Generation and succeeding reactions of allenyl isothiocyanates [Elektronische Ressource] / vorgelegt von Baker Salim Yacoub, (Jawabrah Al-Hourani)

Fadi Kheder

Description

Generation and Succeeding Reactions of Allenyl Isothiocyanates Von der Fakultät für Naturwissenschaften der Technischen Universität Chemnitz genehmigte Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat) vorgelegt von M.Sc. Baker Salim Yacoub, (Jawabrah Al-Hourani) geboren am 23.09.1971 in Zarqa, Jordan eingereicht am 15.06.2005 Gutachter: Prof. Dr. Klaus Banert Prof. Dr. Stefan Spange Prof. Dr. Werner Thiel Tag der Verteidigung: 05.10.2005 http://archiv.tu-chemnitz.de/pub/....... Bibliographische Beschreibung und Referat 2 Bibliographische Beschreibung und Referat Jawabrah Al-Hourani, Baker “Darstellung und Folgereaktionen von Allenylisothiocyanaten“ Technische Universität Chemnitz, Fakultät für Naturwissenschaften Dissertation 2005, 127 Seiten, 130 Literaturstellen, 12 Abbildungen, 9 Tabellen und 49 Schemata. In der vorliegenden Arbeit sind die [3,3]-sigmatrope Umlagerung von verschiedenen Propargylthiocyanaten und die doppelte [3,3]-sigmalagerung von Eninylisothiocyan-aten entweder durch Blitzvakuumthermolyse oder Thermolyse in Lösung untersucht worden. Zusätzlich wurden die intramolekularen Reaktionen der resultierten Allenylisothiocyanate studiert. Außerdem sind die Reaktionsmechanismen zur Bildung der Thermolyseprodukte wie z.B. die [1,5]-sigmatropen Umlagerungen und die elektrocyclischen Ringschlüsse erklärt.

Informations

• Publié par: technische_universitat_chemnitz
• Publié le: 01 janvier 2005
• Nombre de lectures: 26
• Langue: Deutsch
• Poids de l'ouvrage: 1 Mo

Extrait

Generation and Succeeding Reactions of Allenyl

Isothiocyanates

Von der Fakultät für Naturwissenschaften der Technischen Universität Chemnitz

genehmigte Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium

(Dr. rer. nat)

vorgelegt von M.Sc. Baker Salim Yacoub, (Jawabrah Al-Hourani) geboren am 23.09.1971 in Zarqa, Jordan

eingereicht am 15.06.2005 Gutachter: Prof. Dr. Klaus Banert Prof. Dr. Stefan Spange Prof. Dr. Werner Thiel Tag der Verteidigung: 05.10.2005 http://archiv.tu-chemnitz.de/pub/.......

Bibliographische Beschreibung und Referat 2 Bibliographische Beschreibung und Referat Jawabrah Al-Hourani, Baker “Darstellung und Folgereaktionen von Allenylisothiocyanaten“ Technische Universität Chemnitz, Fakultät für Naturwissenschaften Dissertation 2005, 127 Seiten, 130 Literaturstellen, 12 Abbildungen, 9 Tabellen und 49 Schemata. In der vorliegenden Arbeit sind die [3,3]-sigmatrope Umlagerung von verschiedenen Propargylthiocyanaten und die doppelte [3,3]-sigmatrope Umlagerung von Eninylisothiocyan- aten entweder durch Blitzvakuumthermolyse oder Thermolyse in Lösung untersucht worden. Zusätzlich wurden die intramolekularen Reaktionen der resultierten Allenylisothiocyanate studiert. Außerdem sind die Reaktionsmechanismen zur Bildung der Thermolyseprodukte wie z.B. die [1,5]-sigmatropen Umlagerungen und die elektrocyclischen Ringschlüsse erklärt. Die hochreaktiven Allenylisothiocyanate sind als geeignet elektrophile Vorläufer zur Synthese von neuen Thiazolen verwendbar, die an der C-2 Position substituiert sind. Dabei kommen verschiedene Nucleophile zum Ansatz. Für die Bildung dieser substituierten Thiazole sind die Regioselektivität, Stereoselektivität, Reaktionsmechanismen und der Bereich der einsetzbaren Nucleophile untersucht worden. Stichworte: Isothiocyanat [= Senföle], Thiocyanat, Propargylthiocyanat, Allenylisothiocyanat, Eninylisothiocyanat, Thiazol, [3,3]-sigmatrope Umlagerung, [1,5]-sigmatrope Verschiebung, elektrocyclische Ringschlussreaktion, Heterocyclen.

