WO2020078262A1 - 一种格氏反应金属有机产物的绿色水解工艺 - Google Patents

一种格氏反应金属有机产物的绿色水解工艺 Download PDF

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WO2020078262A1
WO2020078262A1 PCT/CN2019/110529 CN2019110529W WO2020078262A1 WO 2020078262 A1 WO2020078262 A1 WO 2020078262A1 CN 2019110529 W CN2019110529 W CN 2019110529W WO 2020078262 A1 WO2020078262 A1 WO 2020078262A1
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metal organic
grignard
ether
reaction
salt
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PCT/CN2019/110529
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French (fr)
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郑兆祥
陈梦桥
单国红
陈淳
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上虞新和成生物化工有限公司
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    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01F—COMPOUNDS OF THE METALS BERYLLIUM, MAGNESIUM, ALUMINIUM, CALCIUM, STRONTIUM, BARIUM, RADIUM, THORIUM, OR OF THE RARE-EARTH METALS
    • C01F5/00—Compounds of magnesium
    • C01F5/40—Magnesium sulfates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/05—Alcohols containing rings other than six-membered aromatic rings
    • C07C33/14—Alcohols containing rings other than six-membered aromatic rings containing six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the invention relates to a post-treatment process of Grignard reaction, in particular to a green hydrolysis process of metal organic products of Grignard reaction.
  • the Grignard reagent is an important metal organic compound with the general formula RMgX, which has been widely used in organic synthesis.
  • the Grignard reagent reacts with ketones, aldehydes, esters and other substances to obtain the corresponding alcohol metal organic compounds, and various alcohols can be obtained through the hydrolysis reaction.
  • the hydrolysis method of the alcohol metal organic substance obtained by the Grignard reaction is generally an acidic aqueous solution hydrolysis process.
  • Chinese patent 201611262269.2 discloses a method and device for continuous hydrolysis and neutralization of the vitamin A intermediate double Grignard condensate, wherein the acid water is sulfuric acid, hydrochloric acid, phosphoric acid or ammonium chloride aqueous solution, and the acid water and the vitamin A intermediate double
  • the feed volume ratio of the Grignard condensate in the ether solution is preferably (1.4 to 1.5): 1, while the concentration of the vitamin A intermediate double Grignard condensate in the ether solution is only 1.6 mol / L.
  • the hydrolysis process of the traditional process will generate a large amount of wastewater, and because the Grignard reaction products are generally alcohols, they have a certain solubility in water; at the same time, the Grignard reaction solvents are generally ethers, and there will be more in the water. Great solubility. Therefore, the hydrolysis wastewater generally contains a large amount of organic matter, which not only causes the loss of solvents and products and increases the production cost, but also if these wastewaters are discharged without further treatment (such as biochemical treatment), it will cause serious environmental pollution.
  • the Grignard reaction process requires strict requirements for anhydrous conditions. Since the traditional process requires a large amount of acidic aqueous solution to hydrolyze the Grignard metal organic product, water will enter the solvent during this process, resulting in a very high water content of the solvent, especially tetrahydrofuran, which has very high water solubility. Therefore, the traditional process currently used not only requires a complicated and costly water removal process for the solvent to ensure that the solvent reaches a sufficiently low moisture content, but also it is difficult to reduce the moisture in the solvent to less than 200ppm, thereby affecting the Grignard reaction The yield has a certain adverse effect.
  • the present invention provides a green hydrolysis process of Grignard metal organic products, which can efficiently recover ether solvents and at the same time, realize zero discharge of waste water.
  • a green hydrolysis process of Grignard metal organic products includes the following steps:
  • the acidic organic salt is a salt formed by pyridine organic matter and inorganic acid
  • step 2) filtering or centrifuging the hydrolysis mixture obtained in step 1) to obtain an ether solution of the hydrolysate and a solid metal inorganic salt;
  • the present invention is based on the nature and hydrolysis principle of Grignard metal organic products:
  • pyridine sulfates instead of ammonium chloride or dilute sulfuric acid and other aqueous solutions to hydrolyze the metal organic reaction products of Grignard reaction, it realizes the dehydration operation, and essentially eliminates the discharge of organic waste water.
  • the method is carried out under anhydrous conditions, and also solves the problem of water removal during the circulation application of the Grignard reaction solvent.
  • the solid form metal salt obtained by hydrolysis in the process of this patent is beneficial to the preparation of hydrogen halide products and magnesium sulfate crystal products.
  • the cation in the acidic organic salt is a pyridinium cation, 2-picoline cation, 3-picoline cation or 2,6-dimethylpyridine cation ion;
  • the anionic group is sulfate ion, hydrogen sulfate ion, chloride ion, bromide ion or iodide ion.
  • the metal organic product is obtained by reacting Grignard reagent with ketone, aldehyde or ester, and at the same time does not contain a group capable of reacting with pyridine.
  • the structure of the metal organic product is:
  • R 1 , R 2 and R 4 are selected from hydrogen, alkyl and alkenyl
  • R 3 is selected from hydrocarbylene
  • R 5 is selected from two alkylene groups above C
  • X is chlorine, bromine or iodine.
  • the alkyl group is a substituted group formed after the alkane loses one H.
  • the alkane can be a linear alkane, branched alkane or cycloalkane, and also contains an alkane substituted by a phenyl group, which is preferred ,
  • the alkyl group is a C 1 -C 20 alkyl group;
  • the alkenyl group is a substituent group formed after the olefin loses one H, wherein the olefin may be a linear olefin, a branched olefin or a cyclic olefin.
