Background: Thioamides are an important class of sulfur-containing organic compounds that have attracted considerable attention due to their wide range of applications as key synthetic intermediates and their significant biological and pharmaceutical activities. Despite the availability of various synthetic approaches, many existing methods suffer from drawbacks such as harsh reaction conditions, long reaction times, limited substrate scope, or the use of expensive and toxic catalysts. Therefore, the development of simple, efficient, and scalable strategies for the synthesis of primary and secondary thioamides using readily available starting materials remains highly desirable.
Objective: The main objective of this study was to develop practical and versatile methodologies for the selective synthesis of primary and secondary thioamides under relatively mild conditions. Particular emphasis was placed on the use of azides as nitrogen sources and thiols or disulfides as sulfur sources, aiming to achieve high efficiency, operational simplicity, minimal or no catalyst requirement, and scalability to larger reaction scales.
Methodology: In this work, two complementary synthetic routes were investigated. In the first approach, benzyl mercaptans or their corresponding disulfides were reacted with sodium azide in dimethyl sulfoxide (DMSO) at 120 °C without any catalyst, affording primary thioamides within approximately 3 h. The scalability of this method was also evaluated through gram-scale reactions. In the second approach, alkyl azides were employed as nitrogen sources in the presence of sodium thiosulfate pentahydrate as a catalyst under otherwise similar conditions, leading to the formation of secondary thioamides. The reactions were carried out at 120 °C with an average reaction time of about 3 h, and the products were isolated and characterized using standard spectroscopic techniques.
Findings
The results demonstrated that the catalyst-free protocol efficiently afford
