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Clandestine Manufacture of Amphetamine from Benzaldehyde: an Investigative Analysis of Its Synthesis

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Clandestine Manufacture of Amphetamine from Benzaldehyde: an Investigative Analysis of Its Synthesis Clandestine Manufacture of Amphetamine from Benzaldehyde: An Investigative Analysis of its Synthesis This thesis is presented to the Centre for Forensic Science of The University of Western Australia as a part of the requirements for the degree of Master of Forensic Science. The work recorded in this thesis was carried out during 2000 to 2001 at the Chemistry Centre of WA under the supervision of Dr D. Reynolds and at the University of Western Australia under the supervision of Associate Professor E.L. Ghisalberti. November 2001 Michael B. Tolmie B.Sc. (Hons), Grad. Dip. Ed. i I dedicate this thesis to my parents whose love and belief in my ability has been steadfast. 11 Acknowledgments I would like to thank Mr Colin Priddis for giving the opportunity to work within his team and for all his help throughout the year. I would like to express my appreciation to my supervisor Dr Dominic Reynolds for his guidance, encouragement and sense of humour through the year. I would like to thank Associate Professor Emilio Ghisalberti for his advice, patience and support. I would like to thank everybody in the Forensic Science Unit (WA) and the Chemistry Centre (WA) for generously giving up their time to answer my questions. Finally, my sincerest gratitude to my family for their continued support throughout my years of study. m Abstract A number of chemicals from clandestine amphetamine laboratories were seized in Perth, Western Australia. A common element to all of these laboratories was the chemicals and 'homemade' equipment used. Two of the chemicals recovered from the laboratories, ammonium carbonate and zinc, are not normally associated with amphetamine manufacture. Typed and hand written 'recipes' were also found at two of the laboratories. The research described here is concerned with an investigation of the possible synthetic routes employed in the manufacture of amphetamine. The variation in yields with varying reaction conditions has also been examined. The likely role of ammonium carbonate and zinc in the sequence is suggested and the use of alternative, easily obtainable reagents in some reactions has been considered. This information can be used to provide a more accurate estimation of the yield of this reaction for court proceedings, and to determine past and future production, an aspect which is crucial in the sentencing of manufacturers of illicit drugs. IV Abbreviations used in the text ABCI Australian Bureau of Criminal Intelligence ACT Australian Capital Territory AFP Australian Federal Police Adrenalin Epinephrine Amphetamine 2-Amino-l-phenylpropane b.p. boiling point CDL Clandestine drug laboratory Dopamine 4- (2 -Aminoethyl)-l,2 -benzenediol Ephedrine 1 -Phenyl-1 -hydroxy-2-(aminomethyl)propane Eq equivalents FT-IR Fourier Transform Infrared Spectroscopy GC-MS Gas Chromatography Mass Spectrometry HPLC High Performance Liquid Chromatography Pseudoephedrine 1 -Phenyl-1 -hydroxy-2-(aminomethyl)propane MDA 3,4-Methylenedioxyamphetamine MDMA 3,4-Methylenedioxymethylamphetamine Methylamphetamine 1 -Phenyl-2 - (aminomethyl)propane mol moles mmol milli moles m.p. melting point Noradrenaline (R)-4-(2-amino-l -hydroxyethyl)-!, 2-Benzenediol P2P 1 -Phenyl-2 -propanone PVC Polyvinylchloride TFA Trifluoroacetic acid V Contents Page Title i Dedication ii Acknowledgments iii Abstract iv Abbreviations used in the text v Contents vi Chapter One 1-8 1. Introduction 1 1.1. Effects of amphetamine use 2 1.2. Amphetamine seizures 2 1.3. Clandestine laboratories seizures 3 1.4. Health and Safety 4 1.5. Prosecution 4 1.6. Manufacturing methods 5 1.7. Case report 6 1.8. Research Objectives 6 1.9. References 8 Chapter Two 9-14 2. Syntheses of l-Phenyl-2-nitropropene 9 2.1. Western Australian method 10 2.2. Results and Discussion 11 2.3. Conclusion 13 2.4. References 14 vi Chapter Three 15-31 3. Syntheses of l-Phenyl-2-propanone 15 3.1. Methods of manufacture 15 3.2. Western Australian method 20 3.3. Results and Discussion 21 3.3.1. Synthesis of l-Phenyl-2-propanone 21 3.3.2. Other metals 22 3.3.3. Two phase solvent system 24 3.3.4. Reactivity of l-Phenyl-2-propanone 24 3.3.5. Varying the combination of reactants 24 3.3.6. Extraction with toluene 24 3.3.7. Synthesis of l-Phenyl-2-propanone and Purification 25 3.3.8. Clandestine method (experiment based on handwritten notes) 25 3.3.9. One pot conversion of benzaldehyde to l-phenyl-2-propanone 26 3.4. Determination of P2P in Clandestine reaction mixtures 27 3.5. Conclusion 28 3.6. References 30 Chapter Four 32-42 4. Syntheses of N-Formylamphetamine 32 4.1. Western Australian method 34 4.2. Results and Discussion 35 4.2.1. Commercial grade l-phenyl-2-propanone 35 4.2.2 Reaction with formamide 35 4.2.3. Reaction with formamide and formic acid 36 4.2.4. Reaction with ammonium formate 37 4.2.5. Reduction with ammonium formate in excess