P2
186-188

ESIMS m/z 599
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






11.81 (s, 1H), 9.87 (s,






1H), 9.39 (s, 1H),






8.09-7.94 (m,






4H), 7.62 (d, J = 8.7 Hz,






2H),






7.45-7.36 (m, 3H),






7.16 (dd, J = 10.5, 3.0 Hz,






1H),






7.08-7.01 (m, 1H),






4.52-4.47 (m, 1H),






3.38-3.27 (m,






2H),






3.01-2.83 (m, 3H), 1.17 (d, J = 6.6 Hz,






6H)


P3
167-169

ESIMS m/z 615
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






11.81 (s, 1H), 9.93 (s,






1H), 9.38 (s, 1H),






8.09-8.06 (m,






2H), 8.02 (s, 1H),






7.96 (d, J = 8.0 Hz,






1H), 7.63 (d, J = 8.8 Hz,






2H),






7.57 (d, J = 2.0 Hz, 1H),






7.45-7.31 (m,






4H),






4.52-4.47 (m, 1H),






3.37-3.28 (m, 2H),






3.03-2.96 (m, 1H),






2.93-2.84 (m,






2H), 1.17 (d, J = 6.8 Hz,






6H)


P4
170-172

ESIMS m/z 611
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






11.91 (s, 1H), 9.84 (s,






1H), 9.38 (s, 1H),






8.07 (d, J = 9.2 Hz,






2H), 8.02 (s, 1H),






7.96 (d, J = 8.0 Hz,






2H), 7.62 (d, J = 8.8 Hz,






2H),






7.43 (t, J = 10.0 Hz,






2H), 7.25 (d, J = 8.4 Hz,






1H),






7.10 (d, J = 2.4 Hz, 1H),






6.85 (dd, J = 8.8,






2.4 Hz, 1H),






4.52-4.48 (m, 1H),






3.72 (s, 3H),






3.37-3.28 (m, 2H),






2.98-2.85 (m, 3H),






1.15 (d, J = 6.8 Hz, 6H)


P5
120-122

ESIMS m/z 595
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






11.82 (s, 1H), 9.81 (s,






1H), 9.39 (s, 1H),






8.09-8.06 (m,






2H), 8.01 (s, 1H),






7.95 (d, J = 9.0 Hz,






1H), 7.62 (d, J = 9.0 Hz,






2H),






7.44-7.40 (m, 2H),






7.25 (d, J = 8.1 Hz, 1H),






7.15 (s, 1H),






7.01 (d, J = 8.1 Hz, 1H),






4.50-4.47 (m,






1H),






3.38-3.35 (m, 2H),






3.02-2.83 (m, 3H),






2.30 (s, 3H), 1.16 (d, J = 6.9 Hz,






6H)


P6
133-136

ESIMS m/z 632
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H),






8.07-8.03 (m, 2H),






7.90-7.87 (m, 3H),






7.61 (d, J = 8.4 Hz, 2H),






7.30 (d, J = 8.1 Hz,






1H), 7.11 (d, J = 9.0 Hz,






1H),






6.90-6.81 (m, 2H),






4.44-4.40 (m, 1H),






4.13-4.02 (m,






2H), 3.75 (s, 3H),






3.22-3.10 (m,






2H),






2.96-2.85 (m, 2H), 2.03 (s,






3H)


P7
141-144

ESIMS m/z 635
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H), 8.07 (d, J = 9.2 Hz,






2H),






7.89-7.87 (m, 3H),






7.62 (d, J = 8.4 Hz,






2H),






7.30-7.24 (m, 2H),






7.09-7.02 (m, 2H),






4.42-4.39 (m, 1H),






4.12 (d, J = 17.7 Hz,






1H), 4.00 (d, J = 17.7 Hz,






1H),






3.18-3.08 (m,






2H),






2.90-2.83 (m, 2H),






2.64-2.60 (m, 1H),






2.32 (s, 3H),






1.13-1.07 (m, 6H)


P8
153-155

ESIMS m/z 655
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H), 8.05 (d, J = 8.8 Hz,






2H),






7.95 (d, J = 7.2 Hz, 1H),






7.89-7.87 (m,






2H), 7.60 (d, J = 8.0 Hz,






2H),






7.49-7.42 (m, 3H),






7.30 (d, J = 5.4 Hz, 1H),






4.42-4.39 (m,






1H), 4.14 (d, J = 18.0 Hz,






1H),






3.96 (d, J = 18.0 Hz,






1H),






3.28-3.12 (m, 2H),






2.90-2.84 (m, 2H),






2.69-2.65 (m, 1H),






1.13-1.07 (m, 6H)


P9
137-140

ESIMS m/z 651
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H), 8.05 (d, J = 9.2 Hz,






2H),






7.94-7.87 (m, 3H),






7.60 (d, J = 8.8 Hz,






2H), 7.35 (d, J = 9.2 Hz,






1H),






7.29 (d, J = 7.6 Hz, 1H),






6.98 (dd, J = 8.8,






2.4 Hz, 1H),






6.80 (d, J = 2.4 Hz, 1H),






4.42-4.39 (m,






1H), 4.12 (d, J = 17.6 Hz,






1H),






3.98 (d, J = 17.6 Hz,






1H),






3.20-3.11 (m, 2H),






2.90-2.85 (m, 2H),






2.61-2.58 (m, 1H),






1.11-1.06 (m, 6H)


