Brendan M. Miller , James F. Carter , Sarah L. Cresswell , Wendy A. Loughlin , Peter N. Culshaw
{"title":"丙烯酮、NaNO2和碳酸二甲酯合成甲基苯丙胺的同位素分馏","authors":"Brendan M. Miller , James F. Carter , Sarah L. Cresswell , Wendy A. Loughlin , Peter N. Culshaw","doi":"10.1016/j.forc.2025.100661","DOIUrl":null,"url":null,"abstract":"<div><div>Ephedrine remains a key precursor in the production of methamphetamine. A novel ephedrine-based route to methamphetamine involved the nitrosation of propiophenone to α-isonitrosopropiophenone, followed by catalytic hydrogenation to phenylpropanolamine (± − norephedrine). Cyclization-methylation of phenylpropanolamine to 3,4-dimethyl-5-phenyl-2-oxazolidinone using dimethyl carbonate, followed by basic hydrolysis or catalytic hydrogenolysis formed ephedrine or methamphetamine, respectively.</div><div>An investigation into the stable isotope fractionation during the synthesis of methamphetamine from propiophenone, NaNO<sub>2</sub> and dimethyl carbonate was performed using isotope ratio mass spectrometry. A negative isotopic shift was observed for <em>δ</em><sup>15</sup>N upon nitrosation of propiophenone to α-isonitrosopropiophenone, and a negative isotopic shift for <em>δ</em><sup>2</sup>H during catalytic hydrogenation of α-isonitrosopropiophenone to phenylpropanolamine. Minimal change in <em>δ</em><sup>13</sup>C was observed throughout the reaction until the methylation step with dimethyl carbonate, where a negative isotopic shift was observed.</div><div>The <em>δ</em><sup>13</sup>C values for the methamphetamine presented in a similar range to methamphetamine reported in previous work where the norephedrine/norpseudoephedrine was prepared <em>via</em> different starting materials (benzaldehyde and nitroethane), confirming that similar <em>δ</em><sup>13</sup>C values will result from fractionation during methylation with dimethyl carbonate regardless of the origin of the norephedrine/norpseudoephedrine. Chiral analysis confirmed methamphetamine to be racemic.</div></div>","PeriodicalId":324,"journal":{"name":"Forensic Chemistry","volume":"44 ","pages":"Article 100661"},"PeriodicalIF":2.6000,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Isotope fractionation during synthesis of methamphetamine from propiophenone, NaNO2 and dimethyl carbonate\",\"authors\":\"Brendan M. Miller , James F. Carter , Sarah L. Cresswell , Wendy A. Loughlin , Peter N. Culshaw\",\"doi\":\"10.1016/j.forc.2025.100661\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Ephedrine remains a key precursor in the production of methamphetamine. A novel ephedrine-based route to methamphetamine involved the nitrosation of propiophenone to α-isonitrosopropiophenone, followed by catalytic hydrogenation to phenylpropanolamine (± − norephedrine). Cyclization-methylation of phenylpropanolamine to 3,4-dimethyl-5-phenyl-2-oxazolidinone using dimethyl carbonate, followed by basic hydrolysis or catalytic hydrogenolysis formed ephedrine or methamphetamine, respectively.</div><div>An investigation into the stable isotope fractionation during the synthesis of methamphetamine from propiophenone, NaNO<sub>2</sub> and dimethyl carbonate was performed using isotope ratio mass spectrometry. A negative isotopic shift was observed for <em>δ</em><sup>15</sup>N upon nitrosation of propiophenone to α-isonitrosopropiophenone, and a negative isotopic shift for <em>δ</em><sup>2</sup>H during catalytic hydrogenation of α-isonitrosopropiophenone to phenylpropanolamine. Minimal change in <em>δ</em><sup>13</sup>C was observed throughout the reaction until the methylation step with dimethyl carbonate, where a negative isotopic shift was observed.</div><div>The <em>δ</em><sup>13</sup>C values for the methamphetamine presented in a similar range to methamphetamine reported in previous work where the norephedrine/norpseudoephedrine was prepared <em>via</em> different starting materials (benzaldehyde and nitroethane), confirming that similar <em>δ</em><sup>13</sup>C values will result from fractionation during methylation with dimethyl carbonate regardless of the origin of the norephedrine/norpseudoephedrine. Chiral analysis confirmed methamphetamine to be racemic.</div></div>\",\"PeriodicalId\":324,\"journal\":{\"name\":\"Forensic Chemistry\",\"volume\":\"44 \",\"pages\":\"Article 100661\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Forensic Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2468170925000232\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, ANALYTICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Forensic Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468170925000232","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
Isotope fractionation during synthesis of methamphetamine from propiophenone, NaNO2 and dimethyl carbonate
Ephedrine remains a key precursor in the production of methamphetamine. A novel ephedrine-based route to methamphetamine involved the nitrosation of propiophenone to α-isonitrosopropiophenone, followed by catalytic hydrogenation to phenylpropanolamine (± − norephedrine). Cyclization-methylation of phenylpropanolamine to 3,4-dimethyl-5-phenyl-2-oxazolidinone using dimethyl carbonate, followed by basic hydrolysis or catalytic hydrogenolysis formed ephedrine or methamphetamine, respectively.
An investigation into the stable isotope fractionation during the synthesis of methamphetamine from propiophenone, NaNO2 and dimethyl carbonate was performed using isotope ratio mass spectrometry. A negative isotopic shift was observed for δ15N upon nitrosation of propiophenone to α-isonitrosopropiophenone, and a negative isotopic shift for δ2H during catalytic hydrogenation of α-isonitrosopropiophenone to phenylpropanolamine. Minimal change in δ13C was observed throughout the reaction until the methylation step with dimethyl carbonate, where a negative isotopic shift was observed.
The δ13C values for the methamphetamine presented in a similar range to methamphetamine reported in previous work where the norephedrine/norpseudoephedrine was prepared via different starting materials (benzaldehyde and nitroethane), confirming that similar δ13C values will result from fractionation during methylation with dimethyl carbonate regardless of the origin of the norephedrine/norpseudoephedrine. Chiral analysis confirmed methamphetamine to be racemic.
期刊介绍:
Forensic Chemistry publishes high quality manuscripts focusing on the theory, research and application of any chemical science to forensic analysis. The scope of the journal includes fundamental advancements that result in a better understanding of the evidentiary significance derived from the physical and chemical analysis of materials. The scope of Forensic Chemistry will also include the application and or development of any molecular and atomic spectrochemical technique, electrochemical techniques, sensors, surface characterization techniques, mass spectrometry, nuclear magnetic resonance, chemometrics and statistics, and separation sciences (e.g. chromatography) that provide insight into the forensic analysis of materials. Evidential topics of interest to the journal include, but are not limited to, fingerprint analysis, drug analysis, ignitable liquid residue analysis, explosives detection and analysis, the characterization and comparison of trace evidence (glass, fibers, paints and polymers, tapes, soils and other materials), ink and paper analysis, gunshot residue analysis, synthetic pathways for drugs, toxicology and the analysis and chemistry associated with the components of fingermarks. The journal is particularly interested in receiving manuscripts that report advances in the forensic interpretation of chemical evidence. Technology Readiness Level: When submitting an article to Forensic Chemistry, all authors will be asked to self-assign a Technology Readiness Level (TRL) to their article. The purpose of the TRL system is to help readers understand the level of maturity of an idea or method, to help track the evolution of readiness of a given technique or method, and to help filter published articles by the expected ease of implementation in an operation setting within a crime lab.