CN104478795A - 一种2-氯烟醛的制备方法 - Google Patents

一种2-氯烟醛的制备方法 Download PDF

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CN104478795A
CN104478795A CN201410683129.7A CN201410683129A CN104478795A CN 104478795 A CN104478795 A CN 104478795A CN 201410683129 A CN201410683129 A CN 201410683129A CN 104478795 A CN104478795 A CN 104478795A
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chlorine
cigarette aldehyde
nicotinaldehyde
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李卓才
李苏杨
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Suzhou Jonathan New Materials Technology Co Ltd
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Suzhou Jonathan New Materials Technology Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/60—Heterocyclic 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
    • C07D213/61—Halogen atoms or nitro radicals

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明提供了一种2-氯烟醛的制备方法，合成路线为：

Description

一种2-氯烟醛的制备方法
技术领域
本发明涉及一种2-氯烟醛的制备方法，属于药物中间体合成领域。
背景技术
2-氯烟醛作为一种重要的医药中间体，在制药领域应用日益广泛。2-氯烟醛的合成方法，文献报道很少，而且报道的方法存在种种缺陷，例如反应试剂昂贵，收率低，基本没有工业化生产的价值。
目前市场上的2-氯烟醛，只有小包装的试剂产品，而且价格非常昂贵，该产品的工业合成及规模化生产在市场上还是空白。随着2-氯烟醛市场需求的增大，人们迫切希望寻找到一条可以工业上放大的2-氯烟醛合成工艺。因此，2-氯烟醛的大规模合成和工艺开发研究，有着广阔的发展前景和良好的市场应用价值。
发明内容
鉴于上述问题，本发明提供一种简单易行、环保节能、原料易得成本低，可以实现工业规模大生产的2-氯烟醛制备方法。
本发明提供的2-氯烟醛制备方法，合成路线为：
包括以下步骤：
(1)将原料2-氯烟酸1还原生成2；
(2)将化合物2氧化生成2-氯烟醛3。
优选地，步骤(1)中还原试剂为三氟化硼乙醚溶液和硼氢化钠。
优选地，步骤(2)中氧化试剂为活性二氧化锰。
本发明提供的2-氯烟醛制备方法至少具有以下优点：反应条件温和，原料价廉易得，收率高，易纯化等。
具体实施方式
以下将对本发明进行详细描述。但这些实施方式并不限制本发明，本领域的普通技术人员根据这些实施方式所做出的方法上的变换均包含在本发明的保护范围内。
实施例1
(1)合成2-氯烟醇
向四口瓶中加入NaBH4(72g)和四氢呋喃450ml，冷却至-10℃～0℃。滴加三氟化硼乙醚溶液(575g)，控制内温＜10℃，滴毕，搅拌5min。然后滴加2-氯烟酸(100g)和四氢呋喃600ml混合液，控制温度＜30℃，滴毕，升温至室温反应6h，反应结束，加水淬灭，用质量分数为10％的氢氧化钠溶液调节pH值至8～9，抽滤，滤液用乙酸乙酯萃取两次，有机层用无水硫酸钠干燥，抽滤，浓缩得产物125g，直接用于下步反应。
(2)合成2-氯烟醛
向四口瓶中加入上步产物2-氯烟醇(125g)和二氯甲烷450ml，搅拌均匀，加入二氧化锰(280g)，升温至回流反应3h，反应结束，抽滤，滤液浓缩，冷却得77.8g黄色固体2-氯烟醛，收率86.6％，纯度：99.1％。HNMR(CDCl3，300MHz)δ:9.73(s,1H),8.58(d,1H),8.32(d,1H),7.80(t,1H)。
实施例2
(1)合成2-氯烟醇
向四口瓶中加入NaBH4(80g)和四氢呋喃500ml，冷却至-10℃～0℃。滴加三氟化硼乙醚溶液(590g)，控制内温＜10℃，滴毕，搅拌5min。然后滴加2-氯烟酸(100g)和四氢呋喃550ml混合液，控制温度＜25℃，滴毕，升温至室温反应8h，反应结束，加水淬灭，用质量分数为10％的氢氧化钠溶液调节pH值至8～9，抽滤，滤液用乙酸乙酯萃取两次，有机层用无水硫酸钠干燥，抽滤，浓缩得产物131g，直接用于下步反应。
(2)合成2-氯烟醛
向四口瓶中加入上步产物2-氯烟醇(131g)和二氯甲烷460ml，搅拌均匀，加入二氧化锰(300g)，升温至回流反应5h，反应结束，抽滤，滤液浓缩，冷却得79.2g黄色固体2-氯烟醛，收率88.2％，纯度：98.3％。HNMR(CDCl3，300MHz)δ:9.73(s,1H),8.58(d,1H),8.32(d,1H),7.80(t,1H)。
应当理解，虽然本说明书按照实施方式加以描述，但并非每个实施方式仅包含一个独立的技术方案，说明书的这种叙述方式仅仅是为清楚起见，本领域技术人员应当将说明书作为一个整体，各实施方式中的技术方案也可以经适当组合，形成本领域技术人员可以理解的其他实施方式。
上文所列出的一系列的详细说明仅仅是针对本发明的可行性实施方式的具体说明，它们并非用以限制本发明的保护范围，凡未脱离本发明技艺精神所作的等效实施方式或变更均应包含在本发明的保护范围之内。

Claims (3)

1.一种2-氯烟醛的制备方法，其特征在于，合成路线为：
包括以下步骤：
(1)将原料2-氯烟酸1还原生成2；
(2)将化合物2氧化生成2-氯烟醛3。
2.根据权利要求1所述的2-氯烟醛的制备方法，其特征在于，步骤(1)中还原试剂为三氟化硼乙醚溶液和硼氢化钠。
3.根据权利要求1所述的2-氯烟醛的制备方法，其特征在于，步骤(2)中氧化试剂为活性二氧化锰。
CN201410683129.7A 2014-11-24 2014-11-24 一种2-氯烟醛的制备方法 Pending CN104478795A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118388401A (zh) * 2024-06-28 2024-07-26 成都凯斯坦生物医药有限公司 一种4-氨基-2-氯烟醛的制备方法

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US20020143034A1 (en) * 1998-12-30 2002-10-03 Fujisawa Pharmaceutical Co. Ltd. Aminoalcohol derivatives and their use as beta 3 adrenergic agonists
CN1457339A (zh) * 2000-09-15 2003-11-19 阿诺麦德股份有限公司 趋化因子受体结合性杂环化合物
WO2006104141A1 (ja) * 2005-03-29 2006-10-05 Shionogi & Co., Ltd. ３－プロペニルセフェム誘導体
WO2010132999A1 (en) * 2009-05-21 2010-11-25 Chlorion Pharma, Inc. Methyl sulfanyl pyrmidmes useful as antiinflammatories, analgesics, and antiepileptics

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
CN118388401A (zh) * 2024-06-28 2024-07-26 成都凯斯坦生物医药有限公司 一种4-氨基-2-氯烟醛的制备方法
CN118388401B (zh) * 2024-06-28 2024-08-20 成都凯斯坦生物医药有限公司 一种4-氨基-2-氯烟醛的制备方法

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Application publication date: 20150401