基于DMC法的α-氨基酸-N-环内酸酐的绿色合成  

Green synthesis ofα-amino acid-N-cyclic anhydride based on DMC method

作　　者：李振环[1,2] 彭日丽 苏坤梅[2] LI Zhenhuan;PENG Rili;SU Kunmei(School of Material Science and Engineering,Tiangong University,Tianjin 300387,China;School of Chemical Engineering and Technology,Tiangong University,Tianjin 300387,China)

机构地区：[1]天津工业大学材料科学与工程学院,天津300387 [2]天津工业大学化学工程与技术学院,天津300387

出　　处：《天津工业大学学报》2023年第5期28-35,共8页Journal of Tiangong University

基　　金：国家自然科学基金资助项目(21676202);山东省自然科学基金重点资助项目(ZR2020KE053);天津市自然科学基金重点资助项目(19JCJDJC37300)。

摘　　要：针对传统方法合成α-氨基酸-N-环内酸酐(NCAs)毒性大、对环境不友好的问题,以氨基酸为原料,以乙酸锌为催化剂,以碳酸二甲酯(DMC)为环化剂,通过“一锅法”高效环保地合成了L-苯丙氨酸-N-羧基环内酸酐(Phe-NCA)、L-天冬氨酸-4-苄酯-羧基环内酸酐(H-Asp-Obzl-NCA)和Nε-苄氧羰基-L-赖氨酸环内酸酐(Cbz-Lys-NCA)等3种新型NCAs。通过GC-MS、NMR、FT-IR等对其进行定性表征;讨论了反应温度、反应物比例等因素对氨基酸转化率与NCAs产率的影响;并通过对比催化剂乙酸锌在反应前后的XPS和XRD等表征,分析乙酸锌的催化机理。结果表明:反应中氨基酸∶去质子碱∶催化剂的摩尔比为1:1.5:0.2,反应分别在160、120、140℃进行8 h后,去质子氨基酸与DMC在乙酸锌的作用下发生甲氧羰基化反应,进一步关环,Phe-NCA、H-Asp-Obzl-NCA和Cbz-Lys-NCA最佳产率可分别达到55.22%、56.30%和46.46%;乙酸锌的催化机理为Zn^(2+)与DMC中的羰基氧进行配位络合后实现氨基酸靶向甲氧羰基化,促进邻近COO-与羰基碳发生亲核取代,从而实现精准关环,得到NCAs。In response to the problem of high toxicity and environmental unfriendliness of traditional methods which syn-thesizeα-amino acid-N-cyclic anhydride(NCAs),L-phenylalanine-N-carboxylic intracyclic anhydride(Phe-NCA),L-aspartic acid 4-benzyl ester carboxylic intracyclic anhydride(H-Asp-Obzl-NCA)and Nε-carboxybenzyl-L-lysine intracyclic anhydride(Cbz-Lys-NCA)were prepared from amino acids as raw material and dimethyl carbonate as cyclizing agent under the catalysis of zinc acetate through one-pot synthesis.They were qualitatively characterized by GC-MS,NMR and FT-IR.Meanwhile,the effects of reaction temperature,reactant ratio and other factors on the conversion of amino acids and the yield of NCAs were discussed.Besides,the XPS and XRD characterizations of zinc acetate before and after the reaction were compared to analyze the catalytic mechanism of zinc acetate.The results showed that the reactions were carried out at 160,120 and 140℃for 8 h at the molar ratio of amino acid∶deprotonated base∶catalyst of 1∶1.5∶0.2,and after methoxycarbonylation of deprotonated amino acid with DMC in the presence of zinc acetate and further ring closure,Phe-NCA,H-Asp-Obzl-NCA and Cbz-Lys-NCA could achieve the best yields of 55.22%,56.30%,and 46.46%,respectively.The catalytic mechanism of zinc acetate is the coordination complexation of Zn^(2+)with carbonyl oxygen in DMC to achieve amino acid-targeted methoxycarbonylation and promote the nucleophilic substitution of neighboring COO-with carbonyl carbon to achieve precise ring closure and obtain NCAs.

关 键 词：碳酸二甲酯(DMC) α-氨基酸-N-环内酸酐(NCAs) 乙酸锌 甲氧羰基化 绿色合成 

分 类 号：TQ032[化学工程]