DOCSLIB.ORG

Studies Directed Towards the Synthesis of Naturally Occurring Spiroacetals, Lactones and Biologically Active [1,2,4]Triazino Derivatives

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Studies Directed Towards the Synthesis of Naturally Occurring Spiroacetals, Lactones and Biologically Active [1,2,4]Triazino Derivatives STUDIES DIRECTED TOWARDS THE SYNTHESIS OF NATURALLY OCCURRING SPIROACETALS, LACTONES AND BIOLOGICALLY ACTIVE [1,2,4]TRIAZINO DERIVATIVES A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY (IN CHEMISTRY) TO UNIVERSITY OF PUNE BY ANAND HARBINDU ORGANIC CHEMISTRY DIVISION CSIR-NATIONAL CHEMICAL LABORATORY PUNE-411008 January 2013 CANDIDATE’S DECLARATION I hereby declare that the thesis entitled “Studies Directed Towards the Synthesis of Naturally Occurring Spiroacetals, Lactones and Biologically active [1,2,4]triazino derivatives ” submitted for the degree of Doctor of Philosophy in Chemistry to the University of Pune has not been submitted by me to any other University or Institution. This work was carried out at the National Chemical Laboratory, Pune, India. Anand Harbindu Senior Research Fellow (UGC) Organic Chemistry Division National Chemical Laboratory Pune-411008 January 2013 NATIONAL CHEMICAL LABORATORY Dr. Homi Bhabha Road, PUNE. 411 008, INDIA. Dr. Pradeep Kumar Telephone: + 91-20-25902050 Chief Scientist, FNASc Fax: + 91-20-25902629 Organic Chemistry Division E-mail: [email protected] Pune-411008 Website: http://www.ncl-india.org CERTIFICATE The research work presented in thesis entitled “Studies Directed Towards the Synthesis of Naturally Occurring Spiroacetals, Lactones and Biologically active [1,2,4]triazino derivatives” has been carried out under my supervision and is a bonafide work of Mr. Anand Harbindu. This work is original and has not been submitted for any other degree or diploma of this or any other University. (Dr. Pradeep Kumar) January 2013 Research Guide DEDICATED TO MY BELOVED FAMILY Acknowledgements It gives me great pleasure to express my deep sense of gratitude to my teacher and research guide Dr. Pradeep Kumar, who has helped me a lot to learn and think more about chemistry. I thank him for his excellent and inspiring guidance, constant encouragement, sincere advice and unstinted support during all the times of my Ph.D. work. Working with him was a great pleasure and learning experience. I take this opportunity to specially thank Dr. Santosh Mhaske, Dr. H. B. Borate, Mr. I. Shivakumar, Dr. S. P. Chavan, Dr. N. N. Joshi, Dr. R. A. Joshi, Dr. R. R. Joshi, Dr D. S. Reddy, Dr. R. P. Singh, Dr. Muthukrishnan, Dr. Ashish Bhattacharya, Dr. Jayant Gajbhiye, Dr. Kiran Sonawane, Dr. Borikar, Mr. Kalal, Mrs. Kunte, Late. Dr. D. D. Sawaikar and Dr. Ashish K. Tiwari (BHU) for their helpful suggestions and encouragement. Help from the spectroscopy, and mass group are gratefully acknowledged. I sincerely thank Dr. Rajmohanan, for his helpful discussions and cooperation. My sincere thanks to Mrs. C. Raphel, Mrs. P. Kulkarni, Mr. Iyer, Mr. K. Thangaraj, Mr. Babus, Mr. Ranade and all other office staffs for their cooperation. My sincere thanks to Dr. G. Panday, Head, DOC for his cooperation and support. The warm and friendly attitude of my seniors Dr. Chinmoy, Dr. Rahman, Dr. Sahoo, Dr. Rosy, Dr. Seetaram, Dr. Sabita, Dr. Rita, Dr. Ramesh, Dr. Pradip, Dr. Ganesh, Dr. Sunil, Dr. Kesari, Dr. Satyendra, Dr. Priti, Dr. Puspesh, Dr. Nagendra, Dr. Namarta, Mr. Shijo, Dr. Divya, Dr. Ruchi, Dr. Eeshwar is gratefully acknowledged. I take this opportunity to thank my colleagues Vishwajeet, Partha, Menaka, Mujaheed, Krishanu, Kiran, Shruti, Nookaraju, Brijesh for their help and cheerful atmosphere in the laboratory. I extend my deep sense of gratitude towards my senior as well as friend Dr. Abhishek and Mr. Ankush for helping me in all aspect of research and personal life. Also I heartedly thank friends at NCL