P10
222-224

ESIMS m/z 639
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H), 8.05 (d, J = 8.7 Hz,






2H),






7.91-7.87 (m, 3H),






7.61 (d, J = 8.4 Hz,






2H),






7.32-7.25 (m, 3H),






7.15-7.10 (m, 1H),






4.42-4.39 (m, 1H),






4.14 (d, J = 18.0 Hz,






1H), 4.00 (d, J = 18.0 Hz,






1H),






3.18-3.10 (m,






2H),






2.90-2.83 (m, 2H),






2.68-2.64 (m, 1H),






1.17-1.07 (m, 6H)


P12
122-124

ESIMS m/z 633
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.30 (s, 1H), 8.06 (d, J = 9.0 Hz,






2H),






7.95-7.90 (m, 2H),






7.61 (d, J = 8.7 Hz,






2H),






7.39-7.34 (m, 2H), 7.27 (d, J = 8.1 Hz,






1H),






7.00 (s, 1H), 6.64 (s,






1H),






4.61-4.59 (m, 1H),






3.28-3.23 (m, 2H),






2.99-2.91 (m, 2H),






2.67-2.63 (m,






1H), 2.30 (s, 3H),






2.08 (s, 3H),






1.10 (d, J = 6.6 Hz, 3H),






1.01 (d, J = 6.6 Hz,






3H)


P13
140-142

ESIMS m/z 649
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H),






8.09-8.04 (m, 2H),






7.95-7.87 (m, 3H),






7.61 (d, J = 8.4 Hz, 2H),






7.35-7.28 (m,






2H), 7.21 (d, J = 7.2 Hz,






1H),






7.05 (s, 1H),






4.42-4.36 (m, 1H),






3.17-3.08 (m, 2H),






2.91-2.83 (m, 2H),






2.64-2.55 (m,






1H), 2.27 (s, 3H),






1.60-1.55 (m,






3H),






1.14-1.04 (m, 6H)


P16


ESIMS m/z 650
1H NMR (300 MHz,





([M + H]+)
CD3OD) δ 9.11 (s,






1H),






8.01-7.92 (m, 4H),






7.50-7.30 (m, 5H),






7.19-7.10 (m, 1H),






4.47 (bs, 2H),






3.80 (bs, 1H),






3.52-3.47 (m, 2H),






3.27-3.22 (m, 2H),






2.86-2.72 (m,






3H),






2.43-2.35 (m, 5H),






1.43-1.10 (m, 9H)


P17
170-172

ESIMS m/z 667
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ






8.55-8.54 (m, 1H),






8.06-7.96 (m, 2H),






7.80 (d, J = 8.8 Hz,






2H), 7.54 (s, 1H),






7.44-7.32 (m,






4H), 7.16 (d, J = 8.4 Hz,






1H),






7.01-6.98 (m, 1H),






4.70 (s, 1H),






3.43-3.14 (m, 6H), 3.15 (d, J = 6.0,






1H),






2.96-2.92 (m, 1H),






2.75 (t, J = 6.4, 1H),






2.30 (s, 3H),






1.23-1.10 (m, 6H)


P18
156-158

ESIMS m/z 650
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.53 (s,






1H), 7.97 (s, 1H),






7.95 (s, 1H),






7.78 (d, J = 9.2 Hz, 2H),






7.37 (d, J = 8.4 Hz,






2H), 7.26 (s, 1H),






7.19 (dd, J = 8.4,






4.0 Hz, 1H),






7.08 (d, J = 8.4, 1H),






6.84 (s, 1H),






5.08 (d, J = 8.0 Hz, 1H),






4.59 (d, J = 7.2 Hz,






1H), 3.59 (s, 1H),






3.38 (d, J = 6.8 Hz,






1H),






3.33-3.24 (m, 2H),






3.00-2.73 (m, 4H),






2.49 (bs, 1H), 2.29 (s,






3H),






1.18-1.12 (m, 9H)


P19
105-107

ESIMS m/z 621
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 8.52 (s,






1H),






7.96-7.93 (m, 2H), 7.77 (d, J = 8.7 Hz,






2H),






7.38-7.28 (m, 4H),






7.21-7.02 (m,






3H), 5.05 (d, J = 7.5 Hz,






1H),






4.62-4.54 (m, 1H),






3.72-3.64 (m, 1H),






3.54-3.46 (m,






1H),






3.34-3.22 (m, 2H),






3.10-2.92 (m, 3H),






2.84-2.70 (m, 2H),






2.35-2.29 (m,






2H),






1.24-1.14 (m, 6H)


