Efficient α‐Selective Chlorination of <i>Meta</i> ‐ and <i>Ortho</i> ‐Substituted Phenylacetic Acids

ABSTRACT Treatment with trichloroisocyanuric acid (TCCA) in the presence of catalytic PCl 3 under solvent‐free conditions is a preparative method, simple and efficient, to selectively α‐chlorinate not only phenylacetic acid and its para ‐substituted analogues, but also meta ‐ and more arduous ortho ‐substituted phenylacetic acids. With electron‐withdrawing or weakly electron‐donating substituents, such as NO 2 , CF 3 , COOMe, halogen, and methyl, the potentially competing electrophilic aromatic chlorination did not occur and the substrates were univocally chlorinated at the benzylic position. Within our selection of 13 o ‐ and m ‐substituted phenylacetic acids, the only 2 outliers were m ‐methylphenylacetic acid, which, unlike the ortho and para regioisomers, gave complex mixtures of products, and o ‐nitrophenylacetic acid, which was refractory to any chlorination. α‐Chlorophenylacetic acids are synthons with a great potential, here exemplified by the preparation of clopidogrel, a very important active pharmaceutical ingredient, from α‐chloro‐ o ‐chlorophenylacetic acid.