PREPARATION OF 2-CYANOBENZOIC ACIDS FROM THE REACTION OF BROMOBENZOICACIDS WITH ARYLACETONITRILES AND LDA

The reaction of various bromobenzoic acids 1 with arylacetonitriles 3 in the presence of LDA at -70 degrees C gave predominantly 2-cyanobenz oic acids 4 plus minor amounts of 3-(arylcyanomethyl)benzoic acids 5 a nd debrominated benzoic acids 6. The reaction is thought to proceed th rough a benzyne-3-carboxylate intermediate 2, which is formed at -70 d egrees C upon the addition of the arylacetonitrile 3 to a solution of the appropriate lithium halobenzoate and excess LDA. The base-initiate d generation of an aryne intermediate from a haloarene at such low tem peratures is unprecedented. To confirm the orientation of the cyano an d carboxylic acid groups, 4-methoxy-2-cyanobenzoic acid (4f) was conve rted to the corresponding anhydride (8) via phthalic acid (7) and to 3 ,3-dimethyl- and hoxy-4-(4-methoxyphenyl)-methyl-1H-isoindol-1-ones (9 ).