and GJ hostel especially Umesh, Nawab, Negi, Sunil, Maurya, Ravi, Ajay, Krunal, Gupta, Mishra, Ajeet, Prince, Pitamber, Baba, Malvi, Prakesh, Kiran, Seema, Gowri, Atul, Asif, Abhijeet, Tamboli, Dumare, Chand, Mangesh, Pankaj, Jyoti, Ranjeet, Sangmesh, Paresh, Sutar, Deepak, Satish. I extend my thanks to my childhood friends Javed, Amit, Arvind and my roommate ShyamSundar and friends at spn Amit, Pawan, Namita, Brijesh, Rakesh, Vipin M. Sc. friends Narendra, Shweta, Samareen who made the life memorable. Special thanks to my M.Sc. teachers Dr. Abdul Hasnaat, Prof. S. W. I. Naqvi and my Delhi teachers Dr. H. P. Gupta, and Dr. Raj Tripathi for their constant encouragement and inspiration. It is impossible to express my sense of gratitude for my parent, in mere words. Whatever I am and whatever I will be in future is because of their commitments to my ambitions and their selfless sacrifices. Words fall short to thank my brother Mr. Rajeev, Dr. Ashish, Sister-in-law Ruchi, Neeti, Sister Dr. Arti, Jyoti, Brother-in-law Dr. Vishnu, Rajat, Nephew Avi, Saksham, Niece Shubhi and Shanvi for their never ending encouragement, love and support, I am indeed thankful to my fiancé Kavita for her encouragement and support at the final stage of my thesis, which enable me to pursue my goal whole heartedly. Finally I thank Director, National Chemical Laboratory, Pune for providing infrastructural facilities to complete my work successfully. I am also thankful to UGC/CSIR, New Delhi for the financial assistance in the form of fellowship. Anand CONTENTS Page No. Abbreviation i General Remarks iii Abstract iv Chapter 1 Introduction to Jacobsen’s hydrolytic kinetic resolution, proline-catalyzed reactions and ring closing metathesis (RCM) Hydrolytic Kinetic Resolution (HKR) Introduction 3 Preparation of catalyst and General Experimental Consideration 8 Representative procedures for HKR of terminal epoxides 10 Catalyst recycling 11 Proline Catalyzed Asymmetric Organic Transformations Introduction to organocatalysis 12 Proline a “Universal catalyst” 14 Proline-catalyzed α-aminoxylation 14 Proline-catalyzed α-amination 16 Proline-catalyzed sequential transformations 17 Ring-Closing Metathesis Introduction 20 Tantalum and molybdenum metathesis catalyst 22 Ruthenium based metathesis catalyst 23 23 RCM mechanism 25 References Chapter 2 Introduction 32 Review of Literature 36 Section A: Synthesis of Aculeatins A and B via Iterative Hydrolytic Kinetic Resolution and (PIFA) promoted a tandem phenolic oxidation/dithiane deprotection sequence Present Work 45 Results and Discussion 46 Conclusion 51 Experimental Section 51 Spectra 62 Section B: Synthesis of Aculeatin F and epi-F Present Work 75 Results and Discussion 77 Conclusion 79 Experimental Section 79 Spectra 87 Section C: Studies towards the synthesis of Modiolide B Present Work 98 Results and Discussion 99 Conclusion 102 Experimental Section 102 Spectra 106 References 111 Chapter 3: Introduction 114 Review of Literature 118 Section A: Organocatalytic Enantioselective Approach to the Synthesis of Verbalactone Present Work 131 Results and Discussion 132 Conclusion 135 Experimental Section 135 Spectra 144 Section B: Organocatalytic route to the Synthesis of (R)- Massoialactone Present Work 154 Results and Discussion 155 Conclusion 156 Experimental Section 156 Spectra 160 Section C: Synthesis of insect pheromone, 5-(S)-Hexadecanolide and its enantiomer. Present Work 167 Results and Discussion 169 Conclusion 171 Experimental Section 171 Spectra 179 References 188 Chapter 4 Introduction 192 Review of Literature 196 Section A: Novel application of Leuckart reaction for the synthesis of [1,2,4]triazino[1,6-a]indol-4(3H)-one and pyrrolo[2,1-f][1,2,4]triazine-4(3H)-one Present Work 200 Results and Discussion 201 Conclusion 204 Experimental Section 204 Spectra 209 Section B: Studies towards synthesis of [1,2,4]triazino[1,6-a]indole-2,4(1H,3H) dione