Substituted 2-propenyl derivatives of pyridine

A heterocyclic compound having the structural formula ##STR1## where R is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.6 cycloalkyl, trifluoromethyl, phenyl, substituted phenyl, phenoxy, substituted phenoxy, benzyl or substituted benzyl; and R.sup.1 is at least a partially saturated monocyclic or bicyclic heterocycle of nitrogen which may be substituted with lower alkyl and physiologically acceptable salts thereof is disclosed. A process for forming this compound which involves the reaction of an amine of the formula HR.sup.1 where R.sup.1 has the meanings given above with a substituted 2-propenyl halide having the structural formula ##STR2## where R has the meanings given above; and X is a halogen atom is described. The invention embodies the above-mentioned novel 2-propenyl halide utilized as an intermediate in the formation of the heterocyclic compound of this invention. A method ofcontrolling phytopathogenic fungi by applying a fungicidally effective amount of the heterocyclic compound of the present invention to the locus under attack by said fungi is also taught. Finally, a fungicidally composition comprising the heterocyclic compound of the present invention and a suitable carrier therefor is set forth.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention is directed to a class of substituted 2-propenyl 
derivatives of nitrogen heterocycles. More specifically, the present 
invention is directed to a class of substituted 2-propenyl derivatives of 
nitrogen heterocycles useful as fungicides. 
2. Background of the Prior Art 
The control of phytopathogenic fungi is of great economic importance since 
fungal growth on plants or on parts of plants such as fruits, blossoms, 
foliage, stems, tubers, roots and the like not only inhibit production of 
a plant as well as commercially significant portions thereof, its foliage, 
fruit and seed, but, in addition, reduce the overall quality of the 
harvested crop. 
To overcome or at least reduce the detrimental effects of fungi, plants 
have long been treated with fungicides. However, the enormous economic 
toll taken by identified fungi, as well as the development of new fungus 
strains resistant to known fungicides, establishes a continuing need to 
develop new and more effective fungicides which possess curative, 
preventative and systemic action to protect cultivated plants. These new 
fungicides must not only positively possess these protective properties 
but, negatively, must not possess properties which have an adverse effect 
on the plants to be protected. 
The use of nitrogen-containing heterocyclic compounds to provide 
fungicidally effective compositions is known in the art. For example, U.S. 
Pat. No. 4,202,894 describes a class of heterocyclic compounds, i.e., 
morpholines, piperidines and the like, which are useful as fungicidal 
agents. In addition, the compound, 
4-(3-(4-(1,1-dimethylethyl)phenyl)-2-methyl)propyl-2,6(cis) 
-dimethyl-morpholine is dimethyl-morpholine is disclosed in Agricultural 
Chemicals Book IV - Fungicides, 1985 Revision, W.T. Thomson, Thomson 
Publications, P.O. Box 9335, Fresno, CA 92341 at page 134. The compound is 
therein described as a systemic and foliar fungicide. Although the 
compounds of the above discussed prior art disclosures are nitrogen 
heterocyclic compounds, they are characterized by a structure which is 
clearly distinguished from a substituted 2-propenyl derivative of a 
nitrogen heterocycle. 
The above remarks establish the continual need to develop new compounds, 
distinguished from the compounds utilized in the prior art, that provide 
more effective fungicidal activity against the scourge of phytopathogenic 
fungi. 
SUMMARY OF THE INVENTION 
A new class of substituted 2-propenyl derivatives of nitrogen heterocycles 
has now been discovered which provides surprisingly effective control of 
many commonly encountered phytopathogenic fungi. Not only is this new 
class of compounds effective against many fungi but, in addition, this new 
class of compounds can be used to control fungi by either systemic or 
foliar treatment. 
In accordance with the present invention, a new class of compounds having 
the structural formula 
##STR3## 
where R is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.6 cycloalkyl, 
trifluoromethyl, phenyl, substituted phenyl, phenoxy, substituted phenoxy, 
benzyl or substituted benzyl: and R.sup.1 is an at least partially 
saturated monocyclic or bicyclic nitrogen-containing heterocycle which may 
be substituted with lower alkyl and physiologically acceptable salts 
thereof is disclosed. 
In further accordance with the present invention a process for forming the 
nitrogen heterocyclic compound of the subject invention is described. In 
this process a unique class of substituted 2-propenyl halides having the 
structural formula 
##STR4## 
where R is as defined in the compound of the present invention; and X is a 
halogen atom, is reacted with a compound having the structural formula 
HR.sup.1, where R.sup.1 has the meanings given for the compound of the 
present invention, to form the compound of the subject invention. 
In still further accordance with the present invention an intermediate 
compound, utilized in the formation of the compound of the subject 
invention, a substituted 2-propenyl halide having the structural formula 
##STR5## 
where R is as defined in the nitrogen heterocyclic compound of the present 
invention; and X is a halogen atom, is set forth. 
In yet further accordance with the present invention, a composition 
comprising the compound of the subject invention and a suitable carrier 
therefor is taught. 
Finally, in yet still further accordance with the subject invention, a 
method of controlling fungi is disclosed. In this method a fungicidally 
effective amount of the compound of the present invention is applied to 
the locus to be protected. 
DETAILED DESCRIPTION 
The compound of the present invention is a substituted 2-propenyl 
derivative of a nitrogen heterocycle having the structural formula 
##STR6## 
where R is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.6 cycloalkyl, 
trifluoromethyl, phenyl, substituted phenyl, Phenoxy, substituted phenoxy, 
benzyl or substituted benzyl: and R.sup.1 is an at least partially 
saturated monocyclic or bicyclic nitrogen heterocycle which is linked to 
2-propenyl moiety through the nitrogen atom of the heterocycle, and which 
may contain an oxygen or sulfur atom and which may be substituted with 
lower alkyl and physiologically acceptable salts thereof. 
Preferably, the compound of the present invention has the structural 
formula I where R is C.sub.1 -C.sub.6 alkyl, C.sub.5 -C.sub.6 cycloalkyl, 
trifluoromethyl, phenyl, phenoxy or benzyl; and R.sup.1 is partially or 
fully saturated pyrrolyl, pyridyl, isoindolyl, indolyl, isoquinolyl, 
quinolyl, morpholinyl, thiomorpholinyl or azepinyl which may be 
substituted with C.sub.1 -C.sub.2 alkyl and physiologically acceptable 
salts thereof. 
