摘要/Abstract

以碳酸二甲酯（DMC）代替光气，一锅法合成α-氨基酸-N-羧酸酐（NCAs）是实现绿色制备多肽的重要途径.制备了酸碱协同催化剂NaZnPO₄，用该催化剂催化DMC和丙氨酸"一锅法"合成N-羧基丙氨酸酸酐（Ala-NCA）.在N，N-二甲基甲酰胺（DMF）溶剂中，150℃的反应条件反应8 h时，Ala-NCA的收率最高为46.84%，催化剂循环5次后收率仍达38.62%.NaZnPO₄中Zn²⁺和O-Na具有有效的酸碱协同催化作用，在反应过程中具有去质子化、精准酰基化和高效成环的作用.利用TG-MS-IR技术研究了催化剂表面上原料转化和中间体精准关环过程，并提出了可能的反应催化机理.
关键词: N-羧基丙氨酸酸酐, 碳酸二甲酯, 甲氧基碳酰基化, 酸碱协调催化, 关环反应
In this paper, the environmentally friendly synthesis of N-carboxy alanine anhydride (Ala-NCA) from alanine and dimethyl carbonate (DMC) over NaZnPO₄ was carried out in one-pot, and the NaZnPO₄ catalyst with the acid-base double active sites was prepared by the solid phase synthesis method. The X-ray diffraction spectrometer (XRD) was used to characterize the structure of NaZnPO₄, and the reaction products were analyzed by the high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD). The GC-MS characterized result of obtained Ala-NCA was extremely consistent with that of the standard sample, which indicated that Ala-NCA was synthesized successfully. When the reaction was carried out at 150℃ for 8 h, the maximum 46.84% yield of Ala-NCA can be obtained in DMF solvent. As the reaction temperature increased to 160℃, Ala-NCA yield significantly declined because of the instability of Ala-NCA at higher temperature. However, there was no Ala-NCA formation without catalyst existence because DMC is not easy to undergo carboxymethylation with amino acids. NaZnPO₄ could be recycled, but Ala-NCA yield declined to 38.62% after the fifth cycle. The reasons for that were attributed to the catalyst surface area reduction and the active site loss of Na-O and Zn²⁺. The reaction between DMC and amino acids over NaZnPO₄ were characterized by TG-MS-IR, and the possible catalytic mechanism was provided. Namely, Zn²⁺ and Na-O in NaZnPO₄ perform an effective acid-base synergistic catalysis, on the one hand the basic Na-O active sites play an key role on amino group deprotonation, which promotes the carboxymethylation of amino acids with DMC, on the other hand the acid active sites of Zn²⁺ can well catalyze the cyclization of intermediate into Ala-NCA. In this cyclization process, NaZnPO₄ also can transfer the trapped protons to carboxymethylation intermediate to facile the formation of target compounds.
Key words: N-carboxy alanine anhydride, dimethyl carbonate, carboxymethylation, acid-base coordination catalysis, cyclization


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