P20
220-222

ESIMS m/z 636
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 8.53 (s,






1H), 7.97 (s, 1H),






7.94 (s, 1H),






7.79 (d, J = 8.7 Hz, 2H),






7.37 (d, J = 8.4 Hz,






2H),






7.24-7.19 (m, 2H), 7.08 (d, J = 7.5 Hz,






1H),






6.86 (s, 1H),






5.08-5.06 (m, 1H), 4.60 (m,






1H),






3.71-3.65 (m, 1H),






3.53-3.47 (m, 1H),






3.33-3.26 (m, 2H),






3.09-3.05 (m,






2H),






2.93-2.72 (m, 3H),






2.35-2.25 (m, 5H),






1.21-1.13 (m, 6H)


P21
147-151

ESIMS m/z 609
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 11.84 (s,






1H), 9.86 (s, 1H),






8.60 (s, 1H),






7.90 (d, J = 5.0 Hz, 2H),






7.83-7.78 (m,






2H), 7.38 (d, J = 8.6 Hz,






2H),






7.26-7.09 (m, 4H),






5.97 (s, 1H), 4.15 (s,






1H),






3.24-2.92 (m, 4H), 2.68 (s,






1H), 2.32 (s, 3H),






2.17 (d, J = 11.8 Hz,






1H), 1.76 (s,






1H), 1.23 (d, J = 6.9 Hz,






6H)


P22
171-174

ESIMS m/z 595
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 11.85 (s,






1H), 9.50 (s, 1H),






8.59 (s, 1H),






7.92 (d, J = 5.5 Hz, 2H),






7.83-7.77 (m,






2H), 7.36 (dd, J = 18.0,






10.6 Hz, 3H),






7.16 (d, J = 8.4 Hz,






1H), 5.70 (s, 1H),






4.18 (s, 1H),






3.14 (ddd, J = 28.8,






15.1, 6.0 Hz, 2H),






3.00 (t, J = 6.6 Hz,






2H), 2.71 (s, 1H),






2.15 (s, 1H),






1.80 (s, 1H), 1.25 (d, J = 6.8 Hz,






6H)


P24
128-132

ESIMS m/z 635
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ






8.55-8.58 (m, 1H),






7.91-7.93 (m, 2H),






7.80-7.82 (dd, J = 6.6,






2 Hz, 2H),






7.46 (m, 2H),






7.40-7.41 (d, J = 8.4 Hz, 2H),






7.32 (m, 1H),






7.15 (d, J = 8.7 Hz, 1H),






7.07-7.08 (d, J = 7.8 Hz,






1H),






5.51-5.52 (m, 1H),






4.19-4.20 (m, 1H),






3.93-3.94 (s, 2H),






3.20 (m, 1H),






2.95-2.97 (m, 2H),






2.71 (m, 2H),






2.12-2.14 (br, s, 1H),






1.81-1.83 (br, s,






1H),






1.19-1.21 (m, 6H)


P25
188-191

ESIMS m/z 581
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






11.95 (s, 1H), 9.89 (s,






1H), 9.38 (s, 1H),






8.10-8.05 (m,






2H),






7.92-7.83 (m, 2H),






7.68-7.58 (m, 2H),






7.42 (s, 1H), 7.25 (t, J = 8.1 Hz,






2H),






7.15 (d, J = 7.7 Hz, 1H),






7.00 (dd, J = 7.4,






1.7 Hz, 1H),






4.05 (d, J = 8.7 Hz, 1H),






3.13 (dd, J = 16.9,






5.0 Hz, 1H),






2.95 (t, J = 6.6 Hz, 2H),






2.74 (dd, J = 16.8,






7.2 Hz, 1H),






2.27 (s, 3H), 2.17 (s,






3H), 2.03 (d, J = 11.4 Hz,






1H),






1.83 (dt, J = 13.5, 7.1 Hz,






1H)


P26
179-183

ESIMS m/z 629
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 11.96 (s,






1H), 9.55 (s, 1H),






8.60 (s, 1H),






7.91 (d, J = 5.2 Hz, 2H),






7.83-7.77 (m,






2H), 7.50 (s, 1H),






7.38 (d, J = 8.6 Hz,






2H), 7.28 (d, J = 1.3 Hz,






3H),






7.16 (d, J = 8.5 Hz, 1H),






5.77 (s, 1H)






4.17 (s, 1H),






3.23-2.93 (m, 4H), 2.69 (dd,






J = 16.6, 8.6 Hz,






1H), 2.15 (s, 1H),






1.88-1.73 (m,






1H), 1.23 (d, J = 6.8 Hz,






6H)


P27
152-156

ESIMS m/z 609
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 11.81 (s,






1H), 9.57 (s, 1H),






8.60 (s, 1H),






7.91 (d, J = 5.1 Hz, 2H),






7.84-7.75 (m,






2H),






7.42-7.34 (m, 2H), 7.30 (s,






1H),






7.19-7.12 (m, 2H), 7.07 (d, J = 7.9 Hz,






1H),






4.17 (s, 1H), 3.18 (dd, J = 16.6,






5.2 Hz,






1H), 3.00 (t, J = 6.7 Hz,






2H),






2.70 (s, 1H), 2.55 (t, J = 7.7 Hz,






2H),






2.32 (s, 3H), 2.15 (s,






1H), 1.80 (s, 1H),






1.64-1.56 (m,






5H), 0.95 (t, J = 7.3 Hz,






3H)


