噻唑-4-甲醛的合成工艺研究
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摘要
以廉价的2-氨基-噻唑-4-甲酸甲酯为原料,经Na NO2重氮化后脱去氨基,次磷酸还原制得噻唑-4-甲酸甲酯,再用KBH4/Li Cl还原,次氯酸钠氧化制得噻唑-4-甲醛,总收率达34. 79%,产物经质谱、红外、核磁表征。考察了反应温度、还原体系和硼氢化钾用量对产物收率的影响,最佳还原条件为n(噻唑-4-甲酸甲酯)∶n(KBH4/Li Cl)=1∶1. 5,反应温度为80℃,还原反应收率达75. 3%。
Thiazole-4-carboxaldehyde was synthesized from cheap methyl 2-aminothioazole-4-carboxylate via two steps. The first step was diazotization-reduction of compound 2 by using sodium nitrite and phosphonous acid. The second step was the reduction of ester 3 by potassium borohydride/lithium chloride system,followed by oxidation using sodium chlorite in the presence of TEMPO under mild condition. The total yield was 34. 79%,and the structure was characterized by1 H-NMR,IR and MS. The effects of reaction temperature,reductants and dosage of KBH4 on the yield of the product were investigated. The mole ratio of methyl-thiazole-4-carboxylate to KBH4/Li Cl was 1 ∶ 1. 5,and the reduction temperature was 80 ℃. The yield of reduction reaction was 75. 3%.
Thiazole-4-carboxaldehyde was synthesized from cheap methyl 2-aminothioazole-4-carboxylate via two steps. The first step was diazotization-reduction of compound 2 by using sodium nitrite and phosphonous acid. The second step was the reduction of ester 3 by potassium borohydride/lithium chloride system,followed by oxidation using sodium chlorite in the presence of TEMPO under mild condition. The total yield was 34. 79%,and the structure was characterized by1 H-NMR,IR and MS. The effects of reaction temperature,reductants and dosage of KBH4 on the yield of the product were investigated. The mole ratio of methyl-thiazole-4-carboxylate to KBH4/Li Cl was 1 ∶ 1. 5,and the reduction temperature was 80 ℃. The yield of reduction reaction was 75. 3%.
引文
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[2]郭本恒.益生菌[M].北京:化学工业出版社,2004:122-125.
[3] Jianmin Zhang,Hanna I,Pettersson,et al. Design,Synthesis,and Evaluation of Inhibitors for Severe Acute Respiratory Syndrome 3CLike Protease Based on Phthalhydrazide Ketones or Heteroaromatic Esters[J]. Journal of Medicinal Chemistry,2007,50(8):1850-1864.
[4] Yoshifumi Yuasa, Haruki Tsuruta, Yoko Yuasa. Enantioselective Synthesis of(S)-3-(4-Thiazolyl)-2-tertbutoxycarbonylaminopropionic acid:A Chiral Building Block for Renin Inhibitor[J]. Heterocycles,2004,63(10):2385-2392.
[5] Von Max Erne,F Ramirez,A Burger. Uber Thiazolyl-isopropylamine[J]. Helvetica Chimica Acta,1951,34:143-148.
[6]杨珩,沈宁,任莺歌,等.一种噻唑-4-甲醛的合成方法[P]. CN:102070553,2011-05-25.
[7]钟为慧,郭宝铭,赵永志,等. 4-甲基-5-甲酰基噻唑的合成工艺研究[J].高校化学工程学报,2009,23(3):486-490.
[8]邱滔,吴增辉,吕新宇.噻唑-4-甲酸的合成[J].常州大学学报(自然科学版),2012,24(1):21-23.