Preparation of two novel monobrominated 2-(2′,4′-dihydroxybenzoyl)-3,4,5,6-tetrachlorobenzoic acids and their separation from crude synthetic mixtures using vortex counter-current chromatography
Preparation of two novel monobrominated 2-(2′,4′-dihydroxybenzoyl)-3,4,5,6-tetrachlorobenzoic acids and their separation from crude synthetic mixtures using vortex counter-current chromatography
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DOI：
10.1016/j.chroma.2012.03.040
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发表时间：
2012-05-11
影响因子：
4.1
通讯作者：
Ito, Yoichiro
中科院分区：
文献类型：
--
作者：
Weisz, Adrian;Witten, Jacob J.;Ito, Yoichiro
本工作描述了两种被认为可能是呈交美国食品和药物管理局批次认证的着色剂D&C红27号(颜色指数45410：1)和D&C红28号(颜色指数45410，黄曲霉素B)样品中存在的杂质前体的化合物的制备。用涡旋逆流色谱从合成混合物中分离出两个化合物：2-(2‘，4’-dihydroxy-3‘-bromobenzoyl)-3，4，5，6-tetrachlorobenzoic酸(3BrHBBA)及其5’-溴代位置异构体(5BrHBBA)，这两个化合物均未见文献报道。3BrHBBA是由二羟基苯甲酰基的化学选择性邻溴化反应合成的。以正己烷-乙酸乙酯-甲醇-0.2%三氟乙酸(TFA)为溶剂，体积比分别为8：2：5：5和7：3：5：5的两个两相溶剂系统，用VCCC分离了合成混合物中的两部分，分别为200 mg和210 mg。这两种分离方法分别得到35 mg和78 mg的3BrHBBA，在254 nm处，每一种产物的纯度都在98%以上。5BrHBBA是在冰醋酸存在下，通过二羟基苯甲酰基的一溴代反应合成的。对得到的合成混合物进行分离。以正己烷-乙酸乙酯-甲醇-水(6：4：5：5，v/v)为溶剂体系，TFA为保留酸，氨水为洗脱碱，采用pH区精制方式进行VCCC分离。在此条件下分离1-g混合物，在254 nm处得到142 mg的5BrHBBA，纯度接近99%。用高分辨质谱仪和质子核磁共振波谱对分离得到的化合物进行了表征。爱思唯尔出版公司(Elsevier B.V.)
The present work describes the preparation of two compounds considered to be likely precursors of an impurity present in samples of the color additives D&C Red No. 27 (Color Index 45410:1) and D&C Red No. 28 (Color Index 45410, phloxine B) submitted to the U.S. Food and Drug Administration for batch certification. The two compounds, 2-(2',4'-dihydroxy-3'-bromobenzoyl)-3,4,5,6-tetrachlorobenzoic acid (3BrHBBA) and its 5'-brominated positional isomer (5BrHBBA), both not reported previously, were separated from synthetic mixtures by vortex counter-current chromatography (VCCC). 3BrHBBA was prepared by chemoselective ortho-bromination of the dihydroxybenzoyl moiety. Two portions of the obtained synthetic mixture, 200 mg and 210 mg, respectively, were separated by VCCC using two two-phase solvent systems that consisted of hexane-ethyl acetate-methanol-aqueous 0.2% trifluoroacetic acid (TFA) in the volume ratios of 8:2:5:5 and 7:3:5:5, respectively. These separations produced 35 mg and 78 mg of 3BrHBBA, respectively, each product of over 98% purity by HPLC at 254 urn. 5BrHBBA was prepared by monobromination of the dihydroxybenzoyl moiety in the presence of glacial acetic acid. To separate the obtained synthetic mixture. VCCC was performed in the pH-zone-refining mode with a solvent system consisting of hexane-ethyl acetate-methanol-water (6:4:5:5, v/v) and with TFA used as the retainer acid and aqueous ammonia as the eluent base. Separation of a 1-g mixture under these conditions resulted in 142 mg of 5BrHBBA of similar to 99% purity by HPLC at 254 nm. The isolated compounds were characterized by high-resolution mass spectrometry and proton nuclear magnetic resonance spectroscopy. Published by Elsevier B.V.