Abstract 3 Abstract Jawabrah Al-Hourani, Baker “Generation and Succeeding Reactions of Allenyl Isothiocyanates“ Chemnitz University of Technology, Faculty of Natural Science PhD Thesis 2005, 127 Pages, 130 References, 12 Figures, 9 Tables, and 49 Schemes. In this work, the [3,3] sigmatropic rearrangement of different substituted propargyl thiocyanates and double [3,3] sigmatropic rearrangement of enynyl isothiocyanates either by flash vacuum pyrolysis or by thermolysis in solution are studied. Additionally, the intramolecular reactions of the resulting allenyl isothiocyanates are studied, and the reaction mechanisms for the generation of the final products, such as [1,5] sigmatropic migrations or electrocyclic ring closures, are explained. These highly reactive allenyl isothiocyanates are used as appropriate electrophilic precursors for the preparation of novel examples of thiazoles substituted at C-2 position using different types of nucleophiles. For the formation of these substituted thiazoles, the necessary nucleophilicity as well as the regioselectivity, the stereoselectivity, and the reaction mechanisms are investigated. Keyword: Isothiocyanate [= Mustard oil], Thiocyanate, Propargyl Thiocyanate, Allenyl Isothiocyanate, Enynyl Isothiocyanate, Thiazole, [3,3] Sigmatropic Rearrangement, [1,5] Sigmatropic Migration, Electrocyclic Ring Closure, Heterocycles.

Dedication

In The Memory of My Beloved Mother

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There are many devices in a man’s heart; nevertheless the counsel of the Lord, that shall stand.PROVERBS 19: 21

Table of Contents

Content

I II 1 2

Acknowledgement List of Symbols and Abbreviations Introduction and Task of Study 1.1 Isothiocyanates (ITCs) 1.2 Sigmatropic Rearrangement 1.2.1 [3,3] Sigmatropic Rearrangement of Thiocyanates: Generation of Isothiocyanates 1.3 Preparation of Substituted Thiazoles 1.3.1 From Alk-1-ynyl Thiocyanates 1.3.2 Fromα-Thiocyanato Ketones 1.3.3 From Alk-2-ynylamines and Isothiocyanates or Carbon Disulfide 1.4 The Flash Vacuum Pyrolysis (FVP) Technique 1.5 Task of the Study Results and Discussion 2.1 Synthesis of Allenyl ITCs 2.1.1 Basic System of Allenyl ITC4a 2.1.2 FVP of 1-Methoxy-4-thiocyanato-but-2-yne20 2.1.3 Synthesis and FVP of 1-Methylsulfanyl-3-thiocyanato-prop-1-yne24 2.1.3.1 Synthesis of 1-Methylsulfanyl-3-thiocyanato-prop-1-yne24 2.1.3.2 FVP of 1-Methylsulfanyl-3-thiocyanato-prop-1-yne24 2.1.4 Synthesis of 2-[2-(4-Thiocyanato-but-2-ynyloxy)-ethoxy]-ethanol37and its Thermolysis in Solution 2.1.4.1 Synthesis of 2-[2-(4-Thiocyanato-but-2-ynyloxy)-ethoxy]-ethanol37 2.1.4.2 Thermolysis of 2-[2-(4-Thiocyanato-but-2-ynyloxy)-ethoxy]-ethanol37in Solution 2.1.5 Synthesis and Reactions of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50 2.1.5.1 Synthesis of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50 2.1.5.2 FVP of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50 2.1.5.3 Thermolysis of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50in Solution 2.1.5.4 Oxidation of 3-Isothiocyanato-1-methyl-cyclohexa-1,3-diene53 2.1.6 Synthesis and FVP ofZ/E-1-Isothiocyanato-3-methyl-pent-2-en-4-yne59 2.1.6.1 Synthesis of Z/E-1-Isothiocyanato-3-methyl-pent-2-en-4-yne59 2.1.6.2 FVP of Z/E-1-Isothiocyanato-3-methyl-pent-2-en-4-yne59 2.1.7 Preparation of 1,3,3-Triphenylallenyl Thiocyanate65 2.2 Succeeding Reactions of Allenyl ITCs 4a and 21 with Different Nucleophiles: Synthesis of Substituted Thiazoles 2.2.1 Reaction of Allenyl ITC4awith Dialkyl or Diphenyl Phosphites

