The trans- and cis-forms of 3,4-dimethyl-5-phenyl-2-oxazolidone (DPO) are impurities found in methamphetamine, but their production mechanism has been unclear. Here, the authors examined whether DPOs were produced by the reaction of ephedrines (ephedrine and pseudoephedrine) with deteriorated chloroform containing phosgene.
Two sources of chloroform were used in this experiment: amylene-stabilized chloroform, which had been stored on a laboratory table after opening the bottle, and ethanol-stabilized chloroform, which had been stored without opening the bottle. Samples 1–4 were prepared and analyzed by gas chromatography/mass spectrometry. Sample 1 was prepared by extracting hydrochloride salts of ephedrines with chloroform under basic conditions. Sample 2 represented a chloroform solution of pseudoephedrine hydrochloride. Sample 3 was a methanol solution of pseudoephedrine hydrochloride, which had been exposed to chloroform prior to dissolution. Sample 4 was prepared by extracting pseudoephedrine hydrochloride, which had been exposed to chloroform prior to the extraction, with ethyl acetate under basic conditions.
Phosgene was detected in amylene-stabilized chloroform but not ethanol-stabilized chloroform. The amylene-stabilized chloroform almost completely converted ephedrines to DPOs in samples 1 and 2, and partially converted pseudoephedrine to trans-DPO in samples 3 and 4. In contrast, the ethanol-stabilized chloroform did not give DPOs in any sample.
The experimental results indicated that DPOs were produced by the reaction of ephedrines with deteriorated chloroform containing phosgene and that the reaction proceeds regardless of chemical forms, even at room temperature. DPOs are useful markers of contact between ephedrines and deteriorated chloroform.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
United Nations Office on Drugs and Crime (2019) World drug report 2019, Booklet 4 stimulants, Vienna. https://wdr.unodc.org/wdr2019/index.html. Accessed 30 July 2019
Puthaviriyakorn V, Siriviriyasomboon N, Phorachata J, Pan-ox W, Sasaki T, Tanaka K (2002) Identification of impurities and statistical classification of methamphetamine tablets (Ya-Ba) seized in Thailand. Forensic Sci Int 126:105–113. https://doi.org/10.1016/S0379-0738(02)00018-X
Alouane N, Boutier A, Baron C, Vrancken E, Mangeney P (2006) Remarkably efficient charcoal-promoted ring-closing carbonylations. Synthesis 2006:885–889. https://doi.org/10.1055/s-2006-926340
Cutugno S, Martelli G, Negro L, Savoia D (2001) The reaction of β-amino alcohols with 1,1'-carbonyldiimidazole influence of the nitrogen substituent on the reaction course. Eur J Org Chem 2001:517–522. https://doi.org/10.1002/1099-0690(200102)2001:3%3c517:AID-EJOC517%3e3.0.CO;2-N
Carloni S, De Vos DE, Jacobs PA, Maggi R, Sartori G, Sartorio R (2002) Catalytic activity of MCM-41-TBD in the selective preparation of carbamates and unsymmetrical alkyl carbonates from diethyl carbonate. J Catal 205:199–204. https://doi.org/10.1006/jcat.2001.3439
Hyne JB (1959) Nuclear magnetic resonance spectra and configuration. The n.m.r spectra of diastereoisomeric heterocyclic derivatives of ephedrines. J Am Chem Soc 81:6058–6061. https://doi.org/10.1021/ja01531a049
Wainer IW, Doyle TD, Hamidzadeh Z, Aldridge M (1983) Resolution of norephedrine as its 2-oxazolidone derivative: enantiomeric separation on a chiral high-performance liquid chromatographic stationary phase and preparative regeneration of the resolved isomers. J Chromatogr A 268:107–111. https://doi.org/10.1016/S0021-9673(01)95394-4
Owens CV (2017) Remediation of manufactured methamphetamine in clandestine laboratories. A literature review. J Chem Health Saf 24:23–37. https://doi.org/10.1016/j.jchas.2017.01.004
Kawai S (1966) Discussion on decomposition of chloroform. Yakugaku Zasshi 86:1125–1132. https://doi.org/10.1248/yakushi1947.86.12_1125 (open access article, in Japanese with English abstract)
Maudens KE, Wille SMR, Lambert WE (2007) Traces of phosgene in chloroform: consequences for extraction of anthracyclines. J Chromatogr B 848:384–390. https://doi.org/10.1016/j.jchromb.2006.10.073
Inoue H, Kanamori T, Iwata YT, Ohmae Y, Tsujikawa K, Saitoh S, Kishi T (2003) Methamphetamine impurity profiling using a 0.32 mm i.d. nonpolar capillary column. Forensic Sci Int 135:42–47. https://doi.org/10.1016/s0379-0738(03)00176-2
U.S. National Library of Medicine (2019) Pubchem: phosgene. https://pubchem.ncbi.nlm.nih.gov/compound/Phosgene. Accessed 4 Oct 2019
NIST (2018) NIST Chemistry WebBook, SRD 69: ethanol. https://webbook.nist.gov/cgi/cbook.cgi?ID=C64175%26Mask=2000. Accessed 4 Oct 2019
Ochoa-Terán A, Guerrero L, Rivero IA (2014) A novel one-pot and one-step microwave-assisted cyclization-methylation reaction of amino alcohols and acetylated derivatives with dimethyl carbonate and TBAC. Sci World J 2014:634935. https://doi.org/10.1155/2014/634935(open access article)
Ministry of Health, Labour and Welfare of Japan (2016) The Japanese Pharmacopoeia, 17th edn. https://jpdb.nihs.go.jp/jp17e/. Accessed 22 Nov 2019
United States Pharmacopeial Convention (2019) Revision bulletin of naproxen sodium and pseudoephedrine hydrochloride extended-release tablets. https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/naproxen-na-pseudoephedrine-hcl-ert-rb-notice-20190301.pdf. Accessed 22 Nov 2019
Cox M, Klass G, Koo CW (2009) Manufacturing by-products from, and stereochemical outcomes of the biotransformation of benzaldehyde used in the synthesis of methamphetamine. Forensic Sci Int 189:60–67. https://doi.org/10.1016/j.forsciint.2009.04.010
Konno C, Taguchi T, Tamada M, Hikino H (1979) Ephedroxane, anti-inflammatory principle of Ephedra herbs. Phytochemistry 18:697–698. https://doi.org/10.1016/s0031-9422(00)84307-1(open access article)
Makino Y, Urano Y, Nagano T (2005) Investigation of the origin of ephedrine and methamphetamine by stable isotope ratio mass spectrometry: a Japanese experience. Bull Narc 57:63–78. https://www.unodc.org/pdf/research/Bulletin07/bulletin_on_narcotics_2007_Makino.pdf. Accessed 3 Dec 2019 (open access article)
We would like to thank Editage (www.editage.com) for English language editing.
Conflict of interest
The authors declare no conflicts of interest associated with this manuscript.
This article does not contain any studies with human participants or animals performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Tsujikawa, K., Segawa, H., Kuwayama, K. et al. Phosgene in deteriorated chloroform: presumptive cause of production of 3,4-dimethyl-5-phenyl-2-oxazolidones in methamphetamine. Forensic Toxicol 38, 475–480 (2020). https://doi.org/10.1007/s11419-019-00517-7
- Deteriorated chloroform
- Clandestine methamphetamine synthesis