New Methods and Reagents in Organic Synthesis. 17. Trimethylsilyldiazomethane(TMSCHN2) as a Stable and Safe Substitute for Hazardous Diazomethane. Its Application to the Arndt-Eistert Synthesis

Abstract

Although diazomethane is used in the Arndt-Eistert synthesis, it is both highly toxic and also explosive, and hence should be very carefully handled. In place of this hazardous diazomethane, stable and safe trimethylsilyldiazomethane (TMSCHN2) was found to be very useful for the Arndt-Eistert synthesis. TMSCHN2 was easily acylated with a carboxylic acid chloride in tetrahydrofuran-acetonitrile, and thermal treatment of the acylated product in benzyl alcohol and 2,4,6-trimethylpyridine smoothly gave the benzyl ester of a homologated acid. Nucleophiles other than benzyl alcohol could also be used. TMSCHN2 may also be able to replace diazomethane in other areas of chemistry. © 1981, The Pharmaceutical Society of Japan. All rights reserved.