More preferably, the compound of the present invention is a compound having 
the structural formula I where R is tert-butyl, cyclohexyl, 
trifluoromethyl, phenyl or phenoxy: and R.sup.1 is at least partially 
saturated pyridyl, morpholinyl, indolyl, quinolyl or isoquinolyl which may 
be substituted with one or more methyl groups and physiological acceptable 
salts thereof. 
In a preferred embodiment of the compound of the instant invention, the 
compound having the structural formula I, the substituent R is positioned 
para to the substituted propenyl group on the phenyl ring. 
In the preferred embodiment wherein the nitrogen heterocyclic group of 
R.sup.1 is substituted with lower alkyl groups, the number of such alkyl 
substituents is preferably 1 or 2. Moreover, in the preferred embodiment 
wherein a physiological acceptable salt of the compound having the 
structural formula I is utilized, it is preferably a hydrochloride salt. 
The subject invention is also directed to an intermediate compound, a 
substituted 2-propenyl halide having the structural formula 
##STR7## 
where R has the meanings given for the broadest meaning of the compound 
having the structural formula I; and X is a halogen atom. 
Preferably, the intermediate compound having the structural formula II is 
defined by R having the meanings of the preferred embodiment of the 
compound having the structural formula I; and X is chlorine or bromine. 
More preferably, the compound having the structural formula II is defined 
by R having the meanings of the more preferred embodiment of the compound 
having the structural formula I; and X is chlorine. 
In an another aspect of the present invention, a process is provided for 
making the compound having the structural formula I. In that process a 
Grignard reagent having the structural formula 
##STR8## 
where R has the meanings given for the compound having the structural 
formula I; and X.sup.1 is a halogen atom, is reacted with a methallyl 
halide having the structural formula 
##STR9## 
where X is halogen. Preferably, the compound having the structural formula 
IV is characterized by X being chlorine or bromine. More preferably, X is 
chlorine. 
The reaction of the Grignard reagent, the compound characterized by the 
structural formula III, and the methallyl halide, having the structural 
formula IV, are reacted in a solvent, preferably, diethyl ether or 
tetrahydrofuran. 
The product of this reaction is the intermediate compound of the present 
invention, the substituted 2-propenyl halide defined by structural formula 
II. This intermediate compound is reacted with a compound of the formula 
EQU HR.sup.1 (V) 
wherein R.sup.1 has the same meanings as that given to the broadest meaning 
of R.sup.1 in the definition of the compound having the structural formula 
I. 
The reaction between the substituted propenyl halide, having the structural 
formula 11, and the amine, having the structural formula V, occurs at a 
temperature in the range of between about 80.degree. C. and 130.degree. C. 
The reaction can occur in the presence or absence of a solvent. If a 
solvent is employed, the reactants, the compounds having the structural 
formulas II and V, are heated to the reflux temperature of the solvent. 
In the preferred embodiment wherein a solvent is employed it is an inert 
hydrocarbon or an inert chlorohydrocarbon of sufficiently high boiling 
point to meet the temperature constraint mentioned above. Thus, solvents 
preferred for use in this application include toluene, xylene and 
dichlorobenzenes. 
The preferred stoichiometric ratio of the reactants which result in the 
formation of the desired compound having the structural formula I is two 
molar equivalents of the amine having the structural formula V to one 
molar equivalent of the intermediate compound having the structural 
formula II. 
For completeness, it should be mentioned that the formation of the compound 
having the structural formula I includes the step of neutralizing the 
crude product obtained by the reaction of compounds having the structural 
formula II and V with a base prior to the isolation of the product, the 
compound having the structural formula I. 
In addition to the compound having the structural formula I, the instant 
invention encompasses physiologically acceptable salts thereof. These 
salts are obtainable by dissolving a compound having the structural 
formula I, synthesized by the above-defined procedure, in a suitable inert 
solvent and adding an acid thereto. The reaction product is isolated and 
purified. For example, the product may be filtered and, if necessary, 
purified by washing with an inert organic solvent. The preferred acid 
utilized in the salt formation process is hydrochloric acid, resulting in 
the formation of the preferred salt, the hydrochloride salt of the 
compound having the structural formula I. Other acids which may be used in 
forming a salt within the contemplation of the present invention include 
nitric acid and sulfuric acid. 
In the preferred embodiment wherein the compound of the present invention, 
having the structural formula I, is characterized by a substituted 
nitrogen heterocyclic, that compound is obtained by employing an amine, 
having the structural formula V, wherein one or more of the ring carbon 
atoms are substituted with lower alkyl, preferably methyl. 
It should be appreciated that in the case where R.sup.1 has a meaning 
wherein the heterocyclic nitrogen ring is substituted with two lower alkyl 
groups that compound may be present as a pair of cis and trans isomers. 
These isomers may or may not be separated. Thus, the compound of the 
present invention, wherein the nitrogen heterocyclic ring is substituted 
with two lower alkyl groups, contemplates mixtures of cis and trans 
isomers. 
It is also emphasized that in the case where the compound having the 
structural formula I is characterized by lower alkyl substitution on the 
heterocyclic nitrogen ring, that substitution is preferably C.sub.1 
-C.sub.2 alkyl. More preferably, the substituent is methyl. It is 
particularly preferred, in the case of heterocycle substitution, that the 
substituent be one or two methyl groups. 
Yet another aspect of the present invention is a method for controlling 
phytopathogenic fungi. In this method a fungicidally effective amount of 
the compound having the structural formula I, where the meanings of R and 
R.sup.1 are those given for the broadest meaning of the compound of that 
formula, is applied to the locus under attack by said fungi. Preferably, 
the method of controlling phytopathogenic fungi comprises applying a 
fungicidally effective amount of a compound having the structural formula 
I, where R and R.sup.1 have the meanings of the preferred embodiment of 
that compound, to the locus under attack by said fungi. More preferably, 
the method of controlling phytopathogenic fungi comprises applying a 
fungicidally effective amount of a compound having the structural formula 
I, where R and R.sup.1 have the meanings given for the more preferred 
embodiment of the compound having the structural formula I, to the locus 
under attack by said fungi. 
