Study On Green Chemistry Synthesis Of Thiophenic Pharmaceutical Intermediates

In this dissertation, we first compared the syntheses of HZSM-5 zeolite catalysts in the presence and absence of tetrapropylammonium hydroxide as templates. The structure and acid sites property of HZSM-5 zeolite catalysts were characterized by X-ray diffraction(XRD) and temperature programmed desorption of ammonia(NH3-TPD). Then the synthesized HZSM-5 molecular sieves were used as catalyst for the isomerization of 2-bromothiophene to 3-bromothiophene. By the chromatographic analysis of the products and reactant, the product distributions dependence on the acidity of the catalysts were investigated. It was found that the catalytic performance of the isomerization of 2-bromothiophene to 3-bromothiophene over the HZSM-5 molecular sieve in the absence of the template was relatively low due to the weak acid sites.Howver, the HZSM-5 molecular siveds with various SiO2/Al2O3 ratio had been synthesized in the presence of tetrapropylammonium hydroxide, It was found that the the catalytic performance of the isomerization of 2-bromothiophene to 3-bromothiophene over these HZSM-5 molecular sieves were relatively high. This result can be explained that the isomerization of 2-bromothiophene to 3-bromothiophene are mainly completed by the coexistence of weak and strong acid sites, while both acid sites can be formed in the HZSM-5 molecular sieves in the presence of template. Moreover, the strength and amount of the acids can be adjusted by the SiO2/Al2O3 ratio.In addition, the synthesis of 2-acetylthiophene by the acetylation of thiophene with acetic anhydride over different solid acids(HZSM-5, Hβ, NKC-9) were investigated. It was found that Hβ showed excellent acetylation activity with almost 99% conversion of thiophene under conditions of normal pressure, Reaction temperature 60℃ and molar ratio of thiophene to acetic anhydride of 1:3. The yield of 2-Acetylthiophene is 98.6%. Therefore, Hβ zeolites with various SiO2/Al2O3 ratio were synthesized and characterized by XRD and NH3-TPD. The property of the Hβ catalysts were investigated by the acetylation of thiophene with acetic anhydride. It was found that the catalytic property of the acetylation is dependent on the acid strength of the catalyst. In the conditions of atomospheric pressure and 60℃, the the molar ratio of acetic anhydride to thiophene was 1:3 and the addition amount of catalyst is 3wt%, the yield of 2-acetylthiophene can be arrived at 98.6%. Furthermore, the catalysts can be recovered, regenerated and reused for several times without any catalytic property loss.