P28
173-176

ESIMS m/z 597
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 11.56 (s,






1H), 9.50 (s, 1H),






8.59 (s, 1H),






7.92 (d, J = 5.8 Hz, 2H),






7.80 (d, J = 9.0 Hz,






2H),






7.41-7.31 (m, 4H), 7.16 (d, J = 8.4 Hz,






1H),






6.78 (d, J = 7.2 Hz, 2H),






5.87 (s, 1H),






4.17 (s, 1H), 3.79 (s,






3H), 3.17 (d, J = 16.3 Hz,






1H),






2.99 (s, 2H), 2.72 (s,






1H), 2.27 (s, 3H),






2.14 (s, 1H),






1.81 (s, 1H)


P29
192-195

ESIMS m/z 596
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 11.46 (s,






1H), 9.85 (s, 1H),






8.59 (s, 1H),






7.92 (d, J = 5.3 Hz, 2H),






7.80 (d, J = 8.9 Hz,






2H), 7.38 (d, J = 8.6 Hz,






2H),






7.21 (d, J = 7.5 Hz, 1H),






7.17-7.09 (m,






3H), 5.82 (s, 1H),






4.16 (s, 1H),






3.17 (dd, J = 16.7, 5.2 Hz,






1H), 2.98 (t, J = 6.6 Hz,






2H),






2.66 (dq, J = 23.2, 8.1 Hz,






3H), 2.28 (s,






3H), 2.15 (s, 1H),






1.86-1.72 (m,






1H), 1.23 (t, J = 7.6 Hz,






3H)


P30
188-191

ESIMS m/z 602
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






12.34 (s, 1H), 10.05 (s,






1H), 9.38 (s, 1H),






8.11-8.00 (m,






2H),






7.93-7.81 (m, 3H),






7.66-7.55 (m, 2H),






7.42 (d, J = 8.2 Hz, 1H),






7.26 (d, J = 7.8 Hz,






2H),






7.14-7.05 (m, 1H), 4.07 (s,






1H), 3.13 (dd, J = 16.8,






5.0 Hz, 1H),






2.95 (t, J = 6.6 Hz,






2H), 2.75 (dd, J = 16.8,






7.1 Hz, 1H),






2.30 (s, 3H),






2.04 (d, J = 13.7 Hz,






1H), 1.83 (dt, J = 13.4,






7.1 Hz, 1H)


P31
171-175

ESIMS m/z 597
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 12.11 (s,






1H), 9.23 (s, 1H),






8.61 (s, 1H),






8.20 (s, 1H), 7.90 (dd, J = 4.2,






2.6 Hz, 2H),






7.85-7.73 (m,






2H), 7.38 (d, J = 8.6 Hz,






2H),






7.12 (d, J = 8.4 Hz, 1H),






6.99 (d, J = 8.6 Hz,






1H), 6.82 (d, J = 8.4 Hz,






1H),






6.08 (s, 1H), 4.17 (s,






1H), 3.87 (s, 3H),






3.15 (dd, J = 16.7,






5.2 Hz, 1H),






2.97 (t, J = 6.6 Hz, 2H),






2.66 (dd, J = 16.7,






8.5 Hz, 1H),






2.31 (s, 3H),






2.21-2.06 (m, 1H), 1.78 (q, J = 11.9,






9.9 Hz,






1H), 1.57 (s, 3H)


P32
160-162

ESIMS m/z 621
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.54 (s,






1H),






7.89-7.93 (m, 2H),






7.77-7.82 (d, J = 8.8 Hz,






2H), 7.38 (d, J = 8.80 Hz,






2H),






7.20-7.24 (d, J = 7.6 Hz,






1H), 7.17 (br d,






J = 9.78 Hz, 2H),






6.91 (s, 1H),






5.53 (d, J = 7.6 Hz,, 1H),






4.18 (br s, 1H),






3.91 (s, 2H),






3.18 (br dd, J = 16.63,






5.38 Hz, 1H),






2.94 (m, 2H), 2.69 (br






dd, J = 16.8, 8.4,






Hz, 1H), 2.35 (s,






3H),






2.08-2.14 (m, 4H),






1.74-1.87 (m, 1H)


P33
146-148

ESIMS m/z 669
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.55 (s,






1H), 7.91 (d, J = 4.89 Hz,






2H),






7.75-7.82 (dd, J = 6.8,






2 Hz, 2H),






7.34-7.45 (m, 4H),






7.12-7.18 (m, 1H),






7.07 (t, J = 2.45 Hz,






1H),






5.48-5.54 (dd, J = 8,






3.6 HZ, 1H),






4.15-4.22 (m, 1H),






3.91-3.98 (s, 2H),






3.15-3.27 (m, 1H),






2.86-3.00 (m,






2H),






2.57-2.75 (m, 2H), 2.12 (br s,






1H),






1.74-1.87 (m, 1H),






1.12-1.20 (m, 6H)