and pyrrolo[2,1-f][1,2,4]triazine-2,4(1H,3H)-dione Present Work 218 Results and Discussion 220 Conclusion 221 Experimental Section 221 Spectra 223 References 228 Curriculum Vitae 230 ABBREVIATIONS Ac - Acetyl AcOH - Acetic acid BuLi - Butyl Lithium DCM - Dichloromethane DDQ - 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone de - Diastereomeric excess ds - Diastereoselectivity DIBAL-H - Diisobutylaluminiumhydride DMP - Dess–Martin periodinane DMP - 2,2-Dimethoxypropane DMF - N, N'-Dimethylformamide DMAP - N,N'-Dimethylaminopyridine DMSO - Dimethyl sulfoxide ee - Enantiomeric excess eq. or equiv - Equivalents EtOH - Ethanol Et - Ethyl Et2O - Diethyl ether EtOAc - Ethyl acetate Et3N - Triethylamine h - Hours Hz - Hertz HMPA - Hexamethylphosphoramide IBX - Iodoxybenzoic Acid i | Page Im - Imidazole i-Pr - Isopropyl IR - Infrared m-CPBA - m-Chloroperbenzoic acid MeOH - Methanol Me - Methyl MeI - Methyl iodide NaBH4 - Sodiumborohydride NaH - Sodium hydride Ph - Phenyl Py - Pyridine PDC - Pyridiniumdichromate p-TSA - para-Toluenesulfonic acid RCM - Ring closing metathesis TEA - Triethylamine TBAI - Tetra-n-butylammonium iodide TBAF - Tetra-n-butylammonium fluoride TBDMSCl - tert-Butyldimethyl chlorosilane TBDMS - tert-Butyldimethyl silyl THF - Tetrahydrofuran TPP - Triphenylphosphine PTSA - p-Toluenesulphonic acid TsCl - p-Toluenesulphonyl chloride ii | Page GENERAL REMARKS ¾ 1H NMR spectra were recorded on AC-200 MHz, MSL-300 MHz, and DRX-500 MHz spectrometer using tetramethylsilane (TMS) as an internal standard. Chemical shifts have been expressed in ppm units downfield from TMS. ¾ 13C NMR spectra were recorded on AC-50 MHz, MSL-75 MHz, and DRX-125 MHz spectrometer. ¾ EI Mass spectra were recorded on Finnigan MAT-1020 spectrometer at 70 eV using a direct inlet system. ¾ Infrared spectra were scanned on Shimadzu IR 470 and Perkin-Elmer 683 or 1310 spectrometers with sodium chloride optics and are measured in cm-1. ¾ Optical rotations were measured with a JASCO DIP 370 digital polarimeter. ¾ Melting points were recorded on Buchi 535 melting point apparatus and are
Load more

Recommended publications
  • Journal of Organic Chemistry, 9, 5291 (1944)
    [CONTRIBUTIONFROM THE MEDICAL-RESEARCHDIVISION, SHARP AND DOHME,INC. ] STUDIES ON THE LEUCKART REACTION FRANK S. CROSSLEY AND MAURICE L. MOORE Received July 21, 194.4 In 1885, Leuckart (1) first described the conversion of certain aldehydes and ketones to the corresponding amines by heating with excess ammonium formate. Wallach (2) applied the method to a number of alicyclic and terpenoid ketones, as well as certain aldehydes, and showed its general application. Despite the excellent results reported by Wallach, the reaction had found little use by others until Ingersoll (3) and his co-workers published a review of the method and re- ported the synthesis of a series of substituted a-phenethylamines by an improved modification of the procedure. Since the appearance of this publication, other workers have been stimulated to use the reaction in the preparation of a number of amines with varying success. Although the exact mechanism has not been definitely established, the reaction has been studied by Wallach (2) and Ingersoll (4)and explained by the following steps: (a) The ammonium formate dissociates into ammonia and formic acid at the temperature of the reaction; and (b) ammonia adds to the carbonyl group or condenses to form the corresponding imine. (c) The formic acid then acts as a reducing agent to remove the hydroxyl or reduce the imino group; and (d) if in excess, may form the formyl derivative which is subsequently hydrolyzed to the free amine. HCOONH, HCOOH f NHj rR OH 7 R R \ + HCOOH + CHNHz + CO* / R’ H20 R’ R R \ \ CHNHz + HCOOH - CHNHCHO + HzO / / R R Formamide (90-9575) may be substituted for ammonium formate and prob- ably hydrolyzes in the reaction to undergo the same steps as above.
