The Pfitzinger reaction with unsymmetrical ketones

Abstract

The ratios of the products obtained from the Pfitzinger reaction with a series of dialkyl, alkyl arylalkyl, and alkyl aryloxymethylketones have been determined. These results, and the Friedlander reaction on ethyl methyl ketone, show that steric effects have a marked influence on the product ratio from dialkyl ketones, but that with compounds of similar steric requirements in the aromatic series electronic effects are also important. Analysis of the u.v. and n.m.r. spectra of the cinchoninic acids shows that in the 3-unsubstituted compounds the carboxy-group is coplanar with the aromatic rings even when the ring is protonated, but that the carboxy-group of the 3-substituted compounds is very much out of plane except where the substituent is a hydroxy-group. Hückel molecular orbital calculations of π-electron energy and other quantities in the intermediate anions have been carried out.