Characterization of the Trimethylsilyl Derivatives of 6-Amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile and Its Analogs by Electron Ionization Gas Chromatography/Mass Spectrometry

Abstract

Pyranopyrazoles, especially pyrano[2,3-c]pyrazoles, have broad applications as pharmaceutical ingredients and biodegradable agrochemicals, with new compounds and synthesis methods continually emerging. Gas chromatography/mass spectrometry (GC/MS) has difficulty obtaining useful mass spectra under typical measurement conditions due to thermal degradation of the analyte. However, the analysis of the trimethylsilyl (TMS) derivatives of 6-amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile and 19 closely related analogs provided characteristic ions by which the mass spectral fragmentation pathways could be determined. Nuclear magnetic resonance (NMR) tests showed that the pyran ring cleaved during the TMS derivatization of the compounds with the TMS group connected to oxygen. The fragmentation mechanism involved an alpha cleavage reaction, with the loss of a C₃HN₂ radical to form a stable characteristic cation [M-65]⁺. The mass spectra of positional isomers (o-, m-, and p-) of substituent X (X = Cl, Br, F, CH₃, or OCH₃) on the 4-phenyl group were compared, revealing that the ortho compound has a unique fragment ion peak m/z 261. Lastly, two isomeric di-TMS derivatives were observed: one with both TMS groups connected to nitrogen of the 6-amino substituent (N,N-di-TMS) and the second on the oxygen where the pyran ring was cleaved (N,O-di-TMS). Their mass spectra have apparent differences involving different cleavage pathways.