    [Show full text]
  • Aromatic and Aliphatic Amines
    Aromatic and Aliphatic Amines 1. Preparation: Amines are prepared by the alkylation of ammonia, Gabriel synthesis, reduction of amides, reduction of nitriles, reduction of nitro-compounds, and reductive amination of aldehydes and ketones. Alkylation of ammonia (Hoffmann,s method): Ethanolic solution of ammonia reacts with an alkyl halide to form primary amine which can further reacts with the alkyl halide to form a secondary amine that can further react to form a tri-substituted amine (i.e., 3o amine). Therefore a mixture of three classes of amines is obtained, alongwith some quaternary ammonium salts. The order of reactivity of halides is RI > RBr > RCl and follow the SN2 pathway. Reduction of alkylazides: A primary amine can be best prepared from alkyl azide by reduction with Na/alcohol or Zn/CH3COOH. Gabriel synthesis: In Gabriel synthesis, phthalimide is converted into its salt potassium phthalimide by the reaction of ethanolic KOH. That salt on heating with an alkyl halide Dr. Debsankar Das, Assistant Prof. P. K. College, Contai Page 1 produces N‐alkyl phthalimide. This can be hydrolyzed by aqueous acids or bases into the primary amine and phthalic acid. Reduction of nitriles: Nitriles can be reduced by lithium aluminum hydride (LiAIH4) or Na/ethanol to primary amines. Reduction of amides: Primary amines can be prepared from amides by reduction with lithium aluminum hydride, while N‐substituted and N, N‐disubstituted amides give secondary and tertiary amines, respectively. Dr. Debsankar Das, Assistant Prof. P. K. College, Contai Page 2 Reduction of nitrocompounds: Aromatic amines are normally prepared by reduction of the corresponding aromatic nitrocompounds with metal/acid or Ni/H2 or LAH.
    [Show full text]
  • Review: Synthetic Methods for Amphetamine
    Review: Synthetic Methods for Amphetamine A. Allen1 and R. Ely2 1Array BioPharma Inc., Boulder, Colorado 80503 2Drug Enforcement Administration, San Francisco, CA Abstract: This review focuses on synthesis of amphetamine. The chemistry of these methods will be discussed, referenced and precursors highlighted. This review covers the period 1985 to 2009 with emphasis on stereoselective synthesis, classical non-chiral synthesis and bio-enzymatic reactions. The review is directed to the Forensic Community and thus highlights precursors, reagents, stereochemistry, type and name reactions. The article attempts to present, as best as possible, a list of references covering amphetamine synthesis from 1900 -2009. Although this is the same fundamental ground as the recent publication by K. Norman; “Clandestine Laboratory Investigating Chemist Association” 19, 3(2009)2-39, this current review offers another perspective. Keywords: Review, Stereoselective, Amphetamine, Syntheses, references, Introduction: It has been 20 years since our last review of the synthetic literature for the manufacture of amphetamine and methamphetamine. Much has changed in the world of organic transformation in this time period. Chiral (stereoselective) synthetic reactions have moved to the forefront of organic transformations and these stereoselective reactions, as well as regio-reactions and biotransformations will be the focus of this review. Within the synthesis of amphetamine, these stereoselective transformations have taken the form of organometallic reactions, enzymatic reactions, ring openings, - aminooxylations, alkylations and amination reactions. The earlier review (J. Forensic Sci. Int. 42(1989)183-189) addressed for the most part, the ―reductive‖ synthetic methods leading to this drug of abuse. It could be said that the earlier review dealt with ―classical organic transformations,‖ roughly covering the period from 1900-1985.
