CN110963912B - Method for preparing 2, 4-dibromo methyl butyrate by catalyzing bromosulfonic acid resin - Google Patents
Method for preparing 2, 4-dibromo methyl butyrate by catalyzing bromosulfonic acid resin Download PDFInfo
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- CN110963912B CN110963912B CN201911346273.0A CN201911346273A CN110963912B CN 110963912 B CN110963912 B CN 110963912B CN 201911346273 A CN201911346273 A CN 201911346273A CN 110963912 B CN110963912 B CN 110963912B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/49—Esterification or transesterification
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
- B01J31/08—Ion-exchange resins
- B01J31/10—Ion-exchange resins sulfonated
Abstract
The invention discloses a method for preparing 2, 4-dibromobutyric acid methyl ester by catalyzing bromosulfonic acid resin, which comprises the following steps: adding 2-5% of brominated sulfonic acid resin catalyst in the gamma-butyrolactone; heating to 80-90 ℃, dropwise adding a certain amount of liquid bromine, preserving the temperature at 90-100 ℃, and reacting for 3-5 h; cooling to room temperature, dripping methanol, and reacting for 10-15 h; filtering to remove the catalyst, washing the catalyst with a detergent, drying and reusing the catalyst; and distilling the filtrate to obtain a target product. The catalyst has high catalytic activity, short reaction time and high utilization rate of raw materials; the catalyst can be reused, the damage of phosphorus-containing wastewater to the environment is avoided, the wastewater amount is small, and the production cost is reduced; the post-treatment is convenient, the links of extraction, washing, drying and the like are reduced, the operation is simple, the product quality is high, and the concept of environmental protection is met.
Description
Technical Field
The invention relates to a preparation method of an organic compound, in particular to a method for preparing 2, 4-dibromobutyric acid methyl ester by catalyzing bromosulfonic acid resin.
Background
Methyl 2, 4-dibromobutyrate is an important medical intermediate. Currently, the preparation of methyl 2, 4-dibromobutyrate mainly comprises the following steps:
(1) the method comprises the steps of taking gamma-butyrolactone as a starting material, firstly carrying out ring opening on HBr to obtain 4-bromobutyric acid, separating and purifying a product, then reacting the product with a brominating agent to obtain 2, 4-dibromobutyric acid, and then carrying out esterification reaction on the product and methanol to obtain methyl 2, 4-dibromobutyrate. A lot of byproducts are generated due to poor control, so that the purity of the product is extremely low, and large-scale industrial production is difficult to realize at present.
(2) Adding the phosphorus-containing substance into gamma-butyrolactone, then cooling and dropwise adding a brominating agent to generate 4-bromobutyryl bromide, then dropwise adding a brominating agent to generate 2, 4-dibromobutyryl bromide, and finally dropwise adding methanol to generate 2, 4-dibromobutyric acid methyl ester. The phosphorus-containing substances in the reaction mainly comprise red phosphorus and phosphorus tribromide. The phosphorus-containing catalyst used in the reaction is large in dosage, and a lot of phosphorus-containing wastewater is formed in subsequent treatment, so that the method is not environment-friendly.
Disclosure of Invention
The invention aims to provide a method for preparing 2, 4-dibromo methyl butyrate by catalyzing bromosulfonic acid resin, which has no by-product and is safe to operate.
The Amberlyst 15 resin catalyst is a novel strong acid catalyst specially used for replacing concentrated sulfuric acid in organic chemical synthesis reaction, and is widely applied to catalysis of chemical reactions such as alkylation, acylation, esterification, acetal, ketal, etherification, hydrolysis, hydration, ring opening and the like. After bromine atoms are introduced to the benzene ring of Amberlyst 15 resin, the hydrophobicity of the resin can be increased, and the thermal stability of sulfonic acid groups on the benzene ring can be improved. The invention aims to find a novel method for preparing 2, 4-dibromo methyl butyrate by utilizing catalysis of brominated sulfonic acid resin.
