CN104402811A - 一种合成二甲氨基吡啶甲酸的方法 - Google Patents

一种合成二甲氨基吡啶甲酸的方法 Download PDF

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CN104402811A
CN104402811A CN201410632883.8A CN201410632883A CN104402811A CN 104402811 A CN104402811 A CN 104402811A CN 201410632883 A CN201410632883 A CN 201410632883A CN 104402811 A CN104402811 A CN 104402811A
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formic acid
picolinic acid
pyridine
dimethylamino
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董燕敏
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Changzhou University
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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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3

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  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明公开了一种合成吡啶甲酸的方法，其处理方法为：烷基吡啶加入到高锰酸钾溶液中，调节pH为碱性，加入冠醚催化，反应物用无离子水洗涤，烘干得吡啶甲酸备用。再用吡啶甲酸，氯化亚砜，乙酸乙酯混合，加热回流6小时，常压下蒸出，冷却析出晶体，再加入无水乙醇，搅拌析出沉淀，过滤，用氯化钠溶液清洗3次，蒸干，得到甲酸双吡啶盐备用。在三口反应瓶中，加入甲酸双吡啶盐，甲基盐酸盐升温至170-180℃，搅拌反应，冷却，调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，重结晶，脱色，得到二甲氨基吡啶甲酸，产率为68.9％，本发明产率高，无污染。

Description

一种合成二甲氨基吡啶甲酸的方法
技术领域
本发明属于有机化学合成领域，涉及到一种二甲氨基吡啶甲酸的合成方法。
背景技术
吡啶甲酸是典型的杂环类两性化合物。吡啶甲酸衍生物广泛应用于医药，化工，食品及生活中，具有不可替代的作用与价值。其衍生物二甲氨基吡啶甲酸是重要的化学中间体，也是精细化工的重要原材料，市场需求量巨大，传统合成二甲氨基吡啶甲酸的方法是：煤焦油中提取吡啶，再经脱水，精馏。这种方法催化剂对原料的纯度要求高，反应条件高和有毒气体，造成环境污染，现在很少使用。本发明提供一种新型二甲氨基吡啶甲酸的合成方法，合成简单，不会造成空气污染。
发明内容
为了解决现有技术中存在的容易产生环境污染的问题，本发明提供了一种合成二甲氨基吡啶甲酸方法，用该方法合成二甲氨基吡啶甲酸，避免了传统方法中造成环境污染的问题，大大提高了产率。
达到上述目的，本发明二甲氨基吡啶甲酸的合成路线为：
本发明涉及的二甲氨基吡啶甲酸的合成过程包括以下步骤：
1.吡啶甲酸的合成：
(1)将2g的高锰酸钾放入50℃的蒸馏水中溶解，搅拌20分钟，静置1小时后加入2mol/L氢氧化钠溶液调节pH为9-10，加入10g烷基吡啶，5g冠醚，搅拌升温至80-90℃，在此温度下搅拌1-2小时；
(2)反应完后，抽滤，反应物用0.4g的无离子水洗涤，烘干得8.2g的固体粉末吡啶甲酸。
2.二甲氨基吡啶甲酸的合成：
(1)在圆底烧瓶中加入8.2g吡啶甲酸，20mL0.18mol/L的氯化亚砜，20mL0.32mol/L的乙酸乙酯，加热至120-140℃回流6小时，常压下蒸出，冷却析出晶体，再加入20mL无水乙醇，搅拌析出沉淀，过滤，用饱和的氯化钠溶液清洗3次，蒸干，得到6.9甲酸双吡啶盐备用；
(2)在三口反应瓶中，加入6.9g甲酸双吡啶盐，3g甲基盐酸盐升温至170-180℃，搅拌反应5小时；
(3)冷却至60-80℃，加入2mol/L的氢氧化钠溶液调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，用乙酸乙酯进行重结晶，用硅胶柱脱色，得到白色结晶6.89g二甲氨基吡啶甲酸，产率为68.9％。
具体实施方案：
将2g的高锰酸钾放入50℃的蒸馏水中溶解，搅拌20分钟，静置1小时后加入2mol/L氢氧化钠溶液调节pH为9-10，加入10g烷基吡啶，5g冠醚，搅拌升温至80-90℃，在此温度下搅拌1-2小时，反应完后，抽滤，反应物用0.4g的无离子水洗涤，烘干得8.2g的固体粉末吡啶甲酸备用。在圆底烧瓶中加入8.2g吡啶甲酸，20mL0.18mol/L的氯化亚砜，20mL0.32mol/L的乙酸乙酯，加热至120-140℃回流6小时，常压下蒸出，冷却析出晶体，再加入20mL无水乙醇，搅拌析出沉淀，过滤，用饱和的氯化钠溶液清洗3次，蒸干，得到6.9甲酸双吡啶盐备用。在三口反应瓶中，加入6.9g甲酸双吡啶盐，3g甲基盐酸盐升温至170-180℃，搅拌反应5小时，冷却至60-80℃，加入2mol/L的氢氧化钠溶液调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，用乙酸乙酯进行重结晶，用硅胶柱脱色，得到白色结晶6.89g二甲氨基吡啶甲酸，产率为68.9％。
实例1
将2g的高锰酸钾放入50℃的蒸馏水中溶解，搅拌20分钟，静置1小时后加入2mol/L氢氧化钠溶液调节pH为9，加入10g烷基吡啶，5g冠醚，搅拌升温至80℃，在此温度下搅拌1小时，反应完后，抽滤，反应物用0.4g的无离子水洗涤，烘干得8.0g的固体粉末吡啶甲酸备用。在圆底烧瓶中加入8.0g吡啶甲酸，20mL0.18mol/L的氯化亚砜，20mL0.32mol/L的乙酸乙酯，加热至120℃回流6小时，常压下蒸出，冷却析出晶体，再加入20mL无水乙醇，搅拌析出沉淀，过滤，用饱和的氯化钠溶液清洗3次，蒸干，得到6.3g甲酸双吡啶盐备用。在三口反应瓶中，加入6.3g甲酸双吡啶盐，3g甲基盐酸盐升温至170℃，搅拌反应5小时，冷却至80℃，加入2mol/L的氢氧化钠溶液调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，用乙酸乙酯进行重结晶，用硅胶柱脱色，得到白色结晶6.80g二甲氨基吡啶甲酸，产率为68.0％。
实例2
将2g的高锰酸钾放入50℃的蒸馏水中溶解，搅拌20分钟，静置1小时后加入2mol/L氢氧化钠溶液调节pH为9，加入10g烷基吡啶，5g冠醚，搅拌升温至85℃，在此温度下搅拌1-2小时，反应完后，抽滤，反应物用0.4g的无离子水洗涤，烘干得8.1g的固体粉末吡啶甲酸备用。在圆底烧瓶中加入8.1g吡啶甲酸，20mL0.18mol/L的氯化亚砜，20mL0.32mol/L的乙酸乙酯，加热至130℃回流6小时，常压下蒸出，冷却析出晶体，再加入20mL无水乙醇，搅拌析出沉淀，过滤，用饱和的氯化钠溶液清洗3次，蒸干，得到6.8g甲酸双吡啶盐备用。在三口反应瓶中，加入6.8g甲酸双吡啶盐，3g甲基盐酸盐升温至175℃，搅拌反应5小时，冷却至70℃，加入2mol/L的氢氧化钠溶液调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，用乙酸乙酯进行重结晶，用硅胶柱脱色，得到白色结晶6.85g二甲氨基吡啶甲酸，产率为68.5％。
实例3
将2g的高锰酸钾放入50℃的蒸馏水中溶解，搅拌20分钟，静置1小时后加入2mol/L氢氧化钠溶液调节pH为10，加入10g烷基吡啶，5g冠醚，搅拌升温至90℃，在此温度下搅拌2小时，反应完后，抽滤，反应物用0.4g的无离子水洗涤，烘干得8.1g的固体粉末吡啶甲酸备用。在圆底烧瓶中加入8.1g吡啶甲酸，20mL0.18mol/L的氯化亚砜，20mL0.32mol/L的乙酸乙酯，加热至140℃回流6小时，常压下蒸出，冷却析出晶体，再加入20mL无水乙醇，搅拌析出沉淀，过滤，用饱和的氯化钠溶液清洗3次，蒸干，得到6.9g甲酸双吡啶盐备用。在三口反应瓶中，加入6.9g甲酸双吡啶盐，3g甲基盐酸盐升温至170-180℃，搅拌反应5小时，冷却至60℃，加入2mol/L的氢氧化钠溶液调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，用乙酸乙酯进行重结晶，用硅胶柱脱色，得到白色结晶6.89g二甲氨基吡啶甲酸，产率为68.9％。

