CN107827823B - Preparation method of 4, 5-dibromoimidazole - Google Patents
Preparation method of 4, 5-dibromoimidazole Download PDFInfo
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- CN107827823B CN107827823B CN201711174336.XA CN201711174336A CN107827823B CN 107827823 B CN107827823 B CN 107827823B CN 201711174336 A CN201711174336 A CN 201711174336A CN 107827823 B CN107827823 B CN 107827823B
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- tribromoimidazole
- dibromoimidazole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/68—Halogen atoms
Abstract
The invention discloses a preparation method of 4, 5-dibromoimidazoles, which belongs to the field of preparation of fine chemical products.4, 5-dibromoimidazoles is prepared by reacting 2,4, 5-tribromoimidazole with triphenylphosphine in methanol.4, 5-dibromoimidazole is prepared by using triphenylphosphine as a reducing agent to reduce 2,4, 5-tribromoimidazole into 4, 5-dibromoimidazole.
Description
Technical Field
The invention relates to a preparation method of 4, 5-dibromoimidazole, belonging to the field of preparation of fine chemical products.
Background
4, 5-dibromo imidazole is important pesticides and medical intermediates, and the following reports exist in domestic and foreign published technologies.
Advanced Synthesis & Catalysis,355(2-3),499-507,2013, introduces brominating imidazole in sulfuric acid with dibromohydantoin to obtain 4, 5-dibromoimidazole, which has more waste water and uses acid which is easy to corrode kettle body and has higher requirements on equipment.
The bromination of imidazole with NBS in DMF to give 4, 5-dibromoimidazole, but the product is a mixture of bromo, dibromo and tribromoimidazole, is described in Journal of the Chemical Society, Perkin Transactions 1: Organic andBi-Organic Chemist (1972-1999), (1), 95-9; 1989, and purification is difficult.
Journal of the Chemical Society, Perkin Transactions 1: Organic andBi-Organic chemistry (1972-1999), (7), 1455-51; 1987 describes a method for preparing 4, 5-dibromoimidazole from 2,4, 5-tribromoimidazole by using a Grignard reagent or butyl lithium at-78 ℃, which is not beneficial to industrial production due to high requirements on equipment because of low-temperature reaction.
Disclosure of Invention
Aiming at the technical problems, the invention provides a preparation method of kinds of 4, 5-dibromoimidazole, which directly reduces 2,4, 5-tribromoimidazole into 4, 5-dibromoimidazole, reduces the generation of waste, improves the reaction yield, is beneficial to reducing the production cost and reducing the environmental pollution.
The preparation method of kinds of 4, 5-dibromoimidazole is characterized by comprising the following steps:
(1) reacting 2,4, 5-tribromoimidazole with a reducing reagent and a catalyst in an organic solvent to prepare 4, 5-dibromoimidazole;
(2) adding an ethyl acetate solution into the product obtained in the step (1), dropwise adding an alkali solution while stirring, layering, and desolventizing;
(3) the resulting solid was isolated and dried with a yield of 70% to 75%.
In the technical scheme, the reaction temperature is preferably 60-65 ℃, and the heat preservation time is 1 hour.
Further , the process for preparing 4, 5-dibromoimidazole of the present invention is carried out in a reactor equipped with a condensing unit and a stirring unit.
The reduction reagent in all technical schemes of the preparation method of the 4, 5-dibromo imidazole is hydriodic acid, stannous chloride, zinc powder, ethanolamine and triphenylphosphine. Triphenylphosphine is preferred and is commercially available.
The dosage of the reducing agent in all technical schemes of the preparation method of the 4, 5-dibromoimidazole is 0.8-1 time, preferably 0.9 time of the weight of the 2,4, 5-tribromoimidazole.
In all technical schemes of the preparation method of the 4, 5-dibromoimidazole, the catalyst is preferably tetramethylammonium chloride, tetrabutylammonium bromide and the like, and preferably tetramethylammonium chloride.
In all technical schemes of the preparation method of the 4, 5-dibromoimidazole, the dosage of the catalyst is preferably 0.3-0.8 time, preferably 0.5 time of the weight of the 2,4, 5-tribromoimidazole.