P34
140-142

ESIMS m/z 650
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.54 (s,






1H),






7.89-7.95 (m, 2H), 7.79 (dd,






J = 6.8, 2.0 Hz,






2H), 7.39 (d, J = 8.8 Hz,






1H),






7.21 (d, J = 8.31 Hz,






2H), 7.14 (d, J = 8 Hz,






1H),






6.89-6.97 (m, 2H),






5.52 (dd, J = 8.1, 4.5 Hz,






1H), 4.19 (br s,






1H), 3.90 (d, J = 2.0 HZ,






2H),






3.18 (dd, J = 16.6,






5.2 Hz, 1H),






2.93-2.96 (m, 2H),






2.70-2.62 (m, 1H),






2.34 (m, 5H),






2.1 (br, s, 1H),






1.79 (m, 1H), 1.5 (s,






2H), 0.94 (t, J = 7.2 Hz,






3H)


P35
173-180

ESIMS m/z 637
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.53 (s,






1H), 7.89 (d, J = 5.0 Hz,






2H),






7.80-7.75 (m, 2H),






7.37 (d, J = 8.4 Hz, 2H),






7.13 (d, J = 8.1 Hz,






1H), 6.99 (dd, J = 7.8,






4.3 Hz, 1H),






6.82 (d, J = 8.6 Hz,






2H),






5.57-5.50 (m, 1H), 4.18 (s,






1H),






4.12-3.88 (m, 2H), 3.79 (s,






3H), 3.16 (dd, J = 16.6,






5.4 Hz, 1H),






2.93 (d, J = 7.3 Hz,






2H),






2.73-2.63 (m, 1H), 2.10 (d, J = 1.9 Hz,






4H),






1.81 (s, 1H)


P36
128-130

ESIMS m/z 635
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ






8.55-8.53 (m, 1H),






7.90 (d, J = 4.4 Hz, 2H),






7.82-7.77 (dd, J = 6.8,






2.0 Hz, 2H),






7.38 (d, J = 8.3 Hz,






2H), 7.31 (d, J = 7.8 Hz,






1H),






7.13-7.23 (m, 3H),






5.53 (d, J = 7.8 Hz, 1H),






4.17 (br s, 1H),






3.94 (s, 2H),






3.21-3.16 (dd, J = 16.4,






5.2 Hz, 1H),






2.99-2.93 (m, 2H),






2.69 (m 1H), 2.43 (q, J = 7.66 Hz,






2H),






2.13 (m , 4H),






1.85-1.75 (m, 1H),






1.23-1.15 (m, 3H)


P37
152-154

ESIMS m/z 641
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.54 (s,






1H),






7.96-7.90 (m, 2H),






7.82-7.76 (dd, J = 6.8,






2.0 Hz, 2H),






7.43-7.37 (m, 3H),






7.22 (d, J = 6.8 Hz, 1H),






7.18-7.13 (dd, J = 8.4,






2.4 Hz, 1H),






7.06 (br s, 1H),






5.50 (dd, J = 8.0,






4.0 Hz, 1H),






4.20 (br s, 1H), 3.95 (m,






2H), 3.19 (m, 1H),






3.00-2.92 (m,






2H),






2.76-2.66 (m, 1H), 2.38 (s,






3H),






2.16-2.10 (m, 1H), 1.84 (br d,






J = 7.8 Hz, 1H)


P38
165-168

ESIMS m/z 637
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.54 (s,






1H),






7.93-7.89 (m, 2H), 7.79 (dd,






J = 6.8, 2.0 Hz, 2H),






7.38 (d, J = 8.8 Hz,






2H), 7.21 (d, J = 8.4 Hz,






1H),






7.14 (dd, J = 8.4, 3.2 Hz,






1H),






6.97-6.89 (m, 2H),






5.52 (d, J = 7.6 Hz, 1H),






4.19 (br s, 1H),






3.96-3.91 (m,






2H), 3.77 (d, J = 2.0 Hz,






3H),






3.23-3.13 (m, 1H),






2.95 (m, 2H),






2.72-2.65 (m, 1H),






2.32 (s, 3H),






2.17-2.06 (m, 1H),






1.86-1.75 (m, 1H)
















TABLE 9







Analytical Data for Compounds in Table 6

















13CNMR;


No.
Mp (° C.)
IR (cm−1)
Mass (m/z)
1H NMR
19F NMR














FA1
124-126

ESIMS m/z 619
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.35 (s, 1H),






8.07-8.04 (m, 2H),






7.88-7.86 (m, 2H),






7.60 (d, J = 9.0 Hz, 2H),






7.53-7.42 (m,






2H),






7.34-7.29 (m, 2H), 7.20 (d, J = 7.5 Hz,






1H),






7.13 (d, J = 7.5 Hz, 1H),






6.50 (s, 1H),






4.46-4.38 (m, 1H),






3.18-3.05 (m, 2H),






2.88-2.80 (m,






2H), 2.45 (d, J = 6.6 Hz,






1H),






2.30 (s, 3H), 1.13 (t, J = 6.9 Hz,






6H)


