Các chất lỏng ion 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) đã được điều chế và nhận danh bằng phương pháp 1H và 13C-NMR kết hợp với phương pháp MS. Chất lỏng ion ([BMIM][PF6] đã được sử dụng làm dung môi xanh cho phản ứng tổng hợp pravadoline, một loại thuốc kháng viêm không chứa steroid, với hiệu suất cao mà không cần xúc tác acid Lewis. Phản ứng cũng được thực hiện thành công trong các chất lỏng ion họ imidazolim khác, bao gồm 1-hexyl-3-methylimidazolium hexafluorophosphate ([HMIM][PF6]) và 1-octyl-3-methylimidazolium hexafluorophosphate ([OMIM][PF6]). Theo hiểu biết của chúng tôi, đây là lần đầu tiên ở Việt Nam, quá trình tổng hợp pravadoline được nghiên cứu và tiến hành trong dung môi xanh là chất lỏng ion. | TAÏP CHÍ PHAÙT TRIEÅN KH&CN, TAÄP 14, SOÁ K3 - 2011 PRAVADOLINE SYNTHESIS USING AN IMIDAZOLIUM-BASED IONIC LIQUID AS A GREEN SOLVENT Phan Thanh Son Nam, Le Vu Ha University of Technology, VNU-HCM (Manuscript Received on May 13th, 2011, Manuscript Revised November 01st, 2011) ABSTRACT: An easily accessible ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) was synthesized, and characterized using 1H and 13 C NMR, and MS. The ionic liquid was demonstrated to be an efficient green solvent for the synthesis of pravadoline, one of non-steroidal drugs. High yield was achieved without the presence of an anhydrous Lewis acid catalyst. The reaction was also successfully carried out using other imidazolium-based ionic liquids, including 1-hexyl-3-methylimidazolium hexafluorophosphate ([HMIM][PF6]), and 1-octyl-3- methylimidazolium hexafluorophosphate ([OMIM][PF6]). To our best knowledge, this is the first report in Viet Nam on the synthesis of a pharmaceutical chemical in ionic liquids as green solvents. Key words: A variety of ionic liquids have been 1. INTRODUCTION Pravadoline, being commercialized under the investigated, in which dialkylimidazolium- name of Win 48098 by Sterling Drug (Sterling based ionic liquids exhibit several advantages Research Group, Rensselaer, New York), was such as keeping the liquid condition under a developed as a new antiinflammatory and wide range of temperature and having excellent prostaglandin acting solubility for many substrates and molecular enzyme catalysts [5,6]. We recently reported the use of Pravadoline and more an imidazolium-based ionic liquid as a green through synthesis inhibition cyclooxygenase [1]. inhibitor, of the importantly some of its analogues have also solvent been used as a probe for neurochemical morpholino)-2-chloroethane hydrochloride and receptors, since it has been found to be an 2-methylindole agonist of the cannabinoid receptor [1,2]. .
