CN109081824A - 2-氨基噻吩类化合物的制备方法 - Google Patents

2-氨基噻吩类化合物的制备方法 Download PDF

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CN109081824A
CN109081824A CN201811165670.3A CN201811165670A CN109081824A CN 109081824 A CN109081824 A CN 109081824A CN 201811165670 A CN201811165670 A CN 201811165670A CN 109081824 A CN109081824 A CN 109081824A
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preparation
class compound
grams
aminothiophene
sulphur
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方标
许萌
柯军梁
王哲
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Shangyu Research Institute of ZJUT
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Shangyu Research Institute of ZJUT
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/66—Nitrogen atoms not forming part of a nitro radical

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

本发明公开了一种2‑氨基噻吩类化合物的制备方法，包括如下步骤：利用酮、腈和硫磺为原料，摩尔比1:1:1，三组分催化环合制备2‑氨基噻吩类化合物。本发明以邻氨基噻吩腈和酮为原料，操作步骤简单，产物收率高，成本较低等优点，具有较高的工业化价值。

Description

2-氨基噻吩类化合物的制备方法
技术领域
本发明属于化学药物中间体制备方法技术领域，具体涉及一种2-氨基噻吩类化合物的制备方法。
背景技术
2-氨基噻吩类化合物，结构如式(Ⅰ)所示，是一种重要的化学药物中间体，用于合成他克林类似物，他克林是治疗阿尔茨海默痴呆的药物，他克林能够抑制脑内AChE，增加脑内ACh含量；促进脑内AChE的释放；增加大脑皮质和海马的N-R密度；促进脑组织对葡萄糖的利用，改善学习、记忆能力的降低。
国内外公开的有关2-氨基噻吩类化合物的制备方法很少。
发明内容
本发明提供了一种2-氨基噻吩类化合物的制备方法，该以邻氨基噻吩腈和酮为原料，操作步骤简单，产物收率高，成本较低等优点，具有较高的工业化价值。
2-氨基噻吩类化合物的制备方法，包括如下步骤：利用酮、腈和硫磺为原料，摩尔比1:1:1，三组分催化环合制备2-氨基噻吩类化合物；其反应路线如下：
所述的原料酮选自下面的任一种：
所述的原料腈选自下面的任一种：
所述的催化剂用量为5-20％，选自下述有机碱中的一种或几种：
所述的反应温度为20～110℃，反应时间为30～180min。
所述的溶剂选自以下的一种：甲醇、乙醇、甲苯、DMF、NMP、三氯甲烷和水，溶剂的用量1g:1～10mL。
本发明同现有技术相比，其有益效果体现在：
(1)以腈、酮和硫磺为原料，价廉易得，成本较低，产品市场竞争能力强。
(2)合成路线采用三组分一锅法，反应操作简单，工艺安全，产品收率高。
具体实施方式
实施例1的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲苯50mL和0.5mL催化剂哌啶，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品17.5克，摩尔收率77.8％。
实施例2：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂哌啶，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品21.7克，摩尔收率96.4％。
实施例3：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂吗啉，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品18.6克，摩尔收率93.9％。
实施例4：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂三乙胺，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品16.5克，摩尔收率83.3％。
实施例5：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂甲醇钠，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品8.9克，摩尔收率44.9％。
实施例6：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂喹啉，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品12.9克，摩尔收率65.2％。
实施例7：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、6.6克丙二腈和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂哌啶，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品16.9克，摩尔收率94.9％。
实施例8：的制备：
在200mL密闭的四口反应瓶中，加入9.8克环己酮、8.6克3-硝基丙腈和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂哌啶，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品19.4克，摩尔收率98.0％。
实施例9：的制备：
在200mL密闭的四口反应瓶中，加入15.5克对氯苯乙酮、11.3克氰乙酸乙酯和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂哌啶，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品25.7克，摩尔收率91.2％。
实施例10：的制备：
在200mL密闭的四口反应瓶中，加入15.5克对氯苯乙酮、6.6克丙二腈和3.2克硫磺，加入溶剂甲醇50mL和0.5mL催化剂哌啶，搅拌控温30℃，反应60min，反应结束，过滤重结晶得目标产品20.7克，摩尔收率88.2％。

Claims (6)

1.2-氨基噻吩类化合物的制备方法，包括如下步骤：其特征在于：利用酮、腈和硫磺为原料，摩尔比1:1:1，三组分催化环合制备2-氨基噻吩类化合物；其反应路线如下：
2.根据权利要求1中所述的2-氨基噻吩类化合物的制备方法，其特征在于：所述的原料酮选自下面的任一种：
3.根据权利要求1中所述的2-氨基噻吩类化合物的制备方法，其特征在于：所述的原料腈选自下面的任一种：
4.根据权利要求1中所述的2-氨基噻吩类化合物的制备方法，其特征在于：所述的催化剂用量为5-20％，选自下述有机碱中的一种或几种：
5.根据权利要求1中所述的2-氨基噻吩类化合物的制备方法，其特征在于：所述的反应温度为20～110℃，反应时间为30～180min。
6.根据权利要求1中所述的2-氨基噻吩类化合物的制备方法，其特征在于：所述的溶剂选自以下的一种：甲醇、乙醇、甲苯、DMF、NMP、三氯甲烷和水，溶剂的用量1g:1～10mL。
CN201811165670.3A 2018-10-08 2018-10-08 2-氨基噻吩类化合物的制备方法 Pending CN109081824A (zh)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101065100A (zh) * 2004-11-30 2007-10-31 荷兰联合利华有限公司 作为清凉剂的噻吩并嘧啶
CN101854933A (zh) * 2007-09-10 2010-10-06 钙医学公司 调节细胞内钙的化合物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101065100A (zh) * 2004-11-30 2007-10-31 荷兰联合利华有限公司 作为清凉剂的噻吩并嘧啶
CN101854933A (zh) * 2007-09-10 2010-10-06 钙医学公司 调节细胞内钙的化合物

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Application publication date: 20181225