AZLACTONE FORMATION IN ISOXAZOLIUM SALT METHOD OF PEPTIDE SYNTHESIS

The reaction of hippuric acid with isoxazolium salts to give enol esters has been found to be accompanied by azlactone formation. The extent of the side reaction with N-t-butyl-5-methylisoxazolium perchlorate (7) decreases with increasing basicity of the medium, although the ester (12) from 7 itself decomposes to azlactone in the presence of strong base. The ester 12 free of azlactone may be obtained by use of 2-picoline as the reaction solvent to maintain a medium of intermediate base strength. The peptide reagent N-ethyl-5-phenylisoxazolium 3ぴ-sulfonate (1) does not give appreciable azlactone in the normal procedure for its use because the low rate of solution of the reagent fortuitously controls the basicity of the reaction mixture. © 1969, American Chemical Society. All rights reserved.