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9 10 12 12 13 14 17 17 18 18 19 20 21 21 21 21 22 22 23 24 24 26 28 28 31 33 34

34 34 35 37 38 38

Table of Contents  2.2.2 Reaction of Allenyl ITC4awith Five-Membered Ring Heteroaromatic Compounds Containing One Heteroatom  2.2.2.1 Reaction of Allenyl ITC4awith Pyrrole using Alkyllithium  2.2.2.2 Reaction of Allenyl ITC4aThienylmagnesium Bromide with 80 and Thienyllithium86  2.2.3 Reaction of Allenyl ITC4awith 10,11-Dihydro-5H-dibenzo[b,f]azepine88 2.2.4 Reaction of Allenyl ITCs4aand21with Heterocycles Containing Two Nitrogen Atoms 2.2.5 Reaction of Allenyl ITC4awith Histamine103 2.2.6 Reaction of Allenyl ITC4awith Adenine107 2.3 Advanced Succeeding Reactions of Allenyl ITC 4a: Synthesis of Bifunctional Thiazoles

3 4

2.3.1

2.3.2

Reaction of Allenyl ITC4awith Hydrazoic Acid

Reaction of Allenyl ITC4awithN,N-Disubstituted Hydroxylamine Derivatives

Summary Experimental Section 4.1Instrumentation 4.2Working Procedures and Conditions 4.3 Synthesis of Allenyl ITCs 4.3.1FVP of 1-Methoxy-4-thiocyanato-but-2-yne20 4.3.2Synthesis of 1-Methylsulfanyl-3-thiocyanato-prop-1-yne24 4.3.2.1Preparation of 3-Chloro-1-methylsulfanyl-prop-1-yne23 4.3.2.2Preparation of 1-Methylsulfanyl-3-thiocyanato-prop-1-yne24 4.3.3FVP of 1-Methylsulfanyl-3-thiocyanato-prop-1-yne24 4.3.4 Trapping of 1-Isothiocyanato-1-methylsulfanyl-propa-1,2-diene25 with Dibenzylamine26 4.3.5Synthesis of 2-[2-(4-Thiocyanato-but-2-ynyloxy)-ethoxy]-ethanol37 4.3.5.1Preparation of 3-[2-(2-Prop-2-ynyloxy-ethoxy)-ethoxy]-propyne302-(2-Prop- and 2-ynyloxy-ethoxy)-ethanol31 4.3.5.2Preparation of 2-[2-(2-Prop-2-ynyloxy-ethoxy)-ethoxy]-tetrahydro-pyran32 4.3.5.3Preparation of 4-{2-[2-(2-Tetrahydro-pyran-2-yloxy)-ethoxy]-ethoxy}-but-2-yn-ol 33 4.3.5.4Preparation of Toluene-4-sulfonic Acid 4-{2-[2-(2-Tetrahydro-pyran-2-yloxy)- ethoxy]-ethoxy}-but-2-ynyl Ester34 4.3.5.5Preparation of 2-{2-[2-(4-Bromo-but-2-ynyloxy)-ethoxy]-ethoxy}-tetrahydro-pyran 35 4.3.5.6 Preparation of 2-[2-(4-Bromo-but-2-ynyloxy)-ethoxy]-ethanol36