  • the alkenyl group is a C 1 to C 20 alkenyl group;
  • the hydrocarbylene group may be linear or branched; preferably, the hydrocarbylene group is a hydrocarbylene group of 20 carbons or less.
  • metal organic product is one of the following structures:
  • the ether solvent is diethyl ether, tetrahydrofuran, methyltetrahydrofuran or isopropyl ether.
  • the solvent of the ether solution of the metal organic product is also the same as the ether solvent here.
  • the ether solvent for washing mentioned in step 3) is also the same as the ether solvent.
  • the reaction temperature in step 1) is -50 to 100 ° C, preferably -50 to 50 ° C, more preferably -20 to 50 ° C, even more preferably -20 to 30 ° C;
  • the molar ratio of the acidic organic salt to the Grignard metal organic product described in step 1) is (0.5 to 3): 1.
  • step 1) the ether solution of the metal organic product is added to the reaction system by dropwise addition, the dropwise addition time is 20-90 min; the reaction time after the dropwise addition is kept is 10-90 min.
  • Step 2) The obtained metal inorganic salt solid is MgX or a mixture of MgX and MgSO 4 .
  • step 3 the metal inorganic salt solid is dissolved with ethanol, and the unreacted acidic organic salt is recovered, and then used to prepare HX, MgSO 4 or MgX by-product.
  • the solid is a mixture of MgSO 4 and MgX, acid is added to prepare HX and MgSO 4 ;
  • the solid salt is MgX, the MgX by-product is obtained by recrystallization;
  • X has the same definition as above.
  • the ethers obtained by the distillation and rectification in step 3 can be directly used in the Grignard reaction because the water content is very low; the resulting pyridine organics are reacted with HX or sulfuric acid again to prepare acidic organic salts.
  • the invention effectively solves the problems of wastewater discharge and solvent treatment, and realizes zero wastewater discharge in the Grignard reaction hydrolysis process.
  • the acidic organic salt in the present invention also basically realizes recycling, and the metal inorganic salt produced in the hydrolysis process is further processed to prepare by-products such as MgSO 4 .
  • the ether solvent since the anhydrous hydrolysis process used in the present invention, the ether solvent only needs to be distilled and rectified and separated from the pyridine substance to obtain an ether solvent with extremely low water content, which does not require a complicated water removal process.
  • the circulation application of ether solvents can be realized without adversely affecting the Grignard reaction yield.
  • the metal organic product obtained by the Grignard reaction is abbreviated as dichloromagnesium condensate, and its structure is as follows:
  • the solid is washed with 100ml of pure ether to remove a small amount of condensate.
  • the washing liquid can be used as the solvent for the next dissolution of pyridine bisulfate solid; the solid is mainly magnesium sulfate and magnesium chloride.
  • the ether solution of the condensate product was first recovered from ether at 30-50 ° C under normal pressure, and then heated to 50-70 ° C under reduced pressure (76mmHg) to recover pyridine to obtain 73.49g of the crude product of the condensate with an HPLC content of 92%. The rate is 99.5%.
  • the obtained ether and pyridine are respectively subjected to atmospheric distillation to obtain 305 ml of high-purity ether and 24 ml of pyridine; wherein the detected moisture content of the ether obtained by rectification is 0.01%.
  • the process wastewater realizes zero discharge.
  • the 280ml ether layer was obtained by static layering.
  • the neutralization reaction was carried out with 100ml of a 1.1mol / h sodium carbonate aqueous solution for 5 to 10 minutes. After the water layer was separated, the ether layer was distilled and recovered at 30 to 50 ° C to obtain 220ml of ether. The moisture content was 3.2%.
  • the metal organic product obtained by the Grignard reaction is abbreviated as dibromomagnesium condensate, and its structure is as follows:
  • the solid is washed with 100ml of pure methyltetrahydrofuran to remove a small amount of condensate.
  • the washing liquid can be used as the solvent for the next dissolution of pyridine sulfate solid; the solid is mainly magnesium sulfate and magnesium bromide, and concentrated sulfuric acid can be added for hydrogen bromide and sulfuric acid Preparation of magnesium.
  • the condensate product methyltetrahydrofuran solution was first recovered at 30-50 ° C under reduced pressure (76mmHg), and then heated to 50-70 ° C under reduced pressure (76mmHg) to recover pyridine, to obtain 64.76g of the crude condensate product, HPLC content was 92.9 %, The yield of products in the hydrolysis process is 99.6%.
  • the obtained methyltetrahydrofuran and pyridine are respectively subjected to atmospheric distillation to obtain 206 ml of high purity methyltetrahydrofuran and 33 ml of pyridine; wherein the detected moisture content of methyltetrahydrofuran obtained by rectification is 0.02%.
  • the process wastewater realizes zero discharge.
  • 220ml of hydrolyzed wastewater was obtained by static stratification, and the COD of the wastewater was 80,000ppm after vacuum distillation of methyltetrahydrofuran in the water at 30-50 °C.
  • the COD of the wastewater is again detected to be 3500 ppm.
  • the waste water still needs to be sent to the sewage station for further biochemical treatment, and can only be discharged after reaching the national standard.
  • the static layer was separated to obtain 180 ml of ether layer.
