A new process of ketamine synthesis from 2-(2-chlorophenyl)-2-nitrocyclohexanone proposed by analyzing drug materials and chemicals seized in Taiwan.

Because of its hallucinogenic and dissociative effects, ketamine is often abused for recreational purposes. Thus, the seizure of ketamine manufacturing units is crucial for preventing drug abuse. The precursors popularly used for ketamine synthesis include 1-[(2-chlorophenyl)(methylimino)methyl]cyclopentanol hydrochloride and 2-(2-chlorophenyl)-2-nitrocyclohexanone (2-CPNCH). Herein, we report a case of the seizure of a ketamine manufacturing unit by law enforcement officers. The seized materials were sent to our laboratory for confirmation. We found that 2-CPNCH was used as the precursor. Using zinc powder and formic acid, 2-CPNCH was reduced to norketamine. Through the Eschweiler-Clarke reaction, norketamine was reacted with formaldehyde and formic acid to synthesize ketamine; the advantages of this process are a short duration of reaction and the requirement of small amounts of chemicals. We further identified an impurity (N-methyl ketamine), which was used as a marker to validate this new process of ketamine synthesis. To the best of our knowledge, this study is the first to report illegal ketamine synthesis through the Eschweiler-Clarke reaction when using 2-CPNCH as the precursor. Our findings inform law enforcement officers and forensic practitioners about this new process of ketamine synthesis.