2.2- Dichloro-acetic acid phenyl ester

Fenclofenac Fenclofenac, o-[2,4-dichlorophenoxy)phenyl]acetic acid (3.2.45), is synthesized from 2,4-dichlorophenol and 2-chloroacetophenone, the reaction of which in the presence of sodinm hydroxide and powdered copper forms the corresponding 2-acetyl-2, 4 -dichloro-diphenyl ester (3.2.43). The resulting product is reacted with sulfur and morpholine according to Willgerodt method, giving thioamide (3.2.44), which is further hydrolyzed to the desired fenclofenac [109,110]. 

Indeed, the reaction of an equimolar quantity of bromodichloromethyl(phenyl)mercury with alk-2-enoic acids affords the dichloromethyl esters. Dichlorocyclopropanation is only possible if a second mole of carbene source is used (see Houben-Weyl, Vol. 4/3, pp 178-179). Competition between acetic acid and cyclohexene for dichlorocarbene indicates that the acid is considerably more reactive.Furthermore, dichloromethyl 2,2-dichlorocyclopropane-carboxylates cannot be hydrolyzed to the corresponding acids. To avoid all of these difficulties, addition of dichlorocarbene, generated under nonhydrolytic conditions using dichloro-halomethyl(phenyl)mercury, to the bromides of alk-2-enoic acids is possible. 

The resolved acid [515] could be racemized only by a peculiar thionyl chloride of a certain purity [516]. Addition of sodiumdifluorochloro acetate to the phenyl-acrylate 260 produces the even more interesting difluoro-analogues [516]. Component of the pyrethroid cycloprothrin is the dichloro ester shown above. 

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