CN103724257A - 一种制备2，3-二羧酸酯吡啶类化合物的方法 - Google Patents

一种制备2，3-二羧酸酯吡啶类化合物的方法 Download PDF

Info

Publication number
CN103724257A
CN103724257A CN201210384297.7A CN201210384297A CN103724257A CN 103724257 A CN103724257 A CN 103724257A CN 201210384297 A CN201210384297 A CN 201210384297A CN 103724257 A CN103724257 A CN 103724257A
Authority
CN
China
Prior art keywords
compound
palladium
acetic acid
formic acid
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201210384297.7A
Other languages
English (en)
Other versions
CN103724257B (zh
Inventor
姜鹏
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenyang Sinochem Agrochemicals R&D Co Ltd
Original Assignee
Shenyang Research Institute of Chemical Industry Co Ltd
Sinochem Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shenyang Research Institute of Chemical Industry Co Ltd, Sinochem Corp filed Critical Shenyang Research Institute of Chemical Industry Co Ltd
Priority to CN201210384297.7A priority Critical patent/CN103724257B/zh
Publication of CN103724257A publication Critical patent/CN103724257A/zh
Application granted granted Critical
Publication of CN103724257B publication Critical patent/CN103724257B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

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

Abstract

本发明公开了一种制备2，3-二羧酸酯吡啶类化合物的方法，如反应式一所示，由化合物1在甲酸/乙酸体系中与钯盐反应制备2，3-二羧酸酯吡啶。具体操作为将钯盐分散于乙酸中，滴加甲酸并加入化合物1，升温至50-120。C，并在此温度下加热2-15小时后停止加热，反应物料温度降至室温，过滤出生成的钯，滤液减压蒸馏回收乙酸，得到对应的2，3-二羧酸酯吡啶。钯盐与化合物1的摩尔比为0.005-0.3:1，甲酸与化合物1的摩尔比为1.1-5:1。本实验操作简便，原料易得，是一种环境友好且高纯度、高收率的2，3-二羧酸酯吡啶制备方法。
Figure DDA00002242662400011
式中R1选自H,CH3或CH2-O-CH3；R2、R3可相同或不同，选自CH3或CH2-CH3。