FA2
130-132

ESIMS m/z 635
1H NMR (400 MHz,





([M + H]+)
DMSO-d6) δ






9.36 (s, 1H), 8.06 (d, J = 9.6 Hz,






2H),






7.93-7.87 (m, 3H),






7.60 (d, J = 8.4 Hz,






2H),






7.47-7.39 (m, 2H),






7.30-7.26 (m, 2H),






7.22-7.20 (m, 1H),






4.42-4.27 (m,






1H),






3.19-3.10 (m, 2H),






2.70-2.62 (m, 1H),






1.59 (t, J = 7.2 Hz, 3H),






2.30 (s, 3H),






1.17-1.10 (m, 3H),






1.09 (t, J = 6.8 Hz, 3H)


FA3
94-96

ESIMS m/z 622
1H NMR (300 MHz,





([M + H]+)
DMSO-d6) δ






9.85 (d, J = 6.6 Hz, 1H),






9.35 (s, 1H),






8.05 (d, J = 8.7 Hz, 3H),






7.96 (s, 1H),






7.90 (d, J = 8.1 Hz, 1H),






7.61 (d, J = 8.4 Hz,






3H),






7.37-7.35 (m, 1H), 7.17 (d, J = 7.2 Hz,






1H),






7.12-7.01 (m, 2H),






6.77 (d, J = 7.2 Hz,






1H), 4.49 (t, J = 6.6 Hz,






1H),






4.59 (bs, 1H),






3.45-3.41 (m, 1H),






2.87 (d, J = 11.1 Hz,






3H),






2.73-2.68 (m, 1H),






1.36-1.23 (m, 3H),






0.97-0.92 (m, 6H)


FA4
190-192

ESIMS m/z 653
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.55 (s,






1H),






8.06-8.02 (m, 2H), 7.95 (bs,






1H), 7.80 (d, J = 8.8 Hz,






2H),






7.61 (bs, 1H),






7.40-7.33 (m, 4H),






7.20-7.19 (m, 2H),






4.47 (bs, 1H),






3.49-3.37 (m, 2H),






3.28-3.26 (m,






2H), 3.15 (bs, 1H),






2.99-2.96 (m,






2H),






2.78-2.76 (m, 2H), 1.22 (d, J = 6.4 Hz,






6H)


FA5
103-106

ESIMS m/z 636
1H NMR (400 MHz,





([M + H]+)
CDCl3) δ 8.53 (s,






1H),






7.97-7.94 (m, 2H), 7.78 (d, J = 9.2 Hz,






2H),






7.37 (d, J = 8.8 Hz, 2H),






7.33-7.30 (m,






1H),






7.26-7.17 (m, 2H),






7.03-7.00 (m, 2H),






5.05 (d, J = 8.0 Hz, 1H),






4.61-4.56 (m,






1H),






3.60-3.56 (m, 1H),






3.40-3.20 (m, 4H),






3.01-2.90 (m, 2H),






2.88-2.70 (m,






3H),






2.55-2.45 (m, 2H),






1.40-1.10 (m, 6H)


FA6
146-148

ESIMS m/z 636
1H NMR (300 MHz,





([M + H]+)
CDCl3) δ 8.52 (s,






1H),






7.95-7.93 (m, 2H), 7.77 (d, J = 9.0 Hz,






2H),






7.60-7.32 (m, 5H),






7.22-7.13 (m,






2H),






4.42-4.39 (m, 1H),






3.90-3.66 (m, 1H),






3.40-3.20 (m, 3H),






3.16-2.90 (m,






3H),






2.50-2.30 (m, 3H),






1.46-1.40 (m, 3H),






1.30-1.20 (m, 6H)



















