CN106674011A - 一种由二甲基亚砜合成茚酮衍生物的方法 - Google Patents
一种由二甲基亚砜合成茚酮衍生物的方法 Download PDFInfo
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Abstract
本发明公开了一种由二甲基亚砜合成茚酮衍生物的方法。所述方法以苯乙酰乙酸乙酯和二甲基亚砜为原料,在三氟甲磺酸亚铜的催化下,以过量的二甲基亚砜为溶剂,在80~120℃下反应8~24h,反应结束后,反应液经分离纯化得到2‑乙氧基甲酰基‑1‑茚酮。本发明方法利用二甲基亚砜作为碳源,属于二甲基亚砜的新应用,工艺条件合理,操作简单安全,三废少,环境友好。
Description
技术领域
本发明属于有机合成领域,涉及一种由二甲基亚砜(DMSO)合成茚酮衍生物的方法。
技术背景
茚酮衍生物是有机合成领域中一种重要的合成中间体。许多天然化合物和药物的结构中也具有该片段,这一特殊的结构使其具有较好的生物活性和药理作用。因此,二羰基茚酮衍生物的合成是有机合成中的重要课题。目前已报道的合成方法中使用的方法主要有如下几种:
文献1(Anna Maria Zawisza,et al.Heck-type reactions of allylicalcohols:Part IV:(2-Substituted)-1-indanones via,5-endo-trig,cyclizations[J].Journal of Molecular Catalysis A Chemical,2008,283(s 1–2):140-145.)使用烯烃醇为原料,在弱碱条件下,以醋酸钯合奎宁衍生物辛可宁为催化剂,在DMF溶剂中合成茚酮衍生物。该方法所用原料需要自制,也具有较广的底物适用性,其反应式如下:
文献2(Brown D S,et al.Epoxidation with dioxiranes derived from 2-fluoro-2-substituted-1-tetralones and-1-indanones[J].ChemInform,1995,51(33):3587-3606.)使用茚酮作为原料,钠氢作为催化剂,在THF溶剂中与碳酸二乙酯反应合成茚酮衍生物。该方法原料易得,经济实惠,其反应式如下:
文献3(Sartori G,et al.ChemInform Abstract:Selective Synthesis of 1-Indanones via Tandem Knoevenagel Condensation-Cycloalkylation ofβ-DicarbonylCompounds and Aldehydes.[J].ChemInform,1996,27(9):12179-12192.)使用苯乙酰乙酸乙酯为原料,路易斯酸催化下,与甲醛反应,硝基乙烷为溶剂,合成茚酮衍生物。其反应式如下:
以上方法中有的使用的原料昂贵难得,有的反应条件苛刻,有的采用毒性较大的甲醛,有的反应步骤较复杂。因此,减少反应成本,避免使用对环境影响较大的试剂参与反应,有着非常重要的现实意义。
发明内容
本发明的目的在于提供一种工艺合理、低毒性、产品质量好的由DMSO合成茚酮衍生物的方法。
实现本发明目的的技术方案是:
一种由DMSO合成茚酮衍生物的方法,反应式为:
步骤如下:以苯乙酰乙酸乙酯和二甲基亚砜为原料,在三氟甲磺酸亚铜(CuOTf)的催化下,以过量的DMSO为溶剂,在80~120℃下反应8~24h,反应结束后,反应液经分离纯化得到2-乙氧基甲酰基-1-茚酮。
所述的苯乙酰乙酸乙酯和DMSO的摩尔比为1:20~1:30,优选为1:25~1:30。
所述的催化剂三氟甲磺酸亚铜用量为苯乙酰乙酸乙酯摩尔量的1~2.5倍,优选为1~2倍。
所述的反应温度优选为100~120℃。
所述的反应时间优选为8~12h。
所述的反应液经分离纯化方法为:反应结束后,反应液加入乙酸乙酯稀释,饱和食盐水洗涤3次,分离取有机层,经无水硫酸钠干燥后减压蒸馏除去溶剂,得到粗产物,粗产物经由以乙酸乙酯和石油醚的体积比为6:1的洗脱剂柱层析分离得到2-乙氧基甲酰基-1-茚酮。
与现有技术相比,本发明的显著优点是:
(1)工艺条件合理,操作简单安全,原料便宜易得;
(2)三废少,环境友好;
(3)利用DMSO作为碳源,是DMSO的新应用。
具体实施方式
下面结合实施例对本发明作进一步详述。
实施例1
在25mL真空反应管中加入0.960g(5mmol)苯乙酰乙酸乙酯、7.1mL DMSO和1.805g(5mmol)三氟甲基亚磺酸铜。80℃搅拌反应12h。反应结束后,反应液加入20mL乙酸乙酯稀释,饱和食盐水洗涤3次,分离取有机层,经无水硫酸钠干燥后减压蒸馏除去溶剂。粗产物经由柱层析(洗脱剂为乙酸乙酯和石油醚混合液,二者体积比为6:1)分离得到2-乙氧基甲酰基-1-茚酮0.810g,产率为79%。
实施例2
在25mL真空反应管中加入0.960g(5mmol)苯乙酰乙酸乙酯、10.7mL DMSO和4.513g(12.5mmol)三氟甲基亚磺酸铜。100℃搅拌反应24h。反应结束后,反应液加入20mL乙酸乙酯稀释,饱和食盐水洗涤3次,分离取有机层,经无水硫酸钠干燥后减压蒸馏除去溶剂。粗产物经由柱层析(洗脱剂为乙酸乙酯和石油醚混合液,二者体积比为6:1)分离得到2-乙氧基甲酰基-1-茚酮0.850g,产率为83%。
