CHAPTER XVI - Ketimines, Acyl Ketimines and Ketones (I:R = CNHR', CNCOR”R', COR')

Abstract

This chapter discusses the preparation of ketimines, acyl ketimines, and ketones. Ketimines and ketones related to methadone are usually prepared by Grignard reaction of the corresponding nitriles. The methyl branching of the side chain stabilizes ketimines. This stability is especially pronounced among ketimines of the iso methadone-type that require prolonged heating under pressure for conversion. As expected, branched alkyl magnesium halides are even less reactive than unbranched Grignard reagents. However, iso propylketones could not be obtained from the nitriles by Grignard reaction in drastic conditions, but satisfactory yields have been noted when the corresponding ethyl esters have been used instead. Ketones have also been prepared by Grignard reaction from amino acids, acid chlorides, and primary amides. In spite of the extensive research conducted with ketones, the physical properties of these substances are not known with a desirable degree of accuracy. Most bases are oils or low melting solids. The fact that their hydrochloride salts are always hygroscopic accounts for the large differences among the melting points as reported by various authors.