Preparation of substituted 3-aryl-5-trifluoromethyl-1,2,4-oxadiazoles

Abstract

The present invention relates to a process for the preparation of 3-aryl-5-trifluoromethyl-1,2,4-oxadiazoles, which are useful as fungicidal compounds or as intermediates for the synthesis of fungicidal oxaciazole compounds, using trifluoroacetyl halides.

1 .- 15 . (canceled) 
     
     
         16 . A process for preparing compounds of formula I, 
       
         
           
           
               
               
           
         
         wherein 
         A 1  is CH; 
         A 2  is N CH; 
         R A  is hydrogen or fluorine; 
         R is —COOH, —COOR 1  or —C(═W)NR 1 R 2 ; 
         W is O or S; 
         R 1  is C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxyimino-C 1 -C 4 -alkyl, C 3 -C 11 -cycloalkyl, C 3 -C 8 -cycloalkenyl, phenyl-C 1 -C 4 -alkyl, heteroaryl-C 1 -C 4 -alkyl, phenyl or heteroaryl; and wherein the heteroaryl group is a 5- or 6-membered aromatic heterocycle, wherein the ring includes besides carbon atoms 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S as ring member atoms; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3 or up to the maximum possible number of identical or different radicals selected from the group consisting of halogen, cyano, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy; 
         R 2  is hydrogen, formyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyl, propargyl, C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkenyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, phenyl, C 1 -C 6 -alkylamino or diC 1 -C 6 -alkylamino; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or up to the maximum possible number of identical or different radicals selected from the group consisting of halogen, cyano, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy; 
         the process comprising: 
         reacting a compound of formula II, 
       
       
         
           
           
               
               
           
         
         wherein A 1 , A 2 , R A  and R is as defined above, with a trifluoroacetyl halide of formula IIa, 
       
       
         
           
           
               
               
           
         
         wherein Hal is chlorine or fluorine. 
       
     
     
         17 . The process of  claim 16 , wherein the process is conducted in the presence of an inert organic solvent. 
     
     
         18 . The process of  claim 16 , wherein Hal in compound IIa is chlorine. 
     
     
         19 . The process of  claim 16 , wherein the process is conducted in the presence of a base selected from trimethylamine, triethylamine, tributylamine, diisopropylethylamine, pyridine, 2,4,6-collidine, 2,6-lutidine, 2-picoline, 3-picoline, 4-picoline, 5-ethyl-2-methyl-pyridine, sodium acetate, potassium acetate, sodium carbonate, potassium carbonate and mixtures thereof. 
     
     
         20 . The process of  claim 16 , wherein the process is conducted at a pressure from 1 atm to 20 atm. 
     
     
         21 . The process of  claim 16 , wherein the process is conducted at a temperature from 0° C. to 100° C. 
     
     
         22 . The process of  claim 16 , the process comprising two steps:
 i) reacting a compound of formula V,   
       
         
           
           
               
               
           
         
         wherein R is as defined in  claim 16 , with hydroxylamine or a salt thereof; 
         ii) reacting the product of step i), a compound of formula II, 
       
       
         
           
           
               
               
           
         
         wherein R is as defined above, with a trifluoroacetyl halide according to the process as defined in  claim 16 . 
       
     
     
         23 . The process of  claim 16 , further comprising the step of reacting the compound of formula I to obtain a compound of formula III 
       
         
           
           
               
               
           
         
       
     
     
         24 . The process of  23 , further comprising the step of reacting the compound of formula III with a compound of formula IV
   R 1 —NH—R 2   IV,
   wherein R 1  and R 2  in the compound of formula IV is as defined in  claim 16  to obtain a compound of formula Ic   
       
         
           
           
               
               
           
         
       
     
     
         25 . The process of  claim 24 , further comprising the step of reacting the compound of formula Ic to obtain a compound of formula Id 
       
         
           
           
               
               
           
         
       
     
     
         26 . The process of  claim 24 , wherein
 R 1  is methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, cyclopropyl, 2-methoxyiminoethyl, bicyclo[1.1.1]pentan-1-yl, or phenyl; and wherein the phenyl group is unsubstituted or substituted with 1, 2, 3 or up to the maximum possible number of identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, methoxy, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy and cyclopropyl;   R 2  is hydrogen, methyl or ethyl.   
     
     
         27 . The process of  claim 24 , wherein
 R 1  is methyl, 2-methoxyiminoethyl, bicyclo[1.1.1]pentan-1-yl, 2-fluoro-phenyl, 4-fluoro-phenyl or 2-difluoromethoxy-phenyl;   R 2  is hydrogen.