In one preferred embodiment, the method by which a fungicidally effective 
amount of the compound having the structural formula I is applied to the 
locus under attack by said phytopathogenic fungi is by application of the 
compound having the structural formula I to the foliage of the plants to 
be protected. This so-called "foliar treatment" is effectuated by applying 
the compound having the structural formula I to the foliage at a 
concentration of between about 10 and about 500 milligrams of the compound 
having the structural formula I per liter of inert liquid in which the 
compound is disposed to the foliage of the plants to be protected from the 
phytopathogenic fungi. 
In another preferred embodiment of the method of controlling 
phytopathogenic fungi, a fungicidally effective amount of the compound 
having the structural formula I is applied to the soil in which the plants 
to be protected from the fungi are grown. In this method, the so-called 
"systemic treatment," a compound having the structural formula I is 
applied to the soil in which the plant to be protected is grown in a 
concentration of between about 0.125 and about 10 kilograms of the 
compound having the structural formula I per hectare (kg/ha) of soil in 
which the plant to be protected is grown. More preferably, systemic 
control involves application of between about 0.125 kg/ha to about 5 kg/ha 
of the compound having the structural formula I to the soil in which the 
plant to be protected is grown. 
Independent of which preferred embodiment of controlling fungi is utilized, 
either the foliar or systemic treatment, the application may be applied 
prior to or after infection by fungi. Furthermore, it should be 
appreciated that the exact dosage, applied systemically or to the foliage, 
is dictated by the fungus to be controlled and the particular plant to be 
protected. 
In still another embodiment of the method of the present invention of 
controlling phytopathogenic fungi, the compound having the structural 
formula I is applied as a coating to the seeds of the plant to be 
protected. This method benefits from the two preferred embodiments 
discussed above, foliar treatment and systemic treatment. That is, the 
fungicidal coating, the coating of the compound having the structural 
formula I, protects the soil from infection by the fungi and is also taken 
up by the plant systemically to protect the plant from fungal attack. In 
this so-called "seed coating method," an appropriate concentration of the 
compound having the structural formula I is in the range of between about 
5 and about 75 grams of the compound per hundred kilograms of seed. 
Another important aspect of the present invention resides in a new 
composition useful as a fungicide. The fungicidal composition of the 
present invention comprises a compound having the structural formula I, 
where R and R.sup.1 have the meanings given for the broadest meaning of 
that compound, and a carrier therefor. 
Preferably, the composition of the instant invention includes a compound 
having the structural formula I, where R and R.sup.1 have the meanings 
given for the preferred embodiment of that compound, and a carrier 
therefor. 
More preferably, the fungicidal composition of the present invention 
includes a compound having the structural formula I, where R and R.sup.1 
have the meanings given for the more preferred embodiment of the compound 
having the structural formula I, and a carrier therefor. 
The utility of the composition, as stated above, is as a fungicide. 
Therefore, in a preferred embodiment, the concentration of the component 
of the composition defined by the compound having the structural formula I 
is a fungicidally effective amount of that compound. This concentration 
applies to the broadest, preferred and more preferred embodiments of the 
composition of this invention. 
The composition of the present invention includes, as one component 
thereof, a carrier suitable for admixture with the active agent of the 
composition, a compound having the structural formula I. The identity of 
the carrier is very broad. The carrier may be a solid, for example, finely 
divided particulate solids, granules, pellets, wettable powders, soluble 
powders and the like. Among the solid carriers within the contemplation of 
the subject invention are such organic and inorganic materials as 
attapulgite clay, sand, vermiculite, corncob, activated carbon and mineral 
silicates. Among the mineral silicates preferred for use in the 
composition of the present invention are mica, talc, pyrophyllite, clays 
and the like. 
A solid composition may be prepared from a solid carrier, such as one of 
those described immediately above. In that case, the active compound is 
impregnated onto the solid carrier. Alternatively, the active compound may 
be formulated into a wettable powder by grinding it into a fine powder and 
mixing it with the solid carrier to which a surface active dispersing 
agent has been added. The wettable powder is then dispersed in water and 
applied as a dispersion. 
Indeed, the above described dispersion is representative of a composition 
which may also be classified as a liquid composition. In addition to 
liquid dispersions, the liquid composition may be in the form of a 
solution or an emulsion. In the case of a liquid solution, the active 
compound, the compound having the structural formula I, is dissolved in an 
aqueous or organic solvent. In most cases the solvent, which acts as the 
carrier, is organic. In addition to aromatic hydrocarbons, such as toluene 
and xylene, other preferred solvents include such organic compounds as 
acetone, methanol, isopropanol, t-butyl alcohol, cyclohexanone, dioxane, 
dimethylformamide, dimethyl sulfoxide, ethylene dichloride, diacetone 
alcohol and N-methylpyrrolidone. 
A water emulsion, another preferred embodiment of a liquid composition 
within the contemplation of the present invention, is prepared from a 
solution, as described above, to which a surface active agent is added. 
Surface active agents suitable for use in forming an emulsion within the 
contemplation of this invention are known to those skilled in the art. 
McCutcheon's Detergents and Emulsifiers, Allured Publishing Corp., 
Ridgewood, N.J. (1970): U.S. Pat. No. 2,514,916, at Columns 2 to 4; and 
U.S. Pat. No. 2,547,734, at Columns 3 and 4, provide detailed examples of 
such surface active agents suitable for this purpose. As indicated in 
these references, the surface active agent may be anionic, non-ionic or 
cationic. 
In yet another embodiment of the carrier component of the composition of 
this invention, the carrier is an aerosol. To prepare an aerosol, the 
active compound, the compound having the structural formula I, is 
dissolved in a first solvent. This first solvent is conventional in the 
sense that although it is volatile, it is not highly volatile. This 
solution is then admixed with a highly volatile solvent, a so-called 
liquid aerosol carrier. The aerosol carrier is liquid only under elevated 
pressure. At ambient temperature and pressure, the aerosol carrier is a 
gas. In a subembodiment of this preferred carrier, the aerosol carrier may 
itself be active. For example, the carrier may be an insecticide, a 
herbicide, a bacteriacide or the like.

The following examples are given to illustrate the present invention. 
Because these examples are given for illustrative purposes only, these 
examples should not be interpreted as limiting the invention to the scope 
of the examples recited hereinafter. 
