CN104016908B - 一种2-氨基-3,5-二氯吡啶的合成方法 - Google Patents

一种2-氨基-3,5-二氯吡啶的合成方法 Download PDF

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CN104016908B
CN104016908B CN201410131637.4A CN201410131637A CN104016908B CN 104016908 B CN104016908 B CN 104016908B CN 201410131637 A CN201410131637 A CN 201410131637A CN 104016908 B CN104016908 B CN 104016908B
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dichloropyridines
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付锐
曹惊涛
来新胜
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Shaanxi Youbang Biomedical Technology Co.,Ltd.
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    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
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Abstract

本发明属于有机合成领域,具体涉及一种2-氨基-3,5-二氯吡啶的合成方法。包括以下步骤:以2-氨基-5-氯吡啶和N-氯代丁二酰亚胺为原料,二者物质的量之比为1:0.5-5,在适当的溶剂中,在0-100℃反应0.5-24个小时生成2-氨基-3,5-二氯吡啶粗品,经提纯后的纯品2-氨基-3,5-二氯吡啶。本发明的原料比较易得,价格合理,同时制备反应中没有使用重金属和腐蚀性气体,反应温和,对反映设备没有特殊的要求,普通的耐腐蚀设备即可生产,另外本发明反应条件适中,反应易于控制,产品纯度高等等优势条件,此工艺易于推广。

Description

一种2-氨基-3,5-二氯吡啶的合成方法
(一)技术领域
本发明属于有机合成领域,具体涉及一种2-氨基-3,5-二氯吡啶的合成方法。
(二)背景技术
2-氨基-3,5-二氯吡啶是有机合成的重要中间体,主要用于医药中间体,有机合成,有机溶剂,也可应用于染料生产、农药生产及香料等方面。
现有的2-氨基-3,5-二氯吡啶的制备存在以下缺点:
(1)副产物较多,导致产品的色泽较深,难以精制提纯。虽然可以用有机溶剂多次重结晶,但品质仍然无法满足高要求,而且反复结晶导致产品收率低,成本增加,操作繁琐;
(2)所使用的化学还原法对设备的腐蚀和环境的污染都十分严重,目前已限制开发;
(3)原料来源有限,价格昂贵,且操作较为麻烦;
(4)需要使用贵金属催化剂,增加了制备成本。
上述问题均需要改进。
(三)发明内容
本发明为了弥补现有技术的不足,提供了2-氨基-3,5-二氯吡啶的合成方法,该合成方法操作简单、产率高,适用于实验室及工业化生产。
本发明是通过如下技术方案实现的:
一种2-氨基-3,5-二氯吡啶的合成方法,其特殊之处在于:包括以下步骤:
以2-氨基-5-氯吡啶和N-氯代丁二酰亚胺为原料,二者物质的量之比为1:0.5-5,在适当的溶剂中,在0-100℃反应0.5-24个小时生成2-氨基-3,5-二氯吡啶粗品,经提纯后的纯品2-氨基-3,5-二氯吡啶。
本发明的2-氨基-3,5-二氯吡啶的合成方法,反应物与溶剂的投料量为:m2-氨基-5-氯吡啶:m溶剂=1:1-5,为重量之比。
本发明的2-氨基-3,5-二氯吡啶的合成方法,溶剂为叔丁醇与乙醇,甲醇,乙酸乙酯,丙醇,异丙醇,DMF中的一种或两种。
本发明的2-氨基-3,5-二氯吡啶的合成方法,提纯步骤包括蒸发浓缩、重结晶或硅胶柱层析分离。
本发明的2-氨基-3,5-二氯吡啶的合成方法,重结晶的溶剂为乙酸乙酯,乙醇,二氯甲烷,正己烷中的一种或两种物质。
本发明的有益效果:本发明的原料比较易得,价格合理,同时制备反应中没有使用重金属和腐蚀性气体,反应温和,对反映设备没有特殊的要求,普通的耐腐蚀设备即可生产,另外本发明反应条件适中,反应易于控制,产品纯度高等等优势条件,此工艺易于推广。
(四)具体实施方式
实施例1:
在一100ml的圆底单口烧瓶中加入DMF与甲醇的体积比为1:1.5的混合溶剂45ml,插入温度计,开动磁力搅拌器,并加入12.8g的2-氨基-5-氯吡啶,加入N-氯代丁二酰亚胺6.75g,在15℃搅拌下反应5小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用硅胶柱层析分离得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率53.1%,纯度96.28%(GC)。核磁共振分析:1HMR(CDCl3)400MHz:δ7.94(s,1H);δ7.51(s,1H);δ4.93(bs,2H)。熔点80℃-84℃(文献79℃-83℃)。
实施例2:
在一2L的圆底单口烧瓶中加入DMF与甲醇的体积比为1.5:1的混合溶剂700ml,插入温度计开动磁力搅拌器,并加入169.7g的2-氨基-5-氯吡啶,N-氯代丁二酰亚胺264.4g,在0℃搅拌下反应8.5小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用乙酸乙酯得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率55.5%,纯度98.50%(GC)。熔点81℃-84℃(文献79℃-83℃)。
实施例3:
在一10L的圆底三口烧瓶中加入DMF与甲醇的体积比为2.5:1的混合溶剂5500ml,插入温度计和安装冷凝回流装置,开动磁力搅拌器,并加入2560.8g的2-氨基-5-氯吡啶,N-氯代丁二酰亚胺6118.4g,,在45℃搅拌反应2.5小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用乙醇重结晶得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率70.5%,纯度98.20%(GC)。熔点80℃-84℃(文献79℃-83℃)。
实施例4:
在一50L的圆底三口烧瓶中加入DMF与甲醇的体积比为3:1的混合溶剂13.6L,插入温度计和安装冷凝回流装置,开动磁力搅拌器,并加入4628.2g的2-氨基-5-氯吡啶,N-氯代丁二酰亚胺9614.3g,在75℃搅拌下反应3小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用二氯甲烷重结晶得到纯产品2-氨基-3,5-二氯吡啶干燥后,计算收率74.6%,纯度99.57%(GC)。熔点81℃-85℃(文献79℃-83℃)。
实施例5:
在一100ml的圆底单口烧瓶中加入叔丁醇与乙醇的体积比为1:4的混合溶剂36ml,插入温度计,开动磁力搅拌器,并加入12.8g的2-氨基-5-氯吡啶,加入N-氯代丁二酰亚胺66.48g,在15℃搅拌下反应5小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用硅胶柱层析分离得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率53.0%,纯度96.24%(GC)。核磁共振分析:1HMR(CDCl3)400MHz:δ7.93(s,1H);δ7.51(s,1H);δ4.93(bs,2H)。熔点80℃-84℃(文献79℃-83℃)。
实施例6:
在一2L的圆底单口烧瓶中加入DMF与异丙醇的体积比为1:2的混合溶剂980ml,插入温度计开动磁力搅拌器,并加入169.7g的2-氨基-5-氯吡啶,N-氯代丁二酰亚胺264.4g,在0℃搅拌下反应8.5小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用正己烷重结晶得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率55.5%,纯度98.50%(GC)。熔点81℃-84℃(文献79℃-83℃)。
实施例7:
溶剂为乙酸乙酯40ml,在0℃搅拌下反应24小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用硅胶柱层析分离得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率53.3%,纯度96.20%(GC)。核磁共振分析:1HMR(CDCl3)400MHz:δ7.91(s,1H);δ7.51(s,1H);δ4.93(bs,2H)。熔点80℃-84℃(文献79℃-83℃),其他步骤与实施例1相同。
实施例8:
溶剂为丙醇30ml,在100℃搅拌下反应0.5小时。TLC和GC确定反应完成。旋蒸除去溶剂,得到粗产品,用乙酸乙酯、乙醇重结晶得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率55.8%,纯度98.50%(GC)。熔点81℃-84℃(文献79℃-83℃),其他步骤与实施例1相同。
上述实施例中,溶剂为叔丁醇与乙醇,甲醇,乙酸乙酯,丙醇,异丙醇,DMF中的一种或两种。重结晶溶剂为乙酸乙酯,乙醇,二氯甲烷,正己烷中的一种或两种。