  • the neutralization reaction was carried out with 100 ml of 1.1 mol / h sodium carbonate aqueous solution for 5 to 10 minutes. After the water layer was separated, the ether layer was distilled under reduced pressure at 30 to 50 ° C to obtain 145 ml of methyltetrahydrofuran. The content is 6.3%, and 65.19g of crude product of the condensate is obtained. The content of HPLC is 92.1%. The yield of the product during the hydrolysis process is 99.4%.
  • the metal organic product obtained by the Grignard reaction is trityl magnesium bromide, the structure is as follows:
  • the solid is washed with 100ml of pure tetrahydrofuran to remove a small amount of triphenylmethane.
  • the washing liquid can be used as the solvent for the next 3-methylpyridine hydrobromide solid dissolution; the solid is mainly magnesium bromide, which can be directly recrystalized and purified as a by-product Concentrated sulfuric acid can also be added for the preparation of hydrogen bromide and magnesium sulfate.
  • the triphenylmethane tetrahydrofuran solution first recovers the tetrahydrofuran at 60-80 ° C, and then raises the temperature to 60-80 ° C under reduced pressure (76mmHg) to recover 3-methylpyridine to obtain 65.61g crude triphenylmethane product, HPLC content 93%, hydrolysis And the product yield in the recycling process is 99.9%.
  • the obtained tetrahydrofuran and 3-methylpyridine were respectively subjected to atmospheric distillation to obtain 144 ml of high-purity tetrahydrofuran and 29 ml of 3-methylpyridine; wherein the detected moisture content of tetrahydrofuran obtained by rectification was 0.01%.
  • the process wastewater realizes zero discharge.
  • the metal organic product obtained by the Grignard reaction is 3-methyl-5-hexene-3-olylmagnesium chloride, the structure is as follows:
  • the solid is washed with 100ml of pure ether to remove a small amount of 3-methyl-5-hexene-3-ol.
  • the washing liquid can be used as the solvent for the next dissolution of pyridine hydrochloride solid; the solid is mainly magnesium chloride, which can be directly recrystallized and purified As a by-product, concentrated sulfuric acid can also be added for the preparation of hydrogen chloride and magnesium sulfate.
  • the ether solution of 3-methyl-5-hexene-3-ol is first recovered at 30-50 ° C, and then heated to 50-80 ° C under reduced pressure (76mmHg) to recover 2-methylpyridine to obtain 25.27g of 3 -Methyl-5-hexene-3-ol crude product, HPLC content is 89.5%, product yield in hydrolysis and recovery process is 99%.
  • the obtained ether and 2-methylpyridine were respectively subjected to atmospheric distillation to obtain 485 ml of high-purity ether and 20 ml of 2-methylpyridine; wherein the detected moisture content of the ether obtained by rectification was 0.01%.
  • the process wastewater realizes zero discharge.
  • the metal organic product obtained by the Grignard reaction is abbreviated as dichloromagnesium condensate, and its structure is as follows:
  • the solid is washed with 100ml of pure ether to remove a small amount of condensate.
  • the washing liquid can be used as the solvent for the next dissolution of pyridine sulfate solid; the solid is mainly magnesium chloride, which can be directly recrystallized and purified as a by-product, or concentrated sulfuric acid can be added for hydrogen chloride and sulfuric acid Preparation of magnesium.
  • the ether solution of the condensate product is first recovered at 30-50 ° C, and then heated to 50-70 ° C under reduced pressure (76mmHg) to recover pyridine.
  • the obtained ether and pyridine are respectively subjected to atmospheric distillation to obtain high-purity ether and pyridine, respectively; wherein the detected moisture content of the ether obtained by rectification is 0.01%.
  • the process wastewater realizes zero discharge.
  • the metal organic product obtained by the Grignard reaction is abbreviated as dibromomagnesium condensate, and its structure is as follows:
  • the solid is washed with 100ml of pure tetrahydrofuran to remove a small amount of condensate.
  • the washing liquid can be used as the solvent for the next 3-methylpyridine hydrobromide dissolution; the solid is mainly magnesium bromide, which can be directly recrystallized and purified as a by-product, or Concentrated sulfuric acid is added for the preparation of hydrogen bromide and magnesium sulfate.
  • the tetrahydrofuran solution of the condensate product is first recovered at 60-80 ° C, and then the 3-methylpyridine is recovered under reduced pressure (76mmHg) when the temperature is raised to 60-80 ° C.
  • the obtained tetrahydrofuran and 3-methylpyridine are respectively subjected to atmospheric distillation to obtain high-purity tetrahydrofuran and 3-methylpyridine; wherein the detected moisture content of the tetrahydrofuran obtained by rectification is 0.01%.
  • the process wastewater realizes zero discharge.
  • the metal organic product obtained by the Grignard reaction is trityl magnesium bromide, the structure is as follows:
  • the solid is washed with 100ml of pure tetrahydrofuran to remove a small amount of triphenylmethane.
  • the washing liquid can be used as the solvent for the next pyridine sulfate solid dissolution; the solid is mainly magnesium bromide and magnesium sulfate, and concentrated sulfuric acid can be added for hydrogen bromide and magnesium sulfate Of preparation.
  • the triphenylmethane tetrahydrofuran solution first recovers tetrahydrofuran at 60-80 ° C, and then recovers 3-methylpyridine at a temperature of 60-80 ° C under reduced pressure (76mmHg).
  • the obtained tetrahydrofuran and pyridine are respectively subjected to atmospheric distillation to obtain high-purity tetrahydrofuran and pyridine; wherein the detected moisture content of the tetrahydrofuran obtained by rectification is 0.02%.
