CN115403518A - 一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺 - Google Patents
一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺 Download PDFInfo
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- 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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- 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
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Abstract
一种5‑烷基吡啶‑2,3‑二羧酸酯的连续流合成工艺，属于有机合成技术领域。其包括以下步骤：将式II所示的2‑卤代‑3‑氧代丁二酸酯溶于含有氨气的醇溶液，与式III所示的1‑烷烯‑3‑酮于负载有固体酸的管道反应器中进行反应；反应液蒸馏脱溶得5‑烷基吡啶‑2,3‑二羧酸酯。本发明通过采用上述技术得到的5‑烷基吡啶‑2,3‑二羧酸酯，收率高，杂质少，后处理方便，三废污染少，且大大了降低安全隐患，适于工业化生产应用。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺。
背景技术
5-烷基吡啶-2,3-二羧酸酯是合成咪唑啉酮类化合物的重要中间体。咪唑啉酮类化合物如咪草烟、甲基咪草烟等在农药方面应用广泛，其作为高效除草剂，通过植物茎叶与根吸收，在木质部与韧皮部进行传导，积累于分生组织，抑制生长，最终造成植物死亡。咪唑啉酮类除草剂开发成功后，由于其选择性强、杀草谱广、用量低及对环境安全等原因，迅速在农业生产中推广使用。
专利US5322948报道以马来酸二乙酯、1-戊烯-3-酮和硫酸氢铵为原料，于95℃反应20小时制备5-乙基吡啶-2,3-二羧酸二乙酯，收率仅为51％。成本高，反应时间久，且收率低。
专利US4948896报道以2-亚氨基-丁二酸二乙酯和2-乙基丙烯醛为原料，在对甲苯磺酸作用下回流15小时制备5-乙基吡啶-2,3-二羧酸二乙酯，收率仅为84.6％。但由于原料昂贵导致成本过高。
专利US4973695报道以2-氯-3-氧代丁二酸二乙酯酯、2-乙基丙烯醛为主原料，加入大量铵盐高温反应4h制备5-乙基吡啶-2,3-二羧酸二乙酯，收率76.5％。后处理产生大量废水废盐，对环境不友好。
现有技术存在成本高、反应时间久、三废污染大等技术问题。
发明内容
针对现有技术存在的问题，本发明的目的在于涉及提供一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺的技术方案，该方法具有收率高，杂质少，后处理方便，三废污染少等优点，且大大了降低安全隐患，适于工业化生产应用。
本发明具体通过以下技术方案实现：
一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其包括以下步骤：
将式II所示的2-卤代-3-氧代丁二酸酯溶于含有氨气的醇溶液，与式III所示的1-烷烯-3-酮于负载有固体酸的管道反应器中进行反应；反应液蒸馏脱溶得5-烷基吡啶-2,3-二羧酸酯；
具体反应式如下：
其中，R1选自C1-C4的烷基或含有一个氧的C1-C4醚；R2选自C1-C4的烷基；X为卤素。
进一步，所述2-卤代-3-氧代丁二酸酯与1-烷烯-3-酮的摩尔比为1:1.01～1.5。
进一步，所述2-卤代-3-氧代丁二酸酯与氨的摩尔比为1:1.1～3.0。
进一步，所述含有氨气的醇溶液的醇为甲醇、乙醇、正丙醇或异丙醇，浓度为2-30％。
进一步，所述固体酸为Al2O3、AL2O3-SiO2或阳离子交换树脂。
进一步，所述管道反应器的反应温度60～90℃，停留时间30～600秒。
进一步，所述管道反应器的反应压力为0～1.5Mpa。
本发明通过采用上述技术，与现有技术相比，具有如下有益效果：
1)本发明通过采用2-卤代-3-氧代丁二酸酯、1-烷烯-3-酮和氨气为原料，其价格相对低廉，可降低成本。
2)本发明使用管道反应器，具有反应时间段，杂质小，收率高的优点，且相比传统反应釜安全隐患大大降低。
3)本发明使用负载固体酸，其可重复利用，副产氯化氢经水吸收得高纯盐酸溶液可用于其它产品生产。三废污染少，适于工业化生产应用。
附图说明
图1为实施例1中的1H NMR图谱；
图2为实施例1中的13CNMR图谱；
图3为实施例2中的1H NMR图谱；
图4为实施例2中的13CNMR图谱。
