CN110698341A - Environment-friendly preparation method of propiolic acid derivative - Google Patents
Environment-friendly preparation method of propiolic acid derivative Download PDFInfo
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
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- C—CHEMISTRY; METALLURGY
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
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Abstract
The invention discloses an environment-friendly preparation method of propiolic acid derivatives, which comprises the following steps: (1) 2, 3-dibromo succinic acid is used as a raw material, and butynedioic acid salt is generated under an alkaline condition; (2) decarboxylating at high temperature under an acidic condition to obtain propiolic acid; (3) adding corresponding methanol or ethanol into propiolic acid in an extraction solvent, and obtaining propiolic acid ester with high yield under the acidic catalysis condition under the condition that trimethyl orthoformate or triethyl orthoformate participates in dehydration. In the invention, the synthesis process of the propiolic acid is environment-friendly and has high safety coefficient; the method can be used for preparing methyl propiolate and ethyl propiolate, and has the advantages of less alcohol consumption, thorough reaction, high yield and easy separation.
Description
Technical Field
The invention relates to the technical field of compound preparation, and in particular relates to a preparation method of a propiolic acid derivative.
Background
Propiolic acid derivatives such as methyl propiolate and ethyl propiolate are important fine chemicals used as additives of electroplating solution formulations, drugs and organic synthesis intermediates of functional materials. Can be used for organic synthesis, and can be used for preparing propionic acid, trimesic acid, halogenated acrylic acid, dihalogenated acrylic acid, diacetylene dicarboxylic acid, ethyl propiolate, pyrazolone, dibromo crotonic acid, ethoxy crotonic acid, etc. Methyl propiolate can be prepared by heating and refluxing propiolic acid, sulfuric acid and methanol, and is a raw material of antiviral drug iodoglycoside.
The traditional preparation of propiolic acid has two types: one is oxidized by propiolic alcohol, which is added into acetone and stirred, a sulfuric acid solution of chromic anhydride is dripped at the temperature of 20 ℃, and after the addition, the mixture is stirred for 14 hours at room temperature to generate propiolic acid; the other is prepared by reacting sodium acetylene and CO2 at 3.55-7.09MPa and below 90 deg.C.
Both of these methods have serious environmental and safety drawbacks.
The first method is characterized in that the raw materials of propiolic alcohol, also called 2-propin-1-ol, ethynyl methanol and propargyl alcohol, are highly toxic chemicals, the 153 th position of the highly toxic chemical in 335 recorded in 2002 poses great threat to the personal safety of practical operators, and the inflow of wastewater can cause serious environmental toxicity.
In addition, the chromic anhydride used in the method can cause serious chromium heavy metal pollution, environmental pollution caused by chromium and compounds thereof can cause poisoning symptoms such as abdominal discomfort, diarrhea and the like, allergic dermatitis or eczema is caused, respiratory tract irritation and corrosion are caused, and pharyngitis, bronchitis and the like are caused. In areas with serious water pollution, people who often contact or take too much water are easy to get rhinitis, tuberculosis, diarrhea, bronchitis, dermatitis and the like. And the heavy metal pollution lasts for a long time and is difficult to degrade.
The second method uses sodium acetylene, which is also a flammable and explosive substance, and uses high pressure, has large potential safety hazard and is not beneficial to industrial production.
The propiolic acid derivatives such as methyl propiolate and ethyl propiolate are obtained by adding methanol or ethanol under the catalysis of sulfuric acid and carrying out reflux reaction in a conventional synthesis method. This method has the following drawbacks:
firstly, the method comprises the following steps: the esterification reaction is a reversible reaction, and the reaction is incomplete, so that the propiolic acid is wasted.
Secondly, the method comprises the following steps: in order to promote the reaction, excessive methanol and ethanol are needed, the water content of the recovered methanol and ethanol is large, and the recovered methanol and ethanol can be recycled and reused only by rectification.
Thirdly, the method comprises the following steps: the boiling point of methanol and ethanol is slightly different from that of methyl propiolate and ethyl propiolate, and higher content can be achieved only by rectification, so that the cost is increased.
Disclosure of Invention
Aiming at the problems of large environmental pollution and high safety risk of the reported propiolic acid synthesis method, the invention firstly provides a novel propiolic acid synthesis method which is environment-friendly and has high safety coefficient; on the basis, the invention further provides a synthesis method of methyl propiolate and ethyl propiolate, which has the advantages of less alcohol consumption, thorough reaction, high yield and easy separation.