  • the process wastewater realizes zero discharge.
  • the metal organic product obtained by the Grignard reaction is 3-methyl-5-hexene-3-olylmagnesium chloride, the structure is as follows:
  • the solid is washed with 100ml of pure ether to remove a small amount of 3-methyl-5-hexene-3-ol.
  • the washing liquid can be used as the solvent for the next dissolution of pyridine bisulfate solid; the solid is mainly magnesium chloride and magnesium sulfate, which can be added Concentrated sulfuric acid is used for the preparation of hydrogen chloride and magnesium sulfate.
  • the ether solution of 3-methyl-5-hexene-3-ol is first recovered at 30-50 ° C, and then the pyridine is recovered under reduced pressure (76mmHg) when the temperature is raised to 50-70 ° C.
  • the obtained ether and pyridine are respectively subjected to atmospheric rectification to obtain high-purity ether and pyridine; wherein the detected moisture content of the ether obtained by rectification is 0.01%.
  • the process wastewater realizes zero discharge.

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Abstract

公开了一种格氏反应金属有机产物的绿色水解工艺，具体包括1)将计量好的吡啶盐加入到反应器中，然后慢慢加入金属有机物的醚类溶液，滴加完继续反应一段时间至反应完全，得到醇类水解产物和金属无机盐混合物；2)得到的混合物进行过滤或离心分离得到醇类水解产物的醚类溶液和相应的金属无机盐固体，固体盐用醚类溶剂洗涤；3)得到的固体盐经过进一步处理后进行回收利用；得到的醇类水解产物的醚类溶液进行蒸馏和精馏回收其中的醚类溶剂和吡啶类有机物。该工艺用吡啶类酸性盐代替酸性水溶液，避免了向反应体系中进一步引入水也能实现处理的目的，有效地解决了废水排放和溶剂处理的问题。

Description

一种格氏反应金属有机产物的绿色水解工艺 技术领域
本发明涉及格氏反应的后处理工艺，具体涉及格氏反应金属有机产物的绿色水解工艺。
背景技术
格氏试剂是一种重要金属有机化合物，通式RMgX，目前已广泛用于有机合成中。格氏试剂与酮、醛、酯等物质进行格氏反应可以得到相应的醇类金属有机物，经过水解反应得到各种醇类物质。
目前，格氏反应得到醇类金属有机物的水解方法一般为酸性水溶液水解工艺。中国专利201611262269.2中公开了一种维生素A中间体双格氏缩合物的连续水解中和的方法及装置，其中酸水为硫酸、盐酸、磷酸或氯化铵水溶液，酸水与维生素A中间体双格氏缩合物的醚类溶液的进料体积比优选为(1.4～1.5):1，而维生素A中间体双格氏缩合物在醚类溶液中的浓度最高只有1.6mol/L。由此可见，传统工艺的水解过程会产生大量的废水，并且由于格氏反应产物一般为醇类，在水中有一定溶解性；同时，格氏反应溶剂一般为醚类，在水中也会有较大的溶解度。因此水解废水中一般含有大量的有机物，不仅造成溶剂和产品的损失而导致生产成本的提高，而且这些废水若未经过深度处理(如生化处理)而进行排放，则会造成严重的环境污染。
另外，本领域技术人员一般都知道，格氏反应过程需要严格要求无水条件。由于传统工艺中需要用大量酸性水溶液进行格氏反应金属有机产物的水解，水分在这个过程中会进入溶剂中导致溶剂水分非常高，尤其是水溶性非常大的四氢呋喃。因此，目前采用的传统工艺中不仅需要对溶剂进行复杂而高成本的除水工序来保证溶剂达到足够低的水分含量，而且很难将溶剂中的水分降至200ppm以下，从而对格氏反应的收率有一定不利影响。
发明内容
针对上述传统工艺中存在的问题，本发明提供了一种格氏反应金属有机产物的绿色水解工艺，该工艺能够对醚类溶剂进行高效的回收，同时，实现废水的零排放。
一种格氏反应金属有机产物的绿色水解工艺，包括如下步骤：
1)将酸性有机盐加入到醚类溶剂中，然后与金属有机产物的醚类溶液进行水解反应，得到水解混合物；
所述的酸性有机盐为吡啶类有机物与无机酸形成的盐；
2)将步骤1)得到的水解混合物进行过滤或离心分离得到水解产物的醚类溶液和金属无机盐固体；
3)所述的水解产物的醚类溶液经过蒸馏和精馏回收醚类溶剂和吡啶类有机物；所述的金属无机盐固体用醚类溶剂洗涤，然后经过进一步处理进行回收利用。
