Ahfad-Hosseini Hamid Reza, Bagheri Hasan, Amidi Salimeh
Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2017 Winter;16(1):158-164.
Celecoxib is classified as none traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This compound has conventional properties of NSAIDs such as anti-inflammatory, analgesic, and antipyretic activities beside reduced risk of gastrointestinal side effect of traditional NSAIDs such as ibuprofen. This compound gets a second sale rank of NSAIDs market at 2016 in the world and sales more than 17000 Kg in Iran during the past 6 month. So, a simple, rapid and green method for synthesis of this compound is important. In the present study, a novel green method was suggested for the synthesis of celecoxib using the ionic liquid. Celecoxib was provided by the reaction of trifluoroacetone, 4-methylbenzoylchloride, and 4-hydrazinobenzenesulfonamide hydrochloride. The tris-(2-hydroxyethyl) ammonium acetate as ionic liquid was prepared by mixing tris-(2-hydroxyethyl) ammonium and acetic acid, and used as an efficient catalyst. The structure of the synthetic products was confirmed by analytical and spectroscopic methods including HNMR, CNMR, IR, MS and elemental analysis. This ionic liquid can play dual roles in the synthesis of celecoxib, as a catalyst to improve electrophilicity of carbonyl group and also as a solvent of reaction. The reaction rate and yield (86%) were improved considerably. Moreover IL showed the same efficiency when used in 4 consecutive reactions.
塞来昔布被归类为非传统非甾体抗炎药（NSAIDs）。该化合物具有NSAIDs的常规特性，如抗炎、镇痛和解热活性，同时降低了传统NSAIDs（如布洛芬）胃肠道副作用的风险。该化合物在2016年全球NSAIDs市场中排名第二，在过去6个月中，伊朗的销量超过17000千克。因此，开发一种简单、快速且绿色的该化合物合成方法具有重要意义。在本研究中，提出了一种使用离子液体合成塞来昔布的新型绿色方法。塞来昔布是由三氟丙酮、4-甲基苯甲酰氯和4-肼基苯磺酰胺盐酸盐反应制得。通过将三（2-羟乙基）铵与乙酸混合制备了三（2-羟乙基）乙酸铵离子液体，并将其用作高效催化剂。通过HNMR、CNMR、IR、MS和元素分析等分析和光谱方法对合成产物的结构进行了确证。这种离子液体在塞来昔布的合成中可发挥双重作用，既作为提高羰基亲电性的催化剂，又作为反应溶剂。反应速率和产率（86%）得到了显著提高。此外，该离子液体在连续4次反应中使用时表现出相同的效率。