In order to solve the technical problems, the environment-friendly preparation method of the propiolic acid derivative comprises the following steps:
(1) 2, 3-dibromo succinic acid is used as a raw material, and butynedioic acid salt is generated under an alkaline condition;
adding 2, 3-dibromo succinic acid into the alkali liquor, heating to 60-100 ℃, and reacting for 8-12 hours under the condition of heat preservation to obtain butynedioic acid salt water solution for later use;
in the step, the alkali liquor is sodium hydroxide solution or potassium hydroxide solution;
in the step, the molar ratio of the 2, 3-dibromo-succinic acid to the alkali liquor is 1: 2 to 5.
(2) Decarboxylating at high temperature under an acidic condition to obtain propiolic acid;
adjusting the butynedioic acid salt obtained in the step (1) to be strongly acidic by using acid, reacting for 3-8 hours at 80-120 ℃, extracting by using dichloromethane, diethyl ether, isopropyl ether or methyl tert-butyl ether, and distilling to obtain a finished product of propiolic acid;
in this step, the acid is selected from sulfuric acid, hydrochloric acid or nitric acid.
(3) Adding corresponding methanol or ethanol into propiolic acid in an extraction solvent, and obtaining propiolic acid ester with high yield under the acidic catalysis condition under the condition that trimethyl orthoformate or triethyl orthoformate participates in dehydration;
the method specifically comprises the following steps: dissolving propiolic acid by using dichloromethane, toluene or tetrahydrofuran as a solvent, adding methanol or ethanol, adding trimethyl orthoformate or triethyl orthoformate, using sulfuric acid or p-toluenesulfonic acid as a catalyst, reacting at 45 ℃ for 10-48 hours, washing with water for three times, washing with saturated sodium chloride, drying, and distilling at normal pressure to obtain a finished propiolic acid ester;
in this step, propiolic acid: alcohol: orthoformate molar ratio is 1: 1-5: 0.5 to 5.
The synthetic route is as follows:
preferably, the first and second liquid crystal materials are,
in the step (1), the reaction temperature is 80 ℃, and the reaction time is 10 hours;
in the step (1), the alkali liquor is sodium hydroxide solution;
in the step (1), the molar ratio of the 2, 3-dibromo-succinic acid to the alkali liquor is 1: 3.
preferably, the first and second liquid crystal materials are,
in the step (2), sulfuric acid is selected as acid;
in the step (2), the reaction time is 5 hours; the reaction temperature is 100 ℃;
in the step (2), the extraction solvent is methyl tert-butyl ether.
Preferably, the first and second liquid crystal materials are,
in the step (3), dichloromethane is used as an organic solvent;
in the step (3), sulfuric acid is used as an acid catalyst;
in the step (3), the reaction time is 24 hours;
in the step (3), propiolic acid: alcohol: orthoformate molar ratio is 1: 1: 0.5.
preferably, the first and second liquid crystal materials are,
in the step (1), the alkali liquor is prepared from methanol and potassium hydroxide, wherein the ratio of methanol: the mass ratio of the potassium hydroxide is 1000: 60.
Compared with the prior art, the invention has the following advantages: little environmental pollution, high operation safety, low raw material cost and convenient operation.
Detailed Description
The following examples are given for the detailed implementation and specific operation of the present invention, but the scope of the present invention is not limited to the following examples.
All chemicals were commercially available chemicals.
The first embodiment is as follows: preparation of butynedioic acid dipotassium salt
A 2L three-neck flask is provided with a thermometer and a condenser, 417g of water and 60g of potassium hydroxide are added, after stirring and dissolving, 50g of 2, 3-dibromo-succinic acid is added for a plurality of times at the temperature of 60 ℃, the temperature is controlled to be less than 100 ℃, and the addition is finished within about 2 hours; heating and preserving the temperature at 80 ℃, reacting for 10 hours, and detecting the completion of the reaction of the raw materials by HPLC for later use.
Example two: preparation of butynedioic acid disodium salt
A 2L three-neck flask is provided with a thermometer and a condenser, 417g of water and 43g of sodium hydroxide are added, after stirring and dissolving, 50g of 2, 3-dibromo-succinic acid is added for a plurality of times at the temperature of 60 ℃, the temperature is controlled to be less than 100 ℃, and the addition is finished within about 2 hours; heating and preserving the temperature at 80 ℃, reacting for 10 hours, and detecting the completion of the reaction of the raw materials by HPLC for later use.
