CN105085255B - 一种咪唑啉酮类除草剂中间体2‑烷氧基‑3‑氧代‑丁二酸二酯的合成工艺 - Google Patents

一种咪唑啉酮类除草剂中间体2‑烷氧基‑3‑氧代‑丁二酸二酯的合成工艺 Download PDF

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CN105085255B
CN105085255B CN201510492032.2A CN201510492032A CN105085255B CN 105085255 B CN105085255 B CN 105085255B CN 201510492032 A CN201510492032 A CN 201510492032A CN 105085255 B CN105085255 B CN 105085255B
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段忠利
李�雨
王旭艳
李继业
王荣良
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Inner Mongolia RUIMI Fine Chemical Co.
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    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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    • 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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    • 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

Abstract

本发明公开了一种咪唑啉酮类除草剂中间体2‑烷氧基‑3‑氧代‑丁二酸二酯的合成工艺，属于精细化工工艺技术领域。该工艺是以烷氧基乙酸酯，草酸二酯为原料，在碱的作用下，经缩合反应制得2‑烷氧基‑3‑氧代‑丁二酸二酯，与现有技术相比，操作简单，收率提高显著。同时用固体醇钠代替醇钠醇溶液，减少了溶剂种类及溶液用量，降低了三废产量，是一种高效，经济，环保的2‑烷氧基‑3‑氧代‑丁二酸二酯制备方法。

