“One-pot” Synthesis of Carbamates via Curtius Rearrangement by Kwaku Kyei-Baffour Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Chemistry Program YOUNGSTOWN STATE UNIVERSITY August, 2014 “One-pot” Synthesis of Carbamates via Curtius Rearrangement Kwaku Kyei-Baffour I hereby release this thesis to the public. I understand that this thesis will be made available from the OhioLINK ETD Center and the Maag Library Circulation Desk for public access. I also authorize the University or other individuals to make copies of this thesis as needed for scholarly research. Signature: Kwaku Kyei-Baffour, Student ĂƚĞ Approvals: Dr. Peter Norris, Thesis Advisor Date Dr. John Jackson, Committee Member Date Dr. Nina Stourman, Committee Member Date Dr. Sal Sanders, Associate Dean of Graduate Studies Date Thesis Abstract In this thesis, acyl chlorides were successfully converted to their corresponding carbamates via Curtius rearrangement in a novel “one-pot” synthesis procedure that uses p- nitrobenzenesulfonyl azide as the azide nucleophile source. In the process alkyl esters were also synthesized as the associated by-product. The thesis also deals with the “one-pot” synthesis of acyl azides from acyl chlorides. iii Acknowledgements I wish to offer my special gratitude and sincerest appreciation to my supervisor, Dr. Peter Norris, for his farsighted guidance, invaluable instruction and teaching, patience and continuous encouragement throughout the course of this work and my graduate program. I am also very thankful to my thesis committee members, Dr. John Jackson and Dr. Nina Stourman. Not only have you both been tremendously helpful and supportive as thesis committee members, you also took the time to step outside of your roles as instructors and become closer mentors. Thank you. I am also grateful to my fellow graduate students, faculty and staff members of the YSU chemistry department for the knowledge they imparted in me, and also for the friendly and pleasant association throughout my stay at Youngstown State University. Special thanks to Collins Aboagye and Amanda Sacco. My heart felt gratitude also goes to the past and present members of the Norris research group: Cephas Afeke, Mike Delost, Angela Kwarkoh, Jen Moore, Caleb Tatebe, Chris Copeland, Omadee Curry, Heather Folkwein and Joseph Mihaly for their help throughout my studies at YSU. Special thanks to Mike and Cephas for always being there to help, to talk to, and to share ideas. I am also very thankful to the wonderful family I have at Westview Church of Christ. Thanks a lot for all the help you gave me in helping make this journey a very memorable one. Special thank you to The Kurishes, The Warfels, The Brewers, The Biggs, Patty Williams, Sandy Butler, and Janice Schroyer. iv I will also like to thank Vincent, Abigail and Victoria Zame for all the help they gave me throughout my studies. Not forgetting all the members of the YSU African Students Union. Special thanks also goes to the wonderful crop of friends I made here in Youngstown. Thank you Aashish Shrestha, Nisha Singh, Rachelle Fair, Carmen Moradian, Sabine Moradian, and Victoria Boulos for always being there to inspire and motivate me, for always putting a smile on my face, for offering your ears to my infrequent whining and for all the positive distractions you gave me. I couldn’t have imagined how this journey would have turned out without you guys. Lastly, and certainly not least I would like to thank my family. Without you, I wouldn’t be where I am. Words cannot express how blessed I am to be able to call myself a son and a brother to you all. Thank you so much for always being there to support and encourage me. I know with the Almighty God on our side we will continue to soldier on from grace to grace. v Table of Contents Title Page………………………………………………………………………………………………………………………………..…i Signature Page…............................................................................................................................ii Thesis Abstract……………………………………………………………………………………………………………………….…iii Acknowledgements……………………………………………………………………………………………………………….…iv Table of Contents………………………………………………………………………………………………………………..…...v List of Equation………………………………………………………………….........................................................vi List of Figures……………………………………………………………………………………………………………………..…….vii List of Schemes…………………………………………………………………………………………………………………………viii Introduction……………………………………………………………………………………………………………………..……..…1 Statement of Problem………………………………………………………............................................................8 Results and Discussion……………………………………………………………………………………………………………..…9 Experimental………………………………………………………………………………………………………………………….…29 References…………………………………………………………………………………………………………………………….