EXAMPLE 1 
Preparation of 2-[(P-t-butylphenyl)methyl]-2-propenyl Chloride 
A solution of p-bromo-(t-butyl)benzene (21.3 g., 0.10 mole) in dry diethyl 
ether (100 ml.) was added dropwise to a mixture of magnesium turnings (2.4 
g.), a single iodine crystal and dry diethyl ether (50 ml.). The mixture 
was allowed to react at ambient temperature for two hours. The resultant 
Grignard solution was transferred to a dry dropping funnel and added 
dropwise to a solution of methallyl dichloride (13 8 g., 0.11 mole) in dry 
diethyl ether (50 ml.). After complete addition of the Grignard solution, 
the mixture was refluxed for three hours and thereafter cooled with an 
ice-water bath while 15% hydrochloric acid (150 ml.) was added thereto. 
The mixture was extracted with diethyl ether and the organic phase dried 
over sodium sulfate, filtered and evaporated to yield a liquid. The liquid 
was distilled to provide 10 grams of 
2-[(p-t-butylphenyl)methyl]-2-propenyl chloride. This product was 
characterized by a boiling point of 105.degree. C. to 111.degree. C. at a 
pressure of 0.25 mm Hg. 
EXAMPLE 2 
Preparation of 
4-[2-[(P-t-butylphenyl)methyl]-2-propenyl]-2,6-dimethylmorpholine 
(Compound No. 1) 
A mixture of 2-[(p-t-butylphenyl)methyl]-2-propenyl chloride (7.4 g., 0.033 
mole), formed in accordance with the procedure of Example 1, and 
2,6-dimethylmorpholine (7.7 g., 0.067 mole) was heated for five hours at 
120.degree. C. The thus heated mixture was cooled to room temperature and 
then treated with 25% aqueous sodium hydroxide (20 ml.). The mixture was 
extracted with toluene, dried over sodium sulfate and evaporated to give 
an oil. The oil was distilled to yield 7.0 grams of 
4-[2-[(p-t-butylphenyl)methyl]-2-propenyl]-2-6-dimethylmorpholine. The 
product was characterized by a boiling point of 143.degree. C.-147.degree. 
C. at 0.25 mm Hg. 
EXAMPLE 3 
Preparation of 
1-[2-[[(P-trifluoromethyl)phenyl]methyl]-2-propenyl]-3,5-dimethylpiperidin 
e (Compound No. 29) 
In a method analogous to that described in Example 2, 
2-(p-trifluoromethyl)benzyl-2-propenyl chloride (5.0 g., 0.021 mole), 
formed in a method analogous to that utilized in Example 1, was reacted 
with 3,5-dimethylpiperidine (4.8 g., 0.042 mole) at 120.degree. C. for six 
hours to produce, after extraction, drying, evaporation and distillation, 
4.5 grams of 
1-[2-[[(p-trifluoromethyl)phenyl]methyl]-2-propenyl]-3,5-dimethylpiperidin 
e. The formed compound was characterized by a boiling point of 80.degree. 
C. to 85.degree. C. at 0.25 mm Hg. 
EXAMPLE 4 
Preparation of 
1-[2-[[(P-trifluoromethyl)phenyl]methyl]-2-propenyl]-3,5-dimethylpiperidin 
e, hydrochloride (Compound No. 31) 
A solution of 
2-[[(p-trifluoromethyl)phenyl]-methyl]-2-propenyl]-3,5-dimethylpiperidine 
(2.0 g.), made in accordance with Example 3, in diethyl ether (50 ml.) was 
treated with a steady stream of hydrogen chloride gas until white solid 
precipitation ceased. The precipitated solid was collected by filtration 
and air dried to give 1.5 grams of 
1-[2-[[(p-trifluoromethyl)phenyl]methyl]-2-propenyl]-3,5-dimethylpiperidin 
e, hydrochloride. This salt product was characterized by a melting point of 
150.degree. C. to 151.degree. C. 
EXAMPLE 5 
Preparation of 
1-[2-[(P-t-butylphenyl)methyl]-2-propenyl]-decahydroquinoline (Compound 
No. 8) 
2-[(P-t-butylphenyl)methyl]-2-propenyl chloride (2.3 g., 0.010 mole), 
formed in accordance with the procedure of Example 1, was reacted with 
perhydroisoquinoline line (3.0 g., 0.022 mole) at 120.degree. C. for five 
hours. The product of this reaction was separated and purified by the 
steps employed in Example 2 to yield 2.8 grams of 
1-[2-](p-t-butylphenyl)-methyl]-Z-propenyl]-decahydroquinoline which was 
identified by its boiling point, 157.degree. C. at 0.025 mm Hg. 
EXAMPLE 6 
Preparation of 
1-[2-[(P-t-butylphenyl)methyl]-2-propenyl]-2,3-dihydro-(1H)-indole 
(Compound No. 23) 
2-[(P-t-butylphenyl)methyl]-2-propenyl chloride (4.5 g., 0.020 mole), 
formed in accordance with the procedure of Example 1, was reacted with 
indoline (4.8 g., 0.040 mole) at 120.degree. C. for five hours and 
processed in accordance with the procedure of Example 2 to provide 2.6 
grams of 
1-[2-[(p-t-butylphenyl)methyl]-2-propenyl]-2,3-dihydro-(1H)-indole which 
was identified by its boiling point, 138.degree. C. to 145.degree. C. at 
0.02 mm Hg. 
EXAMPLE 7 
Preparation of 
1-[2-[(P-phenoxyphenyl)methyl]-2-propenyl]-3-methylpiperidine (Compound 
No. 11) 
2-[(P-phenoxyphenyl)methyl]-2-propenyl chloride (5.0 g., 0.020 mole), 
formed in a method analogous to that utilized in Example 1, was reacted 
with 3-methylpiperidine (3.8 g., 0.038 mole) at 110.degree. C. for five 
hours. The product was processed in accordance with the procedure of 
Example 2 to yield 4.0 grams of 
1-[2-[(p-phenoxyphenyl)methyl]-2-propenyl]-3-methylpiperidine. The thus 
formed compound was characterized by a boiling point of 175.degree. C. to 
183.degree. C. at 0.1 mm Hg. 