具体实施方式
下述的实施案例为本发明的具体描述。本发明实施案例的制备方法仅用于说明本发明，而不是对本发明的限制，本发明的保护范围并不仅限于此，在本发明的构思前提下，对本发明制备方法的简单改进都属于本发明要求保护的范围。
实施例1：5-乙基吡啶-2,3-二羧酸二乙酯的制备
2-氯-3-氧代丁二酸二乙酯100g溶于229g 5％氨乙醇(1.5eq)溶液，与2-氯-3-氧代丁二酸二乙酯溶液与1-戊烯-3-酮41.6g(1.1eq)混合进入90℃的装有阳离子交换树脂的管式反应器，滞留时间为5分钟，管道反应压力为1.5Mpa。所得反应液减压蒸馏至析出固体，降温，过滤，烘干得5-乙基吡啶-2,3-二羧酸二乙酯103.2g，HPLC纯度＞98％，收率91.02％。
5-乙基吡啶-2,3-二羧酸二乙酯的1H NMR图谱和13CNMR图谱如图1和2所示：
1H NMR(CDCl3,500MHz)δ:8.52(d,J＝5.0Hz,1H),7.88(d,J＝5.0Hz,1H),4.35-4.40(q,2H),4.29-4.34(q,2H),2.65-2.70(q,2H),1.34(t,J＝5.0Hz,3H),1.31(t,J＝5.0Hz,3H),1.22(t,J＝5.0Hz,3H)；13CNMRδ:165.2,164.8,150.3,140.2,135.5,125.9,61.10,61.0,24.8,13.9,13.1,13.0。
实施例2：5-甲基吡啶-2,3-二羧酸二乙酯的制备
2-氯-3-氧代丁二酸二乙酯100g溶于280g 3％氨乙醇(1.1eq)溶液，与2-氯-3-氧代丁二酸二乙酯溶液与丁烯酮41g(1.3eq)混合进入80℃的装有Al2O3的管式反应器，滞留时间为8分钟，管道反应压力为1.0Mpa。所得反应液减压蒸馏至析出固体，降温，过滤，烘干得5-甲基吡啶-2,3-二羧酸二乙酯97.8g，HPLC纯度＞97.0％，收率90.7％。
5-甲基吡啶-2,3-二羧酸二乙酯的1H NMR图谱和13CNMR图谱如图3和4所示：
1H NMR(CDCl3,500MHz)δ:8.58(d,J＝5.0Hz,1H),7.941(m,J＝5.0Hz,1H),4.43-4.47(q,2H),4.37-4.41(q,2H),2.43(s,3H),1.42(t,J＝5.0Hz,3H),1.38(t,J＝5.0Hz,3H)；13CNMRδ:166.1,165.8,151.9,147.9,137.6,135.2 126.8,62.1,61.9,18.2,14.1,14.0。
实施例3：5-甲基吡啶-2,3-二羧酸二甲酯的制备
2-氯-3-氧代丁二酸二甲酯100g溶于262.2g 10％氨甲醇(3eq)溶液，与2-氯-3-氧代丁二酸二甲酯溶液与丁烯酮43.2g(1.2eq)混合进入70℃的装有AL2O3-SiO2的管式反应器，滞留时间为10分钟，管道反应压力为0.1Mpa。所得反应液减压蒸馏至析出固体，降温，过滤，烘干得5-甲基吡啶-2,3-二羧酸二甲酯92.2g，HPLC纯度大于97.0％，收率84.16％。13CNMR(CDCl3,500MHz)δ:168.1,164.6,151.0,148.1,135.2,131.3,117.5,51.5,51.5,18.0。
实施例4：5-甲氧基甲基吡啶-2,3-二羧酸二甲酯的制备
2-氯-3-氧代丁二酸二甲酯100g溶于349.6g 5％氨甲醇(2eq)溶液，与2-氯-3-氧代丁二酸二甲酯溶液与4-甲氧基-戊烯-3-酮61.8g(1.2eq)混合进入75℃的装有阳离子交换树脂的管式反应器，滞留时间为5分钟，管道反应压力为0.5Mpa。所得反应液减压蒸馏至析出固体，降温，过滤，烘干得5-甲氧基甲基吡啶-2,3-二羧酸二甲酯106.8g，HPLC纯度＞98.68％，收率85.71％。13CNMR(CDCl3,500MHz)δ:168.1,164.6,156.9,142.0,130.9,121.6,118.5,55.8,51.5,51.5。
Claims (7)
1.一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于包括以下步骤：
将式II所示的2-卤代-3-氧代丁二酸酯溶于含有氨气的醇溶液，与式III所示的1-烷烯-3-酮于负载有固体酸的管道反应器中进行反应；反应液蒸馏脱溶得5-烷基吡啶-2,3-二羧酸酯；
具体反应式如下：
其中，R1选自C1-C4的烷基或含有一个氧的C1-C4醚；R2选自C1-C4的烷基；X为卤素。
2.如权利要求1所述的一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于所述2-卤代-3-氧代丁二酸酯与1-烷烯-3-酮的摩尔比为1:1.01～1.5。