Description

一种制备2,3-二羧酸酯吡啶类化合物的方法
技术领域
本发明属于有机合成领域，具体涉及一种制备2，3-二羧酸酯吡啶类化合物的方法。
技术背景
2，3-二羧酸酯吡啶类化合物是咪唑啉酮类除草剂的关键中间体。美国专利US 5281713公开了采用喹啉或喹啉衍生物氧化再进行酯化反应得到2,3-二羧酸酯类化合物，但是该方法收率低，最好也达不到50%，如果需要高纯度产品还需要在进行纯化；EP 0461401A1公开了采用丁烯二酸卤代衍生物与丙烯醛类化合物在氨或氨盐存在下缩合合成二羧酸酯类化合物，但是这种方法合成的产品副产较多，只能用熔点来表征化合物；日本专利JP1-143857公开了采用2-烯胺丁二酸酯与丙烯醛类化合物缩合合成2,3-二羧酸酯类化合物的方法，但其因副产多而不利于中间体的纯化。
发明内容
本发明的目的在于提供一种高新的2，3-二羧酸酯吡啶类化合物的制备方法。
为达到上述目的，本发明采用如反应式一所示化合物1在甲酸/乙酸体系中与钯盐反应制备2，3-二羧酸酯吡啶，其反应式如下所示：
式中R1选自H,CH3或CH2-O-CH3；R2、R3可相同或不同，选自CH3或CH2-CH3。
本发明操作如下：
将钯盐分散于乙酸中，滴加甲酸并加入化合物1，升温至50-120℃，并在此温度下加热2-15小时后停止加热，反应物料温度降至室温，过滤出生成的钯，滤液减压蒸馏回收乙酸，得到对应的2，3-二羧酸酯吡啶。钯盐与化合物1的摩尔比为0.005-0.3:1，甲酸与化合物1的摩尔比为1.1-5:1。
化合物1是由相应的烯醛与苄胺脱水反应，通过脱水得到的水质量控制反应进程，产生的中间体与丁炔二酸酯在120-180°C反应4-6小时得到化合物1。
乙酸在该反应中为溶剂，用量没有特殊的要求。甲酸在反应中的作用为还原剂，将钯盐中的钯还原为单质钯，单质钯为催化剂。
本发明在实验阶段考察了贵金属盐如三氯化钌、三氯化依、氯铂酸、三氯化铑及氯化钯后，发现氯化钯与甲酸还原后生成的钯具有良好的催化性；进一步实验发现，钯盐可以是乙酸钯、硝酸钯、氯化钯、溴化钯或碘化钯。实验发现，钯盐催化效果主要是钯单质决定的，但催化效率与其负离子的关系明显，其中碘化钯获得的产品收率最高，硝酸钯次之,氯化钯与溴化钯有大致相同的催化效率,而乙酸钯尽管有良好的溶解性，但是在此反应中却是催化效率最低的。
本发明中钯盐与化合物1的摩尔比优选为0.05-0.2:1。
本发明中甲酸与化合物1的摩尔比优选为1.5-3:1。
本发明中优选的反应温度为70-120℃，优选的反应时间为3-12小时。
本实验操作简便，原料易得，虽然使用贵金属钯盐，但反应结束后可以回收钯，而回收钯的可以重复使用，回收的乙酸可以重复使用，因而是一种环境友好且高纯度、高收率的2，3-二羧酸酯吡啶制备方法。
具体实施方式
以下具体实施例用于进一步说明本发明，但本发明绝非仅限于这些实例。钯盐、甲酸以克（g）计量，乙酸以毫升（mL）计，化合物1以克（g）计量。以上原料均有市售，化合物1（如1-苄基-2，3-二羧酸乙酯-5-甲氧甲基-4-氢-吡啶、1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶、1-苄基-2，3-二羧酸乙酯-4-氢-吡啶）为自制。
实施例1
将3.60g碘化钯加入250mL三口瓶中，加入70mL乙酸，搅拌下滴加7.6g甲酸，加入16.5g 1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶，反应混合物在80℃下搅拌9小时，冷却至室温，过滤，回收固体，滤液减压蒸馏回收乙酸，得产品11.1g，收率91.8%。
实施例2
将2.30g硝酸钯加入250mL三口瓶中，加入70mL乙酸，搅拌下滴加8.1g甲酸，加入22.8g 1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶，反应混合物在100℃下搅拌6小时，冷却至室温，过滤，回收固体，滤液减压蒸馏回收乙酸，得产品14.8g，收率87.9%。
实施例3
将2.66g溴化钯加入250mL三口瓶中，加入70mL乙酸，搅拌下滴加甲酸8.3g，加入22.8g 1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶，反应混合物在80℃下搅拌7小时，冷却至室温，过滤，回收固体，滤液减压蒸馏回收乙酸，得产品14.4g，收率86.7%。
实施例4
将2.77g氯化钯加入250mL三口瓶中，加入100mL乙酸，搅拌下滴加9.1g甲酸，加入32.9g 1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶，反应混合物在90。C下搅拌8小时，冷却至室温，过滤，回收固体，滤液减压蒸馏回收乙酸，得产品20.6g，收率85.3%。
实施例5
将2.24g乙酸钯加入250mL三口瓶中，加入100mL乙酸，搅拌下滴加8.6g甲酸，加入32.9g 1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶，反应混合物在90℃下搅拌8小时，冷却至室温，过滤，回收固体，滤液减压蒸馏回收乙酸，得产品19.8g，收率81.9%。
实施例6
将1.12g乙酸钯加入250mL三口瓶中，加入100mL乙酸，搅拌下滴加7.2g甲酸，加入32.9g 1-苄基-2，3-二羧酸乙酯-5-甲基-4-氢-吡啶，反应混合物在90℃下搅拌12小时，冷却至室温，过滤，回收固体，滤液减压蒸馏回收乙酸，得产品19.3g，收率80.2%。

Claims (7)

1.一种制备2，3-二羧酸酯吡啶类化合物的方法，其特征在于：由化合物1在甲酸/乙酸体系中与钯盐反应制备2，3-二羧酸酯吡啶，反应式如下：
Figure FDA00002242662200011
式中R1选自H,CH3或CH2-O-CH3；R2、R3可相同或不同，选自CH3或CH2-CH3。
2.根据权利要求1所述的方法，其特征在于：将钯盐分散于乙酸中，滴加甲酸并加入化合物1，升温至50-120℃，并在此温度下加热2-15小时后停止加热，反应物料温度降至室温，过滤出生成的钯，滤液减压蒸馏回收乙酸，得到对应的2，3-二羧酸酯吡啶；钯盐与化合物1的摩尔比为0.005-0.3:1，甲酸与化合物1的摩尔比为1.1-5:1。
3.根据权利要求1或2所述的方法，其特征在于：所述的钯盐是乙酸钯、氯化钯、溴化钯、硝酸钯或碘化钯。
4.根据权利要求2所述的方法，其特征在于：钯盐与化合物1的摩尔比为0.05-0.2:1。
5.根据权利要求2所述的方法，其特征在于：甲酸与化合物1摩尔比为1.5-3.0：1。
6.根据权利要求2所述的方法，其特征在于：反应温度是70-120℃。
7.根据权利要求2所述的方法，其特征在于：反应时间为3-12小时。
CN201210384297.7A 2012-10-11 2012-10-11 一种制备2,3-二羧酸酯吡啶类化合物的方法 Active CN103724257B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201210384297.7A CN103724257B (zh) 2012-10-11 2012-10-11 一种制备2,3-二羧酸酯吡啶类化合物的方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201210384297.7A CN103724257B (zh) 2012-10-11 2012-10-11 一种制备2,3-二羧酸酯吡啶类化合物的方法

Publications (2)

