邻氯苯甘氨酸甲酯的拆分研究
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摘要
以L-(+)-酒石酸作为手性拆分剂,苯甲醛作催化剂,对外消旋的邻氯苯甘氨酸甲酯混合物进行了化学拆分。S-(+)-邻氯苯甘氨酸甲酯的拆分收率达到93%,ee 99.96%,其结构经~1H NMR和HPLC确证。使用pH电位滴定法研究了邻氯苯甘氨酸甲酯与酒石酸形成的盐的稳定性,采用X-射线单晶衍射确定了一对非对映异构体盐的立体结构,并初步推测了非对映异构体的拆分机理。用共振瑞利散射分析了两种异构体盐结构。
The chemical resolution of S-(+)-o-chlorophenylglycine methyl ester was investigated by using L-(+)-tartaric acid as the chiral resolution agent and benzaldehyde as the catalyst. The resolution yield was 93% and ee was 99.96%. The stability of the salt of chlorophenol methyl esters and tartaric acid was studied with pH potentiometric titration. X-ray single crystal diffraction determines the three-dimensional structure of a pair of diastereomers, and the mechanism of splitting the diastereomer was preliminarily surmised. The structures of two isomer salts were analyzed by resonance Rayleigh scattering method.
The chemical resolution of S-(+)-o-chlorophenylglycine methyl ester was investigated by using L-(+)-tartaric acid as the chiral resolution agent and benzaldehyde as the catalyst. The resolution yield was 93% and ee was 99.96%. The stability of the salt of chlorophenol methyl esters and tartaric acid was studied with pH potentiometric titration. X-ray single crystal diffraction determines the three-dimensional structure of a pair of diastereomers, and the mechanism of splitting the diastereomer was preliminarily surmised. The structures of two isomer salts were analyzed by resonance Rayleigh scattering method.
引文
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[2] BOUISSET M, RADISON J. Proces for the preparation of α-bromophenylacetic acids:US 5036156[P].1991.
[3] SCHROR K. The basic pharmacology of ticlopidine and clopidogrel[J].Platelets,1993,4(2):252-261.
[4] HERBENT J M, FREHEL D, VALLEE K. Clopidogrel:A novel antiplatelet and antithrombotic agent[J].Cardlotuscular Drug Revlews,1993,11(2):180-198.
[5] 陈建中. 氯吡格雷的合成改进研究[D].上海:华东理工大学,2009.
[6] SIDDIQUI J M, YEKANATHSA M A, REYAZ K A. A novel process for the manufacture of S-(+)-clopidogrel bisulfate form-I:WO 2005012300A1[P].2005.
[7] VAGHEL A, MUKES H, NATHALA L. A process for preparation of clopidogrel:WO 2004108665[P].2004.
[8] SIMONIC I, BENKIC P. Process for the synthesis of clopidogrel and new forms of pharmaceutically acceptable salts thereof:WO 2008034912[P].2008.
[9] 房福贤,宋辉,党晓翠,等. 氯吡格雷中间体——邻氯苯甘氨酸甲酯的化学拆分过程中的结晶过程研究[J].科技创新导报,2012,(29):22-24.
[10] YOSHIOKA R. Racemization and crystallization-induced asymmetric transformation[J].Top Curr Chem,2007,269:83-132
[11] EELCO J, EBBER S, GERRY J. Controlled racemization of optically active organic compounds:Prospects for asymmetric transformation[J].Tetrahedron,1997,53(28):9417-9476.
[12] PELLISSER H. Recent development in dynamic kinetic resolution[J].Tetrahedron,2008,64:1563-1601.
[13] BREUER M, DITRICH K, HABICHER T, et al. Industrial methods for the production of optically active intermediates[J].Angewandte Chem Int Ed,2004,43:788-824
[14] 丁桂俐,赵敏,吴范宏,等. 邻氯苯甘氨酸甲酯的拆分[J].广州化工,2007,(06):44-48.
[15] 黎占亭,张丹维. 氢键:分子识别与自组装[M].北京:化学工业出版社,2017.
[16] 殷中意,胥江河. 关于物质溶解过程本质的探讨[J].渝北大学学报(自然科学版),1996,13(1):56-62.
[17] 艳梅,吴环,曾小清,等. 基于功能化的金纳米的共振瑞利散射方法手性识别肉碱对映体[J].光谱学与光谱分析,2017,(6):1965-1972.
[18] 蒋天艳,冉金凤,解小华,等. 卡托普利-维多利亚蓝B体系的共振瑞利散射光谱及应用[J].化学研究与应用,2017,29(11):1710-1713.
[19] 刘红,徐红,徐科,等. 共振瑞利散射法测定硫酸卡那霉素[J].化学与生物工程,2016,33(05):65-67.
[20] 刘绍璞,周光明,刘忠芳,等. 共振瑞利散射法测定硫氰酸盐-碱性三苯甲烷染料体系中的痕量钼[J].高等学校化学学报,1998,(07):35-39.
[21] THORDARSON P. Determining association constants from titration experiments in supramolecular chemistry[J].Cheminform,2011,42(21):1305.
[22] ATWOOD J L, DAVIES J E. Comprehensive Supramolecular Chemistry[M].Oxford:Pergamon,1996.
[23] 王睿,尉志武. Benesi-Hildebrand方程的正确性与可靠性[J].物理化学学报,2007,(09):1353-1359.
[24] SERGE H M, SONTGEN R P. Stability and lifetime of quadruply hydrogen bonded 2-ureido-4[1H]-pyrimidinone dimers[J].J Am Chem Soc,2000,122(31):7487-7493.
[25] ZHAO X. hydrazide-based quadruply hydrogen-bonded heterodimers. structure, assembling selectivity, and supramolecular substitution[J].J Am Chem Soc,2003,125(49):15128-15139.
[26] SIGURSKJOLD B W. Exact analysis of competition ligand binding by displacement isothermal titration calorimetry[J].Analytical Biochemistry,2000,277(2):260-266.
[27] THAYLAN P A. DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex[J].Inorganica Chimica Acta,2016,452:170-175.
[28] ZHU Y K. Kinetics and thermodynamics of Eu(III) adsorption onto synthetic monoclinic pyrrhotite[J].Journal of Molecular Liquids,2016,218:565-570.
[29] ZHONG X J. The adsorption of Eu(III) on carbonaceous nanofibers:Batch experiments and modeling study[J].Journal of Molecular Liquids,2016,222:456-462.
[30] WANG N. Surface complexation modeling of Cd(II) sorption to montmorillonite,bacteria,and their composite[J].Biogeosciences,2016,13(19):5557-5566.