具体包括如下步骤：
本发明根据格氏反应金属有机产物的性质和水解原理：
Figure PCTCN2019110529-appb-000001
用吡啶类硫酸盐代替氯化铵或稀硫酸等水溶液进行格氏反应金属有机反应产物的水解，实现了无水化操作，从工艺本质上杜绝了含有机物废水的排放问题。该方法在无水条件下进行，还解决了格氏反应溶剂循环套用过程中的除水问题。同时，本专利的工艺中水解得到的固体形式金属盐，有利于制备卤化氢产品和硫酸镁结晶产品。
作为优选，所述的酸性有机盐中的阳离子为吡啶氢根正离子、2-甲基吡啶氢根正离子、3-甲基吡啶氢根正离子或2,6-二甲基吡啶氢根正离子；
阴离子基团为硫酸根离子、硫酸氢根离子、氯离子、溴离子或碘离子。
本发明中，所述的金属有机产物由格氏试剂与酮、醛或酯反应得到，同时不含有能与吡啶发生反应的基团。
作为优选，所述的金属有机产物的结构为：
Figure PCTCN2019110529-appb-000002
其中，R 1、R 2、R 4选自氢、烷基、烯基；
R 3选自亚烃基；
R 5选自两个C以上的亚烃基；
X为氯、溴或碘。
本发明中，所述的烷基为烷烃失去一个H后形成的取代基团，其中，烷烃可以为直链烷烃、支链烷烃或者环烷烃，同时，也包含被苯基取代的烷烃，作为优选，所述的烷基为C 1～C 20烷基；
所述的烯基为烯烃失去一个H后形成的取代基团，其中，烯烃可以为直链烯烃、支链烯烃或者环烯烃，作为优选，所述的烯基为C 1～C 20烯基；
所述的亚烃基为烃失去两个H后形成的取代基团，包括饱和直链或带有支链的亚烷基基团、或者含有-C＝C-或-C≡C-的不饱和键亚烷基基团，所述的亚烃基可以为直链也可以带有支链；作为优选，所述的亚烃基为20个碳以下的亚烃基。
进一步的，所述的金属有机产物为以下结构中的一种：
Figure PCTCN2019110529-appb-000003
作为优选，步骤1)中，所述的醚类溶剂为乙醚、四氢呋喃、甲基四氢呋喃或异丙醚，其中，金属有机产物的醚类溶液的溶剂也与此处的醚类溶剂相同，此外，步骤3)中所提到的洗涤用的醚类溶剂也与该醚类溶剂相同。
步骤1)所述的反应温度为-50～100℃，优选-50～50℃，进一步优选-20～50℃，更进一步优选为-20～30℃；
步骤1)中所述的酸性有机盐与格氏反应金属有机产物的摩尔比为(0.5～3)：1。
步骤1)中，金属有机产物的醚类溶液通过滴加的方式加入反应体系，滴加时间为20～90min；滴加完保温反应时间为10～90min。
步骤2)得到的金属无机盐固体为MgX或MgX与MgSO 4的混合物。
步骤3)中，所述的金属无机盐固体用乙醇溶解，回收其中未反应的酸性有机盐，然后再用于制备HX、MgSO 4或MgX副产品。其中，当固体为MgSO 4和MgX的混合物时，加酸制备HX和MgSO 4；当固体盐为MgX时，通过重结晶得到MgX副产品；
X与前文的定义相同。
步骤3)所述的蒸馏和精馏得到的醚类由于含水量非常低，可以直接用于格氏反应；得到的吡啶类有机物重新与HX或硫酸反应制备酸性有机盐。
同现有技术相比，本发明的有益效果体现在：
本发明有效地解决了废水排放和溶剂处理的问题，实现了格氏反应水解过程零废水排放。本发明中的酸性有机盐也基本实现了循环利用，水解过程产生的金属无机盐也通过进一步处理制备MgSO 4等副产品。另外，由于本发明中所用的是无水化水解工艺，醚类溶剂只需要和吡啶类物质进行蒸馏和精馏分离即可得到含水量极低的醚类溶剂，不需要复杂的除水工艺即可实现醚类溶剂的循环套用，对格氏反应收率也不会造成不利影响。
具体实施方式
下面结合具体实施例对本发明作进一步的说明，但本发明的保护范围并不限于此。
实施例1
格氏反应得到的金属有机产物简称为双氯镁缩合物，结构如下：
Figure PCTCN2019110529-appb-000004
将55.81g(0.315mol)吡啶硫酸氢盐固体加入至四口反应器中，加入100ml乙醚溶液并搅拌降温至10℃左右，然后滴加格氏反应得到浓度0.75mol/L双氯镁缩合物的乙醚溶液300ml(含0.225mol双氯镁缩合物)，20min左右滴完，然后继续搅拌90min后停止水解反应。加入过量氢氧化镁将过量的吡啶硫酸氢盐全部反应完，然后过滤得到白色固体65g和缩合物产品乙醚溶液394ml。
固体用100ml纯乙醚洗除其中的少量缩合物，洗涤液可以作为下一次吡啶硫酸氢盐固体溶解所用的溶剂；固体主要为硫酸镁和氯化镁，可以加入浓硫酸进行氯化氢和硫酸镁的制备。
缩合物产品乙醚溶液先在30～50℃常压回收乙醚，然后再升温至50～70℃减压(76mmHg)回收吡啶，得到73.49g缩合物粗产品，HPLC含量为92％，水解过程产品收率99.5％。得到的乙醚和吡啶分别进行常压精馏，分别得到高纯度的乙醚305ml和吡啶24ml；其中精馏得到的乙醚检测水分含量为0.01％。
本工艺废水实现零排放。
对比试验1：
格氏反应的到浓度0.75mol/L双氯镁缩合物的乙醚溶液300ml加入至四口反应器中，控制温度在30℃，边搅拌边滴加1.45mol/L氯化铵水溶液450ml，50min左右滴完，然后继续搅拌10min后停止水解反应。
静止分层得到水解废水500ml，30～50℃蒸除水中的氨气和乙醚后检测废水COD为100000ppm。再用200ml二氯甲烷萃取废水层中的有机物后，再次检测废水COD为4000ppm。该废水仍需送至污水站进一步进行生物化学处理，达到国家规定的标准后才能排放。