3.如权利要求1所述的一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于所述2-卤代-3-氧代丁二酸酯与氨的摩尔比为1:1.1～3.0。
4.如权利要求1所述的一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于所述含有氨气的醇溶液的醇为甲醇、乙醇、正丙醇或异丙醇，浓度为2-30％。
5.如权利要求1所述的一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于所述固体酸为Al2O3、AL2O3-SiO2或阳离子交换树脂。
6.如权利要求1所述的一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于所述管道反应器的反应温度60～90℃，停留时间30～600秒。
7.如权利要求1所述的一种5-烷基吡啶-2,3-二羧酸酯的连续流合成工艺，其特征在于所述管道反应器的反应压力为0～1.5Mpa。
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3580917A (en) * | 1967-06-14 | 1971-05-25 | Daicel Ltd | Process for producing pyridine bases |
| US4723011A (en) * | 1985-10-28 | 1988-02-02 | American Cyanamid Company | Preparation of substituted and disubstituted-pyridine-2,3-dicarboxylate esters |
| US4973695A (en) * | 1987-01-06 | 1990-11-27 | Sugai Chemical Ind. Co., Ltd. | Process for preparing pyridine-2,3-dicarboxylic acid compounds |
| CN103373958A (zh) * | 2012-04-18 | 2013-10-30 | 中国中化股份有限公司 | 5-乙基吡啶-2,3-二甲酸二乙酯的制备方法 |
| CN103619829A (zh) * | 2011-06-24 | 2014-03-05 | 伊士曼化工公司 | 使用固体酸催化剂制造环状缩醛或缩酮 |
| CN105732485A (zh) * | 2016-05-08 | 2016-07-06 | 邯郸市赵都精细化工有限公司 | 一种合成3-甲基吡啶的方法 |
-
2022
- 2022-09-19 CN CN202211133774.2A patent/CN115403518A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3580917A (en) * | 1967-06-14 | 1971-05-25 | Daicel Ltd | Process for producing pyridine bases |
| US4723011A (en) * | 1985-10-28 | 1988-02-02 | American Cyanamid Company | Preparation of substituted and disubstituted-pyridine-2,3-dicarboxylate esters |
| US4973695A (en) * | 1987-01-06 | 1990-11-27 | Sugai Chemical Ind. Co., Ltd. | Process for preparing pyridine-2,3-dicarboxylic acid compounds |
| CN103619829A (zh) * | 2011-06-24 | 2014-03-05 | 伊士曼化工公司 | 使用固体酸催化剂制造环状缩醛或缩酮 |
| CN103373958A (zh) * | 2012-04-18 | 2013-10-30 | 中国中化股份有限公司 | 5-乙基吡啶-2,3-二甲酸二乙酯的制备方法 |
| CN105732485A (zh) * | 2016-05-08 | 2016-07-06 | 邯郸市赵都精细化工有限公司 | 一种合成3-甲基吡啶的方法 |
Non-Patent Citations (1)
| Title |
|---|
| 汪多仁编著: "《绿色医药化学品》", vol. 1, 科技文献出版社, pages: 323 - 324 * |
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