Rapid and mild silylation of β-amino alcohols at room temperature mediated by N-methylimidazole for enhanced detectability by gas chromatography/electron ionization mass spectrometry.

Rationale: In this work, we expand the use of in situ activation of chloro(dimethyl)phenylsilane using N-methylimidazole (NMI) for the effective derivatization of β-aminoethyl alcohols. Due to its enhanced nucleophilic character, NMI is expected to act as an efficient activator in these reactions.

Methods: The derivatization of a panel of β-aminoethyl alcohols was accomplished by reacting the analyte with chloro(dimethyl)phenylsilane in the presence of either NMI or pyridine. After the addition of chloro(dimethyl)phenylsilane, the vials were gently tumbled for 1 h at ambient temperature. The phenyldimethylsilyl derivatives were identified using gas chromatography/electron ionization mass spectrometry (GC/EI-MS).

Results: A total of ten β-aminoethyl alcohols were successfully derivatized via in situ activation of chloro(dimethyl)-phenylsilane with NMI. Derivatization with NMI was significantly more efficient than with pyridine by a factor of 3-6 for the studied alcohols. The derivatizations in the presence of NMI were found to occur in just 1 h and were conveniently executed at ambient temperature.

Conclusions: The use of the nitrogenous base NMI in order to activate chloro(dimethyl)phenylsilane for the efficient silylation of a panel of β-aminoethyl alcohols has been demonstrated. The present work shows that NMI is an efficient base for the smooth derivatization of these types of alcohols. Furthermore, the installation of the bulky PDMS group onto these alcohols adds to the certainty that this is a viable approach for the installation of the more commonly employed, trimethylsilyl group. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.