Process for the preparation of thietane derivatives

1. A process for the preparation of a compound of formula IA

wherein

A 1 , A 2 , A 3 and A 4 are independently of one another C—H, C—R 3 , or nitrogen;

B is O or CH 2 ;

R 1 is C 1 -C 8 haloalkyl;

R 2 is aryl or aryl substituted by one to five R 4 , or heteroaryl or heteroaryl substituted by one to five R 4 ;

each R 3 is independently halogen, cyano, nitro, C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 8 haloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 haloalkenyl, C 2 -C 8 alkynyl, C 2 -C 8 haloalkynyl, C 1 -C 8 alkoxy, C 1 -C 8 haloalkoxy, C 1 -C 8 alkoxycarbonyl-, amino, hydroxy, mercapto, C 1 -C 8 alkylthio, C 1 -C 8 haloalkylthio, C 1 -C 8 alkylsulfinyl, C 1 -C 8 haloalkylsulfinyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 haloalkylsulfonyl, C 1 -C 8 alkylcarbonyl, or two R 3 on adjacent carbon atoms together form a —CH═CH—CH═CH— bridge or a —N═CH—CH═CH— bridge;

each R 4 is independently halogen, cyano, nitro, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 haloalkenyl, C 2 -C 8 alkynyl, C 2 -C 8 haloalkynyl, hydroxy, C 1 -C 8 alkoxy, C 1 -C 8 haloalkoxy, mercapto, C 1 -C 8 alkylthio, C 1 -C 8 haloalkylthio, C 1 -C 8 alkylsulfinyl, C 1 -C 8 haloalkylsulfinyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 haloalkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonyl, aryl or aryl substituted by one to five R 5 , or heterocyclyl or heterocyclyl substituted by one to five R 5 ;

each R 5 is independently halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy-, or C 1 -C 4 haloalkoxy-;

n is 0, 1 or 2;

comprising preparing a compound of formula IV

by either

a. reacting a compound of formula II

with a source of cyanide in the presence of water to give a compound of formula III

b. reducing the compound of formula III with a suitable reducing agent to give a compound of formula IV

c-i. reacting the compound of formula IV with a compound of formula V

wherein R is OH, C 1 -C 6 alkoxy or CI, F or Br, and R 1 , R 2 , B, A 1 , A 2 , A 3 and A 4 are as defined for compounds of formula IA to give a compound of formula I; or

A) reacting a compound of formula VII

with CH 3 NO 2 to give a compound of formula XI

B) reducing the compound of formula XI with a suitable reducing agent to give a compound of formula IV; or

1) homologating a compound of formula VII

to give an ester of formula XII

wherein R is C 1 -C 6 alkyl;

2) reducing the compound of formula XII using a suitable reducing agent to give a compound of formula XIII

3) treating the compound of formula XIII with hydrazoic acid to give a compound of formula IV;

and

c-i. reacting the compound of formula IV with a compound of formula V

wherein R is OH, C 1 -C 6 alkoxy or CI, F or Br, and R 1 , R 2 , B, A 1 , A 2 , A 3 and A 4 are as defined for compounds of formula I to give a compound of formula IA; or

c-ii reacting the compound of formula IV with a compound of formula VI

wherein X B is a leaving group for example a halogen, such as bromo, and R 1 , R 2 , B, A 1 , A 2 , A 3 and A 4 are as defined for compounds of formula IA

with carbon monoxide in the presence of a suitable catalyst to give a compound of formula IA;

and wherein the method optionally comprises oxidizing the sulfur atom of the thietane moiety.