Diazomethane: Improved analytical and distillation techniques for small quantities and some synthetic applications

Abstract

An improved design of apparatus for the small-scale (about 5 μmol to about 50 mmol) preparation of diazomethane is described. The diazomethane is generated from commonly used precursors and distilled by aeration in a glass apparatus connected by Teflon tubing and without a condenser. A new simple and reasonably accurate procedure for assay of diazomethane is described. This depends on reaction with excess [ 14C]benzoic acid in toluene followed by quantitative removal of the excess acid by partitioning with pH 10 aqueous buffer and assaying the methyl [ 14C]benzoate in the toluene by liquid scintillation counting. Examples are given of the use of accurately known amounts of diazomethane and [ 14C] diazomethane for the preparation of methylated derivatives of [2- 14C]barbital, 4′-hydroxy-[2- 14C]phenobarbital, and mephobarbital. Small amount(s) of dimethyl-barbital ( O-methyl) were separated and partly characterized by gas chromatography/mass spectroscopy and NMR.