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Photochemistry of 5-Membered Heteroaryl(Trifluoromethyl)Carbenes In University of Nevada, Reno “Photochemistry of 5-Membered Heteroaryl(trifluoromethyl)carbenes in Low Temperature Matrices” A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry by Rajendra Ghimire Dr. Robert S. Sheridan/Dissertation Advisor December, 2012 THE GRADUATE SCHOOL We recommend that the dissertation prepared under our supervision by RAJENDRA GHIMIRE entitled Photochemistry of 5-Membered Heteroaryl(trifluoromethyl)carbenes in Low Temperature Matrices be accepted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Robert S. Sheridan, Ph.D., Advisor Vincent J. Catalano, Ph.D., Committee Member Benjamin T. King, Ph.D., Committee Member Jonathan Weinstein, Ph.D., Committee Member James H. Trexler, Ph.D., Graduate School Representative Marsha H. Read, Ph. D., Dean, Graduate School December, 2012 i Abstract We have explored the photochemical reactions of 3-benzothienyl(trifluoromethyl)-, 3-N-methyl-indolyl(trifluoromethyl)-, 2-N-methyl-indolyl(trifluoromethyl)-, benzo- thiazolyl(trifluoromethyl)-, and benzoxazolyl(trifluoromethyl)carbenes in low temperature N 2 matrices. The 3-benzothienyl(trifluoromethyl)carbene rearranged to several new reactive intermediates such as bicyclic intermediate, ring expanded carbene and spiro product, which were not observed or characterized before. The 3- benzothienyl(trifluoromethyl)diazirine led us to a new realm of UV-vis transparent diazirines, which behave as normal diazirine photochemically, but have very weak nπ∗ absorptions which are not visible in experimental UV-vis spectra. Also, we were able to synthesize diazirine precursors of both 2- and 3- N-methyl- indolylcarbene and observed and characterized their carbenes spectroscopically. All three carbenes mentioned above are ground state singlets. In the case of the benzothiazole and benzoxazole system, we were able to observe and characterize both syn and anti conformers of diazirine in low temperature matrices. The CF 3 carbenes behaved similarly to chloro carbenes photochemically in both benzothiazole and benzoxazole, but the CF 3 carbenes were triplet ground state compared to the singlet chloro carbenes. ii We believe our work will add to understanding of the reactivity and electronic states of 5-membered heteroaryl carbenes. Application wise, synthesis of heteroaryl CF 3 diazirines might add to the possibility of new photoaffinity labeling agents. Acknowledgements My sincere and deepest gratitude goes to my advisor, Professor Robert S. Sheridan, for his extraordinary patience and exceptional mentoring throughout my graduate career, in both academic and personal areas. His unconditional support and guidance have helped me to better prepare for upcoming challenges, in both personal and professional career, and I hope it continues. I want to thank previous and current Sheridan group members, Dr. Peter Zuev, Dr. Andrea Song, Dr. Jian Wang, Chengliang Zhu, Pei Wang, Binya Yang, Emilia Groso, Danielle Poteete, Rachel Lecker and Sean Ross for their friendship, support and guidance. I want to thank my committee members for their time, patience and continuous guidance. Finally, I want to thank my friends and family. My heartfelt thanks goes to my parents, my brother and especially for my wife, Shikha, who has been with me, with love, support and patience, at all times. iii Table of Contents Abstract i Acknowledgements ii Table of Contents iii List of Schemes vii List of Figures xii Introduction 1 1. Background 1.1. Methylene 2 1.2. Stability and Substitution Effect 5 1.3. Philicity of Carbenes 7 1.4. Observation and Characterization 9 1.5. Applications 11 1.5.1. Photoaffinity labeling 12 1.6. Reactivity of Carbenes 13 1.6.1. Addition 14 1.6.2. Rearrangement 15 1.7. Phenylcarbene 15 1.7.1. Investigation of C 6H7 potential energy surface 21 1.7.2. Phenylchlorocarbene 22 iv 1.7.3. Tolylcarbenes 23 1.8. Naphthylcarbenes 26 1.8.1. Naphthylchlorocarbenes 34 1.9. Vinylcarbenes 36 1.10. Heteroarylcarbenes 38 1.10.1. Pyridylcarbenes 38 1.10.2. Investigation of C 6H7N potential energy surface 44 1.10.3. Naphthylnitrenes 45 1.10.4. 5-membered heteroarylcarbenes 46 1.11. Cyclic Cumulenes 60 1.11.1. 1,2-cyclohexadiene 61 1.11.2. Cumulene From Heteroarylcarbenes 63 1.11.2.1. Atomic Carbon Reaction 63 1.11.2.2. Theoretical study of 6-membered allene 65 1.11.3. Direct observation and characterization of cyclic cumulene 68 1.11.3.1. Observation and characterization of didehydropyran 68 1.11.3.2. Observation and characterization of didehydrothiopyran 70 1.11.3.3. Comparative study of oxo cumulene vs thio cumulene 71 1.11.4. Direct observation and characterization of Didehydrobenzoxazine 74 1.11.4.1. B3LYP energies of benzofuran and benzoxazole system 75 1.11.5. Observation and characterization of didehydrobenzothiazine 75 1.11.6. Observation and characterization of CF 3 didehydrobenzothiopyran 78 v 1.11.7. CF 3 vs Cl cumulene 79 1.12. Application of heteroarylcarbenes 80 2.Research Objective 83 2.1. Trifluoromethyl diazirines 85 2.2. 