Synthesis of some deuterated dialkylaminoethyls as possible standards for the mass spectrometric monitoring of chemical warfare agents

Abstract

Deuterium-labelled derivatives of 2-(dialkylamino)ethanols, 2-(dialkylamino)ethyl chlorides and 2-(dialkylamino)ethanethiols have been prepared in which completely deuterated N-alkyls (Me, Et, n-Pr, iso-Pr) have been introduced as substituents. Such labelled derivatives are of great interest in mass spectrometry as standards for monitoring chemical warfare agents and their precursors.

Synthesis of 2-chloro-N,N,N-trialkylethanaminium salts and related hydroxy-analogues as analytical standards for monitoring potential chemical warfare agent precursors

“…19 Thus, the chemical shift of the singlet signal assigned to ring methylene protons is a clue to discriminate between the 3-or 6-membered rings. We observed the signal in the range typical of piperazinium species which was also supported by 13 This chair-to-chair exchange is relatively fast at 27 °C, the temperature of NMR measurements, thus detection of the signal is difficult. It is also responsible for the rather complex splitting pattern of n-propyl methylene protons and the single signal observed for axial and equatorial protons of the piperazine ring.…”

“…The results obtained suggest that these compounds significantly influence the functioning of cholinergic neurons and that the effect depends on the substitution. 12 This paper, a continuation of our previous research on CWA precursors, [2][3][4]13,14 is focused on the synthesis of choline analogues including some possible combinations of N-substitutions with methyl, ethyl, propyl and isopropyl chains and related 2-chloro-N,N,N-trialkylethanaminium salts for the use as analytical standards.…”

“…In this way (Scheme 1 -Method A) the corresponding commercially available hydrochlorides were treated with an aqueous solution of sodium hydroxide to obtain amines 1a-d 13,15 which were subsequently alkylated with iodoalkane in a mixture of acetone and diethyl ether at ambient temperature for 72 hours. The respective aminium iodide salts 2, resulted.…”

“…The first two intermediates prepared by the Method B were the aminium iodides 5o and 5p. While the alkylation reaction of the similar starting compound N-(2-chloroethyl)-Npropylpropan-1-amine 1d does not proceed to 2-chloroethan-N,N,N-trialkylaminium salts 2 at elevated temperature due to cyclization, the use of 2-(dipropylamino)ethanol 4d 13,15 as a starting material completely eliminated this competitive reaction. It was therefore possible to carry out the alkylation reaction in refluxing acetone providing aminium iodides 5o and 5p in very good purity and with yields > 70%.…”

“…1 These compounds have been widely studied from the standpoint of their synthesis (including tagged compounds) 2 as well as analytical procedures. 3,4 Compared to N,N-dialkylaminoethyls, the related N-quaternary compounds are not officially considered as precursors of CWA (i.e.…”