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

Yen, Yu-Chun; Tseng, Shih-Hao; Zhou, Songlin; Liu, Yuh-Lin

doi:10.1016/j.forsciint.2023.111776

Cited by 3 publications

(5 citation statements)

References 18 publications

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“…49,50 Chen & Lu synthesized Ketamine which primarily functions as a non-competitive NMDA receptor antagonist. 51,52 The Noyori catalytic AH of enone 10 was used to set up the stereogenic center in 11 and the [3,3]-sigmatropic rearrangement of the allylic cyanate intermediate 14 to generate the quaternary stereogenic center in isocyanate 15 with exceptional stereochemical relay were two features of the small-scale asymmetric synthesis of esketamine. For the asymmetric reduction of enone 10, several ruthenium-based catalysts were investigated; however, at 0.1% loading, only [(S,S)-Teth-TsDPEN] RuCl afforded full conversion in 97-98% ee (Scheme 3).…”

Section: Ruthenium-catalyzed Reactionsmentioning

confidence: 99%

Synthesis of anti-depressant molecules via metal-catalyzed reactions: a review

Kanwal,

Afzal,

Zubair

et al. 2024

RSC Adv.

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Section: Ruthenium-catalyzed Reactionsmentioning

confidence: 99%

Synthesis of anti-depressant molecules via metal-catalyzed reactions: a review

Kanwal,

Afzal,

Zubair

et al. 2024

RSC Adv.

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“…A nuclear magnetic resonance (NMR) instrument (Ultrashield-400, Bruker, Billerica, MA, USA) was used to perform qualitative analyses of the seized material (cyclopentanone p-toluenesulfonylhydrazone dissolved in deuterated methyl sulfoxide) and the synthetic product (2-chlorophenyl cyclopentyl ketone in deuterated chloroform) for their 1 H NMR, 13 C NMR, and heteronuclear single quantum correlation (HSQC) measurements.…”

Section: Nuclear Magnetic Resonance Spectroscopymentioning

confidence: 99%

“…The synthesis of ketamine has been studied for the purposes of medicine use or against illicit drug manufacturing [6][7][8][9][10][11][12][13][14][15][16]. In real life, two processes for syntheses of ketamine as indicated in Figure 1A,B were commonly found in illicit ketamine manufacturing units [6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…reported that 2‐CPNCH reacted with zinc powder and formic acid to form norketamine. Subsequently, norketamine underwent the Eschweiler–Clarke reaction to form ketamine using formaldehyde and formic acid, that were seized from an illicit manufacturing unit in 2023, as depicted in Figure 1B(b) [13]. It was also noted that N ‐methyl ketamine was found as the impurity in this novel process.…”

Section: Introductionmentioning

confidence: 99%

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New materials used for the synthesis of 2‐chlorophenyl cyclopentyl ketone seized from an illicit ketamine manufacturing unit

Yen,

Liu,

Wang

et al. 2023

Journal of Forensic Sciences

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Ketamine deemed as a psychoactive substance has gained popularity for recreational use owing to its hallucinogenic and dissociative effects. Understanding the synthetic processes of ketamine can provide essential clues for law enforcement officers against illicit ketamine manufacturing. In this case report, a chemical company was being monitored by law enforcement officers due to its importation of precursors and materials that could be used for the synthesis of illicit drugs. After materials and products seized from this chemical company were employed for analyses using gas chromatography–mass spectrometry, liquid chromatography–high‐resolution mass spectrometry, and nuclear magnetic resonance analyses, ketamine, hydroxylamine, 2‐chlorophenyl cyclopentyl ketone, and cyclopentanone p‐toluenesulfonylhydrazone were identified. In addition, a novel process for the synthesis of ketamine precursor 2‐chlorophenyl cyclopentyl ketone from cyclopentanone p‐toluenesulfonylhydrazone and 2‐chlorobenzaldehyde was validated. This is the first report to uncover this novel process for the synthesis of 2‐chlorophenyl cyclopentyl ketone and can be used to increase awareness among law enforcement officers and forensic practitioners about these novel starting materials for the synthesis of ketamine.

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“…The authors demonstrated that ammonia and its salts can be transformed into trimethylamine under heating with formaldehyde and HCOOH in sealed vessels. Subsequently, this reaction attracted extensive attention and was applied in multiple cases without any strong modifications in natural product synthesis, materials chemistry, and medicinal chemistry. − In particular, in the preparation of pharmaceutical substances, HCOOH as a reducing agent is one of the top five most frequently used reductants in the reductive amination . The inherent problem of the classical variant of the Eschweiler–Clarke reaction is the large excess of concentrated HCOOH (∼9 M) required for the reaction to take place.…”

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confidence: 99%

Simplified Version of the Eschweiler–Clarke Reaction

Biriukov,

Podyacheva,

Tarabrin

et al. 2024

J. Org. Chem.

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The traditional Eschweiler−Clarke reaction is a threecomponent process involving formaldehyde, amine, and formic acid. In this work, we showed that the reductive potential of formaldehyde was sufficient to provide methylation of secondary amines in the absence of acidic additives. Various acid-sensitive moieties remain intact under developed conditions. The scalability of the elaborated approach was shown for several products. Synthesis of the antifungal agent butenafine demonstrated the preparative utility of the developed approach.A mines are vital chemical substances that play crucial roles in a large number of biological processes. Therefore, development of synthetic approaches for their preparation is still greatly important in modern organic chemistry. 1−5 Methylation of amines is often placed into separate groups on the basis of applied synthetic reagents. The value of methylation process is growing today. In the past several decades, methylation more and more often becomes an object of investigation in many biologically vital processes such as gene expression regulated by methylation of DNA. 6−8 However, methylation of much smaller molecules than DNA still concerns researchers as different important organic compounds in pharmaceutical chemistry contain methylamino fragments in their structures.Various agents such as MeHal, Me 2 SO 4 , MeOH, (MeO) 2 C-(O), CO 2 , and formaldehyde can be used to methylate amines. Active methyl halides and dimethylsulfate often lead to overmethylation, but sometimes, the reaction can proceed selectively in the presence of hexafluoropropan-2-ol (HFIP) giving monomethylamines. 9 A wide range of catalytic approaches based on Ru, 10−12 Ir, 13 Ag, 14 Au, 15 Fe, 16 and Ni 17 catalysts allow the introduction of MeOH, (MeO) 2 C(O), and CO 2 as C1 building blocks in methylation. The selectivity of catalytic methods is not always higher than that of

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

Cited by 3 publications

References 18 publications

Synthesis of anti-depressant molecules via metal-catalyzed reactions: a review

Synthesis of anti-depressant molecules via metal-catalyzed reactions: a review

New materials used for the synthesis of 2‐chlorophenyl cyclopentyl ketone seized from an illicit ketamine manufacturing unit

Simplified Version of the Eschweiler–Clarke Reaction

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