The technical scheme adopted by the invention for solving the technical problems is as follows: a method for preparing 2, 4-dibromo methyl butyrate by catalyzing bromosulfonic acid resin comprises the following steps:
(1) adding 2-5% of brominated sulfonic acid resin catalyst in the gamma-butyrolactone;
(2) heating to 80-90 ℃, dropwise adding a certain amount of liquid bromine, preserving the temperature at 90-100 ℃, and reacting for 3-5 h;
(3) cooling to room temperature, dripping methanol, and reacting for 10-15 h;
(4) filtering to remove the catalyst, washing the catalyst with a detergent, drying and reusing the catalyst;
(5) and distilling the filtrate to obtain a target product.
The preparation method of the brominated sulfonic acid resin catalyst comprises the following steps:
(1) adding Amberlyst 15 resin to saturated monohydric alcohol;
(2) then adding liquid bromine, and reacting for 3-10h at 30-50 ℃;
(3) after the reaction is finished, filtering, washing with a small amount of corresponding alcohol, reacting at 30-50 ℃, and drying under reduced pressure for 3-10h to obtain the bromo-sulfonic acid resin.
Preferably, the saturated monohydric alcohol is one or more of methanol, ethanol, butanol and isopropanol; the mass of the saturated monohydric alcohol is 3-5 times of that of Amberlyst 15 resin; the mass ratio of the liquid bromine to the mixture of Amberlyst 15 resin and saturated monohydric alcohol is 0.6-1.
Preferably, the detergent is one of methanol, ethanol and isopropanol.
The method for preparing 2, 4-dibromo methyl butyrate by catalyzing bromosulfonic acid resin has the beneficial effects that:
1. the catalyst has high catalytic activity, short reaction time and high utilization rate of raw materials;
2. the catalyst can be reused, the damage of phosphorus-containing wastewater to the environment is avoided, the wastewater amount is small, and the production cost is reduced;
3. the post-treatment is convenient, the links of extraction, washing, drying and the like are reduced, the operation is simple, the product quality is high, and the concept of environmental protection is met.
Detailed Description
In order that the present invention may be more clearly understood, the following detailed description of the present invention is given with reference to specific examples.
Example 1:
200g Amberlyst 15 resin was added to 600g methanol, followed by 120g liquid bromine, and reacted at 30 ℃ for 3 h. Filtering, washing with a small amount of anhydrous methanol, reacting at 30 ℃, and drying under reduced pressure for 3 hours to obtain the bromo-sulfonic acid resin.
Adding 20g of catalyst into 1.075kg of gamma-butyrolactone, heating to 80 ℃, dropwise adding 2.19kg of liquid bromine, keeping the temperature at 90 ℃ after dropwise adding, and reacting for 3 hours. Cooling to room temperature, dripping 4kg of methanol, and reacting at room temperature for 10h after dripping is finished. Filtering to remove the catalyst, washing the catalyst with methanol, drying and reusing. The filtrate was directly distilled to obtain 2.855kg of the target product with 88% yield.
Example 2:
200g Amberlyst 15 resin was added to 1000g ethanol, then 200g liquid bromine was added and reacted at 50 ℃ for 10 h. Filtering, washing with a small amount of anhydrous methanol, reacting at 50 ℃, and drying under reduced pressure for 10 hours to obtain the bromo-sulfonic acid resin.
54g of catalyst is added into 1.075kg of gamma-butyrolactone, the temperature is raised to 90 ℃, 2.19kg of liquid bromine is dripped, the temperature is kept at 100 ℃ after the dripping is finished, and the reaction is carried out for 5 hours. Cooling to room temperature, dropwise adding 4kg of methanol, and reacting at room temperature for 15h after dropwise adding. Filtering to remove the catalyst, washing the catalyst with methanol, drying and reusing. The filtrate was directly distilled to obtain 3.18kg of the target product with a yield of 98%.
Example 3:
200g Amberlyst 15 resin was added to 1000g isopropanol, then 180g liquid bromine was added and reacted at 40 ℃ for 6 h. Filtering, washing with a small amount of anhydrous methanol, reacting at 40 ℃, and drying under reduced pressure for 6 hours to obtain the bromo-sulfonic acid resin.
Adding 37g of catalyst into 1.075kg of gamma-butyrolactone, heating to 85 ℃, dropwise adding 2.19kg of liquid bromine, keeping the temperature at 100 ℃ after dropwise adding, and reacting for 4 hours. Cooling to room temperature, dripping 4kg of methanol, and reacting at room temperature for 12h after dripping is finished. Filtering to remove the catalyst, washing the catalyst with methanol, drying and reusing. The filtrate was directly distilled to obtain 3.08kg of the target product with a yield of 95%.