BAW & CL Rating Table










% Control (or Mortality)
Rating






50-100
A



More than 0-Less than 50
B



Not Tested
C



No activity noticed in this bioassay
D



















GPA & YFM Rating Table










% Control (or Mortality)
Rating






80-100
A



More than 0-Less than 80
B



Not Tested
C



No activity noticed in this bioassay
D
















TABLE ABC







Biological Results










Insect species














No.
BAW
CL
GPA
YFM






F1
A
A
C
A



F2
A
A
B
A



F3
A
A
C
A



F4
A
A
B
A



F5
A
A
C
C



F6
A
A
C
C



F7
A
A
C
C



F8
A
A
C
C



F9
A
A
C
A



F10
A
A
C
A



F11
A
A
C
A



F12
A
A
D
A



F13
A
A
B
A



F14
A
A
C
C



F15
A
A
B
A



F16
A
A
C
A



F17
A
A
C
A



P1
A
A
C
A



P2
A
A
C
A



P3
A
A
C
A



P4
A
A
C
A



P5
A
A
C
A



P6
A
A
C
A



P7
A
A
C
A



P8
A
A
C
A



P9
A
A
C
A



P10
A
A
C
A



P12
A
A
C
A



P13
A
A
C
B



P16
A
A
C
C



P17
A
A
C
C



P18
A
A
C
A



P19
A
A
C
A



P20
A
A
C
A



P21
A
A
C
A



P22
A
A
C
A



P23
A
A
C
A



P24
A
A
C
A



P25
A
A
C
A



P26
A
A
C
A



P27
A
A
C
A



P28
A
A
C
A



P29
A
A
C
A



P30
A
A
C
A



P31
A
A
C
A



P32
A
A
C
B



P33
A
A
C
A



P34
A
A
C
D



P35
A
A
C
A



P36
A
A
C
A



P37
A
A
C
D



P38
A
A
C
A



FA1
A
A
C
A



FA2
A
A
B
A



FA3
A
D
C
B



FA4
A
A
C
C



FA5
A
A
C
A



FA6
A
A
C
A
















TABLE ABCD







Biological Results










Insect species














No.
BAW
CL
GPA
YFM






C1
A
A
B
A



C2
A
A
C
C



C3
A
A
C
A



C4
C
C
C
D



C5
C
C
C
C



C6
C
C
C
C



C8
C
C
C
D



C15
C
C
C
C



C17
C
C
C
D



C18
C
C
C
D



C19
C
C
C
C



C20
C
C
C
D



C21
C
C
C
C



C22
C
C
C
D



C23
C
C
C
C



C24
C
C
C
C



C25
C
C
C
C



C26
C
C
C
C



C27
C
C
C
C



C28
C
C
C
C



C29
B
A
C
B



C30
D
C
C
D

## Claims

1. A molecule having the following formula




wherein:
(A) R1, R2, R3, R4, R5, R6, R7, and R9 are each independently selected from the group consisting of H, F, Cl, Br, I, CN, NO2, OH, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, and (C3-C6)cycloalkoxy,
wherein each alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, and cycloalkoxy is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo;
(B) R8 is H;
(C) L is a (C1-C4)alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo;
(D) R10 is selected from the group consisting of H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, ((C1-C4)alkyl)((C3-C6)cycloalkyl), (C1-C4)alkylphenyl, (C1-C4)alkylheterocyclyl, ((C1-C4)alkyl)O((C1-C4)alkyl), ((C1-C4)alkyl)OC(O)((C1-C4)alkyl), ((C1-C4)alkyl)OC(O)O((C1-C4)alkyl), C(O)((C1-C4)alkyl), and C(O)phenyl,
wherein each alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, phenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo;
(E) R11, R12, R13, R14, and R15 are each independently selected from the group consisting of H, F, Cl, Br, I, CN, NO2, OH, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, and (C3-C6)cycloalkoxy;
(F) R16 and R17 are each independently selected from the group consisting of (G), H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, ((C1-C4)alkyl)((C3-C6)cycloalkyl), (C1-C4)alkylphenyl, (C1-C4)alkylheterocyclyl, ((C1-C4)alkyl)C(O)((C1-C4)alkyl), and ((C1-C4)alkyl)C(O)O((C1-C4)alkyl),
wherein each alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, phenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, CN, OH, and oxo; and
(G) R16 and R17 together with (S)Cx(Nx) forms a 4 to 8 membered heterocyclyl ring,
wherein said heterocyclyl ring may optionally be substituted with one or more substituents independently selected from R18,
wherein R18 is selected from the group consisting of H, F, Cl, Br, I, CN, OH, (C1-C4)alkyl, oxo, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl, ((C1-C4)alkyl)((C3-C6)cycloalkyl), (C1-C4)alkylphenyl, (C1-C4)alkylheterocyclyl, ((C1-C4)alkyl)C(O)((C1-C4)alkyl), ((C1-C4)alkyl)C(O)O((C1-C4)alkyl), phenyl, and heterocyclyl,
wherein each alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, phenyl, and heterocyclyl are optionally substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, I, CN, OH, and oxo.

2. A molecule according to claim 1 wherein R1, R2, R3, R4, R6, R7, R8, R9, R10, and R14 are H.

3. A molecule according to claim 1 wherein R5 is OCF3 or OCF2CF3.

4. A molecule according to claim 1 wherein L is —CH2— or —CH2CH2—.

5. A molecule according to claim 1 wherein R11 is H or CH3.

6. A molecule according to claim 1 wherein R12 is H, Cl, CH3, or OCH3.

7. A molecule according to claim 1 wherein R13 is H, F, CH3, or OCH3.

8. A molecule according to claim 1 wherein R15 is Cl, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, cyclopropyl, or OCH3.

9. A molecule according to claim 1 wherein R16 and R17 together is —C(R18)—C(R18)—, —C(R18)—C(R18)—C(R18)—, or —C(R18)═C(CR18)—.

10. A molecule according to claim 1 wherein R16 and R17 are H.

11. A molecule according to claim 1 wherein R18 is H, F, CH3, OH, or oxo.

12. A molecule according to claim 1 wherein:
(A) R1, R2, R3, R4, R5, R6, R7, and R9 are each independently selected from the group consisting of H and (C1-C4)haloalkoxy;
(B) R8 is H;
(C) L is (C1-C4)alkyl;
(D) R10 is H;
(E) R11, R12, R13, R14, and R15 are each independently selected from the group consisting of H, F, Cl, Br, I, (C1-C4)alkyl, and (C3-C6)cycloalkyl;
(F) R16 and R17 are (G) or H; and
(G) R16 and R17 together with (S)Cx(Nx) forms a 4 to 8 membered heterocyclyl ring,
wherein said heterocyclyl ring may optionally be substituted with one or more substituents independently selected from R18,
wherein R18 is selected from the group consisting of H, CH3, and oxo.

