UNIVERSITY OF CINCINNATI Date:October 20, 2004 I, _____Sarah Marie Mandel ______________________________, hereby submit this work as part of the requirements for the degree of: Doctorate of Philosophy in: Chemistry It is entitled : Photolysis of Alkyl Azides Containing an Aryl Ketone Chromophore in Solution and the Solid-State This work and its defense approved by: Chair: _Anna Gudmundsdottir __________ _R. Marshall Wilson ___________ _William Connick ______________ _______________________________ _______________________________ 1 Photolysis of Alkyl Azides Containing an Aryl Ketone Chromophore in Solution and the Solid State A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (Ph.D.) In theDepartment of Chemistry of the College of Arts of Sciences 2004 Sarah Marie Mandel B.A. Transylvainia University, 1998 M.S University of Cincinnati, 2002 Committee Chair: Anna Dora Gudmundsdottir 2 Abstract: In this research internal sensitization has been utilized to photochemically generate triplet alkyl nitrenes in solution and solid-state. Irradiating alkyl azides containing aryl ketone chromophores with light over 300 nm allows only the aryl ketone chromophore to be excited. The triplet aryl ketone chromophore created from excitation can then transfer triplet energy to the alkyl azide moiety, forming a triplet alkyl nitrene. Solution irradiation allowed triplet alkyl nitrenes to be trapped in bimolecular reactions. In solution irradiations of Azides 1 the major solution photoproduct was found to be N-benzoyl benzamides derivatives formed by the trapping of a triplet alkyl nitrene with a benzoyl radical. Photolysis of Azides 2 in solution was found to yield three products which can be attributed to bimolecular trapping of the triplet alkyl nitrene. The major photoproducts were identified as 1-phenyl-3-[5-phenylpyrazol-1-yl]-propan1-one derivatives, formed from dimerization of triplet alkyl nitrenes. The remaining photoproducts were found to be 3-(3-oxo-3- phenyl-propylamino)-1-phenyl-propenone derivatives and 3-(3-oxo-3-phenyl-propylamino)-1- phenyl-propan-1-one derivaitves formed from trapping of the triplet alkyl nitrene with propiophenone radicals. When Azides 3 were irradiated in solution the products were found to form acetophenone derivatives and 5-(4-phenyl)-pyrrole derivatives created from 1,4 intramolecular hydrogen atom abstraction. Formation of the triplet alkyl nitrene lead to the creation of 5-(4- phenyl)-3,4- dihydro-2H-pyrrole derivatives. Irradiations of alkyl azides within molecular crystals yielded interesting results. In solid state irradiations of Azides 1 the photoproduct was found to be N-methylene benzamide derivatives in all cases. This was interesting because the bimolecular reactivity observed in solution was changed to unimolecular reactivity within the restraints of a crystal lattice. Oxygen 3 trapping studies indicate that the product is formed from α-cleavage of the triplet aryl ketone, followed by rearrangement of the resultant fragments. In solid state photolysis of Azides 2 energy transfer from the aryl ketone to the alkyl azide moiety was found to create the triplet alky nitrene which underwent dimerizaion. It was found that the products of all solid-state irradiations can be correlated to the X-ray crystallography of the starting azide. 4 Acknowledgements: I would like to thank my family, my friends, and my co-workers for making this long process possible. I truly appreciate all the love and support you gave me before and during graduate school, and that you continue to give to this day. 5 Table of Contents List of Figures and Tables 3 Introduction 10 Objective 26 Preparation of Alkyl Azido Aryl Ketones 34 Chapter One Irradiation of Azides 1 in Solution and Solid-State Product Studies of Solution Irradiations of Azides 1 35 Product Studies of Solution Irradiation of 1-Azido Adamantane in the Prescence of Benzoyl Radicals 43 Product Studies of Solution Irradiations of Azide 1e 52 Product Studies of Solution Irradiations of 2-Azido-1-Phenyl Ethanone In an Oxygen Environment 57 Product Studies of Solution Irradiations of Azide 1e in an Oxygen Environment 58 Phosphorescene Emissions of Azides 1 59 Laser Flash Photolysis Experiments with 2-Azido-1-Phenyl Ethanone And Azides 1 60 Product Studies of Solid-State Irradiations of Azides 1a-1g 64 Product Studies of Solid-State Irradiations of Azide 1e 68 Product Studies of Solid-State Irradiations of Azide 1e in an Oxygen Environment 73 1 X-Ray Crystallography of Azides 1 75 Chapter Two Irradiation of Azides 2 in Solution and Solid-State Product Studies of Solution Irradiations of Azides 2 82 Product Studies of Solution Irradiations of Azide 2a in an Oxygen Environment 91 Phosphorescence Emissions of Azides 2 92 Laser Flash Photolysis Experiments with 3-Azido-1-Phenyl Propanone 94 Product Studies of Solid State Irradiations of Azides 2 95 Product Studies of Solid State Irradiations of Azides 2a in an Oxygen Environment 96 X-Ray Crystallography of Azides 2a and 2b 97 Chapter