EXAMPLE 8 
Preparation of 1-[2 [(4-Phenyl)benzyl]-2-propenyl]-4-methylpiperidine 
(Compound No. 33) 
A mixture of 2-[(4-phenyl)benzyl]-2-propenyl chloride (4 g.), formed in a 
manner analogous to that used in Example 1, and 4-methylpiperidine (3.3 
g.) in p-xylene (15 ml.) was refluxed for five hours, cooled and 
neutralized with 25% aqueous sodium hydroxide (15 ml.). The mixture was 
extracted with toluene, dried over sodium sulfate and evaporated under 
reduced pressure to give an oil. The oil was distilled under vacuum and 
the fraction boiling at 195.degree. C. to 200.degree. C. at a pressure of 
0.7 mm Hg. was collected and identified as 
1-[2-[(4-phenyl)benzyl]-2-propenyl]-4-methylpiperidine. The compound, 
obtained in a yield of 3.5 g., solidified after being left at room 
temperature for a few hours. The solid was characterized by a melting 
point of 53.degree. C. 
EXAMPLE 9 
Preparation of 1-[2-[(4-Phenyl)benzyl]-2-propenyl]-3,5-dimethylpiperidine 
(Compound No.34) 
A mixture of 2-[(4-phenyl)benzyl]-2-propenyl chloride (4 g.), synthesized 
by method utilized in Example 1, and 3,5-dimethylpiperidine (3.7 g.) was 
heated at 120.degree. C. for five hours. The mixture was cooled to room 
temperature and neutralized with 25% aqueous sodium hydroxide (15 ml.). 
The mixture was extracted with toluene, dried over sodium sulfate and 
evaporated to give an oil which partially solidified on standing. The 
product was triturated with petroleum ether, having a boiling point range 
of 30.degree. C. to 60.degree. C., and the insoluble material was removed 
by filtration. The filtrate was evaporated under reduced pressure to yield 
1-[2-[(4-phenyl)benzyl]-2-propenyl]-3,5-dimethylpiperidine in a yield of 
4.9 grams. 
The compound was identified by its nuclear magnetic resonance data which 
was as follows: NMR (CDCl.sub.3) .delta.: 7.1-7.6(9H,m), 4.95(1H,s), 
4.85(1H,s), 3.4(2H,s), 2.8(2H,s), 1.2-2.5(8H,m), 0.95(3H,d), 0.8(3H,d). 
EXAMPLE 10 
Preparation of Compound Nos. 2-7, 9, 10, 12-22, 24-28, 30, 32 and 35-49 
Additional compounds characterized by structural formula I, wherein R and 
R.sup.1 have meanings within the contemplation of the present invention, 
were prepared in accordance with the procedures enurerated in Examples 1 
to 9. These compounds, including their characterizing boiling points, 
melting points or NMR data are summarized in Table I, which appears below. 
For convenience, the equivalent data for Compound Nos. 1, 8, 11, 23, 29, 
31, 33 and 34, formed in accordance with Examples 2 to 9, respectively, 
are also included in Table I. 
TABLE 1 
__________________________________________________________________________ 
##STR10## 
Cpd. NMR or 
No. R R.sup.1 B.P. (.degree.C.)/mm Hg 
M.P. (.degree.C.) 
__________________________________________________________________________ 
1 4-C(CH.sub.3).sub.3 
##STR11## 143-147/0.25 
2 4-C(CH.sub.3).sub.3 
##STR12## 170/1.80 
3 4-C(CH.sub.3).sub.3 
##STR13## 124/0.025 
4 4-C(CH.sub.3).sub.3 
##STR14## 135/0.20 
5 4-C(CH.sub.3).sub.3 
##STR15## 178-180/1.30 
6 4-C(CH.sub.3).sub.3 
##STR16## 115/0.10 
7 4-C(CH.sub.3).sub.3 
##STR17## 120-124/0.10 
8 4-C(CH.sub.3).sub.3 
##STR18## 157/0.025 
9 4-C.sub.6 H.sub.5 
##STR19## 175-180/0.05 
10 4-C.sub.6 H.sub.5 O 
##STR20## 175-180/0.05 
11 4-C.sub.6 H.sub.5 O 
##STR21## 175-183/0.10 
12 4-C.sub.6 H.sub.5 O 
##STR22## 165-175/0.10 
13 3-CF.sub.3 
##STR23## 88-90/0.10 
14 3-CF.sub.3 
##STR24## 75-78/0.10 
15 3-CF.sub.3 
##STR25## 114-116/0.60 
16 3-CF.sub.3 
##STR26## 95-97/0.50 
17 3-CF.sub.3 
##STR27## 110-112/0.50 
18 3-CF.sub.3 
##STR28## 162-164 
19 3-CF.sub.3 
##STR29## 144-146 
20 3-CF.sub.3 
##STR30## 135-138 
21 3-CF.sub.3 
##STR31## * 
22 4-cyclohexyl 
##STR32## 180-185/0.05 
23 4-C(CH.sub.3).sub.3 
##STR33## 138-145/0.02 
24 4-C(CH.sub.3).sub.3 
##STR34## 140-145/0.025 
25 4-C(CH.sub.3).sub.3 
##STR35## 140/0.025 
26 4-C(CH.sub.3).sub.3 
##STR36## ** 
27 4-C(CH.sub.3).sub.3 
##STR37## 134-136/0.02 
28 4-CF.sub.3 
##STR38## 90-95/0.025 
29 4-CF.sub.3 
##STR39## 80-85/0.025 
30 4-CF.sub.3 
##STR40## 100-105/0.70 
31 4-CF.sub.3 
##STR41## 150-151 
32 4-CF.sub.3 
##STR42## 161-163 
33 4-C.sub.6 H.sub.5 
##STR43## 195-200/0.70 
53 
34 4-C.sub.6 H.sub.5 
##STR44## *** 
35 4-C.sub.6 H.sub.5 
##STR45## 192-196/0.25 
36 4-C.sub.6 H.sub.5 
##STR46## 161-163 
37 4-C.sub.6 H.sub.5 
##STR47## 176-183/0.25 
38 4-C.sub.6 H.sub.5 
##STR48## **** 
39 4-C.sub.6 H.sub.5 
##STR49## 200-201 
40 4-C.sub.6 H.sub.5 
##STR50## 185-193/0.25 
41 4-CH.sub.3 
##STR51## 135-140/5.00 
42 4-C.sub.6 H.sub.5 O 
##STR52## 192-198/0.05 
43 4-C.sub.6 H.sub.5 O 
##STR53## 190-198/0.05 
44 4-C.sub.6 H.sub.5 O 
##STR54## 190-192/0.05 
45 4-C.sub.6 H.sub.5 O 
##STR55## 175-182/0.02 
46 4-C.sub.6 H.sub.5 
##STR56## 183-186 
47 4-C.sub.6 H.sub.5 O 
##STR57## 165-173/0.02 
48 4-C.sub.6 H.sub.5 O 
##STR58## 180-191/0.25 
49 4-C.sub.6 H.sub.5 O 
##STR59## 165-173/0.05 
__________________________________________________________________________ 
*NMR (CDCl.sub.3) .delta.: 9.5(1H, broad), 7.1-7.5(8H, m), 5.45(1H, s), 
5.35(1H, s), 3.9(2H, s), 3.5(2H, s), 3.2(4H, m), 1.3(9H, s) 
**NMR (CDCl.sub.3) .delta.: 11.5(1H, broad), 7.2-7.6(4H, m), 5.5(1H, s), 
5.3(1H, s), 3.8(2H, s), 3.6(2H, s), 3.3(2H, m), 1.6(6H, m), 1.4(3H, t), 
1.2(2H, t) 
***NMR (CDCl.sub.3) .delta.: 7.1-7.6(9H, m), 4.95(1H, s), 4.85(1H, s), 
3.4(2H, s), 2.8(2H, s), 1.2-2.5(8H, m), 0.95(3H, d), 0.8(3H, d) 