Description

一种咪唑啉酮类除草剂中间体2-烷氧基-3-氧代-丁二酸二酯 的合成工艺
技术领域
本发明涉及精细化工技术领域，具体涉及一种咪唑啉酮类除草剂中间体2-烷氧基-3-氧代-丁二酸二酯的合成工艺。
背景技术
咪唑啉酮类除草剂是20世纪80年代美国氰胺公司研发的一类高效除草剂，其亩用量为2.3～16.7g有效成分，主要用于大豆、花生、蔬菜等旱田作物。防除一年生和多年生禾本科杂草以及阔叶杂草、莎草科等杂草。应用广泛，是一类环境友好型低毒高效的农田除草剂。因而越来越受到各国的重视，成为竞相研发、生产和应用的热点农药。
咪唑啉酮类除草剂主要包括灭草烟、咪草烟、甲基咪草烟和甲氧咪草烟四种，其制备过程均涉及到关键中间体5位不同取代-2,3-吡啶二羧酸酯的合成，而2-烷氧基-3-氧代-丁二酸二酯是制备该中间体的重要前体化合物。因此，2-烷氧基-3-氧代-丁二酸二酯的制备成本对于降低咪唑啉酮类除草剂合成工艺成本就显得尤为重要。
目前制备2-烷氧基-3-氧代-丁二酸二酯的常用技术方案主要以合成单一酯为主。方案一（US6080867）合成路线如式（2）所示，该方案原料转化较慢，消耗碱量大，收率较低，不适于工业化生产。
（2）
方案二（US6080867）合成路线如式（3）所示，此法原料转化较慢，产品有较强的挥发性，后处理较困难。
（3）
方案三（J. Org. Chem. 50(22), 4404,1985）合成路线如式（4）所示，此法原料成本较高，同时原料具有较高危险性，产品收率较低，不适合工业化生产。
（4）。
发明内容
针对以上述技术方案存在的原料转化慢、收率低、碱及溶剂消耗量大、环境污染严重等弊端，本发明提出了一种混合酯制备工艺，即一种咪唑啉酮类除草剂中间体2-烷氧基-3-氧代-丁二酸二酯的合成工艺。
本发明的技术方案是：
一种咪唑啉酮类除草剂中间体2-烷氧基-3-氧代-丁二酸二酯的合成工艺，该合成工艺是以甲氧基乙酸甲酯和草酸二乙酯为原料，在醇钠的作用下，依次经取代反应和盐酸酸化制备获得所述2-烷氧基-3-氧代-丁二酸二酯。该合成工艺具体包括如下步骤：
（1）取代反应：
在装有温度计及机械搅拌的四口瓶中，加入第一溶剂和固体醇钠，室温搅拌10分钟后，将甲氧基乙酸甲酯和草酸二乙酯混合均匀，滴加至四口瓶内反应液中，升温至40～70℃，搅拌1～3小时；其中：所述草酸二乙酯、甲氧基乙酸甲酯和醇钠的摩尔比例为1:(1.0～1.5):(1.0～1.5)；所述草酸二乙酯与第一溶剂的重量比例为1:（5～15）；
（2）盐酸酸化：
向步骤（1）反应体系中滴加稀盐酸，控制反应体系温度在25℃以下，通过控制稀盐酸的滴加速度调节反应体系pH范围为2～3，搅拌1～3小时；
（3）中间体分离：
将经步骤（2）盐酸酸化后的反应体系静置分液，保留有机相；水相加入第二溶剂萃取两次；合并有机相，经浓缩获得棕黄色油状2-烷氧基-3-氧代-丁二酸二酯。
上述步骤（1）中，所述第一溶剂为苯、甲苯、四氢呋喃、1,2二氯乙烷、甲醇、乙醇和乙腈中的一种或几种的混合溶剂。
上述步骤（1）取代反应和步骤（2）酸化过程是在氮气保护下进行。
上述步骤（2）中，所滴加稀盐酸浓度为0.1～0.2 mol/L。
上述步骤（3）中，所述第二溶剂为苯、甲苯、乙酸乙酯、1,2二氯乙烷、二氯乙烷和氯仿中的一种或几种。
采用上述工艺制备的咪唑啉酮类除草剂中间体2-烷氧基-3-氧代-丁二酸二酯的通式如下式（1）所示：
（1）；
式（1）中，R1，R2和R3分别为-CH3或-CH2CH3，且R1，R2和R3相同或者不同。
经上述工艺所合成中间体为2-甲氧基-3-氧代-丁二酸二甲酯、2-乙氧基-3-氧代-丁二酸二乙酯、2-甲氧基-3-氧代-丁二酸-1-甲酯-4-乙酯和2-甲氧基-3-氧代-丁二酸-1-乙酯-4-甲酯的混合酯。
本发明具有以下优点和有益效果：
1、本发明所选择的原料成本低，简单易得，反应条件温和，后处理简单，收率由40%提高至90%以上，显著降低了工艺成本。
2、本发明工艺以固体醇钠取代醇钠溶液，减少了溶剂种类，便于单一溶剂回收再利用，同时醇钠的用量显著降低，减少了三废的排放，有利于环境保护。因此，本发明是一种较为适合工业化生产的合成方法。
附图说明
图1为本发明实施例3制备的中间体GC-MS谱图(GC-MS:190[M]+)。
图2为本发明实施例3制备的中间体GC-MS谱图(GC-MS:204[M]+)。
图3为本发明实施例3制备的中间体GC-MS谱图(GC-MS:218[M]+)。
具体实施方式
以下结合实施例对本发明进一步说明。
本发明为咪唑啉酮类除草剂中间体2-烷氧基-3-氧代-丁二酸二酯的合成工艺，其合成路线如反应式（5）所示：
（5）
