Process for the preparation of N-halomethylpyrrole and intermediates

Abstract: This invention relates to N-alkanoylaminomethyl and N-aroylaminomethyl pyrrole compounds of formula I It also relates to the use of said compounds as insecticidal and acaricidal agents and to a method of protecting plants from attack by insects and acarina by application of an N-alkanoylaminomethyl or N-aroylaminomethyl pyrrole to said plants or to the locus in which they are growing.

Description: SUMMARY OF THE INVENTION The present invention relates to a process for the preparation of specific N-halomethylpyrrole compounds that are highly effective insecticidal and acaricidal agents useful for the control of insect and acarid pests and for protecting agronomic crops from the ravages of said pests. The present invention also relates to N-alkanoylaminomethyl and N-aroylaminomethyl pyrroles that are useful as intermediates for preparing N-halomethylpyrrole compounds. EP 0 407 790 refers to N-vinyl-3-cyano-4-phenyl-pyrrole derivatives and their use as fungicides. Pyrrole carbonitrile and nitro-pyrrole insecticidal, acaricidal and molluscicidal agents and methods for the preparation thereof are disclosed in EP 0 372 263. Further uses of the compounds of the present invention are known from EA-A 0 530 515. The N-alkanoylaminomethyl and N-aroylaminomethyl pyrroles of the present invention have the structural formula I wherein W is halogen, CN or NO 2 ; X is halogen or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Y is halogen, CF 3 or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Z is halogen or CF 3 ; R 1 is hydrogen or C 1 -C 4 alkyl; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, 2- or 3-thienyl or 2- or 3-furyl; provided that when W is halogen, then X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups and Y and Z are CF 3 . DESCRIPTION OF THE PREFERRED EMBODIMENTS The N-alkanoylaminomethyl and N-aroylaminomethyl pyrroles of this invention are useful as intermediates for the preparation of N-halomethylpyrrole compounds which are excellent insecticidal and acaricidal agents. Preferred formula I compounds are those in which W is CN or NO 2 ; X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Y is halogen or CF 3 ; Z is halogen or CF 3 ; R 1 is hydrogen; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, 2- or 3-thienyl or 2- or 3-furyl. Other formula I compounds which are especially effective as insecticidal and/or acaricidal agents are those in which W is CN or NO 2 ; X is phenyl optionally substituted with one or two halogen or CF 3 groups; Y is Cl, Br or CF 3 ; Z is Cl, Br or CF 3 ; R 1 is hydrogen; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, or 2- or 3-thienyl. Preparation of the N-alkanoylaminomethyl and N-aroylaminomethyl pyrroles of the invention generally involves the alkylation of a pyrrole having the structural formula II wherein W, X, Y and Z are as described for formula I above. Alkylation of the formula II pyrrole can be achieved by the reaction of said formula II pyrrole with an alkali metal hydride or alkali metal C 1 -C 6 alkoxide and an alkylating agent having the structural formula III wherein R and R 1 are as described above for formula I. In the reaction an alkali metal hydride such as sodium hydride or an alkali metal C 1 -C 6 alkoxide such as potassium t -butoxide is generally dispersed in an anhydrous organic solvent such as dry tetrahydrofuran which contains the formula II pyrrole compound. The thus formed mixture is then added to a mixture of the formula III alkylating agent in an anhydrous organic solvent such as tetrahydrofuran. Thereafter, the thus prepared mixture is heated to refluxing temperatures until the N-alkanoylaminomethyl or N-aroylaminomethyl pyrrole is formed. The reactions are preferably conducted under a blanket of inert gas such as nitrogen or argon. The reaction scheme is shown below in Flow Diagram I: The formula I compounds of this invention can be converted into formula IV N-halomethyl pyrroles which can then be converted into formula V N-alkoxymethyl pyrrole compounds. Advantageously, this process for converting formula I compounds into formula V N-alkoxymethyl pyrrole compounds avoids the use of certain undesirable reactants such as chloromethyl ethyl ether. The N-alkoxymethyl pyrrole compounds are particularly effective for controlling insect, acarid and nematode pests and for protecting agronomic crops, both growing and harvested, against the ravages of these pests. Formula IV N-alkoxymethyl pyrroles are prepared by reacting a formula I N-alkanoylaminomethyl or N-aroylaminomethyl pyrrole with an excess of phosphorus oxychloride or phosphorus oxybromide at reflux temperature. The thus obtained formula IV compound is then reacted with an alkali metal C 1 -C 6 alkoxide such as sodium ethoxide in the presence of an inert organic solvent such as tetrahydrofuran, preferably at an elevated temperature, to obtain formula V N-alkoxymethyl pyrroles. The reaction scheme is