40 41 43 46 48 53

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59 59

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69 75 75 76 77 77 77 77 78 78 79 80 80 81 81 82 83 83

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Table of Contents  4.3.5.7Preparation of 2-[2-(4-Thiocyanato-but-2-ynyloxy)-ethoxy]-ethanol37  4.3.6 Trapping of 2-[2-(2-Isothiocyanato-buta-2,3-dienyloxy)-ethoxy]-ethanol38 with Methanol  4.3.7Preparation of Potassium 2-[2-(2-Methoxy-5-methyl-thiazol-4-ylmethoxy)-ethoxy]- ethanolate41  4.3.8Synthesis of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50  4.3.8.1 Preparation of Toluene-4-sulfonic Acid 1-Isopropyl-4-(tetrahydro-pyran-2-yloxy)- but-2-ynyl Ester43  4.3.8.2Preparation oftrans- andcis-2-(5-Methyl-hex-1-en-3-ynyloxy) tetrahydro-pyran45  4.3.8.3Preparation of 5-Methyl-hex-4-en-2-yn-1-ol46  4.3.8.4Preparation of Toluene-4-sulfonic Acid 5-Methyl-hex-4-en-2-ynyl Ester49  4.3.8.5Preparation of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50  4.3.9FVP of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50  4.3.10Oxidation of 3-Isothiocyanato-1-methyl-cyclohexa-1,3-diene53  4.3.11Thermolysis of 2-Methyl-6-thiocyanato-hex-2-en-4-yne50in Solution  4.3.12Synthesis ofZ/E-1-Isothiocyanato-3-methyl-pent-2-en-4-yne59  4.3.13 FVP ofZ/E-1-Isothiocyanato-3-methyl-pent-2-en-4-yne59  4.3.14Synthesis of 1,3,3-Triphenylallenyl Thiocyanate65 Reactions of Allenyl ITCs 4a and 21 with Different4.4 Succeeding Nucleophiles

4.4.1 4.4.1.1 4.4.1.2 4.4.1.3 4.4.2

4.4.3

4.4.4 4.4.5 4.4.5.1

4.4.5.2

4.4.5.3 4.4.5.4

Synthesis of Thiazole Derivatives69a–c; General ProcedureI Synthesis of Dimethyl 5-Methyl-thiazole-2-phosphonate69a Synthesis of Diphenyl 5-Methyl-thiazole-2-phosphonate69b Synthesis of Dibenzyl 5-Methyl-thiazole-2-phosphonate69c Synthesis of 5-Methyl-2-pyrrol-1-yl-thiazole78 and 5-Methyl-2-(1H-pyrrol-2-yl)- thiazole79 Synthesis of 5-Methyl-2-thiophen-2-yl-thiazole82 and 5-Methyl-2`-(thiophen-2- yl)-2,5`-methylenebisthiayole84 Synthesis of 5-(5-Methyl-thiazol-2-yl)-10,11-dihydro-5H-dibenzo[b,f]azepine90 Synthesis of Other Thiazole Derivatives; General ProcedureII Synthesis of 5-Methyl-2-(3,4,5-trimethyl-pyrazol-1-yl)-thiazole97a5- and Methylene -2- (3,4,5-trimethyl-pyrazol -1-yl) - 4,5 -dihydro-thiazole98a Synthesis of 4-Methoxymethyl-5-methyl-2-(3,4,5-trimethyl-pyrazol-1-yl)-thiazole 97b and 4-Methoxymethyl-5-methylene-2-(3,4,5-trimethyl-pyrazol-1-yl)-4,5- dihydro-thiazole98b Synthesis of 2-[1-(5-Methyl-thiazol-2-yl)-1H-pyrazol-3-yl]-pyridine97c Synthesis of 2-[1-(4-Methoxymethyl-5-methyl-thiazol-2-yl)-1H-pyrazol-3-yl]- pyridine97d

