Novel Synthesis Of Benzothiazole Derivatives By Disulfide And Aldehyde As Raw Materials

Benzothiazole and its derivatives are the most important heterocyclic compounds, which are extensively presented in natural products and mainly used in medicine, agriculture, industry and other fields. In recent years, as more and more benzothiazole compounds have been finding out, the synthetic method has been widespread concern.Benzothiazole derivatives were mainly synthesized by the starting material of o-aminobenzenethiol, 2- haloaniline, thioamide or thiourea. However, o-aminobenzen ethiol was not stable and readily oxidized to form disulfide, the synthetic route of thioamide and thiourea as raw material is long and higher production cost. There fore, the synthesis of benzothiazole derivatives from stable and readily available d isulfide as raw material had become a research focus of organic chemistry.This dissertation is a new kind of method to synthesize benzothiazles from disulfides and aldehyde mediated by sodium sulfide in one-pot tandem reactions. This synthetic method has the advantages of simple operation, environmentally friendly and higher yield.The main work of this dissertation is shown as follows:1. The new method for the synthesis of benzothiazole derivatives was produced by the reaction of disulfides, aromatic aldehyde, sodium sulfide and sodium bicarbonate or acetic acid by DMF as a solvent. By optimizing the reaction conditions, the optimal conditions to synthesize benzothiazole derivatives was obtained, which the ratio of disulfide, aromatic aldehydes, sodium sulfide and sodium bicarbonate(acetic acid) was 1∶2∶0.2-0.5∶0.2-0.5 with DMF as the solvent at 100℃, firstly stirred for 6h under an inert atmosphere, then stirred for 2h in the air, got the benzothiazole derivatives in the yield of 73%-97%.2. The new method for the synthesis of benzothiazole derivatives was produced by the reaction of disulfides, aldehyde and sodium sulfide, using water as a solvent, in the catalytic carbonate. By optimizing the reaction conditions, the optimal conditions to synthesize benzothiazole derivatives was obtained, which the ratio of disulfide, aldehydes and sodium sulfide was 1∶2∶0.5 with H2 O as the solvent at 80℃, stirred for 24 h under carbon dioxide gas at 2 MPa, got the benzothiazole derivatives in the yield of 63%-90%.3. To investigate the versatility of this kind of method, inspect the influence of aldehydes with different substituents for the reaction. Through experiments found that either the electron-withdrawing or electron donating groups, the target compounds can be obtained in higher yields. So, the versatility of this reaction is good. By the above experiments, twelve kinds of benzothiazole derivatives were obtained, and in order to determine the structure of the compounds obtained, the synthetic compounds were characterized by mass spectrometry, nuclear magnetic resonance and so on.4. The possible reaction mechanism of this method was detected by the LC-MS and HNMR experiments. Through the experiments, it was the similar reaction mechanism of the two methods. Firstly, the S-S bond was cleaved by the dynamic exchange reaction of disulfide with sodium sulfide, then it and aldehyde produced benzothiazoline under acidic conditions. Bnzothiazoline and disulfide occurred self- redox reaction, the disulfide was reduced to the o-aminobenzenethiol, benzothiazoline was oxidized to the 2-substituted benzothiazole. The production o-aminobenzenethiol continue reacted with aldehyde to benzothiazoline. After this cycle reaction, the last remained 2-substituted benzothiazole and excess benzothiazoline. Finally, the excess benzothiazoline was oxidized into benzothiazole by air.