Publication Number Publication Date
CN103724257A true CN103724257A (zh) 2014-04-16
CN103724257B CN103724257B (zh) 2015-06-10

Family

ID=50448591

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201210384297.7A Active CN103724257B (zh) 2012-10-11 2012-10-11 一种制备2,3-二羧酸酯吡啶类化合物的方法

Country Status (1)

Country Link
CN (1) CN103724257B (zh)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5281713A (en) * 1991-12-20 1994-01-25 American Cyanamid Company Process for the manufacture of 2-alkoxymethylacrolein
JPH0656787A (ja) * 1992-03-10 1994-03-01 American Cyanamid Co ２，３−ピリジンジカルボン酸ジアルキル及びその誘導体の製法
US5892050A (en) * 1998-01-28 1999-04-06 American Cyanamid Company Process for the preparation of pyridine dicarboxylate derivatives
US5925764A (en) * 1998-06-15 1999-07-20 Wu; Wen-Xue Process and intermediated for the manufacture of pyridine-2, 3-dicarboxylate compounds
CN101768111A (zh) * 2009-01-07 2010-07-07 上海开拓者化学研究管理有限公司 一种2-氯-5-氟吡啶-3-甲酸的制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5281713A (en) * 1991-12-20 1994-01-25 American Cyanamid Company Process for the manufacture of 2-alkoxymethylacrolein
JPH0656787A (ja) * 1992-03-10 1994-03-01 American Cyanamid Co ２，３−ピリジンジカルボン酸ジアルキル及びその誘導体の製法
US5892050A (en) * 1998-01-28 1999-04-06 American Cyanamid Company Process for the preparation of pyridine dicarboxylate derivatives
US5925764A (en) * 1998-06-15 1999-07-20 Wu; Wen-Xue Process and intermediated for the manufacture of pyridine-2, 3-dicarboxylate compounds
CN101768111A (zh) * 2009-01-07 2010-07-07 上海开拓者化学研究管理有限公司 一种2-氯-5-氟吡啶-3-甲酸的制备方法

Also Published As

Publication number Publication date
CN103724257B (zh) 2015-06-10

Similar Documents

Publication Publication Date Title
CN100503601C (zh) 托烷司琼的制备工艺
CN103524383B (zh) 一种制备帕拉米韦的方法
CN111646922B (zh) 一种2-（4-溴-2-氰基-6-氟苯基）乙酸的合成方法
CN105001028A (zh) 一种不对称共轭二炔烃类化合物的合成方法
CN105330598A (zh) 一种吡非尼酮的制备方法
CN104311485B (zh) 一种治疗白血病的药物博舒替尼的制备方法
CN101654419A (zh) 马来酸氟伏沙明的制备方法
CN101863829B (zh) 一种3-氟-4-氨基吡啶的合成方法
CN103172639B (zh) 一种基于盐酸胍的六元二环胍的制备方法
CN104817583B (zh) 碳桥联双酰胺基稀土胺化物及其制备和在催化醛与胺酰胺化合成反应中的应用
CN103724257B (zh) 一种制备2,3-二羧酸酯吡啶类化合物的方法
TW202206412A (zh) 製備（ｓ）－２－胺基－３－（４－（２，３－二甲基吡啶－４－基）苯基）丙酸甲酯及其鹽酸鹽的方法
KR100574350B1 (ko) 2-아미노피리딘 유도체의 제조방법
CN108840806B (zh) 一种苯甲酰胺类化合物的制备方法
CN106748725B (zh) 一种4-氯-2-氟-苯丙酸的制备方法
CN111848430B (zh) 2-([1,1’-联苯]-4-基)-2-甘氨酸类化合物的合成方法
CN111320622A (zh) 一种莫西沙星盐酸盐的合成方法
CN109096105A (zh) 烯基活泼亚甲基化合物的还原方法及还原产物
CN102993116A (zh) 一种苯并噁嗪类激动剂的制备方法
CN103755657A (zh) 一种利伐沙班中间体的制备方法
CN109336795B (zh) 3-三氟甲基苯硫酚及3-甲硫基三氟甲苯的制备方法
CN104710345B (zh) 用于制备4‑（2‑（4‑甲基苯基硫基））苯基哌啶的化合物、其制备方法及应用
CN102286024A (zh) 利塞膦酸钠的合成方法
CN103058884A (zh) 1-羟甲基环丙基乙腈的合成方法
CN112745205B (zh) 辛波莫德中间体的制备方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C41 Transfer of patent application or patent right or utility model
TR01 Transfer of patent right

Effective date of registration: 20160115

Address after: 110021 Liaodong Road, Tiexi District, Liaoning, No. 8-1, No.

Patentee after: SHENYANG SINOCHEM PESTICIDE CHEMICAL RESEARCH AND DEVELOPMENT CO., LTD.

Address before: 100031 Beijing, Xicheng District, the door of the revitalization of the main street, No. 28

Patentee before: Sinochem Corporation

Patentee before: Shenyang Research Institute of Chemical Industry