A one-pot, microwave-assisted synthesis of aryl ureas and carbamates using HATU and HOSA
| dc.contributor.author | Szymanski, Paul | |
| dc.contributor.examiningcommittee | Lakowski, Ted (Pharmacy) | en_US |
| dc.contributor.examiningcommittee | Sorensen, John (Chemistry) | en_US |
| dc.contributor.supervisor | Tranmer, Geoff | |
| dc.date.accessioned | 2023-01-05T18:01:08Z | |
| dc.date.available | 2023-01-05T18:01:08Z | |
| dc.date.copyright | 2023-01-03 | |
| dc.date.issued | 2023-01-03 | |
| dc.date.submitted | 2023-01-03T10:35:53Z | en_US |
| dc.degree.discipline | Pharmacy | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | The synthesis of ureas and carbamates has been accomplished using a wide variety of approaches over the past several decades. However, the development of such methods continues to be an important research topic as a result of advancing technology as well as efforts to reduce cost and environmental impact. Bao et al. (2018) previously reported a new synthetic method for aryl ureas and carbmates which is defined by the combination of benzoyl chloride with various nucleophilic starting materials. However, several disadvantages have been identified with the use of benzoyl chloride which can compromise product yield. Therefore, a revised method which replaced the role of benzoyl chloride with the combination of a carboxylic acid and HATU was developed. Once the parameters of the HATU method had been optimized, its versatility was tested through the synthesis of twenty aryl ureas and five aryl carbamates. In addition, ten of the twenty aryl ureas were synthesized a second time using a different combination of starting materials in order to better understand how reagent selection affects product yield. Although none of the aryl carbamate yields exceeded 70%, several aryl urea yields above 90% were obtained. After testing of the HATU method was completed, its alternative application as an approach to primary amine synthesis was briefly explored by using water as the nucleophilic starting material. However, all attempts to optimize the application resulted in negligible product formation. Afterwards, a total synthesis for the anticancer drug Sorafenib was designed using aspects of the HATU method. However, employment of the total synthesis revealed that only the Sorafenib precursors could be successfully prepared through this approach. It is possible that the effectiveness of the HATU method could be improved with additional refinements to both the synthetic and purification procedures. Also, its use in amine preparation and the total synthesis of drugs requires further investigation before such applications can be considered practical. | en_US |
| dc.description.note | February 2023 | en_US |
| dc.description.sponsorship | Research Manitoba, U of M Pharmacy | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/37055 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Synthesis | en_US |
| dc.subject | Urea | en_US |
| dc.subject | Carbamate | en_US |
| dc.subject | HATU | en_US |
| dc.subject | HOSA | en_US |
| dc.title | A one-pot, microwave-assisted synthesis of aryl ureas and carbamates using HATU and HOSA | en_US |
| dc.type | master thesis | en_US |
| local.subject.manitoba | no | en_US |
| oaire.awardTitle | Discovery Grant | en_US |
| project.funder.identifier | https://doi.org/10.13039/501100000038 | en_US |
| project.funder.name | Natural Sciences and Engineering Research Council of Canada | en_US |