In all technical schemes of the preparation method of the 4, 5-dibromoimidazole, the organic solvent is preferably methanol, ethanol, isopropanol, acetone, 2-butanone, tetrahydrofuran, glycol dimethyl ether and the like, and preferably methanol.
In all technical schemes of the preparation method of the 4, 5-dibromoimidazole, the dosage of the methanol is preferably 2-5 times, preferably 2.6 times of the weight of the 2,4, 5-tribromoimidazole.
In all technical schemes of the preparation method of the 4, 5-dibromoimidazole, the alkali solution is preferably aqueous solution of sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methoxide, potassium carbonate, sodium bicarbonate, sodium acetate, ammonia water and the like, and is preferably aqueous solution of sodium bicarbonate.
In all technical schemes of the preparation method of the 4, 5-dibromoimidazole, the dosage of the alkali solution is preferably 5-10 times of the weight of the 2,4, 5-tribromoimidazole. Preferably 5.5 times.
, in the technical scheme, 2,4, 5-tribromoimidazole reacts with triphenylphosphine and a catalyst in methanol to prepare 4, 5-dibromoimidazole.
, in the technical proposal, triphenylphosphine is used as a reducing agent, tetramethylammonium chloride is used as a catalyst, and 2,4, 5-tribromoimidazole is reduced into 4, 5-dibromoimidazole.
, the preferable preparation method of 4, 5-dibromoimidazole comprises the steps of placing 2,4, 5-tribromoimidazole, methanol and tetramethylammonium chloride in a reaction kettle, adding triphenylphosphine in batches while stirring, preserving heat at 60-65 ℃ for 1 hour, adding ethyl acetate and sodium bicarbonate, layering, desolventizing, separating the obtained solid, and drying to obtain 4, 5-dibromoimidazole with the yield of 75%.
The method has the beneficial effects that the triphenylphosphine is used as a reducing agent, tetramethylammonium chloride is used as a catalyst, and the 2,4, 5-tribromoimidazole is reduced into the 4, 5-dibromoimidazole, the 2,4, 5-tribromoimidazole can be directly reduced into the 4, 5-dibromoimidazole in steps, so that the generation of waste is reduced, the reaction yield is improved, the production cost is favorably reduced, and the environmental pollution is reduced.
Detailed Description
The following non-limiting examples are presented to enable those of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way.
The test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
Adding 422.5g of 2,4, 5-tribromoimidazole and 1126.7g of methanol into a reaction kettle, adding 21.1g of tetramethylammonium chloride, adding 384.5g of triphenylphosphine in batches while stirring, after the addition is finished, carrying out heat preservation reaction at 60-65 ℃ for about 1 hour, cooling to room temperature, adding ethyl acetate, dropwise adding a sodium bicarbonate solution while stirring, layering, desolventizing an organic layer, precipitating a large amount of solid, cooling to room temperature, filtering, and drying to obtain 234.8g of 4, 5-dibromoimidazole with the yield of 75%.
Example 2
Adding 248.4g of 2,4, 5-tribromoimidazole and 662g of methanol into a reaction kettle, adding 9.9g of tetrabutylammonium bromide, stirring while adding 226g of triphenylphosphine in batches, after the addition is finished, keeping the temperature at 60-65 ℃ for reaction for about 1 hour, cooling to room temperature, adding ethyl acetate, stirring while adding a sodium bicarbonate solution, layering, desolventizing an organic layer, separating out a large amount of solids, cooling to room temperature, filtering, and drying to obtain 132.5g of 4, 5-dibromoimidazole with the yield of 72%.
Example 3
Adding 496g of 2,4, 5-tribromoimidazole and 1325g of ethanol into a reaction kettle, adding 24.8g of quaternary ammonium chloride, stirring while adding 452g of triphenylphosphine in batches, after the addition is finished, keeping the temperature at 60-65 ℃ for reaction for about 1 hour, cooling to room temperature, adding ethyl acetate, stirring while dropwise adding a sodium bicarbonate solution, layering, desolventizing an organic layer, separating out a large amount of solids, cooling to room temperature, filtering, and drying to obtain 257g of 4, 5-dibromoimidazole with the yield of 70%.
