Synthesis of 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic Acid and (E)-3-(1-Methyl-1H-imidazol-2-ylthio)acrylic Acid.
ChristopherM Hattan, Jalil Shojaie, SerrineS Lau, MW Anders
文献索引：Synth. Commun. 43(1) , 1-8, (2013)
全文：HTML全文
摘要
The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the antioxidant methimazole, are described. The method of Fan et al. (Fan et al., Synthesis 2006, 2286) for the reaction of phenols with propiolic acid and propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3-bromopropanoic acid and methimazole under conditions that gave preferential substitution on sulfur and minimized substitution on nitrogen.
相关化合物
相关文献：
[Tetrahedron 48 , 669, (1992)]
[Tetrahedron Lett. 30 , 3625, (1989)]
[J. Am. Chem. Soc. 112 , 7682, (1990)]
[Tetrahedron Lett. 29 , 6183, (1988)]
Structures of three lithium ester enolates by X-ray diffraction: derivation of reaction path for cleavage into ketene and alcoholate. Seebach D, et al.
[J. Am. Chem. Soc. 170(19) , 5403-9, (1985)]