氨噻肟酸乙酯的合成
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摘要
本文对采用乙酰乙酸乙酯法制备氨噻肟酸乙酯路线中的卤代反应进行优化,以1,3-二氯-5,5-二甲基海因和1,3-二溴-5,5-二甲基海因作卤代试剂,对甲苯磺酸作催化剂的条件下,制备得到相应的4-氯/溴-2-甲氧亚胺基乙酰乙酸乙酯卤代产物。该卤代产物进一步与硫脲进行环合反应得到目标产物(Z)-2-(2-氨基-4-噻唑)-2-甲氧基亚胺基乙酸乙酯(即氨噻肟酸乙酯)。该合成路线具有成本低、绿色环保和易于工业化的优点。
In this paper, we reported a new way to realize the halogenation reaction in the preparation of ethyl(Z)-2-methoxyimino-2-(2-aminothiazole-4-yl) acetate with ethyl acetoacetate method. We took the 1,3-dichloro-5,5-dimethylhydantoin and 1,3-dibromo-5,5-dimethylhydantoin as the halogenation reagents and p-toluenesulfonic acid as the catalyst, to prepare the corresponding ethyl 4-chloro/bromo-2-methoxyimino-3-oxobutanoate product. Then, the product was further subjected to a cyclization reaction with thiourea to obtain the objective product ethyl(Z)-2-methoxyimino-2-(2-aminothiazole-4-yl) acetate. The synthetic route has the advantages of low cost, environmentally friendly and ease of industrialization.
In this paper, we reported a new way to realize the halogenation reaction in the preparation of ethyl(Z)-2-methoxyimino-2-(2-aminothiazole-4-yl) acetate with ethyl acetoacetate method. We took the 1,3-dichloro-5,5-dimethylhydantoin and 1,3-dibromo-5,5-dimethylhydantoin as the halogenation reagents and p-toluenesulfonic acid as the catalyst, to prepare the corresponding ethyl 4-chloro/bromo-2-methoxyimino-3-oxobutanoate product. Then, the product was further subjected to a cyclization reaction with thiourea to obtain the objective product ethyl(Z)-2-methoxyimino-2-(2-aminothiazole-4-yl) acetate. The synthetic route has the advantages of low cost, environmentally friendly and ease of industrialization.
引文
[1]Dürckheimer W,Blumboch J,Lattrell R,et al.Recent development in the field of b-lactam antibiotics[J].Angew Chem Int Ed Engl,1985,24(3):180-202.
[2]李从宝,赵美法.氨噻肟酸的生产和应用(上)[J].化工科技市场,2002(10):15-21.
[3]宋芹.氨噻肟酸的生产与应用(一)[J].化工中间体,2003(1):11-17.
[4]葛洪玉,张静,方志杰.氨噻肟酸的生产及工艺评析[J].江苏化工,2005,33(1):47-50.
[5]肖海焕.氨噻肟酸与AE-活性酯合成的研究进展[J].河南化工,2008,25(7):4-7.
[6]崔晓雪,孙娜,杨静,等.头孢类药物中间体氨基噻肟酸合成研究进展[J].天津职业院校联合学报,2016,18(8):59-64.
[7]王之德.氨噻肟酸的制法[J].四川化工,1989(4):41-43.
[8]傅德才,周鸿娟.氨噻肟酸的合成[J].杭州化工,1996,26(1):16-17.
[9]张小林,梁兵,全水清,李晓燕,姚彦红.氨噻肟酸及其衍生物合成新工艺的研究[J].南昌大学学报(工科版),2000,22(3):93-96.
[10]朱赛芬.氨噻肟酸生产技术与应用[J].化工生产与技术,2001,8(5):39-41.
[11]刘静,杨锋,鹿峰,等.氨噻肟酸乙酯的生产工艺改进[J].青岛科技大学学报,2003,24(5):412-414.
[12]胡艾希,徐娟娟,伍小云.氨噻肟酸乙酯的合成[J].中国医药工业杂志,2006,37(4):229-230.
[13]徐娟娟,胡艾希.氨噻肟酸的合成[J].精细化工,2007,24(4):385-386.
[14]程清蓉,刘志雄,周红,等.氨噻肟酸乙酯的合成研究[J].应用化工,2009,38(5):675-677.
[15]孙健,彭学伟.氨噻肟酸的合成[J].化学与生物工程,2011,28(12):54-55.
[16]孙梦珂,毕彩丰,赵宇,等.氨噻肟酸乙酯的合成研究[J].精细化工中间体,2012,42(2):27-29.
[2]李从宝,赵美法.氨噻肟酸的生产和应用(上)[J].化工科技市场,2002(10):15-21.
[3]宋芹.氨噻肟酸的生产与应用(一)[J].化工中间体,2003(1):11-17.
[4]葛洪玉,张静,方志杰.氨噻肟酸的生产及工艺评析[J].江苏化工,2005,33(1):47-50.
[5]肖海焕.氨噻肟酸与AE-活性酯合成的研究进展[J].河南化工,2008,25(7):4-7.
[6]崔晓雪,孙娜,杨静,等.头孢类药物中间体氨基噻肟酸合成研究进展[J].天津职业院校联合学报,2016,18(8):59-64.
[7]王之德.氨噻肟酸的制法[J].四川化工,1989(4):41-43.
[8]傅德才,周鸿娟.氨噻肟酸的合成[J].杭州化工,1996,26(1):16-17.
[9]张小林,梁兵,全水清,李晓燕,姚彦红.氨噻肟酸及其衍生物合成新工艺的研究[J].南昌大学学报(工科版),2000,22(3):93-96.
[10]朱赛芬.氨噻肟酸生产技术与应用[J].化工生产与技术,2001,8(5):39-41.
[11]刘静,杨锋,鹿峰,等.氨噻肟酸乙酯的生产工艺改进[J].青岛科技大学学报,2003,24(5):412-414.
[12]胡艾希,徐娟娟,伍小云.氨噻肟酸乙酯的合成[J].中国医药工业杂志,2006,37(4):229-230.
[13]徐娟娟,胡艾希.氨噻肟酸的合成[J].精细化工,2007,24(4):385-386.
[14]程清蓉,刘志雄,周红,等.氨噻肟酸乙酯的合成研究[J].应用化工,2009,38(5):675-677.
[15]孙健,彭学伟.氨噻肟酸的合成[J].化学与生物工程,2011,28(12):54-55.
[16]孙梦珂,毕彩丰,赵宇,等.氨噻肟酸乙酯的合成研究[J].精细化工中间体,2012,42(2):27-29.