实施例3
在25mL真空反应管中加入0.960g(5mmol)苯乙酰乙酸乙酯、8.9mL DMSO和3.610g(1mmol)三氟甲基亚磺酸铜。120℃搅拌反应8h。反应结束后,反应液加入20mL乙酸乙酯稀释,饱和食盐水洗涤3次,分离取有机层,经无水硫酸钠干燥后减压蒸馏除去溶剂。粗产物经由柱层析(洗脱剂为乙酸乙酯和石油醚混合液,二者体积比为6:1)分离得到2-乙氧基甲酰基-1-茚酮0.830g,产率为81%。
Claims (8)
1.一种由二甲基亚砜合成茚酮衍生物的方法,其特征在于,步骤如下:以苯乙酰乙酸乙酯和二甲基亚砜为原料,在三氟甲磺酸亚铜的催化下,以过量的二甲基亚砜为溶剂,在80~120℃下反应8~24h,反应结束后,反应液经分离纯化得到2-乙氧基甲酰基-1-茚酮。
2.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的苯乙酰乙酸乙酯和二甲基亚砜的摩尔比为1:20~1:30。
3.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的苯乙酰乙酸乙酯和二甲基亚砜的摩尔比为1:25~1:30。
4.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的催化剂三氟甲磺酸亚铜用量为苯乙酰乙酸乙酯摩尔量的1~2.5倍。
5.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的催化剂三氟甲磺酸亚铜用量为苯乙酰乙酸乙酯摩尔量的1~2倍。
6.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的反应温度为100~120℃。
7.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的反应时间为8~12h。
8.根据权利要求1所述的由二甲基亚砜合成茚酮衍生物的方法,其特征在于,所述的反应液经分离纯化方法为:反应结束后,反应液加入乙酸乙酯稀释,饱和食盐水洗涤3次,分离取有机层,经无水硫酸钠干燥后减压蒸馏除去溶剂,得到粗产物,粗产物经由以乙酸乙酯和石油醚的体积比为6:1的洗脱剂柱层析分离得到2-乙氧基甲酰基-1-茚酮。
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Citations (3)
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WO2005058848A1 (en) * | 2003-12-17 | 2005-06-30 | Merck & Co., Inc. | (3,4-disubstituted)propanoic carboxylates as s1p (edg) receptor agonists |
WO2006045246A1 (en) * | 2004-10-29 | 2006-05-04 | China Petroleum & Chemical Corporation | Cyclopentane carboxylate compounds, process and intermediates for preparing the same and use thereof |
CN104211598A (zh) * | 2013-06-04 | 2014-12-17 | 上海爱普植物科技有限公司 | 2-(邻羟基苯基)环丙烷-1-甲酸的制备方法 |
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WO2005058848A1 (en) * | 2003-12-17 | 2005-06-30 | Merck & Co., Inc. | (3,4-disubstituted)propanoic carboxylates as s1p (edg) receptor agonists |
WO2006045246A1 (en) * | 2004-10-29 | 2006-05-04 | China Petroleum & Chemical Corporation | Cyclopentane carboxylate compounds, process and intermediates for preparing the same and use thereof |
CN104211598A (zh) * | 2013-06-04 | 2014-12-17 | 上海爱普植物科技有限公司 | 2-(邻羟基苯基)环丙烷-1-甲酸的制备方法 |
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SARTORI, GIOVANNI等: "Friedel-Crafts coordinated processes: highly selective synthesis of ethyl 1-oxo-2-indancarboxylates and 1-oxo-2-acetylindanes", 《TETRAHEDRON LETTERS》 * |
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