****NMR (CDCl.sub.3) .delta.: 7.1-7.8(9H, m), 5.0(1H, s), 4.9(1H, s), 
3.5(2H, s), 3.0(2H, s), 2.5-2.9(4H, m), 0.9-2.1(12H, m) 
EXAMPLE 11 
Preparation of Fungicidal Compositions 
Compound Nos 1 to 49, summarized in Table I above, were each dissolved in 
acetone or other suitable solvent (0.3 g. of each of the compounds in 10 
ml. of acetone or other suitable solvent). One or two drops of an 
emulsifying agent, Triton [trademark]X-100, and water were added to the 
solution to form an emulsion. The amount of water added was a function of 
the desired concentration of the emulsion composition, reported in 
milligrams per liter (mg/1). 
EXAMPLE 12 
Control of Powdery Mildew Fungus by Systemic Root Uptake 
Compositions of Compound Nos. 1 to 49, formed in accordance with the 
procedure of Example 11, were tested to evaluate their effectiveness in 
preventing or controlling powdery mildew disease of barley caused by the 
fungus, Erysiphe graminis and powdery mildew disease of cucumber caused by 
the fungus, Erysiphe cichoracearum. This prevention or control capability 
was tested by utilizing the compounds of the present invention to control 
these diseases by systemic root uptake. 
In accordance with this aim, pots (4.times.4.times.3.5 inches) containing 
10 plants of barley (Variety "Herta") or 10 plants of cucumber (Variety 
"Marketmore 70") were grown to an age of six days and ten days, 
respectively. Upon reaching these ages, emulsion compositions (45 ml.) of 
Compounds 1 to 49, formed in accordance with the procedure of Example 11, 
were added to each pot. That is, 45 ml. an emulsion composition of each of 
the compounds tabulated in Table I were separately added to pots 
containing 10 barley or 10 cucumber plants of the type enumerated above. 
The 45 ml. of each of the emulsion compositions were added to each of the 
pots and saturated the soil in each pot without significant loss through 
drainage into the saucers below the pots. Each of the compositions 
contained the compounds of the present invention in a concentration of 250 
milligrams of the compound per liter of water (mg/1). A number of pots 
containing the same barley and cucumber plants were left untreated as 
controls. 
The barley and cucumber plants in all the pots, including those treated and 
those untreated, were inoculated with powdery mildew fungus 24 hours after 
emulsion composition treatment with the compounds of the present 
invention. Fungus inoculation was accomplished by tapping leaves of 
previously infected barley and cucumber plants over the treated and 
untreated pots containing the barley and cucumber plants, respectively, to 
distribute spores of the fungus over the plants growing in the pots. 
Six days after inoculation, disease control was evaluated on a 0 to 6 
rating scale. A 0 rating was assigned when no disease was evidenced. A 6 
rating was given for severe disease. Intermediate ratings were assigned 
depending on the degree of disease. Percent control was computed by 
comparing the ratings of the treated and untreated plants. 
The results of this test are reported in Table II wherein systemic control 
of powdery mildew disease in barley is reported under the title "BMS 250." 
Control of cucumber powdery mildew disease is reported, in Table II, under 
the title "CMS 250." 
EXAMPLE 13 
Control of Powdery Mildew Fungus by Foliar Application 
Eight plants of barley (Variety "Larker") were planted in a pot. The number 
of pots, as in Example 12, were sufficient to accommodate testing in 
duplicate or triplicate for each of the 49 compounds tabulated in Table I. 
This number included a duplicate number of pots, each containing eight 
plants, which acted as controls. 
In this test each of the compounds formulated into emulsion compositions, 
at a concentration of 1,000 milligrams of the compound per liter of water 
(1,000 mg/1), were prepared. These emulsions were then sprayed onto the 
foliage of the barley plants. The pots in which the plants were unsprayed 
acted as controls. The number of pots which were unsprayed equalled the 
number sprayed. 
After the foliage of the sprayed pots were dried the pots containing the 
sprayed and the unsprayed plants were all placed in a greenhouse 
maintained at 21.degree. C. All the plants in the pots were thereupon 
inoculated with barley powdery mildew fungus, Erysiphe graminis. 
Inoculation of the fungus was again accomplished by distributing spores of 
the fungus over the leaves of the plants to be tested from plants which 
had previously been infected with the disease. 
Five days after inoculation, the plants were evaluated and assigned a 
disease rating of 0 to 6 in accordance with the criterion explained in 
Example 12. Percentage control was computed in accordance with the 
description of Example 12. The results of these tests are summarized in 
Table II under the title "BMP 1,000." 
Similarly, pinto bean plants were prepared, treated and innoculated with 
Erysiphe Polygoni (PMP) as described above and reported in Table II. 
EXAMPLE 14 
Control of Rice Blast Disease by Foliar Treatment 
Five rice plants (Variety "Bellemont") were grown in a plurality of pots. 
The number of pots utilized equalled two times the number of compounds of 
the present invention in Table I plus a control for each replication of 
the test. 