    [Show full text]
  • Simple Ruthenium-Catalyzed Reductive Amination Enables the Synthesis of a Broad Range of Primary Amines
    ARTICLE DOI: 10.1038/s41467-018-06416-6 OPEN Simple ruthenium-catalyzed reductive amination enables the synthesis of a broad range of primary amines Thirusangumurugan Senthamarai1, Kathiravan Murugesan1, Jacob Schneidewind 1, Narayana V. Kalevaru1, Wolfgang Baumann1, Helfried Neumann1, Paul C.J. Kamer1, Matthias Beller 1 & Rajenahally V. Jagadeesh 1 1234567890():,; The production of primary benzylic and aliphatic amines, which represent essential feed- stocks and key intermediates for valuable chemicals, life science molecules and materials, is of central importance. Here, we report the synthesis of this class of amines starting from carbonyl compounds and ammonia by Ru-catalyzed reductive amination using H2. Key to success for this synthesis is the use of a simple RuCl2(PPh3)3 catalyst that empowers the synthesis of >90 various linear and branched benzylic, heterocyclic, and aliphatic amines under industrially viable and scalable conditions. Applying this catalyst, −NH2 moiety has been introduced in functionalized and structurally diverse compounds, steroid derivatives and pharmaceuticals. Noteworthy, the synthetic utility of this Ru-catalyzed amination protocol has been demonstrated by upscaling the reactions up to 10 gram-scale syntheses. Further- more, in situ NMR studies were performed for the identification of active catalytic species. Based on these studies a mechanism for Ru-catalyzed reductive amination is proposed. 1 Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany. Correspondence and requests for materials should be addressed to M.B. (email: [email protected]) or to R.V.J. (email: [email protected]) NATURE COMMUNICATIONS | (2018) 9:4123 | DOI: 10.1038/s41467-018-06416-6 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-06416-6 fi 25 he development of ef cient catalytic reactions for the Cl]2-BINAS catalysts were also applied .
    [Show full text]
  • WASIMP Chemical Profiling of Waste from Clandestine Synthetic Drug Production
    WASIMP Chemical Profiling of Waste from Clandestine Synthetic Drug Production. CATHOLIC UNIVERSITY OF LEUVEN LABORATORY OF TOXICOLOGY AND BROMATOLOGY The research is part of the "Research programme in support of the federal drugs policy document", commissioned and financed by the Belgian Science Policy Office 1 Introduction The large profits that can be realized by the trading of clandestine drugs have attracted the attention of organized crime and caused its proliferation in the domain. Both national and international judicial and police intelligence departments are confronted with this problem and are trying to find a fitting answer to the issue, sometimes with the assistance of science. More specific for the clandestine synthesis of so-called designer drugs, this is usually translated as the chemical profiling of confiscated drugs, synthetic precursors and chemical waste. Such analyses may assist law enforcement agencies to interconnect drugs sold on the street with manufacturing and dumping sites, and hence may result in the dismantlement of a criminal organization. Objective The WASIMP project attempted to find reliable chemical parameters that allow interconnection of chemical ditching sites, and/or permit to interlink dumping sites with underground drug laboratories. Research was focused on MDMA (XTC) and amphetamine (Speed), the two most popular clandestine designer drugs in Belgium. Most of the confiscated amphetamine has been manufactured via the Leuckart reductive amination, while MDMA is often synthesized using PtO2-catalyzed
