A Methods For The Preparation Of2-acetobenzothiazoles And Dialkyl Benzothiazole-2-yl Phosphonates

a-Ketobenzothiazoles and dialkyl benzothiazole-2-yl phosphonates are both important in medical and biological fields, however, only a few methods, aiming to synthesize a-ketobenzothiazoles or dialkyl benzothiazole-2-yl phosphonates have been developed, which still suffer from obvious disadvantages such as harsh reaction condition, metallic residuals, complicated starting materials and too expensive reagents. Hydroperoxides are promising green reagent to overcome these problems and thus they are widely used in organic synthesis. The dialkyl H-phosphonates occupy a major position in organophosphorus chemistry as they are frequent intermediates in the synthesis of a variety of bioactive products.We herein present a new, green, one-step and metal-free approach for the synthesis of a-ketobenzothiazoles or dialkyl benzothiazole-2-yl phosphonates. Using benzothiazoles with readily available dialkylphisphites in the presence of tert-butyl hydroperoxide (TBHP), a-ketobenzothiazoles are formed; while by using benzothiazoles with dialkylphisphites in the presence of di-tert-butyl peroxide (DTBP), dialkyl benzothiazole-2-yl phosphonates are obtained. This method is shown in the following Scheme.Herein, we would like to disclose a very new aspect of H-phosphonate chemistry: due to its "flexibility", dialkyl phosphites would be unexpectedly efficient synthetic precursors in the preparation of the two kinds of very important benzothiazole derivatives, and hydroperoxides are testified to determine the direction of the reaction. The tautomeric equilibria between the phosphite and phosphonate form: tricoordinated phosphorus(Ⅲ) form and tetracoordinated phosphorus(Ⅴ) form, tend to be accounted for the complex reaction results, whereas hydroperoxide tend to be the "switch" of this process. The content of the thesis:(1) Two novel reactions are found and a proper reaction mechanism has been proposed, which concludes that the oxygen atom in the carbonyl group is generated form the hydroxyl radical in the reaction. Controlled tests are carried out to corroborate the mechanism by varying the peroxides in the reaction, performing31P NMR tracing and so on.(2) The reaction condition has been optimized:CH3CN is chosen as the optimal solvent; the best reaction temperature is80℃; the ratios of different reagents are optimized; this reaction gives the best yield after24h of reaction.(3)By using6-substituted benzothiazoles to react with different dialkylphisphites in the presence of tert-butyl hydroperoxide (TBHP) in CH3CN for24h under80℃, a-ketobenzothiazoles are synthesized. All the compounds are identified by NMR, HRMS tests.(4)By using6-substituted benzothiazoles to react with different dialkylphisphites in the presence of di-tert-butyl peroxide (DTBP) in CH3CN for24h under80℃, dialkyl benzothiazole-2-yl phosphonates are obtained. All the compounds are identified by NMR, HRMS tests.