静止分层得到醚层280ml用1.1mol/h的碳酸钠水溶液100ml进行中和反应5～10min，分去水层后，醚层在30～50℃蒸馏回收得到乙醚220ml， 检测水分含量为3.2％,得到74.3g缩合物粗产品，HPLC含量为91％，收率为99.5％；加入片碱搅拌10min左右，静止分层，得到的乙醚检测水分含量为0.5％；加入15ml浓度为1.6mol/L的甲基氯化镁乙醚溶液进行深度除水，并在30～50℃蒸馏得到215ml乙醚，检测水分含量为0.09％。
实施例2
格氏反应得到的金属有机产物简称为双溴镁缩合物，结构如下：
Figure PCTCN2019110529-appb-000005
将53.82g(0.21mol)吡啶硫酸盐固体加入至四口反应器中，加入100ml甲基四氢呋喃溶液并搅拌降温至-20℃左右，然后滴加格氏反应得到浓度1mol/L双溴镁缩合物的甲基四氢呋喃溶液200ml(含0.2mol双溴镁缩合物)，90min左右滴完，然后继续搅拌20min后停止水解反应。加入过量氢氧化镁将过量的吡啶溴化氢全部反应完，然后过滤得到白色固体65.5g和缩合物产品甲基四氢呋喃溶液295ml。
固体用100ml纯甲基四氢呋喃洗除其中的少量缩合物，洗涤液可以作为下一次吡啶硫酸盐固体溶解所用的溶剂；固体主要为硫酸镁和溴化镁，可以加入浓硫酸进行溴化氢和硫酸镁的制备。
缩合物产品甲基四氢呋喃溶液先在30～50℃减压(76mmHg)回收甲基四氢呋喃，然后升温至50～70℃减压(76mmHg)回收吡啶，得到64.76g缩合物粗产品，HPLC含量为92.9％，水解过程产品收率99.6％。得到的甲基四氢呋喃和吡啶分别进行常压精馏，得到高纯度的甲基四氢呋喃206ml和吡啶33ml；其中精馏得到的甲基四氢呋喃检测水分含量为0.02％。
本工艺废水实现零排放。
对比试验2：
格氏反应的到浓度1mol/L双溴镁缩合物的甲基四氢呋喃溶液200ml加入至四口反应器中，控制温度在20℃，边搅拌边滴加1.1mol/L稀硫酸 200ml，30min左右滴完，然后继续搅拌10min后停止水解反应。
静止分层得到水解废水220ml，30～50℃减压蒸除水中的甲基四氢呋喃后检测废水COD为80000ppm。再用200ml二氯甲烷萃取废水层中的有机物后，再次检测废水COD为3500ppm。该废水仍需送至污水站进一步进行生物化学处理，达到国家规定的标准后才能排放。
静止分层得到醚层180ml用1.1mol/h的碳酸钠水溶液100ml进行中和反应5～10min，分去水层后，醚层在30～50℃减压蒸馏回收得到甲基四氢呋喃145ml，检测水分含量为6.3％，，得到65.19g缩合物粗产品，HPLC含量为92.1％，水解过程产品收率99.4％；加入片碱搅拌10min左右，静止分层，得到的甲基四氢呋喃检测水分含量为0.6％；加入15ml浓度为1.6mol/L的乙基溴化镁甲基四氢呋喃溶液进行深度除水，并在30～50℃减压蒸馏得到150ml甲基四氢呋喃，检测水分含量为0.08％。
实施例3
格氏反应得到的金属有机产物为三苯甲基溴化镁，结构如下：
Figure PCTCN2019110529-appb-000006
将52.2g(0.3mol)3-甲基吡啶氢溴酸盐固体加入至四口反应器中，加入100ml四氢呋喃溶液并搅拌升温至50℃左右，然后滴加格氏反应得到浓度2.5mol/L三苯甲基溴化镁的四氢呋喃溶液100ml(含0.25mol三苯甲基溴化镁)，60min左右滴完，然后继续搅拌30min后停止水解反应。加入过量氢氧化镁将过量的3-甲基吡啶氢溴酸盐全部反应完，然后过滤得到白色固体51g和三苯甲烷四氢呋喃溶液220ml。
固体用100ml纯四氢呋喃洗除其中的少量三苯甲烷，洗涤液可以作为下一次3-甲基吡啶氢溴酸盐固体溶解所用的溶剂；固体主要为溴化镁，可以直接重结晶提纯作为副产品，也可以加入浓硫酸进行溴化氢和硫酸镁的制备。
三苯甲烷四氢呋喃溶液先在60～80℃回收四氢呋喃，然后再升温至60～80℃减压(76mmHg)回收3-甲基吡啶，得到65.61g三苯甲烷粗产品，HPLC含量为93％，水解和回收过程产品收率99.9％。得到的四氢呋喃和3-甲基吡啶分别进行常压精馏，得到高纯度的四氢呋喃144ml和3-甲基吡啶29ml；其中精馏得到的四氢呋喃检测水分含量为0.01％。
本工艺废水实现零排放。
实施例4
格氏反应得到的金属有机产物为3-甲基-5-己烯-3-醇基氯化镁，结构如下：
Figure PCTCN2019110529-appb-000007
将27g(0.21mol)2-甲基吡啶盐酸盐固体加入至四口反应器中，加入100ml乙醚溶液并搅拌降温至0℃左右，然后滴加格氏反应得到浓度0.5mol/L3-甲基-5-己烯-3-醇基氯化镁的乙醚溶液400ml(含0.2mol3-甲基-5-己烯-3-醇基氯化镁)，70min左右滴完，然后继续搅拌30min后停止水解反应。加入过量氢氧化镁将过量的2-甲基吡啶盐酸盐全部反应完，然后过滤得到白色固体19.5g和3-甲基-5-己烯-3-醇的乙醚溶液510ml。
固体用100ml纯乙醚洗除其中的少量3-甲基-5-己烯-3-醇，洗涤液可以作为下一次吡啶盐酸盐固体溶解所用的溶剂；固体主要为氯化镁，可以直接重结晶提纯作为副产品，也可以加入浓硫酸进行氯化氢和硫酸镁的制备。
3-甲基-5-己烯-3-醇的乙醚溶液先在30～50℃回收乙醚，然后再升温至50～80℃减压(76mmHg)回收2-甲基吡啶，得到25.27g的3-甲基-5-己烯-3-醇粗产品，HPLC含量为89.5％，水解和回收过程产品收率99％。得到的乙醚和2-甲基吡啶分别进行常压精馏，得到高纯度的乙醚485ml和2-甲基吡啶20ml；其中精馏得到的乙醚检测水分含量为0.01％。
