Impurity profiling and synthesis of precursors to the hallucinogenic amphetamine DOB
| dc.check.date | 2023-08-04T10:36:55Z | |
| dc.check.embargoformat | Both hard copy thesis and e-thesis | en |
| dc.check.entireThesis | Entire Thesis Restricted | |
| dc.check.info | Restricted to everyone for five years | en |
| dc.check.opt-out | Not applicable | en |
| dc.check.reason | This thesis is due for publication or the author is actively seeking to publish this material | en |
| dc.contributor.advisor | Fitzpatrick, Dara | en |
| dc.contributor.advisor | Keating, J J | en |
| dc.contributor.author | Quille, Jonathan | |
| dc.contributor.funder | Irish Research Council | en |
| dc.date.accessioned | 2016-08-04T10:36:55Z | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015 | |
| dc.description.abstract | DOB (4‐bromo‐2,5‐dimethoxyamphetamine) is a newly emerging hallucinogenic amphetamine that sparked serious health warnings in Ireland, following its first seizure back in 2003. Known more commonly as “snowball”, this drug is highly potent and may be used as a substitute to ecstasy (MDMA) and lysergic acid diethylamide (LSD). To date, the work carried out on the impurity profiling of DOB is limited in comparison to amphetamine, methamphetamine and MDMA. In this work, the impurity profile of 4‐bromo‐2,5‐dimethoxyphenyl‐2‐propanone (4‐Br‐2,5‐P2P) is explored. This ketone is a direct precursor to DOB. Its more versatile non‐bromo analogue, 2,5‐ dimethoxyphenyl‐2‐propanone (2,5‐P2P) is also examined, as in addition to DOB, it may be used in the synthesis of a range of several other hallucinogenic amphetamines. A number of different routes to both 2,5‐P2P and 4‐Br‐2,5‐P2P were investigated. For each of these routes, the impurities produced were carefully isolated. Following isolation, the impurities were fully characterised (by 1H‐NMR/13C‐NMR spectroscopy, IR, MS), in order to aid structure elucidation. Compounds not easily resolved by flash column chromatography were analysed by LC‐MS and/or independently synthesised for the purpose of attaining reference standards. Adaptation of the well‐known ‘phenylacetic acid route’ to synthesis of both 2,5‐P2P and 4‐Br‐2,5‐P2P, was found to provide low yields of the expected ketone products. Four impurities were isolated during the preparation of both ketones. The yield of one of these impurities (possessing a dibenzylketone core), was greatly influenced by the amount of acetic anhydride reagent used during the reaction. Having carried out the reaction with several different equivalents of acetic anhydride, it was found that formation of the ‘dibenzylketone’ could not be eliminated. This may increase its likelihood of being detected in the final drug product. The ‘Darzens route’, having very recently emerged as a synthetic route to amphetamine and MDMA precursors, was discovered to be a viable route for manufacture of 2,5‐P2P and 4‐Br‐2,5‐P2P. Despite execution of the reaction being more tedious, the route provides superior yields (≈50–60%) to those achieved using the ‘phenylacetic acid route’ (≈35–38%). Incorporation of a bromine atom (at the aromatic 4‐position) is required at some stage during synthesis of DOB. The bromination of many intermediates/starting materials was therefore also examined in detail. Bromination of the acid starting material 2,5‐dimethoxyphenylacetic acid (2,5‐PAA) was found to be clean and high yielding. This was in stark contrast to the bromination of the benzaldehyde starting material, the ketone precursor 2,5‐P2P and the dibenzylketone‐based impurity. Numerous brominated products were isolated from each of these reactions, many of which were novel compounds, and previously unreported as impurities in the literature. The unpredictable/nondescript nature of these brominations is likely to have a significant impact on the impurity profile of illicitly produced DOB. | en |
| dc.description.status | Not peer reviewed | en |
| dc.description.version | Accepted Version | |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Quille, J. 2015. Impurity profiling and synthesis of precursors to the hallucinogenic amphetamine DOB. PhD Thesis, University College Cork. | en |
| dc.identifier.endpage | 344 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/2963 | |
| dc.language.iso | en | en |
| dc.publisher | University College Cork | en |
| dc.rights | © 2015, Jonathan Quille. | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | en |
| dc.subject | DOB | en |
| dc.subject | Amphetamine | en |
| dc.subject | Impurity profiling | en |
| dc.thesis.opt-out | false | |
| dc.title | Impurity profiling and synthesis of precursors to the hallucinogenic amphetamine DOB | en |
| dc.type | Doctoral thesis | en |
| dc.type.qualificationlevel | Doctoral | en |
| dc.type.qualificationname | PhD (Science) | en |
| ucc.workflow.supervisor | d.fitzpatrick@ucc.ie |
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