3-Heteroarylcarbenes 85 3.Result and Discussion 87 3.1. 3-benzothienyl(CF 3)carbene 87 3.1.1. Synthesis 88 3.1.2. Twisted diazirines 91 3.1.3. Observation and characterization of 3-benzothienyl(CF 3)carbene 96 3.1.4. Trapping reactions of 3-benzothienyl(CF 3)carbene 103 3.1.5. Photochemical rearrangement of 3-benzothienyl(CF 3)carbene 106 3.1.6. Deuterium labeling 115 3.1.7. Possible Mechanisms 119 3.1.8. Study of C 10 H5F3S Potential Energy Surface 120 3.2. N-Methyl-2-indolyl(CF 3)diazirine 122 3.2.1. Synthesis of N-Methyl-2-indolyl(CF 3)diazirine 124 3.2.2. Direct observation of N-Methyl-2-indolyl(CF 3)carbene 128 3.2.3. Photochemical rearrangement of N-Methyl-2-indolyl(CF 3)carbene 133 3.2.4. Study of C 11H8F3N Potential Energy Surface 138 3.3. N-Methyl-3-indolyl(CF 3)carbene 143 3.3.1. Synthesis of N-Methyl-3-indolyl(CF 3)diazirine 143 vi 3.3.2. Direct observation of N-Methyl-3-indolyl(CF 3)carbene 147 3.3.3. Trapping reactions of N-Methyl-3-indolyl(CF 3)carbene 150 3.3.4. Photochemical rearrangement of N-Methyl-3-indolyl(CF 3)carbene 151 3.3.5. Study of C 11H8F3N Potential Energy Surface 155 3.4. Benzothiazolyl(CF 3)carbene 158 3.4.1. Matrix isolation study of benzothiazolylchlorodiazirine 159 3.4.2. Synthesis of benzothiazolyl(CF 3)diazirine 163 3.4.3. Observation and characterization of syn and anti diazirine 166 3.4.4. Photochemical rearrangement of benzothiazolyl(CF 3)carbene 172 3.4.5. Trapping reactions of benzothiazolyl(CF 3)carbene 179 3.4.6. Study of C9H4N3F3S potential energy surface 181 3.5. Benzoxazolyl(CF 3)carbene 183 3.5.1. Synthesis of benzoxazolyl(CF 3)diazirine 183 3.5.2. Observation and characterization of syn and anti diazirine 186 3.5.3. Observation and characterization of benzoxazolyl(CF 3)carbene 189 3.5.4. Photochemical rearrangement of benzoxazolyl(CF 3)carbene 193 3.5.5. Trapping reaction of benzoxazolyl(CF 3)carbene 198 3.5.6. Study of C9H4N3F3O potential energy surface 199 3.6. Conclusion 201 3.7. Experimental 203 3.7.1. General 203 3.7.2. Matrix Isolation 203 vii 3.7.3. DFT Calculation 205 3.7.4. Synthesis 206 References 227 Supporting Information (B3LYP 6-31G**) 231 B3LYP 6-31+ G** Computed vibrational frequencies and intensities 359 NMR Spectra 389 List of Scheme Scheme 1 .Thermolysis of phenyl diazomethane 1 to heptafulvalene 2 16 Scheme 2 .Thermolysis of phenyl diazomethane 1 16 Scheme 3 .Bicyclic product 6 proposed as an intermediate to 4 and 5 17 Scheme 4 .Matrix isolation study of phenyl diazomethane 1 diazirine 8 18 Scheme 5 .Matrix isolation study summary of phenyl carbene 3 20 Scheme 6.Thermal dimerization of 5 to 2 via 17 21 Scheme 7 .Phenylchlorocarbene 18 rearrangement to allene 19 22 Scheme 8 .Trapping reaction of phenylchlorocarbene 18 with O 2 23 viii Scheme 9 .Thermolysis of tolyldiazomethanes 26 , 27 and 28 24 Scheme 10 .Tolylcarbene rearrangement 25 Scheme 11 .Flash vacuum pyrolysis of naphthyldiazomethane 41 and 42 27 Scheme 12 .Interconversion of napthylcarbene 39 and 44 28 Scheme 13 .Matrix isolation study of naphthyl diazomethane 41 and 42 29 Scheme 14 .Interconversion of 2-naphthylcarbene 44 into bicyclic intermediate 48 30 Scheme 15 .Interconversion of 1-naphthylcarbene 39 into bicyclic product 46 31 Scheme 16 .Spectroscopic evidence of benzocycloheptatetraene 45 32 Scheme 17 .Matrix isolation study of benzodiazocycloheptatriene 53 33 Scheme 18 .Matrix isolation study of benzocycloheptadienyldiazomethane 54 34 Scheme 19 .Matrix isolation study of1-naphthylchlorodiazirine 56 35 Scheme 20 .Matrix isolation study of 2-naphthylchlorodiazirine 59 35 Scheme 21 .Matrix isolation study of singlet vinylchlorocarbene 65 37 Scheme 22 .Matrix isolation study of cyclopentylchlorodiazirine 68 38 Scheme 23 .Interconversion of pyridylcarbene 75 and phenylnitrene 76 39 Scheme 24 .Matrix isolation study of pyridylcarbene interconversion 40 ix Scheme 25 .Rearrangment of pyridylcarbene and phenylnitrene 41 Scheme 26 .Cyclic ylide 86 a possible link between carbenes 85 and 75 42 Scheme 27 .Wentrup matrix isolation study of pyridyl carbenes rearrangement 43 Scheme 28 .Matrix isolation study of deuterated 3-pyridylcarbene 93 44 Scheme 29 .Matrix isolation study of naphthylazides 97 and 98 46 Scheme 30 .Pyrolysis and trapping reaction of furyldiazomethane 108 47 Scheme 31 .Carbon addition reaction with furan 48 Scheme 32 .Matrix isolation study of furyldiazomethane 108 48 Scheme 33 .First observation and characterization of furylchlorocarbene 115 49 Scheme 34 .Thermolysis and trapping reactions
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