13. A molecule according to claim 1 wherein said molecule is selected from one of the following molecules











No.
Structure







F1 






 


F2 






 


F3 






 


F4 






 


F5 






 


F6 






 


F7 






 


F8 






 


F9 






 


F10






 


F11






 


F12






 


F13






 


F14






 


F15






 


F16






 


F17

14. A molecule according to claim 1 wherein said molecule is selected from one of the following molecules











No.
Structure







P1 






 


P2 






 


P3 






 


P4 






 


P5 






 


P6 






 


P7 






 


P8 






 


P9 






 


P10






 


P11






 


P12






 


P13






 


P14






 


P15






 


P16






 


P17






 


P18






 


P19






 


P20






 


P21






 


P22






 


P23






 


P24






 


P25






 


P26






 


P27






 


P28






 


P29






 


P30






 


P31






 


P32






 


P33






 


P34






 


P35






 


P36






 


P37






 


P38

15. A molecule according to claim 1 wherein said molecule is selected from one of the following molecules











No.
Structure







FA1






 


FA2






 


FA3






 


FA4






 


FA5






 


FA6

16. A pesticidal composition comprising a molecule according to claim 1 and a carrier.

17. A pesticidal composition according to claim 16 further comprising one or more compounds having a mode of action selected from: acetylcholinesterase (ACh E) inhibitors; GABA-gated chloride channel antagonists; sodium channel modulators; nicotinic acetylcholine (nAChR) agonists; nicotinic acetylcholine receptor (nAChR) allosteric activators; chloride channel activators; juvenile hormone mimics; miscellaneous non-specific (multi-site) inhibitors; selective homopteran feeding blockers; mite growth inhibitors; microbial disruptors of insect midgut membranes; inhibitors of mitochondrial ATP synthase; uncouplers of oxidative phosphorylation via disruption of the proton gradient; nicotinic acetylcholine receptor (nAChR) channel blockers; inhibitors of chitin biosynthesis, type 0; inhibitors of chitin biosynthesis, type 1; moulting disruptor, dipteran; ecdysone receptor agonists; octopamine receptor agonists; mitochondrial complex III electron transport inhibitors; mitochondrial complex I electron transport inhibitors; volatage-dependent sodium channel blockers; inhibitors of acetyl CoA carboxylase; mitochondrial complex IV electron transport inhibitors; mitochondrial complex II electron transport inhibitors; and ryanodine receptor modulators.

18. A pesticidal composition according to claim 16 further comprising one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, and/or virucidal properties.

19. A pesticidal composition according to claim 16 further comprising one or more compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, and/or synergists.

20. A pesticidal composition according to claim 16 further comprising one or more of the following compounds—(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-diolamine, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, afidopyropen, afoxolaner, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, anabasine sulfate, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzovindiflupyr, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, broflanilide, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloroprallethrin, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, cholecalciferol, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clacyfos, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclaniliprole, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclopyrimorate, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalodiamide, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dicloromezotiaz, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-P-potassium, dichlorprop-P-sodium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipymetitrone, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, enoxastrobin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, epsilon-metofluthrin, epsilon-momfluorothrin, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenaminstrobin, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenquinotrione, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazaindolizine, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenoxystrobin, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, fluhexafon, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, fluralaner, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halauxifen, halauxifen-methyl, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptafluthrin, heptenophos, heptopargil, herbimycin, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isofetamid, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, kappa-bifenthrin, kappa-tefluthrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, Ivdingjunzhi, Ivxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, mandestrobin, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, momfluorothrin, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, napropamide-M, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxathiapiprolin, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentachlorophenyl laurate, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picarbutrazox, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pydiflumetofen, pyflubumide, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyraziflumid, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyriminostrobin, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrisoxazole, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, rescalure, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetraniliprole, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiafenacil, tiaojiean, tiocarbazil, tioclorim, tioxazafen, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolprocarb, tolpyralate, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyricarb, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, trifludimoxazin, triflumezopyrim, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneacetic acid.

21. A pesticidal composition according to claim 16 further comprising one or more biopesticides.

22. A pesticidal composition according to claim 16 further comprising a seed.

23. A process comprising applying a pesticidal composition according to claim 16 to a locus to control a pest, in a sufficient amount to control said pest.

24. A process according to claim 23 wherein said pest is selected from ants, aphids, beetles, bristletails, cockroaches, crickets, earwigs, fleas, flies, grasshoppers, leafhoppers, lice, locusts, mites, moths, nematodes, scales, symphylans, termites, thrips, ticks, wasps, and whiteflies.

25. A process according to claim 23, wherein said pest is Spodoptera exiqua (LAPHEG), Myzus periscae (MYZUPE), Aedes aegypti (AEDSAE) or Trichoplusia ni (TRIPNI).

26. A process according to claim 23 wherein said locus is
(a) where crops, trees, fruits, cereals, fodder species, vines, turf, and/or ornamental plants, are growing;
(b) where domesticated animals are residing;
(c) the interior or exterior surfaces of buildings (such as places where grains are stored);
(d) the materials of construction used in buildings (such as impregnated wood); and/or
(e) the soil around buildings.

27. A process according to claim 23 wherein said locus has one or more of the following growing apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, and beans.