以上四种不同的酯，构成了2-烷氧基-3-氧代-丁二酸二酯混合酯，在后续工艺中，这四种酯均可以有效的与不同的丙烯醛关环，生成相应的5位不同取代-2,3-吡啶二羧酸酯。因此，这四种酯均是本发明的目标产物。
实施例1
2-甲氧基-3-氧代-丁二酸二甲酯
40℃下，向25wt.%甲醇钠的甲醇溶液5.9 g（0.11 mol,1.1 eq）中加入甲苯（52mL），反应体系呈轻微混浊液。将草酸二甲酯20.0 g（0.11 mol，1.1 eq）与甲氧基乙酸甲酯10.4 g（0.10 mol，1.0 eq）室温下混合均匀，滴加至上述混浊液中，反应体系逐渐由混浊液变为淡黄色透明溶液，升温至45～50℃，搅拌1小时。补加25wt.%甲醇钠的甲醇溶液5.9 g（0.11 mol,1.1 eq）继续反应2小时。冰水浴控温25℃以下，向体系中滴加14 %的HCl 37g（0.14 mol，1.28 eq），调节pH=2～3，室温下搅拌1.5小时。过滤，滤液静置分层，有机相保留，水相用甲苯（90 mL×2）萃取两次，合并有机相，浓缩得黄色油状目标产物7.6 g，收率40%。GC-MS:190[M]+。
实施例2
2-乙氧基-3-氧代-丁二酸二乙酯
向100 mL三口瓶中依次加入乙氧基乙酸乙酯3.0 g（23 mmol，1.0 eq），草酸二乙酯4.0 g（27 mmol，1.2 eq），19.5 %乙醇钠乙醇溶液9.5 g（27 mol，1.2 eq）和甲苯（15mL），升温至55℃搅拌。反应2小时，补加19.5 %乙醇钠乙醇溶液1.6 g（4.5 mmol,0.2 eq）搅拌2小时。冰水浴控温25℃以下，向体系中滴加14 % HCl6.0 g（29.4 mmol,1.28eq），调节pH=2～3，室温下搅拌1.5小时。过滤，滤液静置分层，有机相保留，水相用甲苯（15 mL×2）萃取两次，合并有机相，浓缩得黄色油状目标产物4.0 g，收率80.5 %。GC-MS:232[M]+。
实施例3
2-甲氧基-3-氧代-丁二酸二酯
氮气保护下，向装有机械搅拌及温度计的10 L四口瓶中，依次加入甲苯（3.5 L）、96 %固体乙醇钠572 g（8.07 mol，1.2 eq），室温搅拌10分钟。将99 %甲氧基乙酸甲酯700 g（6.72 mol，1.0 eq）和99 %草酸二乙酯1179 g（8.07 mol，1.2 eq）混合均匀，滴加至上述反应液中，滴加完毕升温至40～45℃反应1小时，反应体系呈红棕色澄清液，冰水浴冷却，向反应液中滴加14 %盐酸水溶液2244 g（8.61 mol，1.28 eq），控制温度在25℃以下，调pH=2～3。搅拌1.5～2小时，过滤，滤液静置分层，有机相保留，水相用氯仿（2.1 L）萃取一次，合并有机相并浓缩得黄色油状目标产物1435.7 g，以2-甲氧基-3-氧代-丁二酸二乙酯计算收率为97.8 %。 GC-MS:190[M]+，204[M]+，218[M]+。
实施例4
2-甲氧基-3-氧代-丁二酸二酯
氮气保护下，向装有机械搅拌及温度计的2 L四口瓶中，依次加入99 %甲氧基乙酸甲酯120 g（1.15 mol，1.0 eq），99 %草酸二乙酯202 g（1.38 mol，1.2 eq）和19.6 %乙醇钠乙醇溶液480 g（1.38 mol，1.2 eq），升温至50℃反应4小时，反应体系呈红棕色澄清液。加入甲苯（480 mL），冰水浴冷却，向反应液中滴加14 %盐酸水溶液384 g（1.76 mol，1.28eq），控制温度在25℃以下，调pH=2～3。搅拌0.5小时，静置分层，有机相保留，水相用甲苯（250 mL）萃取一次，合并有机相并浓缩得黄色油状目标产物201 g，以2-甲氧基-3-氧代-丁二酸二乙酯计算收率为80 %。 GC-MS:190[M]+，204[M]+ ，218[M]+。

Claims (1)

1.一种咪唑啉酮类除草剂中间体2-甲氧基-3-氧代-丁二酸二酯的合成工艺，其特征在于：
氮气保护下，向装有机械搅拌和温度计的10L四口瓶中，依次加入3.5L甲苯和8.07mol96%固体乙醇钠，室温搅拌10分钟，将6.72mol甲氧基乙酸甲酯和8.07mol 99%草酸二乙酯混合均匀，滴加至上述反应液中，滴加完毕升温至40~45℃反应1小时，反应体系呈红棕色澄清液，冰水浴冷却，向反应液中滴加8.61mol 14%盐酸水溶液，控制温度25℃以下，调pH=2~3，搅拌1.5~2小时，过滤，滤液静置分层，有机相保留，水相用2.1L氯仿萃取一次，合并有机相并浓缩得黄色油状目标产物，以2-甲氧基-3-氧代-丁二酸二乙酯计算收率为97.8%。
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