Three: Irradiation of Azides 3 in Solution Product Studies of Solution Irradiations of Azides 3 102 X-Ray Crystallography of Azide 3c 106 Phosphorescence Emission of Azide 3a 108 Laser Flash Photolysis Experiments of 4-Azido-1-Phenyl Butanone 109 Conclusions 111 Experimental Section 113 References 145 Appendix 1 149 2 List Of Figures Figure 1. Resonance Structures of the Azide Group Figure 2. Traditional Synthetic Uses of Azides Figure 3. New Synthetic Uses of Azides Figure 4. Reaction Pathways of Directly Excited Alkyl Azides Figure 5. Products of Gas Phase Thermolysis of N-Butyl Azide Figure 6. Pyrollosis Products of Azides 1 Figure 7. Reaction Pathways of Phenyl Azides Figure 8. Spin Allowed and Spin Forbidden Intramolecular Reactions of Triplet Alkyl Nitrenes Figure 9. Intermolecular Sensitization of Alkyl Azides Figure 10. Singlet Reactivity of Benzyl Azide Figure 11. Reaction Scheme of Benzyl Azide Sensitized with Acetophenone Figure 12. Intramolecular Sensitization of Napthalene with an Acetophenone Chromophore Figure 13. Cage Effect on Triplet Species Figure 14. Reaction Scheme Benzoin Methyl Ether (16) Figure 15. Solid-State Reactivity of Phenyl Azides Figure 16. Reaction Mechanisms of Phenyl Azides in the Solid-State 3 Figure 17. Intramolecular Sensitization of an Alkyl Azide with Acetophenone to Form a Triplet Alkyl Nitrene Figure 18. Possible π-orbital Overalp of the Aryl Ketone Chromophore and the Alky Azide Figure 19. Classes of Molecules Studied in This Reseach Figure 20. Competing Reactions of the Excited Triplet Ketone in Azides 1 Figure 21. Possible Reaction Pathway of Azides 2 Figure 22. Competing Reactions of Azides 3 Figure 23. Photoreactivity of Acetophenone in Solution Figure 24. Displacement Reaction of Alkyl Halides to Create Alkyl Azides Figure 25. Reaction Scheme of Azides 1 in Solution Figure 26. Formation of Benzoyl Radicals in Irradiation of Azides 1 Figure 27. Benzoyl Trapping of Molecular Triplet Oxygen Figure 28. Formation of Benzoyl Benzamide,(5) Figure 29. Products Isolated From Solution Irradiation of Azide 1g Figure 30. Observed Products of Solution Irradiation of 2-Azido 1-Phenylethanone at Two Temperatures Figure 31. Benzoyl Radical Attack of a Ground State Alkyl Azide to Give Benzoyl Benzamides Figure 32. Observed Product of Solution Irradiation of Darocur 1173, (13) 4 Figure 33. Direct Photolysis Products of 1-Azido Adamantane in the Presence of Methanol Figure 34. Possible Products of 1-Azido Adamantame and Benzoyl Radicals Figure 35. Energy Transfer from Darocur 1173 to 1-Azido Adamantane Figure 36. Solution Photochemistry of Benzoin Methyl Ether Figure 37. Observed Products of Solution Irradiations of 1-Azido Adamantane and 16 Figure 38. Solution Irradiation of Azide 1e Figure 39. The α-Cleavage Mechanism for the Formation of Deoxybenzoin, ( 9) Figure 40. Nitrene and Non-nitrene mechanism for formation of 1.2 Acyl Shift Product in Irradiations of Azide 1e Figure 41. Possible Intramolecular Shift Products for Azide 1e Figure 42. Oxygen Trapping of 2-Nitreneo-1-phenyl ethanone in Solution Figure 43. Low Temperature Phosphoresecnce Spectra of 4’Bromo Acetophenone and 2- Azido(4- Bromphenyl)ethanone in Ethanol Figure 44. Esimated Triplet Energy of Triplet Excited Alkyl Azides in Azides 1 Figure 45. Stern-Volmer Quenching of α-Azido Acetophenone with Isoprene Figure 46. Transient UV Spectra of 2-Nitreno 1-Phenylethanone Figure 47. Transient Spectra of 2-Azido-1-phenylethanone under Oxygen and Argon Atmosphere Figure 48. Kinetic Trace of 2-Nitreno 1-Phenylethanone 5 Figure 49. Possible Solid-State Mechanisms for Formation of 23 Figure 50. Reduction of 23 by Sodium Cyanoborohydride and BTPPTB Figure 51. Synthesis of N-Methyl Benzamides Figure 52. Observed Crystalline Photoreactivity of 2-Azido (4- methoxythiophenyl)ethanone Figure 53. Mechanism for Acid and Ester Formation in Crystalline Irradiations of Azides 1 Figure 54. Solid State Photoproduct of 2,6 Diphenyl Cyclohexanone Figure 55. Solid-State Reaction of Azide 1e at Low Conversion Figure 56. Observed Solid-State Photoproducts of Azide 1e in an Oxygen Atmosphere Figure 57. Unit Cell of Azide 1a Figure 58. Unit Cell of Azide 1c Figure 59. Unit Cell of Azide 1e Figure 60. Crystal Lattice of Azide 1a Figure 61. Crystal Lattice of Azide 1c Figure 62. Crystal Lattice of Azide 1e Figure 63. Products Isolated from Solution Irradiations of 3-Azido 1-Phenyl Propanone Derivatives. Figure 64. Products Isolated From Solution Irradiations of Azides 2 Figure 65. Reacitve Pathways of the Azo dimer ( 26 ) 6 Figure 66. Formation of Product 27 Figure 67. Nitrene Mechanism for the Formation of Product 30 Figure 68. Formation of N-centered Imine Radical Figure 69. Non-Nitrene mechanism for Formation of Product 30 Figure 70. Formation of Product 31 Figure 71. Products Resulting From α-Cleavage of Excited Chromophores of Azides 2 Figure 72. Synthesis of 1-(4-Chlorophenyl) 3-Nitro Propanone Figure 73. New Product Observed in O 2 Solution Irradiation of Azide 2a Figure 74.