The Synthesis Of Some Nitrogen Heterocyclic Compounds And Derivatives

The nitrogen heterocycles are widely present in bioactive natural products and pharmaceutical compounds with physiological activity. Compounds with thiazole, indole ketone and piperidine backbone structures are of great value in synthesis because of their unique biological activities and pharmacological activities.The article is divided into five parts as follows:In chapter1, A general review on synthesis of nitrogen heterocyclic compounds, especially the hetero aromatic compounds containing nitrogen heteroatom, such as thiazole, indole ketone and piperidine ketone.In chapter2, Synthesis of2-aryl benzothiazoles via K2S2O8mediated oxidative condensation of benzothiazoles with aryl aldehydes has been developed. In this reaction we only used K2S2O8as the cheap oxidant, DMSO/H2O as the solvent and set the temperature at100℃. We found that the reaction actually involved the oxidative opening of the thiazole ring to form2-amino thiophenol under the standard conditions. Then2-amino thiophenol would react with benzaldehyde to generate unstable imine compounds, and after cyclization and oxidation reaction,2-aryl benzothiazole was formed. Benzothiazoles and aryl aldehydes are commercial avilable, so with our protocol we can synthesis of2-aryl benzothiazoles easily.In chapter3, Synthesis of2-aryl benzothiazoles via K2S2O8mediated oxidative condensation of benzothiazoles with benzylamines or phenylglyoxylic acids were shown. This reaserch is a complement for the previous study. In our reaction, we also used K2S2O8as the oxidant, DMSO/H2O as the solvent and set the temperature at100℃. By changing the addition order of K2S2O8, we are able to synthesize2-aryl benzothiazoles from glyoxylic acids with benzothiazoles; we found that the addition of a stoichiometric amount of tBuOK promoted the conversion of benzylamine into benzaldehyde, which will subsequently react and then with benzothiazole to produce2-aryl benzothiazole.In chapter4, Pd-catalyzed decarboxylative coupling of aryl carboxylic acids with unsaturated piperidone was discussed. A variety of electron-withdrawing and electron-donating group substituted aryl carboxylic acids were employed to react with unsaturated piperidone forming two different kinds of products. Two proposed mechanism of the cross-coupling between the unsaturated piperidones and aryl carboxylic acids are presented according to the results. The palladium catalyzed decarboxylative coupling between electron-withdrawing group substituted aryl acids and unsaturated piperidone is based on Heck type reaction, and palladium catalyzed decarboxylation coupling between electron-donating group substituted aryl carboxylic acids and unsaturated piperidone is based on C-H activtion.In chapter5, Synthesis of perfluoroalkyl substituted oxindoles via photoredox catalyzed perfluoroalkylation of N-arylacrylamides with RFI was demonstrated. Based on the results obtained, we decided to use1.0equiv of N-phenyl-methyl acrylamide,3.0equiv of RFI,5%mol eosin Y as the catalyst,1.0equiv of Cs2CO3as the base, DMA as the solvent, and set the temperature at65℃with two26W light bulb as the standard conditions. By adding TEMPO, we confirmed the reaction is a free radical reaction, and proposed a possible reaction mechanism based on this. RFI generated RF free radical under visible light and attacked N-arylacrylamides compounds to form a free radical intermediate. The resultant free radical intermediate will be transformed into perfluoroalkyl substituted oxindole after cyclization and oxidation.In chapter6, Pd-catalyzed decarboxylative ortho-acylation of O-methyl oximes with phenylglyoxylic acids was discussed. Based on numerous experiments, we used10%mol Pd(OAc)2as the catalyst,3.0equiv of (NH4)2S2O8as the oxidant, diglyme as the solvent, and set the temperature at35℃as the standard conditions. With the optimized protocol in hand, we also explored the scope and limitation of the reaction, and we found that the reaction worked well between different benzaldoximes and phenylglyoxylic acids. Meanwhile, we have done some control reactions to probe the possible reaction mechanism. We think the critical step of the reaction may actually involve a Pd (Ⅲ) or Pd (Ⅳ) intermediate, not a Pd (Ⅱ) intermediate. This reaction proceeded satisfactorily at ambiant temperature while using cheap (NH4)2S2O8as the oxidant.