Example three: preparation of butynedioic acid dipotassium salt
A2L three-neck flask is provided with a thermometer and a condenser, 1000g of methanol and 60g of potassium hydroxide are added, after stirring and dissolving, 50g of 2, 3-dibromosuccinic acid is added at one time at the temperature of 60 ℃, reflux is carried out, the reaction is carried out for 24 hours, HPLC detection raw materials are completely reacted, the mixture is cooled to room temperature, and 92g of a mixture of butynedioic acid dipotassium salt and potassium bromide is obtained by suction filtration for later use.
Example four: preparation of propiolic acid.
In the first embodiment, 78g of concentrated sulfuric acid is added dropwise into a dipotassium butynedioate aqueous solution until the pH value is strong, the temperature is raised to 80 ℃, the reaction is kept for 5 hours, HPLC (high performance liquid chromatography) detection is carried out to detect that the raw material reaction is complete, 500ml of methyl tert-butyl ether is used for extracting for 3 times, 100ml of saturated sodium chloride is used for washing, drying and concentrating to dryness to obtain 9.8g of crude product and 5mmHg, reduced pressure distillation is carried out to obtain 8.9g of finished product, and the total yield of the two. The GC content was 95.2%.
Example five: preparation of propiolic acid.
In the second embodiment, 78g of concentrated sulfuric acid is added dropwise to an aqueous solution of butynedioic acid disodium salt until the pH value is strong, the temperature is raised to 80 ℃, the reaction is kept for 5 hours, HPLC (high performance liquid chromatography) detection is performed to ensure that the raw material reaction is complete, 500ml of methyl tert-butyl ether is used for extraction for 3 times, 100ml of saturated sodium chloride is used for washing, drying and concentrating to dryness to obtain 11g of crude product and 5mmHg, reduced pressure distillation is performed to obtain 9.5g of finished product, and the total yield of the two. The GC content was 95.1%.
Example five: preparation of propiolic acid.
In the third embodiment, 85g of concentrated sulfuric acid is added dropwise into a butynedioic acid disodium salt aqueous solution until the pH value is strong, the temperature is raised to 80 ℃, the reaction is kept for 5 hours, HPLC (high performance liquid chromatography) detection is performed to ensure that the raw material reaction is complete, 500ml of methyl tert-butyl ether is used for extraction for 3 times, 100ml of saturated sodium chloride is used for washing, drying and concentrating to dryness to obtain 8g of crude product and 5mmHg, reduced pressure distillation is performed to obtain 6.8g of finished product, and the total yield of the. The GC content was 95.4%.
Example six: and (3) preparing methyl propiolate.
A1L three-neck flask is provided with a thermometer and a condenser, 70g of propiolic acid with the content of more than 95 is added, 500ml of dichloromethane and 1g of sulfuric acid are added, 32g of methanol and 55g of trimethyl orthoformate are added, the reaction is carried out at 40 ℃, GC tracking is carried out until the raw material is less than 5 percent, about 28 hours are needed, cooling is carried out, 500ml of water is washed for 3 times, 100ml of saturated sodium chloride is washed for one time, anhydrous sodium sulfate is dried, atmospheric distillation is carried out, 100-fold 105 ℃ fraction is collected, 71g of finished product is obtained, GC99.5 percent is obtained, and the yield is 84.5 percent.
1H NMR (400 MHz, CDCl3, δ): 2.92 (s, C≡CH, 1H), 1.33 (t, 3JH-H=7.2Hz, CH3, 3H).
Example seven: and (3) preparing methyl propiolate.
A1L three-neck flask is provided with a thermometer and a condenser, 70g of propiolic acid with the content of more than 95 is added, 500ml of dichloromethane and 2g of p-toluenesulfonic acid are added, 32g of methanol and 55g of trimethyl orthoformate are added, the reaction is carried out at 40 ℃, GC tracking is carried out until the raw material is less than 5 percent, about 28 hours are needed, the reaction is cooled, 500ml of water is washed for 3 times, 100ml of saturated sodium chloride is washed for one time, anhydrous sodium sulfate is dried, normal pressure distillation is carried out, 100-fold 105 ℃ fraction is collected, 65g of finished product is obtained, GC99.1 percent and the yield is 77.1 percent.
Example eight: and (3) preparing ethyl propiolate.
A1L three-neck flask is provided with a thermometer and a condenser, 70g of propiolic acid with the content of more than 95 is added, 500ml of dichloromethane and 1g of sulfuric acid are added, 46g of ethanol and 55g of trimethyl orthoformate are added, the reaction is carried out at 40 ℃, GC tracking is carried out until the raw material is less than 5 percent, about 24 hours are needed, cooling is carried out, 500ml of water is washed for 3 times, 100ml of saturated sodium chloride is washed for one time, anhydrous sodium sulfate is dried, atmospheric distillation is carried out, and fractions with the temperature of 118 degrees and 125 degrees are collected, thus 85g of finished products, 99.1 percent of GC and the yield of 86.7.
