Structure identification and analysis of the suspected chemical precursor of 2-fluorodeschloroketamine and its decomposition products.

A suspected chemical precursor of the drug 2-fluorodeschloroketamine (2-FDCK), called 2-fluorodeschlorohydroxylimine, was identified using gas chromatography-mass spectrometry and gas chromatography-quadrupole/time-of-flight mass spectrometry, with comparisons to ketamine and its precursor hydroxylimine. The fragmentation pathway under electron ionization was theorized, and decomposition mechanisms in protic solvents were elucidated. In such solvents, the imine group protonates, then traces of water hydrolyze it, yielding a carbon cation that either forms the major product (2'-fluorophenyl)(1″-hydroxycyclopentyl)methanone via classical imine decomposition or undergoes loop expansion to 2-(2'-fluorophenyl)-2-hydroxycyclohexan-1-one. Structures were confirmed by theoretical calculation, GC-MS, NMR, ACDLabs-Structure Elucidator Suite, and diffusion-ordered spectroscopy. Methods for qualitative analysis of the precursor were established.

Study at a glance

Abstract

In this work, 1-[(2″-fluorophenyl)(methylimino)methyl]cyclopentan-1-ol (2-fluorodeschlorohydroxylimine) was identified as a suspected chemical precursor of 2-fluorodeschloroketamine (2-FDCK) using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-quadrupole/time-of-flight mass spectrometry (GC-Q/TOF-MS) and comparing the data with those of ketamine and its chemical precursor, hydroxylimine. Furthermore, the entire fragmentation pathway of 2-fluorodeschlorohydroxylimine was theorized from the GC-MS spectrum recorded using an electron ionization (EI) source, and the mechanisms and decomposition pathways of 2-fluorodeschlorohydroxylimine were elucidated. In protic solvents, the nitrogen atom in the C═N group of 2-fluorodeschlorohydroxylimine underwent a protonation reaction. Thereafter, the traces of water present in protic solvents promoted the hydrolysis of the protonated imine, and a carbon cation was obtained following the loss of methylamine. The carbon cation could follow the classical decomposition mechanism of imines and yield an α-hydroxyl ketone, which was the major decomposition product, (2'-fluorophenyl)(1″-hydroxycyclopentyl)methanone. The cation could also undergo a loop expansion rearrangement and yield another α-hydroxyl ketone, 2-(2'-fluorophenyl)-2-hydroxycyclohexan-1-one. The structures of the two aforementioned decomposition products were elucidated using several techniques including theoretical calculation, GC-MS, nuclear magnetic resonance (NMR), the prediction and assistance elucidation functions of ACDLabs-Structure Elucidator Suite, and the virtual separation technology of diffusion-ordered spectroscopy. The aforementioned study revealed important information about the chemical precursor of 2-FDCK and its decomposition. Furthermore, a set of methods for the qualitative analysis of 2-fluorodeschlorohydroxylimine were established, which facilitated accurate analysis of 2-fluorodeschlorohydroxylimine samples following decomposition or destruction.