The above embodiments are described in further detail to solve the technical problems, technical solutions and advantages of the present invention, and it should be understood that the above embodiments are only examples of the present invention and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (6)
1. A method for preparing 2, 4-dibromo methyl butyrate by catalyzing bromosulfonic acid resin is characterized by comprising the following steps:
(1) adding 2-5% of brominated sulfonic acid resin catalyst in the gamma-butyrolactone;
(2) heating to 80-90 ℃, dropwise adding a certain amount of liquid bromine, preserving the temperature at 90-100 ℃, and reacting for 3-5 h;
(3) cooling to room temperature, dripping methanol, and reacting for 10-15 h;
(4) filtering to remove the catalyst, washing the catalyst with a detergent, drying and reusing the catalyst;
(5) and distilling the filtrate to obtain a target product.
2. The method for preparing 2, 4-dibromobutyric acid methyl ester by catalyzing the bromosulfonic acid resin according to claim 1, wherein the preparation method of the bromosulfonic acid resin catalyst comprises the following steps:
(1) adding Amberlyst 15 resin to saturated monohydric alcohol;
(2) then adding liquid bromine, and reacting for 3-10h at 30-50 ℃;
(3) after the reaction is finished, filtering, washing with a small amount of corresponding alcohol, reacting at 30-50 ℃, and drying under reduced pressure for 3-10h to obtain the bromo-sulfonic acid resin.
3. The method for preparing 2, 4-dibromo-butyric acid methyl ester under catalysis of bromosulfonic acid resin according to claim 2, wherein the saturated monohydric alcohol is one or more of methanol, ethanol, butanol and isopropanol.
4. The method for preparing 2, 4-dibromo methyl butyrate under catalysis of brominated sulfonic acid resin according to claim 2, wherein the mass of the saturated monohydric alcohol is 3-5 times that of Amberlyst 15 resin.
5. The method for preparing methyl 2, 4-dibromobutyrate by catalysis of bromosulfonic acid resin according to claim 2, wherein in the step (2), the mass ratio of liquid bromine to the mixture of Amberlyst 15 resin and saturated monohydric alcohol is 0.6-1.
6. The method for preparing 2, 4-dibromo-butyric acid methyl ester under catalysis of bromosulfonic acid resin according to claim 1, wherein the detergent is one of methanol, ethanol and isopropanol.
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| CN114940648B (en) * | 2022-06-30 | 2023-11-21 | 常州夏青科技有限公司 | Method for preparing malonic acid mono-tert-butyl ester by catalysis of strong acid resin |
| CN116440951B (en) * | 2023-06-19 | 2023-08-11 | 山东河清化工科技有限公司 | Cis-trans isomerism catalyst and preparation method and application thereof |
Citations (3)
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| CN101880230A (en) * | 2010-07-26 | 2010-11-10 | 江苏技术师范学院 | Preparation method of 2,4-dibromo-butyricacid methyl ester |
| CN105503903A (en) * | 2014-09-26 | 2016-04-20 | 南京明德新药研发股份有限公司 | Preparation method of benzoxazoloxazone compound and intermediate and crystal form |
| CN109134406A (en) * | 2018-08-02 | 2019-01-04 | 丽珠集团新北江制药股份有限公司 | A kind of synthetic method of Bu Waxitan intermediate and Bu Waxitan |
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Patent Citations (3)
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| CN101880230A (en) * | 2010-07-26 | 2010-11-10 | 江苏技术师范学院 | Preparation method of 2,4-dibromo-butyricacid methyl ester |
| CN105503903A (en) * | 2014-09-26 | 2016-04-20 | 南京明德新药研发股份有限公司 | Preparation method of benzoxazoloxazone compound and intermediate and crystal form |
| CN109134406A (en) * | 2018-08-02 | 2019-01-04 | 丽珠集团新北江制药股份有限公司 | A kind of synthetic method of Bu Waxitan intermediate and Bu Waxitan |
Non-Patent Citations (1)
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| Halogenated macroporous sulfonic resins as efficient catalysts for the Biginelli reaction;Pengfei Shen et al.;《Catalysis Communications》;20160112;第77卷;第18-21页 * |
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