本工艺废水实现零排放。
实施例5
格氏反应得到的金属有机产物简称为双氯镁缩合物，结构如下：
Figure PCTCN2019110529-appb-000008
将75.7g(0.65mol)吡啶盐酸盐固体加入至四口反应器中，加入100ml乙醚溶液并搅拌降温至-20℃左右，然后滴加格氏反应得到浓度1mol/L双氯镁缩合物的乙醚溶液300ml(含0.3mol双氯镁缩合物)，60min左右滴完，然后继续搅拌20min后停止水解反应。加入过量氢氧化镁将过量的吡啶盐酸盐全部反应完，然后过滤得到白色固体59.5g和缩合物产品乙醚溶液450ml。
固体用100ml纯乙醚洗除其中的少量缩合物，洗涤液可以作为下一次吡啶硫酸盐固体溶解所用的溶剂；固体主要为氯化镁，可以直接重结晶提纯作为副产品，也可以加入浓硫酸进行氯化氢和硫酸镁的制备。
缩合物产品乙醚溶液先在30～50℃回收乙醚，然后在升温至50～70℃减压(76mmHg)回收吡啶。得到的乙醚和吡啶分别进行常压精馏，分别得到高纯度的乙醚和吡啶；其中精馏得到的乙醚检测水分含量为0.01％。
本工艺废水实现零排放。
实施例6
格氏反应得到的金属有机产物简称为双溴镁缩合物，结构如下：
Figure PCTCN2019110529-appb-000009
将79g(0.457mol)3-甲基吡啶氢溴酸盐固体加入至四口反应器中，加入100ml四氢呋喃溶液并搅拌降温至-10℃左右，然后滴加格氏反应得到浓度1.1mol/L双溴镁缩合物的四氢呋喃溶液200ml(含0.22mol双溴镁 缩合物)，40min左右滴完，然后继续搅拌50min后停止水解反应。加入过量氢氧化镁将过量的3-甲基吡啶溴化氢全部反应完，然后过滤得到白色固体82.6g和缩合物产品四氢呋喃溶液343ml。
固体用100ml纯四氢呋喃洗除其中的少量缩合物，洗涤液可以作为下一次3-甲基吡啶氢溴酸盐溶解所用的溶剂；固体主要为溴化镁，可以直接重结晶提纯作为副产品，也可以加入浓硫酸进行溴化氢和硫酸镁的制备。
缩合物产品四氢呋喃溶液先在60～80℃回收四氢呋喃，然后在升温至60～80℃减压(76mmHg)回收3-甲基吡啶。得到的四氢呋喃和3-甲基吡啶分别进行常压精馏，得到高纯度的四氢呋喃和3-甲基吡啶；其中精馏得到的四氢呋喃检测水分含量为0.01％。
本工艺废水实现零排放。
实施例7
格氏反应得到的金属有机产物为三苯甲基溴化镁，结构如下：
Figure PCTCN2019110529-appb-000010
将38.44g(0.15mol)吡啶硫酸盐固体加入至四口反应器中，加入100ml四氢呋喃溶液并搅拌升温至40℃左右，然后滴加格氏反应得到浓度2.5mol/L三苯甲基溴化镁的四氢呋喃溶液100ml(含0.25mol三苯甲基溴化镁)，30min左右滴完，然后继续搅拌30min后停止水解反应。加入过量氢氧化镁将过量的吡啶硫酸盐全部反应完，然后过滤得到白色固体44.5g和三苯甲烷四氢呋喃溶液230ml。
固体用100ml纯四氢呋喃洗除其中的少量三苯甲烷，洗涤液可以作为下一次吡啶硫酸盐固体溶解所用的溶剂；固体主要为溴化镁和硫酸镁，可以加入浓硫酸进行溴化氢和硫酸镁的制备。
三苯甲烷四氢呋喃溶液先在60～80℃回收四氢呋喃，然后在升温至60～80℃减压(76mmHg)回收3-甲基吡啶。得到的四氢呋喃和吡啶分别进行常压精馏，得到高纯度的四氢呋喃和吡啶；其中精馏得到的四氢呋喃 检测水分含量为0.02％。
本工艺废水实现零排放。
实施例8
格氏反应得到的金属有机产物为3-甲基-5-己烯-3-醇基氯化镁，结构如下：
Figure PCTCN2019110529-appb-000011
将37.2g(0.21mol)吡啶硫酸氢盐固体加入至四口反应器中，加入100ml乙醚溶液并搅拌降温至-10℃左右，然后滴加格氏反应得到浓度0.5mol/L3-甲基-5-己烯-3-醇基氯化镁的乙醚溶液400ml(含0.2mol3-甲基-5-己烯-3-醇基氯化镁)，60min左右滴完，然后继续搅拌40min后停止水解反应。加入过量氢氧化镁将过量的吡啶硫酸氢盐全部反应完，然后过滤得到白色固体30.1g和3-甲基-5-己烯-3-醇的乙醚溶液510ml。
固体用100ml纯乙醚洗除其中的少量3-甲基-5-己烯-3-醇，洗涤液可以作为下一次吡啶硫酸氢盐固体溶解所用的溶剂；固体主要为氯化镁和硫酸镁，可以加入浓硫酸进行氯化氢和硫酸镁的制备。
3-甲基-5-己烯-3-醇的乙醚溶液先在30～50℃回收乙醚，然后在升温至50～70℃减压(76mmHg)回收吡啶。得到的乙醚和吡啶分别进行常压精馏，得到高纯度的乙醚和吡啶；其中精馏得到的乙醚检测水分含量为0.01％。
本工艺废水实现零排放。

Claims (11)

  1. 一种格氏反应金属有机产物的绿色水解工艺，其特征在于，包括如下步骤：
    1)将酸性有机盐加入到醚类溶剂中，然后与金属有机产物的醚类溶液进行水解反应，得到水解混合物；
    所述的酸性有机盐为吡啶类有机物与无机酸形成的盐；
    2)将步骤1)得到的水解混合物用氢氧化镁中和后进行过滤或离心分离得到水解产物的醚类溶液和金属无机盐固体；
    3)所述的水解产物的醚类溶液经过蒸馏和精馏回收醚类溶剂和吡啶类有机物；所述的金属无机盐固体用醚类溶剂洗涤，然后经过进一步处理进行回收利用。
  2. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，所述的酸性有机盐中的阳离子为吡啶氢根正离子、2-甲基吡啶氢根正离子、3-甲基吡啶氢根正离子或2,6-二甲基吡啶氢根正离子；
