氯胺酮、羟亚胺及邻氯苯基环戊酮合成工艺的判别研究

Discrimination of Synthesizing Routines for Ketamine,Hydroxylimine and o-Chlorophenyl Cyclopentyl Ketone Samples Using Profiling Impurities

氯胺酮通常以羟亚胺和邻氯苯基环戊酮为主要合成原料。该文采用气相色谱-质谱联用(GC-MS)检测缴获邻氯苯基环戊酮样品中的杂质,并筛选出邻氯苯甲腈以及格氏试剂合成过程中的副反应产物环戊酮、环戊醇、环戊基环戊烷、2-环戊基环戊酮和2-环戊基环戊醇作为特征杂质。通过邻氯苯基环戊酮合成实验,验证了6种特征杂质为邻氯苯甲腈与格氏试剂反应所产生。通过液-液萃取的前处理方法,从缴获羟亚胺样品检测出残留的4种特征杂质。采用顶空/气相色谱-质谱联用(HS/GC-MS)方法从氯胺酮样品中检出残留的2种特征杂质。结果表明,所有缴获的邻氯苯基环戊酮和羟亚胺样品,以及105份氯胺酮样品中的102份均检出2种以上特征杂质,由此推测,格氏试剂法是国内非法工厂生产邻氯苯基环戊酮普遍采用的工艺路线。

Ketamine is one of the most frequently abused illicit drug in China while hydroxylimine and o-chlorophenyl cyclopentyl ketone are the main chemical precursors.Most of articles on drug profiling were about tracing the geographical origins or determining synthesizing routine of"worldwide popular drugs"such as heroin,cocaine,methamphetamine and MDMA,by analyzing impurities or by-products of the samples,few articles were about ketamine and its chemical precursors.In this article,ketamine and its chemical precursors profiling were investigated by determine the relevant impurities.Unlike methamphetamine having more than one chemical precursor(ephedrine and phenylactone)and many synthesizing methods(Emde,Ngai,Birch and Reductive amination),all ketamine samples in illicit factory were produced by heating hydroxylimine to reconstruct its molecular structure,and all hydroxylimine samples were synthesized with o-chlorophenyl cyclopentyl ketone which were synthesized by Grignard reagent reaction or Friedel-Crafts reaction.Therefore,it is very important to determine the impurities of samples from the o-chlorophenyl cyclopentyl ketone synthesizing reaction.Gas chromatography-mass spectrometry(GC-MS)was used to detect the impurities in the seized o-chlorophenyl cyclopentyl ketone samples,2-chlorobenzonitile and byproducts of Grignard reagent reactions,including cyclopentanone,cyclopentanol,cyclopentylcyclopentane,2-cyclopentylcyclopentanone and 2-cyclopentylcyclopentanol were signed as the profiling impurities.By synthesizing o-chlorophenyl cyclopentyl ketone in lab and detecting it by GC-MS,these 6 profiling impurities were proved to be produced by the reaction of 2-chlorobenzonitile and grignard reagents.Coupling reactions and oxidation reactions of Grignard reagent to produce these profiling impurities were discussed.Hydroxylimine samples were extracted by liquid-liquid extraction method,and 4 of those profiling impurities were detected in hydroxylimine samples by GC-MS while the samples were purified in the recrystallization step.Ketamine samples were detected by head space injector GC-MS(HS/GC-MS),and 2 of those profiling impurities were detected while the samples were purified by proceeding recrystallization.Finally,all hydroxylimine and o-chlorophenyl cyclopentyl ketone samples,and 102 of 105 ketamine samples were found to contain 2 of the profiling impurities at least.It could be inferred that Grignard reagent method is the most common routine for the synthesization of o-chlorophenyl cyclopentyl ketone in illicit factory.