84 85 86 86 86 87 88

89 89 90 91 91 91 93 94 95 95 95 96 96 97 98 100 101 101 102 103 104

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Table of Contents  4.4.5.5 Synthesis of 2-(3,5-Dimethyl-pyrazol-1-yl)-5-methyl-thiazole97e2-(3,5- and Dimethyl-pyrazol-1-yl)-5-methylene-4,5-dihydro-thiazole98e  4.4.5.6 Synthesis of 2-(3,5-Dimethyl-pyrazol-1-yl)-4-methoxymethyl-5-methyl-thiazole97f and 2-(3,5-Dimethyl-pyrazol-1-yl)-4-methoxymethyl-5-methylene-4,5-dihydro-

4.4.5.7

4.4.5.8 4.4.5.9

4.4.6 4.4.6.1 4.4.6.2

4.4.6.3

4.4.7 4.5

thiazole98f Synthesis of 2-(2-Ethyl-4-methyl-imidazol-1-yl)-4-methoxymethyl-5-methyl- thiazole97g2-(2-Ethyl-4-methyl-imidazol-1-yl)-4-methoxymethyl-5- and methylene-4,5-dihydro-thiazole98g Synthesis of 5-Methyl-2-(4-nitro-imidazol-1-yl)-thiazole97h Synthesis of 2-Ethyl-1-(4-methoxymethyl-5-methyl-thiazol-2-yl)-1H- benzoimidazole97i2-Ethyl-1-(4-methoxymethyl-5-methylene-4,5-dihydro- and thiazol-2-yl)-1H-benzoimidazole98i Reaction of Allenyl ITC4awith Histamine and Histamine Derivatives Synthesis of [2-(1H-Imidazol-4-yl)-ethyl]-(5-methyl-thiazol-2-yl)-amine104 Synthesis of (5-Methyl-thiazol-2-yl)-{2-[1-(5-methyl-thiazol-2-yl)-1H-imidazol-4- yl]-ethyl}-amine105 Synthesis ofN-(5,5'-Dimethyl-2,3'-bi-1,3-thiazol-2'-ylidene)-N-{2-[1-(5-methyl-1,3- thiazol-2-yl)-1H-imidazol-4-yl]-ethyl}-amine106 Synthesis of 7-(5-Methyl-thiazol-2-yl)-9H-purin-6-ylamine111 Advanced Succeeding Reactions of ITC 4a: Synthesis of Bifunctional Thiazoles

 4.5.1 Reaction of Allenyl ITC4awith Hydrazoic Acid  4.5.2 Reaction of Allenyl ITC4awithN,N-Disubstituted Hydroxylamine Derivatives  4.5.2.1 Reaction of Allenyl ITC4awithN,N-Diethylhydroxylamine130a  4.5.2.2 Reaction of Allenyl ITC4awithN-Hydroxypiperidine130b  4.5.2.3 Reaction of Allenyl ITC4awithN,N-Dibenzylhydroxylamine130c  4.5.2.4 Reaction of Allenyl ITC4awithN,N-Dimethylhydroxylamine Hydrochloride130d  4.5.2.5 Detection of Compounds131a–cand134a–cin NMR Experiments  4.5.2.6 Control Experiment for the Formation of 2-(Piperidin-1-yl)-5-methyl-thiazole133b and 2-Dibenzylamino-5-methyl-thiazole133c 5 References Appendix