Claims (2)

1.一种合成二甲氨基吡啶甲酸的方法，其特征在于吡啶甲酸的合成：
(1)将2g的高锰酸钾放入50℃的蒸馏水中溶解，搅拌20分钟，静置1小时后加入2mol/L氢氧化钠溶液调节pH为9-10，加入10g烷基吡啶，5g冠醚，搅拌升温至80-90℃，在此温度下搅拌1-2小时；
(2)反应完后，抽滤，反应物用0.4g的无离子水洗涤，烘干得8.2g的固体粉末吡啶甲酸。
2.根据权利要求1所述一种合成二甲氨基吡啶甲酸的方法，其特征在于：
(1)在圆底烧瓶中加入8.2g吡啶甲酸，20mL0.18mol/L的氯化亚砜，20mL0.32mol/L的乙酸乙酯，加热至120-140℃回流6小时，常压下蒸出，冷却析出晶体，再加入20mL无水乙醇，搅拌析出沉淀，过滤，用饱和的氯化钠溶液清洗3次，蒸干，得到6.9甲酸双吡啶盐备用；
(2)在三口反应瓶中，加入6.9g甲酸双吡啶盐，3g甲基盐酸盐升温至170-180℃，搅拌反应5小时；
(3)冷却至60-80℃，加入2mol/L的氢氧化钠溶液调节pH为14，蒸馏，用1,2-二氯乙烷取出剩余的水分，用乙酸乙酯进行重结晶，用硅胶柱脱色，得到白色结晶4.2g二甲氨基吡啶甲酸。
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104987308A (zh) * 2015-06-26 2015-10-21 林达钦 一种5-溴-2-吡啶甲酸的制备方法

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Application publication date: 20150311