….47 Appendix A…IR/NMR data………………………………………………………...................................................57 vi List of Equations Equation 1: General synthesis of acyl azides from the corresponding N-acyl benzotriazoles. Equation 1: General synthesis of acyl azides from aliphatic and aromatic aldehydes. Equation 3: Synthesis of acyl azides from carboxylic acids. Equation 4: Proposed method for the synthesis of acyl azides from acyl chlorides using p-NBSA. Equation 5: Curtius rearrangement of acyl azides to carbamates. Equation 6: “One-pot” protocol for the preparation of tert-butyl carbamates (Lebel and Leogane). Equation 7: Conversion of acyl azides into carbamates. Equation 8: Synthesis of carbamates of various sugar and other functionalities using their corresponding acids (Iklegami and co-workers). Equation 9: Proposed method for the “one-pot” synthesis of carbamates via Curtius rearrangement. Equation 10: Conversion of para-nitrobenzenesulfonyl chloride (1) to para-nitrobenzenesulfonyl azide (2). Equation 11: Conversion of 4-nitrobenzoyl chloride (3) to 4-nitrobenzoyl azide (4). Equation 12: Conversion of 3,5-dinitrobenzoyl chloride (5) to 3,5-dinitrobenzoyl azide (6). Equation 13: Conversion of 4-methoxybenzoyl chloride (7) to 4-methoxybenzoyl azide (8). Equation 14: Conversion of 4-nitrobenzoyl chloride (3) to ethyl (4-nitrophenyl) carbamate (9). Equation 15: Conversion of 4-nitrobenzoyl chloride (3) to isopropyl (4-nitrophenyl) carbamate (10). Equation 16: Conversion of 4-nitrobenzoyl chloride (3) to propyl (4-nitrophenyl) carbamate (11). Equation 17: Conversion of 4-nitrobenzoyl chloride (3) to butyl (4-nitrophenyl) carbamate (12). Equation 18: Conversion of 3,5-dinitrobenzoyl chloride (5) to ethyl (3,5-dinitrophenyl) carbamate (13). Equation 19: Conversion of 3,5-dinitrobenzoyl chloride (5) to butyl (3,5-dinitrophenyl) carbamate (14). Equation 20: Conversion of 4-nitrobenzoyl chloride (3) to ethyl 4-nitrobenzoate (15). vii Equation 21: Conversion of 4-nitrobenzoyl chloride (3) to propyl 4-nitrobenzoate (16). Equation 22: Conversion of 4-nitrobenzoyl chloride (3) to isopropyl 4-nitrobenzoate (17). Equation 23: Conversion of 3,5-dinitrobenzoyl chloride (5) to ethyl 3,5-dinitrobenzoate (18). List of Figures Figure 1: Resonance structures for a general organic azide. Figure 2: Structure of para-nitrobenzenesulfonyl azide (p-NBSA) Figure 3: 1H NMR of para-nitrobenzenesulfonyl azide (2). Figure 4: 13C NMR of para-nitrobenzenesulfonyl azide (2). Figure 5: IR spectrum of para-nitrobenzenesulfonyl azide (2). Figure 6: 1H NMR of 4-nitrobenzoyl chloride (3). Figure 7: 13C NMR of 4-nitrobenzoyl chloride (3). Figure 8: 1H NMR of 3,5-dinitrobenzoyl chloride (5). Figure 9: 13C NMR of 3,5-dinitrobenzoyl chloride (5). Figure 10: 1H NMR of 4-methoxybenzoyl chloride (7). Figure 11: 13C NMR of 4-methoxybenzoyl chloride (7). Figure 12: 1H NMR of 4-nitrobenzoyl azide (4). Figure 13: 13C NMR of 4-nitrobenzoyl azide (4). Figure 14: 13C NMR of 4-nitrobenzoyl azide (4). Figure 15: 1H NMR of 3,5-dinitrobenzoyl azide (6). Figure 16: 13C NMR of 3,5-dinitrobenzoyl azide (6). Figure 17: 13C NMR of 3,5-dinitrobenzoyl azide (6). Figure 18: 1H NMR of 4-methoxybenzoyl azide (8). Figure 19: 13C NMR of 4-methoxybenzoyl azide (8). Figure 20: IR spectrum of 4-methoxybenzoyl azide (8). Figure 20: 1H NMR of ethyl (4-nitrophenyl) carbamate (9). viii Figure 21: 13C NMR of ethyl (4-nitrophenyl) carbamate (9). Figure 22: 1H NMR of isopropyl (4-nitrophenyl) carbamate (10). Figure 23: 1H NMR of isopropyl (4-nitrophenyl) carbamate (10). Figure 24: 1H NMR of propyl (4-nitrophenyl) carbamate (11). Figure 25: 13C NMR of propyl (4-nitrophenyl) carbamate (11). Figure 26: 1H NMR of butyl (4-nitrophenyl) carbamate (12). Figure 27: 13C NMR of butyl (4-nitrophenyl) carbamate (12). Figure 28: 1H NMR of ethyl (3,5-dinitrophenyl) carbamate (13). Figure 29: 13C NMR of ethyl (3,5-dinitrophenyl) carbamate (13). Figure 30: 1H NMR of butylyl (3,5-dinitrophenyl) carbamate (14). Figure 31: 13C NMR of butyl (3,5-dinitrophenyl) carbamate (14). Figure 32: 1H NMR of ethyl 4-nitrobenzoate (15). Figure 33: 13C NMR of ethyl 4-nitrobenzoate (15). Figure 34: 1H NMR of propyl 4-nitrobenzoate (16). Figure 35: 1H NMR of propyl 4-nitrobenzoate (16). Figure 36: 1H NMR of isopropyl 4-nitrobenzoate (17). Figure 37: 1H NMR of ethyl 3,5-dinitrobenzoate (18). Figure 38: 13C NMR of ethyl 3,5-dinitrobenzoate (18). Figure 39: 1H NMR of butyl 3,5-dinitrobenzoate (19). Figure 40: 13C NMR of butyl 3,5-dinitrobenzoate (20). List of Schemes Scheme 1: Proposed mechanism for acyl azide formation. Scheme 2: Proposed mechanism for “one-pot” synthesis of carbamates via Curtius rearrangement. Scheme 3: Proposed mechanism for alkyl ester formation. ix INTRODUCTION -