8 105 106 107 108 108 110 110 110 111 112 113 113 114 114 115 116 117 118 119

Acknowledgement

Acknowledgement

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The experimental part of this research was performed from October 2002 until December 2004 in the laboratories of Prof. Dr. K. Banert, Chemnitz University of Technology. I am indebted and greatly thankful to my professor Klaus Banert, who welcomed me to his team, advised as well as guided my research, and suggested key points that lead to the success of my work. I am grateful and indebted to the DAAD (German Academic Exchange Service) organization for their care and continuous support without which I could not have achieved all of this success. My sincere thanks go to the organic chemistry group specially Dr. J. Lehmann, Dr. F. Köhler, and Dr. R. Fotsing who helped in revising my paper and provided important guidelines as well as helped in performing some of the important NMR experiments. My thanks go to Dr. M. Hagedorn who also helped in performing some of the important NMR experiments and guided me with his helpful discussions. Special thanks go to Miss J. Buschmann, R. Franzky, and N. Wetzold for performing the elemental analysis and MS measurements. I am also thankful to all of my lab colleges and friends for their help and support. Thanks go to W. Al-halasah, Dr. R. Tahir, Jake, Kevin, Montgomery’s family, A. Ihle, E. Penk, Axtell, Martin, Größe, Dr. A. Abu Rayyan, Dr. M. Al Anber, and Dr. M. Al Omari. I acknowledge the organic chemistry laboratory members, E. Gutzeit, S. Schoeneich, M. Lindner and J. Buschmann for their help and support. Thanks also go to Prof. W. Thiel and his coworkers Dr. M. Jia, who provided me with compound94b, in addition to Dr. Y. Sun for his help, Prof. S. Spange for writing a recommendation letter to the DAAD and for his help, and to Prof. E. Klemm for his permission to do the GC–MS measurements in his lab in addition to his coworkers Dr. E. Dietzsch and Frau M. Wienzek. Further, thanks go to Prof. H. Lang, Dr. B. Walfort, and Dr. T. Rüffer for their cooperation in executing the X-ray, some IR, MS measurements and for their support. Warm thanks to Dr. M. Müller and Miss E. Schepplerfor their care and support for my stay in Germany. My love and appreciation go also, to my father, sisters’ families, and brother in Jordan for their continued support and love. Finally, I deeply appreciate the Chemnitz University of Technology that embraced me as one of its students.

List of Symbols and Abbreviations List of Symbols and Abbreviations δ Chemical shift brBroad Cy Cyclohexyl d Doublet dd Doublet of doublet ddd Doublet of doublet of doublet DMF Dimethylformamide DMSO Dimethyl sulfoxide dt Doublet of triplet ESI Electron Spray Ionization Et Ethyl Et 2 etherO Diethyl EtOH Ethanol FVP Flash Vacuum Pyrolysis g Gram(s) °C Grade Celsius h Hour(s) Hz Hertz IR Infrared ITC Isothiocyanate ITCs Isothiocyanates J  Coupling constant m Multiplet Me Methyl MHz Mega Hertz ml Milliliter m.p. Melting Point + [M ] Molecule Ion MS Mass Spectrometer m/z Mass/Charge

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List of Symbols andAbbreviation min Minute(s) MeOH Methanol mmol Millimol NMR Nuclear Magnetic Resonance NOE Nuclear Overhauser Effect n-BuLin-Butyllithium Ph Phenyl Ph i position of phenyl Ipso Ph m position of phenyl Meta Ph o  Ortho position of phenyl Ph p  Para position of phenyl q Quartet qt Quartet of triplet Roman numbers Table of contents, General procedure numbers, and Summary s Singlet sept.d Septet of doublet t Triplet t-BuOK Potassium-tert-butanolate THF Tetrahydrofuran THP Tetrahydropyran Ts Tosyl TsOH Toluene-4-sulfonic acid monohydrate wk Weak

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