1H NMR (400 MHz, CDCl3, δ): 4.26 (q, 3JH-H=7.1 Hz, CH2, 2H), 2.92 (s,C≡CH, 1H), 1.33 (t, 3JH-H=7.2 Hz, CH3, 3H).
Example nine: and (3) preparing ethyl propiolate.
A1L three-neck flask is provided with a thermometer and a condenser, 70g of propiolic acid with the content of more than 95 is added, 500ml of dichloromethane and 2.5g of p-toluenesulfonic acid are added, 46g of ethanol and 55g of trimethyl orthoformate are added, the reaction is carried out at 40 ℃, GC tracking is carried out until the raw material is less than 5 percent, about 24 hours are needed, cooling is carried out, 500ml of water is washed for 3 times, 100ml of saturated sodium chloride is washed for one time, anhydrous sodium sulfate is dried, atmospheric distillation is carried out, fractions at 125 ℃ of 118 are collected, 81g of finished products are obtained, GC is 99.1 percent, and the yield is 84.3 percent.
The embodiments of the present invention include, but are not limited to, the above-mentioned embodiments, and those skilled in the art can make various corresponding changes and modifications according to the present invention without departing from the spirit and the substance of the present invention, and still fall into the scope of the present invention.
Claims (5)
1. An environment-friendly preparation method of propiolic acid derivatives comprises the following steps:
(1) adding 2, 3-dibromo succinic acid into the alkali liquor, heating to 60-100 ℃, and reacting for 8-12 hours under the condition of heat preservation to obtain butynedioic acid salt water solution for later use;
in the step, the alkali liquor is sodium hydroxide solution or potassium hydroxide solution;
in the step, the molar ratio of the 2, 3-dibromo-succinic acid to the alkali liquor is 1: 2-5;
(2) adjusting the butynedioic acid salt obtained in the step (1) to be strongly acidic by using acid, reacting for 3-8 hours at 80-120 ℃, extracting by using dichloromethane, diethyl ether, isopropyl ether or methyl tert-butyl ether, and distilling to obtain a finished product of propiolic acid;
in the step, the acid is selected from sulfuric acid, hydrochloric acid or nitric acid;
(3) dissolving propiolic acid by using dichloromethane, toluene or tetrahydrofuran as a solvent, adding methanol or ethanol, adding trimethyl orthoformate or triethyl orthoformate, using sulfuric acid or p-toluenesulfonic acid as a catalyst, reacting at 45 ℃ for 10-48 hours, washing with water for three times, washing with saturated sodium chloride, drying, and distilling at normal pressure to obtain a finished propiolic acid ester;
in this step, propiolic acid: alcohol: orthoformate molar ratio is 1: 1-5: 0.5 to 5.
2. The process for the environmentally friendly preparation of a propiolic acid derivative according to claim 1, wherein:
in the step (1), the reaction temperature is 80 ℃, and the reaction time is 10 hours;
in the step (1), the alkali liquor is sodium hydroxide solution;
in the step (1), the molar ratio of the 2, 3-dibromo-succinic acid to the alkali liquor is 1: 3.
3. the process for the environmentally friendly preparation of a propiolic acid derivative according to claim 1, wherein:
in the step (2), sulfuric acid is selected as acid;
in the step (2), the reaction time is 5 hours; the reaction temperature is 100 ℃;
in the step (2), the extraction solvent is methyl tert-butyl ether.
4. The process for the environmentally friendly preparation of a propiolic acid derivative according to claim 1, wherein:
in the step (3), dichloromethane is used as an organic solvent;
in the step (3), sulfuric acid is used as an acid catalyst;
in the step (3), the reaction time is 24 hours;
in the step (3), propiolic acid: alcohol: orthoformate molar ratio is 1: 1: 0.5.
5. the process for the environmentally friendly preparation of a propiolic acid derivative according to claim 1, wherein:
in the step (1), the alkali liquor is prepared from methanol and potassium hydroxide, wherein the ratio of methanol: the mass ratio of the potassium hydroxide is 1000: 60.
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| CN113845421A (en) * | 2021-09-18 | 2021-12-28 | 杭州盛弗泰新材料科技有限公司 | Method for preparing ethyl propiolate by one-pot method |
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