Example 4
Adding 165g of 2,4, 5-tribromoimidazole and 441g of ethanol into a reaction kettle, adding 8.2g of quaternary ammonium chloride while stirring, adding 150g of hydroiodic acid in batches, after the addition is finished, keeping the temperature at 60-65 ℃ for reaction for about 1 hour, cooling to room temperature, adding ethyl acetate, dropwise adding a sodium bicarbonate solution while stirring, layering, desolventizing an organic layer until a large amount of solids are separated out, cooling to room temperature, filtering, and drying to obtain 85g of 4, 5-dibromoimidazole with the yield of 70%.
Claims (5)
- The preparation method of kinds of 4, 5-dibromoimidazole is characterized by comprising the following steps:(1) reacting 2,4, 5-tribromoimidazole with a reducing agent and a catalyst in an organic solvent at the temperature of 60-65 ℃ for 1 hour; the reducing agent is selected from hydriodic acid or triphenylphosphine; the catalyst is selected from tetramethylammonium chloride and tetrabutylammonium bromide; the organic solvent is selected from methanol or ethanol;(2) adding an ethyl acetate solution into the product obtained in the step (1), adding an alkali solution, layering, and desolventizing;(3) the resulting solid was isolated and dried with a yield of not less than 70%.
- 2. The method of claim 1, wherein: the dosage of the reducing agent is 0.8-1 time of the weight of 2,4, 5-tribromoimidazole.
- 3. The method of claim 1, wherein: the dosage of the catalyst is 0.03-0.08 time of the weight of 2,4, 5-tribromoimidazole.
- 4. The method of claim 1, wherein: the dosage of the organic solvent is 2-5 times of the weight of 2,4, 5-tribromoimidazole.
- 5. The method of claim 1, wherein: the alkali solution is selected from aqueous solutions of sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methoxide, potassium carbonate, sodium bicarbonate and sodium acetate or ammonia water, and the dosage of the aqueous solution is 5-10 times of the weight of 2,4, 5-tribromoimidazole.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3337550A (en) * | 1963-12-10 | 1967-08-22 | Shell Oil Co | Process for preparing triazines and imidazoles |
| US3962330A (en) * | 1973-09-28 | 1976-06-08 | Ankerfarm, S.P.A. | Process for the preparation of 6-demethyl-6-deoxy-6-methylene-tetracyclines |
| CN102432543A (en) * | 2011-11-07 | 2012-05-02 | 沈健芬 | Method for synthetizing 4-iodo-1H-imidazole |
| CN106674121A (en) * | 2016-11-22 | 2017-05-17 | 杭州励德生物科技有限公司 | Preparation method of 4-halogen-1H-imidazole |
-
2017
- 2017-11-22 CN CN201711174336.XA patent/CN107827823B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3337550A (en) * | 1963-12-10 | 1967-08-22 | Shell Oil Co | Process for preparing triazines and imidazoles |
| US3962330A (en) * | 1973-09-28 | 1976-06-08 | Ankerfarm, S.P.A. | Process for the preparation of 6-demethyl-6-deoxy-6-methylene-tetracyclines |
| CN102432543A (en) * | 2011-11-07 | 2012-05-02 | 沈健芬 | Method for synthetizing 4-iodo-1H-imidazole |
| CN106674121A (en) * | 2016-11-22 | 2017-05-17 | 杭州励德生物科技有限公司 | Preparation method of 4-halogen-1H-imidazole |
Non-Patent Citations (1)
| Title |
|---|
| 卤代芳经催化氢转移脱卤研究的进展;于海涛，等;《河北师范大学学报（自然科学版）》;19961231;第20卷;第137-140页 * |
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Inventor after: Jiang Bin Inventor after: Jiang Dianbao Inventor after: Zhang Hongxue Inventor before: Jiang Bin Inventor before: Jiang Dianping Inventor before: Zhang Hongxue |