Sulfonamides · The Catalytic Synthesis of Sulfonamides
FP7 — People (Marie Curie Actions)
- Duration
- 2012-09-17 → 2014-09-16
- EU contribution
- €209,033
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
The Catalytic Synthesis of Sulfonamides
We have been working on the application of transition-metal catalysts for the synthesis of sulfonamides via carbon-hydrogen activation and carbon-sulfur bond formation, by using DABSO, an air-stable, easy-handled solid SO2 surrogate. We started by evaluating reaction system according to the analogy of carbonylative carbon-hydrogen bond activation reaction through all the reaction parameters, such as “SO2” source, palladium source, ligand, base, solvent, additive and temperature. Unfortunately, under a wide variety of different conditions no desired product was observed, and the majority of reactions returned only starting material (1-methylindole) and decomposed hydrazine (in case of N,N-dialkylhydrazine) or homocoupling product (in case of aryl boronic acid). This is presumably due to a problem of coexistence of oxidant and reductant in the reaction system. We have also investigated the application of DABSO and ortho-iodo benzyl amines for the preparation of sulfonamides via intramolecular reactions using palladium catalysis. Due to the ortho-positioning causing steric hindrance, poor nuclephilic properties of secondary amine, and the excess of DABCO in the reaction, no desired transformation was observed under various conditions, but starting material was recovered unchanged, or the iodo-substituent was reduced in reaction system at high temperature. Morever, we have explored a two-pot, three-step simple, potentially green synthetic methodology for the conversion of readily accessible N-aminosulfonamides to the corresponding sulfonamides without transition metal catalysis under mild reaction conditions in aqueous media, with good functional group tolerance. We have also exmamined the use of DABSO for the hydrosulfination of functionalized alkenes under palladium catalysis to generate sulfonic acids or sulfonate esters via one-step synthetic methodology without employing toxic, gaseous SO2. Due to the instability and dissociation of formed sulfonic acid, and harsh reaction condition, this procedure is quite limited for further transformation. However, we did developed another interesting reactions occured between alcohol and sulfur dioxide under basic condition. It could be performed at room temperature and have good functional group tolerance. In addition, we have inverstigated the methodology for the synthesis of useful heterocyclic sulfones by using DABSO, and we have currently got some important results. Further completion work is undergoing.
Data: CORDIS, © European Union
Project objective
Sulfonamides are functional groups that feature in a significant number of pharmaceuticals, with applications in a variety of indications. Conventional syntheses of sulfonamides usually involve two or three synthetic operations, and often feature low-yielding steps. The chemistry involved also limits the substrates that can be converted to sulfonamides. This proposal seeks to develop an alternative synthesis of sulfonamides; the proposed synthesis will be achieved in a single operation, employ readily available reagents and substrates, and be conducted under mild conditions. The key to the proposed synthesis is to employ a three-component synthesis involving the catalytic combination of an aryl halide, an amine and sulfur dioxide. Achieving the synthesis in a single operation will have significant advantages in terms of waste production, energy required, as well as the time needed to prepare the desired sulfonamides. These are important considerations for both small scale discovery synthesis, as well as the large scale synthesis of these materials. The developed methodology should also be applicable to the preparation of related sulfonate esters and sulfones. The latter stages of the project will explore the application of the developed method to the synthesis or selected target structures that are difficult to access using conventional methods, and to the synthesis of heterocycles.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union