formic acid 37 4.2.6. Procedure used in clandestine laboratory 37 Vll 4.2.7. Impure l-phenyl-2-propanone 38 4.2.8. Reaction with formamide 38 4.2.9. Reaction with formamide and formic acid 38 4.2.10. Reaction with ammonium formate 39 4.2.11. Reaction with ammonium formate/excess formic acid 39 4.3. Conclusion 40 4.4. References 41 Chapter Five 43-47 5. Syntheses of Amphetamine 43 5.1. Results and Discussion 46 5.2. Conclusion 46 5.3. References 46 Chapter Six 48-50 6. Summary: Synthesis of amphetamine from benzaldehyde 48 Chapter Seven 51-63 Experimental 7. General 51 7.1. Materials 53 7.2. Preparation of Compounds 53 7.2.1. Syntheses of l-Phenyl-2-nitropropene 53 7.2.2. Syntheses of l-Phenyl-2-propanone 55 7.2.3. Syntheses of N-Formylamphetamine 59 7.2.3.1. Leuckart reactions using commercial l-phenyl-2-propanone 59 7.2.3.2. Leuckart reactions using impure l-phenyl-2-propanone 61 7.2.4. Synthesis of Amphetamine 62 7.3. References 63 Appendix 64 Vlll Chapter One 1. Introduction Amphetamines are potent psychomotor stimulants that directly affect the central nervous system (CNS). Their use causes a release of excitatory neurotransmitters dopamine and noradrenaline from storage vesicles in the CNS. The generic term "amphetamines" is used to describe compounds that incorporate the phenylethylamine pharmacophore, and includes drugs such as pseudoephedrine, phentermine, dextroamphetamine, methylamphetamine, methylenedioxyamphetamine (MDA) and ecstasy (MDMA). Some of these have become popular drugs of abuse and thus, targets for clandestine laboratories for over 50 years.1 Particular amphetamines can be acquired legally by prescription, however their medical uses are limited and include the treatment of respiratory congestion, childhood hyperactivity, obesity and narcolepsy, a rare disorder in which persons often lapse into deep sleep. HO, NHR HO' ^nf Dopamine R= H, Noradrenaline Pseudoephedrine R=CH3, Adrenaline NHR ^^ NHR ^=- \-6 Phentermine R=H, Amphetamine R=H, MDA R=CH3, Methylamphetamine R=CH3, MDMA 1 1.1. Effects of amphetamine use Since the mid-1980s, illicit use of amphetamines has remained a significant problem in Australia. Amphetamines are the most commonly used illicit drugs after cannabis, with approximately 9% of the population having used them. They are particularly common among younger groups, as many as 21% of 20 to 29 year olds have become long term users.2 Amphetamines can be administered orally, by inhalation or intravenous injection. High doses of amphetamines, especially by injection, can result in a form of schizophrenic paranoid psychosis, delusions and hallucinations. However psychosis is not the only psychological outcome associated with regular amphetamine use. High proportions of users demonstrate symptoms such as anxiety, panic attacks, paranoia and depression. The emergence of such symptoms is associated with injection of the drugs, greater frequency of use and dependence upon amphetamines.1 The estimated direct health care cost of drug dependence and harmful use of drugs in Australia in 1992 was $1.0 billion, of which $43 million is the cost arising from the use of illicit drugs.3 1.2. Amphetamine seizures During 1999-2000, Australian Customs seized 21.5 kilograms of amphetamines destined for the Australian market. Although the number of seizures (60) were nine less than those recorded for the previous year4, the average weight of amphetamine per seizure increased from 145 grams to 358 grams. Despite further seizures in 2000/01 by the Australian Federal Police (AFP) of amphetamine-type substances totalling 412 kg, of which 152 kg was methylamphetamine (Ice)5, large quantities of amphetamines continues to be produced domestically. Domestic seizures of amphetamines during 1999-2000 totalled 4861 (where the drug weight was recorded), in which 381.3 kg were recovered, an increase of 124.4 kg on the previous year (1998-1999).4 2 The samples of amphetamine seized in Australia is generally of low quality. Forensic analysis of samples seized in 1999-2000 revealed that the amount of amphetamine varied between 1 to 65 %.4 These results relate to unrepresentative sample, since samples of drugs seized are analysed for forensic purposes only in contested court cases. 1.3. Clandestine laboratories seizures A Clandestine Drug Laboratory (CDL), by definition, is an illicit operation consisting of sufficient combination of apparatus and chemicals that either have been or could be used in the manufacture or synthesis of prohibited drugs.6 Such operations are potentiality hazardous to the operator, neighbours, investigators and to the environment. Police intelligence continues to link organised crime groups - among them outlaw motorcycle gangs (OMCG) - to the manufacture and distribution of amphetamine-type substances. The Australian Bureau of Criminal Intelligence (ABCI) has reported that the number of importations of amphetamines to Australia has decreased in recent years. This could indicate that domestic production has increased, lessening the demand for costly and high-risk imported substances.
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