Claims (1)

1.一种2-氨基-3,5-二氯吡啶的合成方法,其特征在于:包括以下步骤:在一10L的圆底三口烧瓶中加入DMF与甲醇的体积比为2.5:1的混合溶剂5500ml,插入温度计和安装冷凝回流装置,开动磁力搅拌器,并加入2560.8g的2-氨基-5-氯吡啶,N-氯代丁二酰亚胺6118.4g,在45℃搅拌反应2.5小时,TLC和GC确定反应完成,旋蒸除去溶剂,得到粗产品,用乙醇重结晶得到纯产品2-氨基-3,5-二氯吡啶,干燥后,计算收率70.5%,通过GC测试得纯度为98.20%。
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010083246A1 (en) * 2009-01-15 2010-07-22 Amgen Inc. Fluoroisoquinoline substituted thiazole compounds and methods of use
CN102811723A (zh) * 2010-01-06 2012-12-05 约瑟夫·P·埃里科 靶向药物研发的方法和组合物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010083246A1 (en) * 2009-01-15 2010-07-22 Amgen Inc. Fluoroisoquinoline substituted thiazole compounds and methods of use
CN102811723A (zh) * 2010-01-06 2012-12-05 约瑟夫·P·埃里科 靶向药物研发的方法和组合物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
One-Pot Chemoselective Bis(Suzuki–Miyaura Cross-Coupling): Efficient Access to 3,9-Bis[(hetero)aryl]-4H-pyrido[1,2-a]pyrimidin-4-one Derivatives Under Microwave Irradiation;Youssef Kabri et al;《European Journal of Organic Chemistry》;20120823;第2012卷(第28期);5595-5604,第5599页右栏最后一段 *

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