    [Show full text]
  • Impurity Profiling Amphetamine Made from Benzyl Cyanide and Phenylacetic Acid
    School of Chemical Technology Degree Program of Chemical Technology Joel Ormala ONE MORE STEP BACK – IMPURITY PROFILING AMPHETAMINE MADE FROM BENZYL CYANIDE AND PHENYLACETIC ACID Master’s thesis for the degree of Master of Science in Technology, submitted for inspection in Espoo, 3rd of October, 2016. Supervisor Professor Ari Koskinen Instructor Dr. Pekka Joensuu Instructor M. Sc. Sami Huhtala Aalto University, P.O. BOX 11000, 00076 AALTO www.aalto.fi Abstract of master's thesis Author Joel Ormala Title of thesis ONE MORE STEP BACK – IMPURITY PROFILING AMPHETAMINE MADE FROM BENZYL CYANIDE AND PHENYLACETIC ACID Department Department of Chemistry Professorship Organic Chemistry Code of professorship Kem-4 Thesis supervisor Professor Ari Koskinen Thesis advisor(s) / Thesis examiner(s) Dr. Pekka Joensuu & M. Sc. Sami Huhtala Date 03.10.2016 Number of pages Language English 60 (+ 98) Abstract The aim of this theses was to employ a multi-disciplinary approach to chemical impurity profiling of illicitly produced amphetamine. Based on the literature on the illicit amphetamine market in Finland and Europe, the globally seized amphetamine pre- and pre-precursors, and the most commonly used illicit manufacturing methods, the synthetic routes to be studied in this research were determined. The role of chemical impurity profiling of drugs in intelligence-led policing strategies was explored, and the particular requirements of analytical methods employed in service of the forensic intelligence process were identified. Using this background knowledge, permission to conduct research on internationally controlled substances was applied and received from FIMEA. Amphetamine was synthesized from benzyl cyanide and phenylacetic acid, using the Leuckart re- action and reductive amination.
    [Show full text]
  • January March 2014 67Kb
    The Indian Police Journal The Indian Police Journal Vol LXI. No. 1 ISSN 0537-2429 Jan-March, 2014 IPJ Jan-March, 2014 Vol. LXI No. 1 EDITORIAL BOARD CONTENTS Editorial 2 Shri Rajan Gupta, IPS 1. The Commoner Goes Berserk: The Socio-Psychological DG, BPR&D Subset of a Rebel and a Terror Monger Dr. Manan Dwivedi 4 Chairman 2. “Maoist-Naxalite Problem : Threat Perception and Tackling Strategy through Responsive Governance” Dr. Krishna Kumar 19 Shri Radhakrishnan Kini, IPS 3. Terrorism and Human Rights: Critical Analysis Inderpreet Kaur 28 ADG, BPR&D 4. Human Rights-Obstacle for Police and Safety for Criminals Member Dr. Dalvir Singh Gahlawat 41 5. Intelligent Emergency Response System for Police Vehicles in India Smt. Nirmal Kaur, IPS Ishan Ganeshan 49 6. Clandestine Drug Laboratories: The Problem, IG/Director (SU) Dangers and Solution Member Ashok Juneja IPS 66 7. Digitalized Terrorism -The Technological Advancement of Crime Dr. Nidhi S & Dr. Priti Saxena 85 Shri Sunil Kapur 8. “Safe City – Surat”- Suraksha Setu DIG/DD (SU) Rakesh Asthana 103 9. Image Crisis of Indian Police Member Umesh Sharraf 121 10. Public Perception About Indian Police: An Empirical Analysis Bushara Bano & Dr. Parvaiz Talib 132 Editor 11. First Information Report and Criminal Justice Dr. Pradeep Singh 149 Gopal K.N. Chowdhary 12. Eleven Guidelines to be followed in all cases of Arrest and Detention Khush Kalra 182 13. Organisational Health, Leadership Effectiveness and Influence Tactics as Perceived by Police Personnel- Some Reflections of Vadodara Police Dhvani Patel & Urmi Nanda Biswas 192 14. Influence of Emotional Intelligence on Adjustment of Police Personnel Dr.
