Gas chromatographic and mass spectrometric analysis of the products of methylation of sulfonylurea drugs.
Gas chromatographic analysis of the products of reaction of diazomethane with tolbutamide and chlorpropamide indicates the formation of three compounds in both cases. As expected, N-methylation (at sulfonamide nitrogen) is the predominant reaction; minor amounts of O-methylated product are also observed. The third product in both cases is the N-methylsulfonamide formed by decomposition of the N-methylated sulfonylurea during gas chromatography. Electron impact and chemulfonylurea during gas chromatography. Electron impact and chemical ionization mass spectrometric analysis, as well as 1H nuclear magnetic resonance examination of samples collected from gas chromatography, confirm the structural assignments. Additionally, proton magnetic resonance analysis of the crude reaction products established that N-methylsulfonamides are not formed in the course of the diazomethane reaction and that the O-methylated derivatives are true products of the reaction. The use of a paramagnetic shift reagent allowed direct estimation of the ratios of N- to O-methylation, and the demonstration that these ratios are not vitiated during gas chromatographic analysis.
D055598:Chemical Phenomena; D002621:Chemistry; D002747:Chlorpropamide / Q000031:analogs & derivatives* / Q000032:analysis; D002849:Chromatography, Gas; D013058:Mass Spectrometry; D008722:Methods; D008745:Methylation; D014044:Tolbutamide / Q000031:analogs & derivatives* / Q000032:analysis
D014044:Tolbutamide; D002747:Chlorpropamide