Experimental and Theoretical Investigations into Newly
23rd IUPAC Conference on Physical Organic Chemistry (ICPOC23) 3rd – 8th July 2016 • Sydney • Australia
Experimental and Theoretical Investigations into Newly Emerging Clandestine Laboratory Chemistry David Doughtya, Genevieve H. Dennisona, Ben Painterb, Paul Pigoub, Martin R. Johnstona a
Flinders Centre for Nanoscale Science and Technology, Flinders University, School of Chemical and Physical Sciences, GPO Box 2100 Adelaide, South Australia 5001, Australia. b Forensic Science South Australia, GPO Box 2790 Adelaide, 5000, South Australia Australia.
Recent investigations the clandestine laboratory manufacture of Amphetamine Type Stimulants (ATS) allowed us to examine the four step Bayer-Villiger pathway. The pathway involves an aldol reaction between an aromatic aldehyde and methyl ethyl ketone (MEK); followed by the Baeyer-Villiger reaction with subsequent ester hydrolysis and finally reductive amination to yield the ATS in Scheme 1. Unexpectedly, we observed a cyclisation reaction during the intitial aldol reaction and we examined this and the effect of conjuation on the Bayer-Villiger reaction via kinetic 1 H NMR spectroscopy, IR and through theoretical calculations. Examination of the aldol reaction between piperonal and MEK, generated a thermodynamically unfavourable and unexpected cyclisation product 1. Monitoring of the aldol reaction over time with 1 H NMR and FTIR spectroscopy combined with theoretical molecular model calculations (DFT level) show the desired aldol product is both the thermodynamic and kinetically favoured product and that 1 forms as the result of extended reaction time or excess HCl concentration. Substituent effects of the aromatic ring and the effect of conjugation on the ketone group, had a large effect on the yields of products isolated from the Baeyer-Villiger reaction. These products were investigated using molecular modelling (DFT level) and rationalised based on differences in transition state stability.
Scheme 1 Bayer-Villger pathway for converting an aromatic aldehyde to ATS in four steps and the formation of the unfavourable and unexpected cyclisation product 1.
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Experimental and Theoretical Investigations into Newly Emerging Clandestine Laboratory Chemistry David Doughtya, Genevieve H. Dennisona, Ben Painterb, Paul Pigoub, Martin R. Johnstona a
Flinders Centre for Nanoscale Science and Technology, Flinders University, School of Chemical and Physical Sciences, GPO Box 2100 Adelaide, South Australia 5001, Australia. b Forensic Science South Australia, GPO Box 2790 Adelaide, 5000, South Australia Australia.
Recent investigations the clandestine laboratory manufacture of Amphetamine Type Stimulants (ATS) allowed us to examine the four step Bayer-Villiger pathway. The pathway involves an aldol reaction between an aromatic aldehyde and methyl ethyl ketone (MEK); followed by the Baeyer-Villiger reaction with subsequent ester hydrolysis and finally reductive amination to yield the ATS in Scheme 1. Unexpectedly, we observed a cyclisation reaction during the intitial aldol reaction and we examined this and the effect of conjuation on the Bayer-Villiger reaction via kinetic 1 H NMR spectroscopy, IR and through theoretical calculations. Examination of the aldol reaction between piperonal and MEK, generated a thermodynamically unfavourable and unexpected cyclisation product 1. Monitoring of the aldol reaction over time with 1 H NMR and FTIR spectroscopy combined with theoretical molecular model calculations (DFT level) show the desired aldol product is both the thermodynamic and kinetically favoured product and that 1 forms as the result of extended reaction time or excess HCl concentration. Substituent effects of the aromatic ring and the effect of conjugation on the ketone group, had a large effect on the yields of products isolated from the Baeyer-Villiger reaction. These products were investigated using molecular modelling (DFT level) and rationalised based on differences in transition state stability.
Scheme 1 Bayer-Villger pathway for converting an aromatic aldehyde to ATS in four steps and the formation of the unfavourable and unexpected cyclisation product 1.
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