    [Show full text]
  • Identification of Impurities in Biological Material Remaining After Amphetamine Synthesis
    IDENTIFICATION OF IMPURITIES IN BIOLOGICAL MATERIAL REMAINING AFTER AMPHETAMINE SYNTHESIS Agnieszka SIWIÑSKA-ZIÓ£KOWSKA1, Dariusz B£ACHUT2, Emilia WIDECKA-DEPTUCH2 1Chair and Department of Forensic Medicine, Medical Academy, Warsaw 2Department of Criminalistic and Special Chemistry, Internal Security Agency, Warsaw ABSTRACT: Toxicological analysis of biological material encompasses searching for different toxic substances, amongst which drugs are a very important group. Con- firmation of the presence of compounds in the amphetamine class is based on detec- tion of particular compounds in this class, for example: amphetamine (AMF), methamphetamine (MAMF), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), p-methoxyamphetamine (PMA) and p-methoxymethamphetamine (PMMA), using instrumental methods. In this paper we show the possibility of identification of contaminations originating from the syn- thesis of amphetamine using Leuckart’s method in biological materials from two au- topsies performed in the Department of Forensic Medicine in Warsaw. In the first case we detected the presence of N-formylamphetamine, N,N-di-(b-phenylisopro- pyl)amine, N,N-di-(b-phenylisopropyl)methylamine, and derivatives of phenylmethyl- pyridine in stomach and blood samples. In the second case we found the same com- pounds only in the blood sample. Despite the lack of data about toxicity of these substances, it is possible that the toxicity may be comparable to that of amphetamine and its analogues. KEY WORDS: Amphetamine; Impurities; Toxicological analysis; Leuckart’s method; Fatal intoxication. Problems of Forensic Sciences, vol. LX, 2004, 130–148 Received 7 July 2005; accepted 1 September 2005 INTRODUCTION Analysis of toxicological results obtained at the Department of Forensic Medicine in Warsaw revealed that in several recent years fatal poisonings caused by drugs of abuse have occupied second position among all poisonings.
    [Show full text]
  • Department of Chemistry, St. Paul's C. M. College
    Lecture note for CC-4-8 (Organic Chemistry-4) Series: Nitrogen Compounds Aliphatic Amines-I Synthesis of aliphatic amines: Let us consider the synthesis of the primary amine R-NH2. Forming a C-N (carbon-heteroatom) bond is easier than forming a C-C bond. So we may consider the following type of disconnections. Thus a primary amine may be obtained by the treatment with ethanolic NH3 on an alkyl halide. But the reaction does not follow the above course absolutely. Over-alkylation is a serious problem: + and so on, i.e. after alkali treatment we get a mixture of RNH2, R2NH, R3N and R4N . But we do want the primary amine RNH2 exclusively. How may we do it? o Separation of primary amine from the above mixture – Hinsberg method. Department of Chemistry, St. Paul's C. M. College 1 Page Lecture note prepared by Kaushik Basu, St. Paul’s C. M. College, Kolkata o As evident from the above scheme, here NH3, RNH2, R2NH, and R3N are in competition to react with RX. If NH3 acts as the nucleophile in preference over the other nucleophilic species, we may get the primary amine. So we have to use a large excess of NH3. Thus we have the following ways to obtain amino acids: o We have to use a masked form of ammonia in which two valences of nitrogen are satisfied by easily removable groups, i.e. Thus we have the Gabriel’s phthalimide synthesis. But phthalimide cannot act as a nucleophile as shown:Department of Chemistry, St. Paul's C.
    [Show full text]
  • For Peer Review Journal: Drug Testing and Analysis
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Drug Testing and Analysis provided by LJMU Research Online ‘APAAN in the neck’ - A reflection on some novel impurities found in seized materials containing amphetamine in Ireland during routine forensic analysis. For Peer Review Journal: Drug Testing and Analysis Manuscript ID DTA-17-0070.R1 Wiley - Manuscript type: Perspective Date Submitted by the Author: 18-Mar-2017 Complete List of Authors: Power, John; Trinity College Dublin, Pharmacology Kavanagh, Pierce; Trinity College Dublin, Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. Jame’s Hospital, Jame’s Street, Dublin 8, D08W9RT, Ireland. McLaughlin, Gavin; University of Dublin Trinity College, Pharmacology & Therapeutics; Athlone Institute of Technology, Life & Physical Sciences Barry, Michael; School of Medicine, Trinity Centre for Health Sciences, St. Jame’s Hospital, Jame’s Street, Dublin 8, D08W9RT, Ireland., Department of Pharmacology and Therapeutics Dowling, Geraldine; Dublin Institute of Technology, School of Chemical and Pharmaceutical Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin Street, Dublin 8, D08NF82, Ireland. Brandt, Simon; School of Pharmacy & Biomolecular Sciences , Liverpool John Moores University Keywords: amphetamine, APAAN, synthesis, by-products, importations, adulturants Abstract: none, as this is a perspective article. http://mc.manuscriptcentral.com/dta Page 1 of 26 Drug Testing and Analysis
    [Show full text]
  • Patented July 15, 1952 Dog +H:0 "..."
