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

Abstract

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.

Practical benzylation of N,N‐substituted ethanolamines related to chemical warfare agents for analysis and detection by electron ionization gas chromatography–mass spectrometry

“…To partially circumvent this issue, a variety of derivatization methods aimed at the conversion of these polar compounds into species possessing superior GC profiles than those of the starting materials have been devised. Specifically, for ethanolamines, some of these methods have involved silylation using BSTFA [14,15], MTBSTFA [16], or the NMI-mediated activation protocol [17,22], as well as equally efficient fluorinations in the form of trifluoroacetyl and heptafluorobutyryl tags [23][24][25]. Even though silylation and acylation are efficient at providing derivatives for N,N-disubstituted ethanolamines, these derivatives are prone to hydrolysis under slightly basic conditions (pH ~ 8-9) unless the amount of steric hindrance on these tags is greatly increased [26].…”

“…One of the most common methods for derivatization of N,N-disubstituted ethanolamines involves silylation using BSTFA [14,15] and MTBSTFA [16] which result in the formation of O-silylated products within 1 h aided by heating (60-70°C). Another one is the use of a binary mixture consisting of N-methylimidazole (NMI) and phenyldimethylsilyl chloride (PDMSCl) [17], which is also rapid (~1 h) but can be carried out at ambient temperature. All these silylation methods provide derivatives that feature significantly longer GC retention times and improved chromatographic profiles in the form of sharper peaks relative to the unmodified ethanolamine.…”

Analysis of Organophosphorus-Based Nerve Agent Degradation Products by Gas Chromatography-Mass Spectrometry (GC-MS): Current Derivatization Reactions in the Analytical Chemist’s Toolbox

“…The installation of the silyl group or tag onto polar analytes convert it into derivatives that are suitable for the technique and in some cases these derivatives possess enhanced detection relative to the underivatized analyte. Two of the most common silylating reagents are N , O -bis(trimethylsilyl)trifluoroacetamide (BSTFA) and N - tert -butyldimethylsilyl- N -methyltrifluoroacetamide (MTBSTFA) but other approaches to install the silyl moiety have found wide applications specially within the scope of OPCW [ 58 , 59 , 60 , 61 , 62 ] ( Figure 3 ). Reaction with BSTFA results in the installation of the trimethylsilyl (TMS) group while reaction with MTBSTFA results in the installation of the tert -butyldimethylsilyl group (TBDMS).…”

Recent advances in catalytic silylation of hydroxyl‐bearing compounds: A green technique for protection of alcohols using Si–O bond formations

“…[77][78][79][80] In this regard, the silylation of β-amino alcohols with chloro(dimethyl)phenylsilane in presence of N-methylimidazole (NMI) was studied by Valdez and coworkers. [71] In this study, a panel of 10 β-aminoethyl alcohols with chloro(dimethyl) phenylsilane in presence of a catalytic amount of either NMI or pyridine as efficient organo bases was used in order to synthesize their corresponding phenyldimethylsilyl derivatives by an in situ activation of chloro(dimethyl)phenylsilane with NMI. In addition, the proton scavenger role of NMI would be able to act as an activating agent in the derivatization by initially reacting with chloro(dimethyl)phenylsilane to generate a more powerful and efficient imidazole-based silylating species (Scheme 1).…”

“…Third, alcohols undergo coupling with hydrosilanes under transition metal and also acid or base catalysis, and the sole by-product is the released dihydrogen gas. [71] The following features can be attached to the perfect protecting group for an active hydrogen moiety, that is, alcohol: It should be introduced in a high yield and remain stable in certain conditions; on the contrary, it should have the capability to be selectively removed in a high yield in other conditions without modifying other functional groups present in the organic molecule. Affording the corresponding trimethylsilyl (TMS) ethers requires applying HMDS which is an inexpensive reagent for the protection of alcohols or phenols.…”