Transition-metal-free Synthesis Of Sulfonamides And Substituted Pyridines

sulfonamides and pyridines with a wide range of bioactivities, which have significant applications in pharmaceutical, agrochemical and other fields. Therefore, the chemists are devoting to developing new methods for the synthesis of these two types of compounds all the time. Up to now, different kinds of methods for the synthesis of these two types of compounds has been reported. Nevertheless, developing simple, efficient, practical and environmentally friendly approaches for the synthesis of these two types of compounds is still needed. Our objectives are to synthesize sulfonamides and substituted pyridines under transition-metal-free conditions. The present dissertation is mainly focused on iodine-mediated coupling reaction for the preparation of sulfonamides and ammonium iodide-promoted cyclization reaction for the preparation of substituted pyridines:(1) Study on sulfonamides synthesis via iodine-mediated coupling reaction of sodium sulfinates with amines in an aqueous medium was made. The effects of different dosage of iodines,reaction medium, reaction temperature and other factors on the results of this reaction were investigated systematically, and the target products were characterized by GC-MS, 1H NMR, 13 C NMR and HR-MS. The experimental results indicate that sodium sulfinates with primary and secondary amines can be converted into the target products sulfonamides smoothly in high to excellent yields at room temperature when using iodine as a initiator and water as reaction medium. In addition, the investigations on reaction mechanism showed that this reaction proceeded through a free radical way, which was initiated by iodine. Initially, the sulfinic acid sodium salt reacts with iodine to afford the sulfonyl iodide intermediate. Then, the sulfonyl radical, which is formed by the homolysis of sulfonyl iodide intermediate, attacks the hydrogen of the amine to afford the desired sulfonamide by a coupling process. In the paper, a green, simple and efficient approach has been developed to synthesize sulfonamides. The advantages of this method include easily available raw materials, wide range of substrates, mild reaction conditions, high yields, simple operation, environmental friendliness and so on.(2) Investigation on substituted pyridines synthesis by ammonium iodide-promoted cyclization of ketones with ammonium acetate and DMSO was performed. The experimental results indicate that only symmetrical or unsymmetrical pyridines,or a mixture of two regioisomers are obtained when non-methyl ketones are used as substrates in this reaction, while methyl ketones always give unsymmetrical pyridines when they are used as substrates. The deuterium-labeling experiments indicated that both C4 and C6 in pyridine rings of the target products resulted from DMSO. The present work provides a new, simple and efficient method for the synthesis of various substituted pyridines.