shown below in Flow Diagram II: wherein W, X, Y, Z, R 1 and R are as described above for formula I. In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purpose of illustrating more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. EXAMPLE 1 Preparation of N-(hydroxymethyl)acetamide Acetamide (200 g, 3.4 mol) is added to a solution of potassium carbonate (20 g, 0.144 mol) in an aqueous formaldehyde solution (274 g, 37%, 3.4 mol). The reaction mixture is heated to 75°C, stirred for 3 1/2 hours at room temperature, quenched with dry ice, diluted with acetone, dried with anhydrous sodium sulfate and filtered. The filtrate is dried with anhydrous sodium sulfate, filtered and concentrated in vacuo to give the title product as an oil (309 g) which is identified by 1 HNMR spectral analysis. Following the above procedure, but substituting the appropriate amide for acetamide yields the following compounds: N-(hydroxymethyl)benzamide; N-(hydroxymethyl)-2-thiophenecarboxamide; N-(hydroxymethyl)-2,2-dimethylpropionamide; or 2,2,2-trifluoro-N-(hydroxymethyl)acetamide. EXAMPLE 2 Preparation of N-(hydroxymethyl)acetamide acetate (ester) Acetic anhydride (25 g) and pyridine (10 drops) is added to N-(hydroxymethyl)acetamide (9 g, 0.1 mol). The reaction mixture is stirred overnight at room temperature, concentrated in vacuo and chased with xylene to give the title product as an oil (11.9 g, 0.9 mol) which is identified by 1 HNMR spectral analysis. Following the above procedure, but substituting the appropriate N-(hydroxymethyl) compound for N-(hydroxymethyl)acetamide yields the following compounds: N-(hydroxymethyl)benzamide acetate (ester); N-(hydroxymethyl)-2-thiophenecarboxamide acetate (ester); N-(hydroxymethyl)-2,2-dimethylpropionamide acetate (ester); 2,2,2-trifluoro-N-(hydroxymethyl)-acetamide acetate (ester); N-(hydroxymethyl)-3-furamide acetate (ester); or N-(hydroxymethyl)-p-chlorobenzamide acetate (ester). EXAMPLE 3 Preparation of N-{[2,3-dichloro-4-cyano-5-(3,4-dichlorophenyl)pyrrol-1-yl]methyl}acetamide A slurry of 4,5-dichloro-2-(3,4-dichlorophenyl)pyrrole-3-carbonitrile (15.3 g, 0.05 mol) and tetrahydrofuran (80 mL) is cooled to 10°C and treated portionwise over 20 minutes with sodium hydride (2.2 g, 60% in oil, 0.055 mol). After stirring for 15 minutes this solution is added dropwise to a 50°C solution of N-(hydroxymethyl)acetamide acetate (ester) (9.18 g, 0.07 mol) and tetrahydrofuran (20 mL). The reaction mixture is refluxed for two hours, cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic extract is washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a solid. Flash chromatography of the solid on silica gel packed in methylene chloride using ethyl acetate/methylene chloride solutions as eluents gives a solid. Recrystallization of the solid from ethyl acetate gives the title product as off white crystals (5.35 g, mp 162.0-162.5°C) which is identified by IR and NMR spectral analyses. Following the above procedure, but substituting the appropriate pyrrole for 4,5-dichloro-2-(3,4-dichlorophenyl)pyrrole-3-carbonitrile and N-(hydroxymethyl) acetate (ester) compound for N-(hydroxymethyl)-acetamide acetate (ester) yields the following compounds. N-{[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methyl}-2-thiophenecarboxamide, mp 180-184°C; N-{[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methyl}pivalamide, mp 155-157.5°C; N-{[3-bromo-5-(p-bromophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methyl}benzamide, mp 159-161°C; N-[(2,3,5-tribromo-4-cyanopyrrol-1-yl)methyl]pivalamide, mp 175-180°C; N-[(2,3,5-tribromo-4-cyanopyrrol-1-yl)methyl]acetamide, mp 180-185°C; N-{[3-bromo-5-chloro-4-cyano-2-(3,4-dichlorophenyl)-pyrrol-1-yl]methyl}benzamide, mp 175-178.5°C; N-{[3-bromo-2-(3,4-dichlorophenyl)-4,5-bis(trifluoromethyl)pyrrol-1-yl]methyl}acetamide, mp 160.5-163.5°C; N-{[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl}methyl}acetamide, mp 135-136°C; N-{[2,4-dichloro-3-cyano-5-(3,4-dichlorophenyl)pyrrol-1-yl]methyl}acetamide, mp 146-148°C; N-{[2,4-bis(p-chlorophenyl)-3-nitro-5-(trifluoromethyl)pyrrol-1-yl]methyl)acetamide, mp 187.0-188°C; N-[(2,3,5-tribromo-4-cyanopyrrol-1-yl)methyl]benzamide, mp 168.5-180.0°C; N-{[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methyl}benzamide, mp 153-155°C; N-{[2,3-dichloro-4-cyano-5-(3,4-dichlorophenyl)pyrrol-1-yl]methyl}benzamide, mp 212-215°C; N-{[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methyl}acetamide, mp 150.0-150.5°C; or N-{[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methyl}-2,2,2-trifluoroacetamide, mp 136.5-138.0°C. EXAMPLE 4 Preparation of 4,5-Dichloro-1-(chloromethyl)-2-(3,4-dichlorophenyl)pyrrol-3-carbonitrile A mixture of N-{[2,3-dichloro-4-cyano-5-(3,4-dichlorophenyl)pyrrol-1-yl]methyl}acetamide (3.2 g, 0.0085 mol) and phosphorus oxychloride (6.51 g, 4 mL, 0.0424 mol) is heated at reflux temperature for 40 minutes, cooled, diluted with water and extracted with ethyl acetate. The combined organic extracts are washed sequentially with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a solid. Recrystallization of the solid from an ethyl acetate/heptane solution gives the title product as a pale brown solid (2.35 g, mp 153.0-156.0°C) which is identified by IR and NMR spectral analyses. Following the procedure, but substituting the appropriate N-[(substituted pyrrol-1-yl)methyl]acetamide for N-{[2,3-dichloro-4-cyano-5-(3,4-dichlorophenyl)pyrrol-1-yl]methyl}acetamide and using either phosphorus oxychloride or phosphorus oxybromide yields the following compounds. 