American Chemical Society
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Preparation of 2-Cyanobenzoic Acids from the Reaction of Bromobenzoic Acids with Arylacetonitriles and LDA

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journal contribution
posted on 1998-04-01, 00:00 authored by Anlai Wang, John A. Maguire, Ed Biehl
The reaction of various bromobenzoic acids 1 with arylacetonitriles 3 in the presence of LDA at −70 °C gave predominantly 2-cyanobenzoic acids 4 plus minor amounts of 3-(arylcyanomethyl)benzoic acids 5 and debrominated benzoic acids 6. The reaction is thought to proceed through a benzyne-3-carboxylate intermediate 2, which is formed at −70 °C upon the addition of the arylacetonitrile 3 to a solution of the appropriate lithium halobenzoate and excess LDA. The base-initiated generation of an aryne intermediate from a haloarene at such low temperatures is unprecedented. To confirm the orientation of the cyano and carboxylic acid groups, 4-methoxy-2-cyanobenzoic acid (4f) was converted to the corresponding anhydride (8) via phthalic acid (7) and to 3,3-dimethyl- and 3,3-di-n-butyl-2,3-dihydro-5-methoxy-4-(4-methoxyphenyl)-methyl-1H-isoindol-1-ones (9).