Differentiation of Regioisomeric N-Substituted Meta-Chlorophenylpiperazine Derivatives

• NCJ Number: 309458
• Journal: Forensic Chemistry Volume: 39 Issue: 100582 Dated: July 2024
• Author(s): C. Randall Clark; Mohammed Almaghrabi; Murali Dhanasakaran; Jack DeRuiter; Younis Abiedalla
• Date Published: July 2024
• Grant Number(s): 2011-DN-BX-K530
• Agencies: NIJ-Sponsored
• Publication Type: Research (Applied/Empirical)
• Award: Analytical and Synthetic Studies on Designer Drugs of the Piperazine Class This project will address issues of resolution and discriminatory capabilities in controlled substance analysis.

Annotation

This article describes research into the synthesis and analytical differentiation of a series of hybrid N,N-disubstituted piperazine analogs containing the structural features of meta-chlorophenylpiperazine (mCPP) and nine methoxybenzyl- and dimethoxybenzylpiperazines.

Abstract

A series of N,N-disubstituted piperazines were synthesized containing the structural elements of meta-chlorophenylpiperazine (mCPP) in combination with methoxybenzyl-, and dimethoxybenzyl substituents to yield nine N,N-disubstituted piperazine compounds. These nine potential designer-like drug analogs were prepared based on common designer trends and regioisomeric differentiation was based on gas chromatography-mass spectrometry (GC–MS) and gas chromatography-vapor phase infrared (GC–vpIR) studies. The compounds in this study have not been reported as drugs of abuse at this time. However, commercial availability of precursor chemicals including mCPP suggests the possibility of further designer exploration. Capillary GC separation showed the regioisomers to elute according to the position of aromatic ring substitution and/or the degree of substituent crowding on the aromatic ring. Numerous electron ionization (EI) mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major EI-MS fragment ions observed in all nine spectra occur at m/z 195 from the loss of the substituted benzyl radical and the cation at m/z 56 (C3H6N)+ from the piperazine ring. Unique radical cations at m/z 136 and m/z 152 are characteristic of the 2,3- and 3,5-dimethoxybenzyl isomers, respectively. The vapor phase infrared spectra for all nine compounds show a strong absorption band in the 1591–1593 cm−1 region indicative of the chloroaniline moiety. Numerous bands in the 1600–650 cm−1 region provide data for the differentiation of the methoxy and dimethoxybenzyl ring substitution patterns. Thus, a combination of EI-MS and vapor phase IR allow for the differentiation and specific identification of each regioisomer in this study. (Published Abstract Provided)