    阴离子为硫酸根离子、硫酸氢根离子、氯离子、溴离子或碘离子。
  3. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，所述的金属有机产物由格氏试剂与酮、醛或酯反应得到，同时不含有能与吡啶发生反应的基团。
  4. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，所述的金属有机产物的结构为：
    Figure PCTCN2019110529-appb-100001
    其中，R 1、R 2、R 4选自氢、烷基或烯基；
    R 3选自亚烃基；
    R 5选自两个C以上的亚烃基；
    X为氯、溴或碘。
  5. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，所述的醚类溶剂为乙醚、四氢呋喃、甲基四氢呋喃或异丙醚。
  6. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺， 其特征在于，步骤1)中，反应温度为-50～50℃，优选为-20～30℃。
  7. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，步骤1)中所述的酸性有机盐与格氏反应金属有机产物的摩尔比为(0.5～3)：1。
  8. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，步骤1)中，金属有机产物的醚类溶液通过滴加的方式加入反应体系，滴加时间为20～90min；滴加完继续保温反应时间为10～90min。
  9. 根据权利要求1或4所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，步骤3)所述的固体盐用于制备HX、MgSO 4或MgX副产品。
  10. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，步骤3)中，通过蒸馏和精馏得到的醚类溶剂直接用于格氏反应；得到的吡啶类有机物重新用于制备酸性有机盐。
  11. 根据权利要求1所述的格氏反应金属有机产物的绿色水解工艺，其特征在于，所述的金属有机产物为以下结构中的一种：
    Figure PCTCN2019110529-appb-100002
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106588958A (zh) * 2015-10-14 2017-04-26 上虞新和成生物化工有限公司 一种连续制备炔醇双格氏试剂的生产系统及方法
CN106748943A (zh) * 2016-12-30 2017-05-31 厦门金达威维生素有限公司 一种维生素a中间体双格氏缩合物的连续水解中和的方法及装置

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* Cited by examiner, † Cited by third party
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US10154983B2 (en) * 2011-04-26 2018-12-18 Retrotope, Inc. Neurodegenerative disorders and muscle diseases implicating PUFAs
CN105085194A (zh) * 2015-08-28 2015-11-25 江西力田维康科技有限公司 一种3-烷氧基苯甲醇的制备方法
EA201991853A1 (ru) * 2017-02-10 2020-02-14 Байер Акциенгезельшафт Композиция для борьбы с вредными микроорганизмами, содержащая производные 1-(феноксипиридинил)-2-(1,2,4-триазол-1-ил)этанола

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106588958A (zh) * 2015-10-14 2017-04-26 上虞新和成生物化工有限公司 一种连续制备炔醇双格氏试剂的生产系统及方法
CN106748943A (zh) * 2016-12-30 2017-05-31 厦门金达威维生素有限公司 一种维生素a中间体双格氏缩合物的连续水解中和的方法及装置

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DONOHOE, T.J. ET AL.: "Regioselective Nucleophilic Addition to Pyridinium Salts: A New Route to Substituted Dihydropyridones", ORGANIC LETTERS, vol. 23, no. 11, 3 December 2009 (2009-12-03), pages 5563 - 5565, XP055702849 *

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