The non-control pots were sprayed with emulsion compositions, formed in 
accordance with the procedure of Example 11, wherein each compound was 
provided in a concentration of 1,000 mg/1. This spraying occurred 3 to 4 
weeks after planting of the plants in the pots. The controls remained 
unsprayed. 
The sprayed and unsprayed plants, five to a pot, were inoculated with 
spores of the rice blast fungus, Pyricularia oryzae. This inoculation was 
accomplished by preparing inoculum containing 20,000 to 30,000 spores per 
milliliter. The inoculum was sprayed onto the plants to which one or two 
drops of ethoxylated sorbitan monolaurate surfactant had been earlier 
applied to ensure proper wetting of the inoculum onto the plant foliage. 
The inoculated plants in the control and non-control pots were incubated in 
a control chamber, at a humidity of 99% and a temperature of 21.degree. 
C., for about 24 hours to allow infection to occur. The plants, after 24 
hours in the control chamber, were transferred to a greenhouse for six 
days to permit disease development to occur. Disease was manifested by 
blast lesions on the leaves. Disease control was calculated by one of two 
methods. In one method the number of lesions were counted, if infection 
was moderate. Alternatively, in the case of severe infection, disease was 
evaluated by the 0 to 6 rating system discussed in Example 12. Whichever 
disease control rating system was employed to determine disease control of 
any particular compound was also utilized in evaluating its control. 
The results of this test are tabulated in Table II under the title of "RCB 
1,000." 
EXAMPLE 15 
Control of Bean Rust Fungus Eradicant Test 
Two pinto bean plants, P. vulgaris, were planted in a plurality of pots. 
When the plants were seven days old, at the primary leaf stage of growth, 
they were all sprayed with a suspension containing 20,000 spores of the 
bean rust fungus, Uromyces phaseoli, per milliliter of suspensing water. 
All the pots containing the inoculated plants were then incubated in a 
controlled environmental chamber, maintained at 99% humidity and 
21.degree. C., for 24 hours to allow infection to develop. The plants were 
then removed from the incubator and allowed to dry. Two days after 
inoculation the infected plants were sprayed with compositions of the 
compounds tabulated in Table I. The compositions were prepared in 
accordance with the procedure of Example 11 to provide a dosage of 1,000 
mg/1. An equal number of infected plants were not sprayed so that they 
could act as controls. All the sprayed and unsprayed plants were placed in 
a greenhouse, maintained at a temperature of 21.degree. C., for five days 
to allow any disease present to be expressed. 
The sprayed and control plants were assessed for disease using the 0 to 6 
rating system described in Example 12. Disease control, as discussed in 
Example 12, was then determined. The control of disease, expressed as 
percent reduction of disease, is included in Table II under the title "BRE 
1,000." 
EXAMPLE 16 
Control of Peanut Cercospora Leafspot by Foliar Treatment 
Four Virginia peanut plants were grown in each of a plurality of pots. 
Enough pots were prepared so that each of the compounds listed in Table I, 
prepared as emulsion compositions in accordance with the procedure of 
Example 11, could be evaluated by spraying each of them on the four plants 
of one pot. An equal number of pots, which were not sprayed, were provided 
as controls. Spraying occurred when the plants were four weeks old. The 
concentration of the emulsion utilized to spray the peanut plants was 900 
mg/1. 
All the plants, both sprayed and unsprayed (the controls), were thereafter 
inoculated with spores of Peanut Cercospora leafspot, Cercospora 
arachidicola. The inoculum contained 20,000 to 30,000 spores per 
milliliter. The inoculum (which had been previously treated with one or 
two drops of ethoxylated sorbitan monolaurate to aid in wetting the 
leaves) was sprayed onto the leaves of the peanut plants. All the pots 
containing the inoculated peanut plants were incubated in a control 
chamber, maintained at 24.degree. C., for 36 hours to develop infection. 
The plants were then placed in a greenhouse for 21 days to allow disease 
development. 
After 21 days in the greenhouse, all the plants were taken out and 
evaluated using the 0 to 6 disease rating system. Percent control was 
computed and the results are reported in Table II under the title "PNT 
900." 
EXAMPLE 17 
Control of Barley Blast by Foliar Treatment A plurality of pots which 
included 10 plants of 6 day old barley (Variety "Herta") were prepared. 
These pots were sprayed with emulsion compositions, formulated in 
accordance with the procedure of Example 11, of each of the compounds set 
forth in Table I. The plants in these pots, plus an equal number of 6 day 
old Variety "Herta" barley plants in control pots, which were unsprayed, 
were inoculated with spores of the blast fungus, Pyricularia oryzae. The 
method of inoculation utilized was the same as that enumerated in Example 
14, which employed the same fungus. 
All the inoculated plants were placed in a greenhouse, maintained at a 
temperature of 21.degree. C. and a humidity of 99%, for five days. At that 
time, the plants were evaluated using the 0 to 6 disease rating system. 
Percent control was computed and the results of this test are included in 
Table II under the title "BBL 1,000." 
EXAMPLE 18 
Control of Eight Fungus Species 
Each of the compounds, Compound Nos. 1 to 49, listed in Table I were 
solubilized in acetone at a concentration of 500 mg/1. Filtered paper 
discs, each 11 mm. in diameter, were dipped in each of the test solutions. 
The discs were allowed to dry in air to drive off the acetone solvent. An 
equal number of discs were untreated and acted as controls. 
Each of the treated and untreated discs were then placed on agar plates and 
seven fungus species: Alternaria solani (ALT), Botrytis cinerea (BOT), 
Fusarium oxysporum (FUS), Helminthosporium maydis (HMAY), Phytophthora 
infestans (PHY), Sclerotinia sclerotiorum (SCM) and Sclerotium rolfsii 
(SCO) were added to the center of each disc in the form of a culture plug 
with the fungus mat in contact with the treated paper of the test disc or, 
in the case of the controls, in contact with the untreated test paper. The 
plates were incubated at 29.degree. C. in an oven. 
Percent growth inhibition by the compounds of the present invention of the 
seven fungus species was evaluated, after incubation, by measuring the 
radius from the center of the fungus colony of the treated discs compared 
to the radius from the center of the fungus colony of the untreated discs. 
That is, inhibition effectuated by each of the compounds was determined as 
a function of the percent difference between the radii of the treated and 
untreated discs. The results of these tests appear in Table II under the 
titles "ALT 500," "BOT 500," "FUS 500," "HMAY 500," "PHY 500," "SCM 500," 
and "SCO 500." 
