一种高收率的4-甲氧基靛红的合成方法
|
摘要
将溴保护法应用在合成4-甲氧基靛红中,可将4-甲氧基靛红总收率提高到55%,且操作便捷,环境友好。该法以对间甲氧基苯胺为原料,通过一锅溴化法,制得2,4-二溴-5-甲氧基-苯胺,收率90%;然后通过桑德迈尔反应制得4-甲氧基-5,7-二溴靛红,收率81%;再将其在氢气氛中进行钯碳催化还原脱溴得4-甲氧基靛红,收率75%。
An overall yield of 55% can be obtained by appling bromo-protection approach to the synthesis of 4-methoxy-isatin, and the operation is convenient and environmental friendly. By one-pot bromination of 3-methoxy-aniline, 2, 4-dibromo-5-methoxy-aniline can be produced in a 90% yield. After that, 81% yield of 4-methoxy-5,7-dibromo-Isatin can be achieved by Sandmeyer method, and then the hydrogenation in the presence of Pd/C can afford 4-methoxy-Isatin in a 75% yield.
An overall yield of 55% can be obtained by appling bromo-protection approach to the synthesis of 4-methoxy-isatin, and the operation is convenient and environmental friendly. By one-pot bromination of 3-methoxy-aniline, 2, 4-dibromo-5-methoxy-aniline can be produced in a 90% yield. After that, 81% yield of 4-methoxy-5,7-dibromo-Isatin can be achieved by Sandmeyer method, and then the hydrogenation in the presence of Pd/C can afford 4-methoxy-Isatin in a 75% yield.
引文
[1] Micklatcher Mark L, Cushman Mark. An improved method for the synthesis of 3-fluorosalicylic acid with application to the synthesis of 3-(Trifluoromethyl)salicylic acid [J]. Synthesis, 1999, 1999(11):1878-1880.
[2] 南柱石. 6-甲氧基-2-萘乙酮制备的改进[J]. 中国医药工业杂志,1994, 25(3): 133-134.
[3] Gurney Mark E, Hategan Georgeta, Kiselyov Alex S, et al. Structure - activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4, 5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor antagonist, as a novel antiplatelet agent that does not prolong bleeding [J]. Journal of Medicinal Chemistry, 2010,53(1):18-36.
[4] Bin Bin, Chen Ying, Corte James R, et al. Synthesis and characterization of 3-arylquinazolinone and 3-arylquinazolinethione derivatives as selective estrogen receptor beta modulators[J]. Journal of Medicinal Chemistry, 2006, 49, 2440-2455.
[5] Xenon Pharmaceuticals INC. Oxindole compounds and their uses as therapeutic agents: WO, 2006113864[P]. 2006-10-26.
[6] Schumacher Richard, Danca Mihaela Diana, Ma Jianguo, et al. Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof: US, 200778147[P]. 2007-04-05.
[7] Hewawasam Piyasena, Meanwell Nicholas A. A General Method for the Synthesis of Isatins: Preparation of Regiospecifically Functionalized Isatins from Anilines[J]. Tetrahedron Letters, 1994, 35(40), 7303-7306.
[8] Wierenga Wendell, Griffin John, Warpehoski Martha A. A versatile and efficient process to 3-substituted indoles from anilines[J]. Tetrahedron Letters, 1983, 24(24), 2437-2440.
[9] Pedras M Soledade C, Yaya Estifanos E. The first isocyanide of plant origin expands functional group diversity in cruciferous phytoalexins: Synthesis, structure and bioactivity of isocyalexin A[J]. Organic and Biomolecular Chemistry, 2012, 10(18), 3613-3616.
[10] Tanabe Seiyaku Co., Ltd. 2-oxoindoline derivative: US, 19985807883[P]. 1998-09-15.
[11] B T Bagmanov, Effect of Structural Factors and Solvent Nature in Bromination of Anilines. Russian Journal of Applied Chemistry, 2009, 82(9), 1570-1576.
[2] 南柱石. 6-甲氧基-2-萘乙酮制备的改进[J]. 中国医药工业杂志,1994, 25(3): 133-134.
[3] Gurney Mark E, Hategan Georgeta, Kiselyov Alex S, et al. Structure - activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4, 5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor antagonist, as a novel antiplatelet agent that does not prolong bleeding [J]. Journal of Medicinal Chemistry, 2010,53(1):18-36.
[4] Bin Bin, Chen Ying, Corte James R, et al. Synthesis and characterization of 3-arylquinazolinone and 3-arylquinazolinethione derivatives as selective estrogen receptor beta modulators[J]. Journal of Medicinal Chemistry, 2006, 49, 2440-2455.
[5] Xenon Pharmaceuticals INC. Oxindole compounds and their uses as therapeutic agents: WO, 2006113864[P]. 2006-10-26.
[6] Schumacher Richard, Danca Mihaela Diana, Ma Jianguo, et al. Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof: US, 200778147[P]. 2007-04-05.
[7] Hewawasam Piyasena, Meanwell Nicholas A. A General Method for the Synthesis of Isatins: Preparation of Regiospecifically Functionalized Isatins from Anilines[J]. Tetrahedron Letters, 1994, 35(40), 7303-7306.
[8] Wierenga Wendell, Griffin John, Warpehoski Martha A. A versatile and efficient process to 3-substituted indoles from anilines[J]. Tetrahedron Letters, 1983, 24(24), 2437-2440.
[9] Pedras M Soledade C, Yaya Estifanos E. The first isocyanide of plant origin expands functional group diversity in cruciferous phytoalexins: Synthesis, structure and bioactivity of isocyalexin A[J]. Organic and Biomolecular Chemistry, 2012, 10(18), 3613-3616.
[10] Tanabe Seiyaku Co., Ltd. 2-oxoindoline derivative: US, 19985807883[P]. 1998-09-15.
[11] B T Bagmanov, Effect of Structural Factors and Solvent Nature in Bromination of Anilines. Russian Journal of Applied Chemistry, 2009, 82(9), 1570-1576.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |