阅读说明：本技术 一种3,3-二甲氧基丙酸甲酯的制备方法 (Preparation method of 3, 3-dimethoxy methyl propionate ) 是由 不公告发明人 于 2020-06-22 设计创作，主要内容包括：本发明的一种3,3-二烷氧基丙酸酯的制备方法,所述方法为向酯的金属醇盐溶液中通入一氧化碳,保温至反应完全；然后蒸掉过量的酯,滴入氯化氢的醇溶液,保温反应完全后,经后处理。制备出3,3-二烷氧基丙酸酯,本发明的反应步骤少,操作简单,收率高,没有引入第三方溶剂且多余的原料酯可以回收利用,进一步节约了成本。(The invention relates to a preparation method of 3, 3-dialkoxy propionate, which comprises the steps of introducing carbon monoxide into a metal alkoxide solution of ester, and keeping the temperature until the reaction is complete; then evaporating off excessive ester, dripping into alcoholic solution of hydrogen chloride, keeping the temperature for reaction completely, and performing post-treatment. The preparation method of the 3, 3-dialkoxypropionate has the advantages of few reaction steps, simple operation, high yield, no introduction of a third-party solvent, and capability of recycling redundant raw material ester, thereby further saving the cost.)

1. A preparation method of 3, 3-dimethoxy methyl propionate is characterized by comprising the following steps: preparing a mixed solution of methyl acetate and sodium methoxide, introducing carbon monoxide into the mixed solution, preserving the temperature until the reaction is complete, distilling, evaporating excessive methyl acetate, dripping a hydrogen chloride methanol solution into the mixed solution, preserving the temperature until the reaction is complete, and carrying out post-treatment to prepare the methyl 3, 3-dimethoxypropionate.

2. The preparation method of methyl 3, 3-dimethoxypropionate as claimed in claim 1, characterized by comprising the following steps:

s100, mixing materials, namely adding a mixed solution of methyl acetate and sodium methoxide into a high-pressure reaction kettle;

s200, carrying out primary reaction, namely introducing carbon monoxide into a high-pressure reaction kettle, and heating to carry out reaction;

s300, primary distillation, namely transferring the feed liquid after the primary reaction into a distillation kettle for distillation, and evaporating and removing excessive methyl acetate;

s400, carrying out secondary reaction, namely slowly dropwise adding a 10% hydrogen chloride methanol solution into the feed liquid obtained after primary distillation to carry out secondary reaction;

s500, post-treatment, namely adding a pH value regulator into the feed liquid after the secondary reaction, regulating the pH value of the feed liquid to 7-8, and performing centrifugal operation after the pH regulation is finished to separate out salt;

s600, secondary distillation, heating, distilling and concentrating the feed liquid obtained after the post-treatment to obtain the required 3, 3-dimethoxy methyl propionate.

3. The process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the molar ratio of methyl acetate to sodium methoxide in step S100 is 1: 1-20: 1.

4. the process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: and in the step S200, introducing carbon monoxide to control the reaction pressure to be 2-4 Mpa.

5. The process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the reaction temperature in the step S200 is 40-70 ℃.

6. The process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the distillation temperature in the step S300 is 60-80 ℃, and the condition for judging the completion of distillation is that no methyl acetate is precipitated after the condensation pipe lasts for more than 5 minutes.

7. The process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the molar ratio of hydrogen chloride in the dropwise added hydrogen chloride methanol solution in the step S400 to sodium methoxide in the step S100 is 1: 1-2: 1.

8. the process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the PH value regulator in the step S500 is specifically any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium methoxide, sodium tert-butoxide and potassium tert-butoxide, and after the PH regulation is finished, centrifugal operation is carried out to separate out salt, and the centrifugal rotating speed is 1000 r/min-2000 r/min.

9. The process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the distillation temperature in the step S600 is 60-80 ℃, and the distillation time is 7-8 h.

10. The process according to claim 2, wherein said methyl 3, 3-dimethoxypropionate is prepared by the following steps: the methyl acetate distilled in the step S300 is recycled for the next preparation and utilization.

Technical Field

The invention belongs to the field of chemistry, and particularly relates to a preparation method of 3, 3-dimethoxy methyl propionate.

Background

The 3, 3-dimethoxy methyl propionate can be used as a chemical reagent, a fine chemical, a medical intermediate, a material intermediate and the like. One of the main uses of methyl 3, 3-dimethoxypropionate is in the synthesis of coumarin and its derivatives, such as coumarin, hyoscyamine (7-hydroxy-6-methoxycoumarin), and anisodamine (6-hydroxy-7-methoxycoumarin). Coumarin and its derivatives are used in preparing industrial and daily-use tobacco essence, are excellent perfume fixative, and are also used in electroplating industry. The coumarin medicine has anticoagulant, antitumor, antithrombotic, and osteoporosis resisting effects, and is effective in protecting liver, regulating sleep. Therefore, the 3, 3-dimethoxypropionic acid methyl ester has wide application and market value.

However, the existing preparation process of the methyl 3, 3-dimethoxypropionate is complex, high in cost and low in yield.

Disclosure of Invention

1. Technical problem to be solved by the invention

The invention aims to solve the problems of complex preparation process, high cost and low yield of the existing 3, 3-dimethoxy methyl propionate.

2. Technical scheme

In order to achieve the purpose, the technical scheme provided by the invention is as follows:

the invention relates to a preparation method of 3, 3-dimethoxy methyl propionate, which comprises the steps of preparing a mixed solution of methyl acetate and sodium methoxide, introducing carbon monoxide into the mixed solution, preserving heat until the reaction is complete, distilling, evaporating excessive methyl acetate, dripping hydrogen chloride methanol solution into the excessive methyl acetate, preserving heat until the reaction is complete, and carrying out post-treatment to prepare the 3, 3-dimethoxy methyl propionate. Under the action of strong alkali sodium alcoholate, alpha carbon on methyl acetate forms carbanion, then is combined with carbon monoxide, and forms enol sodium salt after rearrangement, and the enol sodium salt and methanol respectively undergo addition and substitution reaction in the presence of hydrogen chloride to produce 3, 3-dimethoxy methyl propionate. The method has the advantages of few reaction steps, simple operation, high yield, no introduction of a third-party solvent, and capability of recycling redundant raw material methyl acetate, thereby further saving the cost.

Preferably, the method specifically comprises the following steps:

s100, mixing materials, namely adding a mixed solution of methyl acetate and sodium methoxide into a high-pressure reaction kettle;

s200, carrying out primary reaction, namely introducing carbon monoxide into a high-pressure reaction kettle, and heating to carry out reaction;

s300, primary distillation, namely transferring the feed liquid after the primary reaction into a distillation kettle for distillation, and evaporating and removing excessive methyl acetate;

s400, carrying out secondary reaction, namely slowly dropwise adding a 10% hydrogen chloride methanol solution into the feed liquid obtained after primary distillation to carry out secondary reaction;

s500, post-treatment, namely adding a pH value regulator into the feed liquid after the secondary reaction, and regulating the pH value of the feed liquid to 7-8;

s600, secondary distillation, heating, distilling and concentrating the feed liquid obtained after the post-treatment to obtain the required 3, 3-dimethoxy methyl propionate.

Preferably, the molar ratio of methyl acetate to sodium methoxide in step S100 is 1: 1-20: the excess of methyl acetate allows the sodium methoxide to react to completion.

Preferably, in the step S200, carbon monoxide is introduced to control the reaction pressure to be 2-4 Mpa, when the pressure is too low, the methyl acetate enables alpha carbon on the methyl acetate to form carbanions under the action of the strong alkali sodium alkoxide, and then the carbanions are combined with the carbon monoxide, so that the strong alkali sodium alkoxide and the methyl acetate cannot complete reaction conversion due to insufficient carbon monoxide in the process of forming the sodium enol salt after rearrangement, and the subsequent reaction process is not facilitated.

Preferably, the reaction temperature in the step S200 is 40 to 70 ℃.

Preferably, the distillation temperature in the step S300 is 60 to 80 ℃, and the judgment condition of completion of distillation is that no methyl acetate is precipitated after the condensation tube lasts for more than 5 minutes.

Preferably, the molar ratio of hydrogen chloride in the dropwise added hydrogen chloride methanol solution in step S400 to sodium methoxide in step S100 is 1: 1-2: 1.

preferably, the PH regulator in step S500 is specifically any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium methoxide, sodium tert-butoxide, and potassium tert-butoxide, and after the PH regulation is completed, a centrifugal operation is performed to separate out salt, the centrifugal rotation speed is 1000r/min to 2000r/min, and the salt is separated out to ensure that the purity of the subsequently prepared methyl 3, 3-dimethoxypropionate is not affected by the salt.

Preferably, the distillation temperature in the step S600 is 60-80 ℃, and the distillation time is 7-8 h.

Preferably, the methyl acetate distilled in the step S300 is recycled for the next preparation and utilization.

3. Advantageous effects

Compared with the prior art, the technical scheme provided by the invention has the following beneficial effects:

the invention relates to a preparation method of 3, 3-dimethoxy methyl propionate, which comprises the steps of preparing a mixed solution of methyl acetate and sodium methoxide, introducing carbon monoxide into the mixed solution, preserving heat until the reaction is complete, distilling, evaporating excessive methyl acetate, dripping hydrogen chloride methanol solution into the excessive methyl acetate, preserving heat until the reaction is complete, and carrying out post-treatment to prepare the 3, 3-dimethoxy methyl propionate. Under the action of strong alkali sodium alcoholate, alpha carbon on methyl acetate forms carbanion, then is combined with carbon monoxide, and forms enol sodium salt after rearrangement, and the enol sodium salt and methanol respectively undergo addition and substitution reaction in the presence of hydrogen chloride to produce 3, 3-dimethoxy methyl propionate. The method has the advantages of few reaction steps, simple operation, high yield, no introduction of a third-party solvent, and capability of recycling redundant raw material methyl acetate, thereby further saving the cost.

Drawings

FIG. 1 is a flow chart of a preparation method of methyl 3, 3-dimethoxypropionate of the present invention.

Detailed Description

In order to facilitate an understanding of the invention, the invention will now be described more fully hereinafter with reference to the accompanying drawings, in which several embodiments of the invention are shown, but which may be embodied in many different forms and are not limited to the embodiments described herein, but rather are provided for the purpose of providing a more thorough disclosure of the invention.

It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present; when an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present; the terms "vertical," "horizontal," "left," "right," and the like as used herein are for illustrative purposes only.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs; the terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention; as used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

Example 1

Referring to the attached figure 1, in the preparation method of methyl 3, 3-dimethoxypropionate of this example, 100.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to 4.0MPa, the reaction temperature is 60 ℃, the CO pressure is controlled to 4.0MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 131.4g of 10% hydrogen chloride methanol solution was slowly dropped, the reaction temperature was controlled at 40 ℃, and after the post-treatment, concentration and distillation, methyl 3, 3-dimethoxypropionate was obtained in an amount of 39.0g, the purity was 96.8% and the yield was 85.2%. Under the action of strong alkali sodium alkoxide, alpha carbon on methyl acetate forms carbanion, and then is combined with carbon monoxide to form enol sodium salt after rearrangement. The sodium enol salt and methanol respectively undergo addition and substitution reactions in the presence of hydrogen chloride to produce methyl 3, 3-dimethoxypropionate. The method has the advantages of few reaction steps, simple operation, high yield, no introduction of a third-party solvent, and capability of recycling redundant raw material methyl acetate, thereby further saving the cost.

