Investigation On Synthesis Of Nitrogen-containing Heterocycles From Trimethylsilyl Azide

Nitrogenous Heterocyclic Compounds have important application value and good biological activity and have been used widely in biological areas, pharmaceutical, and pesticide industry. In order to enrich the synthesis methods of Nitrogenous Heterocyclic Compounds, we have studied the synthesis of triazole, tetrazolylazo heterocyclic compounds and obtained meaningful results.After referring a lot of related papers and many experimental tests, we obtained a new synthesis method of 1,2,3-triazole without solvent and catalyst. The yield of 1,2,3 -triazole is very high. This method is suitable for industrial production and there is no reported in literature.According to the reaction mechanism of [3+2] cycloaddition, trimethylsilyl azide reacted with Isothiocyanate under the condition of room temperature and without solvent and catalyst. And the mercapto tetrazole are obtained. This synthesis method is very easy, especially for the Purification Treatment. High purity production can be obtained using Direct Filtration or concentrated in vacuo. This method is suitable for industrial production and there is no reported in literature. The research details and results are listed as follows:1. The synthesis route of trimethylsilyl azide has been optimized. under room temperature, Trimethylchlorosi-licane and sodium azide reacted for 15 hours, without any solvent and catalyst. High purity trimethylsilyl azide was obtained, gas chromat- ography indicated a purity of 89.1%.2. At the temperature of 70℃the high purity 1H-[1,2,3]triazole-4-carboxylic acid ethyl ester are obtained with Trimethylsilyl azid with propiolic acid ethyl ester. The high pressure liquid chromatography gave a purity of 95.8%, yield of 69%, and the compound was identified with ~1HNMR, MS.3. Under the room temperature, the high 1H-[1,2,3] triazole-4,5-dicarboxylic acid dimethyl ester are synthesized by the Trimethylsilyl azid react with 2-butynedioic acid, dimethyl ester without any solvent. The high pressure liquid chromatography indicated a purity of 99.7% and yield of 52.3%. The compound was identified with ~1HNMR, MS.4. Trimethylsilyl azid react with Diethyl acetylenedicarboxylate without any solvent under room temperature, after rotovaping, 1H-[1,2,3]triazole-4,5-dicarboxylic acid diethyl ester was obtained with good purity, High-efficiency liquid chromatography gave a purity of 96.2%, yield of 95%, the compound was identified with ~1HNMR, MS.5. According to methods in literatures, we used aqueous dimethylamine solution, carbon disulfide and hydrogen peroxide as starting material. After a series of reactions methyl isothiocyanate are obtained, then react with sodium azide. After acidification using hydrochloric acid and filtration crude methyl mercapto tetrazole are obtained and then purified many times to give high purity product. From inspiration of triazole synthesis we used the trimethylsilyl azid as a substitute for sodium azide to react with methyl isothiocyanate, and we found that the reaction easily took place and went well under mild conditions. The purity of the product is very high. High-efficiency liquid chromatography gave a purity of 99%, yield of 58.9%, and the product was identified with ~1HNMR, MS.6. According to relevant literature we used aniline and carbon disulfide as raw material to give isothiocyanic acid phenyl ester. The isothiocyanic acid phenyl ester reacted with sodium azide to give phenyl mercapto tetrazole with high purity. Then phenyl isothiocyanate reacted with trimethylsilyl azid at room temperature to give phenyl mercapto tetrazole with very high purity. The high-efficiency liquid chromatography indicated a purity of 99.1%, yield of 70%,and the compound was further identified with ~1HNMR, MS.7. According to the literature, we used glycine, sodium azide and ethyl orthoformate as raw material to synthesize the intermediate 1H-tetrazole-1-acetic acid. The High efficiency liquid chromatography gave a purity of 98.7%, yield of 70%, and it was identified with ~1HNMR, MS.8. According to literature we used glycine and carbon disulfide, and sodium azide as raw material to synthesize 2-(5-mercapto-1H-tetrazol-1-yl)acetic acid. The high pressure liquid chromatography indicated a purity of 92.8%, and the product was identiti-ed with ~1HNMR. According to literatures we used glycine as raw material to synthesize the isothiocyanatoacetate ester, and then the product reacted with trimethylsilyl azid to gave tetrazole-thione. The high pressure liquid chromatography indicated purity of 99%, yield of 50%, and the product was further identified with ~1HNMR, MS. 9. Allyl iso-thiocyanate ester reacted with trimethylsilyl azid rapidly to give 1-allyl-1H-tetrazole-5-thiol with a good purity. The high pressure liquid chromatography gave a purity of 97.7%, yield of 91.3%, and the compound was identified with ~1HNMR, MS.