Syntheses Of Thioamides And Amidines Via Beckmann Rearrangement Of Oximes

Beckmann rearrangement is an important reaction for the synthesis of amides with highly stereo-specificity, and has been applied successfully in the indusrial production of s-caprolactam and laurolactam. With the increasing demand on the environment, the production process can not meet the requirement of the development of green chemical industry. Therefore, Beckmann rearrangement of oximes has always been a research hot topic in the field of chemistry. Oximes, thioamides and amidines, as important organic intermediates, have been applied widely in the manufacture of medicines, pesticides and fine-chemicals. In this thesis, Beckmann rearrangement of oximes mediated by using phosphorus pentasulfide and p-toluene sulfonyl chloride were systematically studied, respectively. Main contents are as follows.Firstly, synthesis of oximes was systematically studied. Synthetic methods of oximes have been well documented at present, among which high yields are provided. Twenty-four oximes were obtained by the reaction of sodium acetate, inexpensive compound, as a base and 95%ethanol as the solvent in excellent yields (83～99%). The present approach has advantages of cheaper raw materials, milder reaction, shorter reaction time, and easier work-up operation. Optimization of the synthetic method for oximes was performed.Secondly, the conversion of ketoximes to thioamides via Beckmann rearrangement using phosphorus pentasulfide was systematically studied. The reaction conditions, such as solvent, temperature and the molor ratio of reactants, were tested in detail. An optimal reaction condtion was achieved such as 0.5 equivalent of phosphorus pentasulfide in anhydrous benzene at reflux temperature. Under the optimized conditions, seventeen thioamides were obtained by the reaction of ketoximes in the yields of 65～90%. The present approach has advantages of higher yields, easier work-up operation, and it has great generality for the transformation of substituted ketoximes.Thirdly, based on the results above, the conversion of aldoximes to primary thioamides via Beckmann rearrangement using phosphorus pentasulfide was systematically studied. The reaction conditions, such as solvent, temperature and the molor ratio of reactant, was tested in detail. An optimal reaction condtion was achieved such as one equivalent of phosphorus pentasulfide in anhydrous benzene at reflux temperature. Under the optimized conditions, twelve thioamides were obtained by the reaction of aldoximes with in the yields of 71～90%, The present approach has advantages of higher yields, shorter reaction time, and also provides a new synthetic method for the conversion of aldehydes to thioamides.Finally, the conversion of oximes to amidirres via Beckmann rearrangement mediated using by p-toluene sulfonyl chloride was systematically studied. Effects of leaving group, solvent, temperature and the molor ratio of reactants on the yield were tested in detail. An optimal reaction condtion was achieved such as 1.1 equivalent of p-toluene sulfonyl chloride and one equivalent of amines in anhydrous methylene chloride at reflux temperature. Under the optimized conditions, eight amidines were obtained by the reaction of ketoximes with in the yields of 78～91%. The present approach has advantages of lower toxicity, easier work-up operation, and also provides a green route for ketone to thioamides via Beckmann rearrangement.