    Patented July 15, 1952 2,603,661 2,603,661 LEUCKART syNTHESIS William F. Bruce, Havertown, Pa., and Wincent J. Webers, Racine, Wis., assignors to Wyeth Incorporated, Philadelphia, Pa., a corporation. of Delaware Application August 19, 1948, Serial No. 45,207 Claims. (C. 260-562) 2 The invention relates to the preparation of The reaction may be postulated by the follow formylamino and amino derivatives and more ing equations: . ". particularly involves a catalytic process for ob R R. taining formylamino compounds by the reaction of a ketOne and a formamide. 5 c=o + NERCHO Dog . The preparation of certain commercially im R77 ; : R N+HRCHIO (i) portant amines has heretofore depended to a great extent on the utilization of the Well-known R oH R oH . Leuckart reaction. This reaction, as first re Nc4 ' , , -m--> c ported in the literature, involved the use of am 10 R? YHRCHO R?. monium formate, which with benzophenone R OF formed. N-benzhydryl formamide. The latter compound when hydrolyzed formed the corre Yo +NHR-Cho - sponding amine. Subsequent to the disclosure of R?. YRCHO this reaction a great many ketones have been 5 . R. H. - - - - - - - - tried and found to proceed as with benzophe - So +NH.R+ co, none. The Leuckart reaction has therefore been R?. YRCho (3) adapted to the preparation of important physiol ogically active amines, such as the Sympatho 20 R H Hydrolysis mimetic amines, by selecting the proper ketone Dog +H:0 "..." for the reaction. As an example, if one starts R. NRCHO - With phenylacetone, the final hydrolysis of the . R E formamide product will yield the central ner Y/ " .
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,710,268 B2 Bobylev (45) Date of Patent: *Apr
    US008710268B2 (12) United States Patent (10) Patent No.: US 8,710,268 B2 Bobylev (45) Date of Patent: *Apr. 29, 2014 (54) METHOD FOR THE HYDROLYSIS OF (58) Field of Classification Search SUBSTITUTED FORMYLAMINES INTO USPC .................................................. 564/336,386 SUBSTITUTEDAMINES See application file for complete search history. (71) Applicant: Mikhail Bobylev, Minot, ND (US) (56) References Cited (72) Inventor: Mikhail Bobylev, Minot, ND (US) U.S. PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this 8.329,948 B2 * 12/2012 Bobylev ........................ 564,215 patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS U.S.C. 154(b) by 0 days. This patent is Subject to a terminal dis EP O 518414 * 12/1992 claimer. * cited by examiner (21) Appl. No.: 13/657,505 Primary Examiner — Shailendra Kumar (74) Attorney, Agent, or Firm — James K Petell (22) Filed: Oct. 22, 2012 (57) ABSTRACT (65) Prior Publication Data An improved method for the synthesis of substituted formy US 2013/OO46111A1 Feb. 21, 2013 lamines and Substituted amines via an accelerated Leuckart reaction. The Leuckart reaction is accelerated by reacting formamide or N-alkylformamide and formic acid with an Related U.S. Application Data aldehyde or aketoneata preferred molar ratio that accelerates (63) Continuation of application No. 12/182,451, filed on the reaction. The improved method is applicable to various Jul. 30, 2008, now Pat. No. 8,329,948. Substituted aldehydes and ketones, including Substituted ben Zaldehydes. An accelerated method for the hydrolysis of sub (60) Provisional application No. 60/962,739, filed on Jul. stituted formylamines into Substituted amines using acid or 31, 2007.
    [Show full text]