It is noted that in the case of the test of the fungus Helminthosporium 
maydis, the concentration of each of Compound Nos. 1 to 49 was 500 
milligrams per liter. 
A separate test was utilized to determine the control of a eighth fungi 
species, Cercospora arachidicola (CER). In this test two drops of the 
fungus were added as a spore suspension (20,000 spores per milliliter) to 
the chemically treated discs, rather than as a mycelial culture plug. 
Scoring of the effectiveness of the compounds in controlling the 
Cercospora arachidicola fungus was determined with control based on the 
following scoring criteria: 100 represented complete inhibition of 
germination and growth of the fungus: 80 represented nearly complete 
inhibition but some growth of the fungus; 50 represented partial 
inhibition of growth or early complete inhibition with later growth: 20 
indicated some, but not significant, inhibition of growth; and 0 indicated 
complete growth of the fungus without any inhibition. 
As in the case of the seven fungus species discussed above, the results 
representing the effectiveness of the compounds of Table I against 
Cercospora arachidicola are included in Table II under the title "CER 
500." 
3 TABLE II 
Percent Fungicidal Control ALT BBL BMP BMS BOT BRE CER CMS FUS HMAY 
PHY PMP PNT RCB SCM SCO Cpd. 500 1000 1000 250 500 1000 500 250 500 500 
500 1000 900 1000 500 500 No. Ex. 18 Ex. 17 Ex. 13 Ex. 12 Ex. 18 Ex. 15 
Ex. 18 Ex. 12 Ex. 18 Ex. 18 Ex. 18 Ex. 18 Ex. 16 Ex. 14 Ex. 18 Ex. 
18 1 50 0 60 90 100 100 100 90 0 100 100 90 -- 100 0 100 2 95 0 100 
100 100 0 100 65 90 100 70 85 82 0 0 65 3 100 0 100 100 100 90 100 90 70 
100 0 100 82 60 0 10 4 90 15 100 100 90 -- 100 90 90 100 100 -- 55 0 0 
50 5 100 0 100 100 100 -- 100 90 90 100 100 90 82 0 0 100 6 95 15 100 
100 100 95 100 100 80 100 100 80 82 0 0 35 7 100 0 90 100 100 100 100 90 
40 100 100 100 95 20 45 10 8 100 -- 100 100 100 100 100 80 95 100 100 
100 -- 100 25 100 9 50 0 100 90 60 100 100 90 0 100 65 65 0 100 25 0 10 
75 0 90 0 100 100 100 0 0 100 40 100 0 85 0 0 11 95 -- 15 60 50 100 100 
80 50 100 0 100 -- 0 0 0 12 80 -- 15 60 0 100 100 60 50 90 0 100 -- 0 0 
0 13 35 -- 0 45 100 0 -- 90 20 80 35 0 -- 0 5 55 14 60 -- 0 0 95 0 0 95 
25 70 30 0 -- 0 0 0 15 65 -- 0 70 90 0 0 100 20 75 20 0 -- 0 15 45 16 70 
-- 0 15 100 0 0 50 30 35 10 0 -- 0 5 0 17 60 -- 0 0 95 0 -- 0 30 20 0 0 
-- 0 0 0 18 60 -- 0 0 100 0 -- 0 30 70 85 0 -- 0 0 45 19 75 -- 65 0 100 
0 -- 25 30 80 65 0 -- 0 0 100 20 60 -- 15 0 100 0 -- 50 10 55 10 0 -- 0 
0 0 21 70 -- 0 0 75 0 -- 100 20 65 0 0 -- 0 0 0 22 0 -- 0 0 25 0 100 0 
10 45 10 0 -- 0 40 20 23 0 -- 50 40 0 0 0 40 0 15 0 0 -- 35 0 40 24 10 
-- 85 0 0 0 100 20 25 70 15 0 -- 0 0 85 25 0 -- 0 0 0 0 0 0 0 30 0 0 -- 
15 0 75 26 0 -- 0 0 0 0 100 0 10 30 0 0 -- 0 0 50 27 100 -- 0 0 100 100 
100 90 75 100 80 95 -- 0 25 100 28 20 -- 0 75 100 0 0 50 10 50 0 0 -- 0 
0 85 29 40 -- 25 50 75 0 100 50 10 70 5 0 -- 0 0 100 30 40 -- 25 90 100 
0 100 50 5 70 10 0 -- 0 0 40 31 20 -- 100 50 85 0 100 0 15 75 5 0 -- 0 0 
100 32 40 -- 80 0 85 0 100 0 0 75 15 0 -- 0 0 70 33 100 -- -- 15 90 100 
100 40 75 65 0 95 -- -- 0 0 34 70 -- -- 65 100 100 100 0 70 65 0 100 -- 
-- 0 0 35 90 -- 0 100 100 100 100 15 100 100 0 50 -- 0 0 25 36 100 -- 0 
90 100 100 100 65 100 100 0 100 -- 0 0 100 37 100 -- 0 100 100 100 100 
15 100 100 15 90 -- 0 0 0 38 100 -- 100 85 75 100 100 0 100 100 25 95 -- 
0 0 50 39 100 -- 100 100 100 100 100 35 90 100 0 70 -- 0 0 25 40 100 -- 
100 100 100 100 100 35 100 100 0 95 -- 0 0 25 41 42 0 -- 0 15 30 100 100 
20 15 35 0 0 -- 0 0 0 43 0 -- 0 15 00 0 20 0 20 0 0 -- 0 0 0 44 70 -- -- 
35 100 100 100 40 60 65 0 100 -- -- 0 100 45 60 -- -- 85 0 95 100 90 85 
75 0 90 -- -- 0 40 46 47 70 -- -- 85 65 100 100 90 95 65 0 95 -- -- 0 40 
48 60 -- -- 90 100 100 100 100 100 75 0 95 -- -- 0 0 49 60 -- -- 15 80 
90 0 0 50 55 0 0 -- -- 0 0 
The above embodiments and examples are given to illustrate the scope and 
spirit of the instant invention. These embodiments will make apparent, to 
those skilled in the art, other embodiments and examples. These other 
embodiments and examples are within the contemplation of the present 
invention. Therefore, this invention should be limited only by the 
appended claims.