Example 2

Referring to the attached figure 1, in the preparation method of methyl 3, 3-dimethoxypropionate of the embodiment, 200.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to 3.5MPa, the reaction temperature is 50 ℃, the CO pressure is controlled to be 2.8-3.2MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 109.3g of 10% methanol hydrogen chloride solution was slowly added dropwise at a reaction temperature of 50 ℃ and subjected to post-treatment, concentration and distillation to give methyl 3, 3-dimethoxypropionate (36.5 g), purity 97.5% and yield 80.2%.

Example 3

Referring to the attached figure 1, in the preparation method of methyl 3, 3-dimethoxypropionate of the embodiment, 300.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to the high-pressure reaction kettle to reach 3MPa, the reaction temperature is 50 ℃, the CO pressure is controlled to be 2.8-3.2MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 131.4g of 10% methanol hydrogen chloride solution was slowly added dropwise at a reaction temperature of 45 ℃ and subjected to post-treatment, concentration and distillation to give methyl 3, 3-dimethoxypropionate, 41.6g, purity of 97.1% and yield of 91.0%.

Example 4

Referring to the attached figure 1, in the preparation method of methyl 3, 3-dimethoxypropionate of this example, 400.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to 3.5MPa, the reaction temperature is 60 ℃, the CO pressure is controlled to 3.5MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 163.4g of a 10% strength methanolic hydrogen chloride solution was slowly added dropwise at a reaction temperature of 55 ℃ and, after the subsequent treatment, concentration and distillation, methyl 3, 3-dimethoxypropionate was obtained in an amount of 40.3g, purity of 97.4% and yield of 88.5%.

Comparative example 1

In the preparation method of methyl 3, 3-dimethoxypropionate of the comparative example, 300.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to 0.2MPa, the reaction temperature is 60 ℃, the CO pressure is controlled to 0.2MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 131.4g of 10% methanol hydrogen chloride solution was slowly added dropwise at a reaction temperature of 45 ℃ and subjected to post-treatment, concentration and distillation to give methyl 3, 3-dimethoxypropionate, 30.0g, purity of 96.4% and yield of 65.2%.

Comparative example No. two

In the preparation method of methyl 3, 3-dimethoxypropionate of the comparative example, 300.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to 3.0MPa, the reaction temperature is 80 ℃, the CO pressure is controlled to be 3.0MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 131.4g of 10% methanol hydrogen chloride solution was slowly added dropwise at a reaction temperature of 45 ℃ and subjected to post-treatment, concentration and distillation to give methyl 3, 3-dimethoxypropionate (35.2 g), purity of 96.7% and yield of 76.8%.

Comparative example No. three

In the preparation method of methyl 3, 3-dimethoxypropionate of the comparative example, 300.0g of methyl acetate and 16.5g of sodium methoxide are put into a high-pressure reaction kettle, then CO gas is introduced to 3.0MPa, the reaction temperature is 60 ℃, the CO pressure is controlled to be 3.0MPa, and after the reaction is finished, the feed liquid is transferred to a distillation kettle to evaporate the excessive methyl acetate. 131.4g of 10% methanol hydrogen chloride solution was slowly added dropwise at a reaction temperature of 65 ℃ and subjected to post-treatment, concentration and distillation to give methyl 3, 3-dimethoxypropionate, 30.6g, purity 95.7% and yield 66.2%.

In conclusion, the preparation method of methyl 3, 3-dimethoxypropionate provided by the invention has the advantages of few reaction steps, simplicity in operation, high yield, no third-party solvent, capability of recycling redundant raw material methyl acetate and further cost saving.

The above-mentioned embodiments only express a certain implementation mode of the present invention, and the description thereof is specific and detailed, but not construed as limiting the scope of the present invention; it should be noted that, for those skilled in the art, without departing from the concept of the present invention, several variations and modifications can be made, which are within the protection scope of the present invention; therefore, the protection scope of the present patent shall be subject to the appended claims.