4-Bromo-1-(bromomethyl)-2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile, mp 131.0-135°C; 4-bromo-1-(chloromethyl)-2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile, mp 128.0-129.0; or 2,4,5-tribromo-1-(chloromethyl)pyrrole-3-carbonitrile, mp 117.0-118.0°C. EXAMPLE 5 Preparation of 4-Bromo-1-(ethoxymethyl)-2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile A solution of 4-bromo-1-(chloromethyl)-2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile (2.0 g, 0.005 mol) in absolute ethanol is treated with a 21% wt/wt ethanolic solution of sodium ethoxide (0.36 g, 0.0053 mol), heated to 75-80°C for 20-30 minutes, cooled to room temperature and diluted with water and ether. The organic phase is dried over anhydrous magnesium sulfate and concentrated in vacuo to give a solid which is recrystallized from heptane to give the title product as a white solid (1.75 g, mp 97-98°C).

Claims: A process for the preparation of a N-halomethylpyrrole having the structural formula wherein W is halogen, CN or NO 2 ; X is halogen or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Y is halogen, CF 3 or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Z is halogen or CF 3 ; and X 1 is Cl or Br; provided that when W is halogen, then X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups and Y and Z are CF 3 ; which comprises reacting an N-alkanoylaminomethyl or N-aroylaminomethyl pyrrole having the structural formula wherein W, X, Y and Z are as described above; R 1 is hydrogen or C 1 -C 4 alkyl; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, 2- or 3-thienyl or 2- or 3-furyl; provided that when W is halogen, then X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups and Y and Z are CF 3 ; with an excess of phosphorous oxychloride or phosphorous oxybromide to form a mixture, heating said mixture to form said N-halomethylpyrrole. A compound having the structural formula wherein W is halogen, CN or NO 2 ; X is halogen or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 - C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups: Y is halogen, CF 3 or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Z is halogen or CF 3 ; R 1 is hydrogen or C 1 -C 4 alkyl; and R is hydrogen or C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, 2- or 3-thienyl or 2- or 3-furyl; provided that when W is halogen, then X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups and Y and Z are CF 3 . The compound according to claim 2 wherein W is CN or NO 2 ; X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Y is halogen or CF 3 ; Z is halogen or CF 3 ; R 1 is hydrogen; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, 2- or 3-thienyl or 2- or 3-furyl. The compound according to claim 3 wherein X is phenyl optionally substituted with one or two halogen or CF 3 groups; Y is Cl, Br or CF 3 ; Z is Cl, Br or CF 3 ; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, or 2- or 3-thienyl. A process for the preparation of an N-alkanoylaminomethyl or N-aroylaminomethyl pyrrole having the structural formula wherein W is halogen, CN or NO 2 ; X is halogen or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Y is halogen, CF 3 or phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups; Z is halogen or CF 3 ; R 1 is hydrogen or C 1 -C 4 alkyl; and R is C 1 -C 6 alkyl optionally substituted with one to three halogen atoms, phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups, 2- or 3-thienyl or 2- or 3-furyl; provided that when W is halogen, then X is phenyl optionally substituted with one or two halogen, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or CF 3 groups and Y and Z are CF 3 ; which comprises reacting a pyrrole having the structural formula wherein W, X, Y and Z are as described above, with an excess of an alkali metal hydride or alkali metal C 1 -C 6 alkoxide, in the presence of an anhydrous inert organic solvent to form a first mixture, adding said first mixture to a second mixture containing an excess of an acetate compound having the structural formula wherein R and R 1 are as described above and an anhydrous inert organic solvent to form a third mixture, and heating said third mixture to form said N-alkanoylaminomethyl or N-aroylaminomethyl pyrrole.

Inventors: KARMESWARAN VENKATARAMAN, KARMESWARAN, VENKATARAMAN
Applicants: BASF AG, BASF AKTIENGESELLSCHAFT
Application year: 1992
Main classification: C07D207
IPC codes: C07D207, C07D409, A01N43, C07D405