CN104496908A - Preparation method of carbonyl diimidazole - Google Patents
Preparation method of carbonyl diimidazole Download PDFInfo
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- CN104496908A CN104496908A CN201410838020.6A CN201410838020A CN104496908A CN 104496908 A CN104496908 A CN 104496908A CN 201410838020 A CN201410838020 A CN 201410838020A CN 104496908 A CN104496908 A CN 104496908A
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- carbonyl dimidazoles
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- tsim
- diphenyl carbonate
- aluminum chloride
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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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
Abstract
The invention discloses a preparation method of carbonyl diimidazole. The method comprises the following steps of preparing N-trimethylsilyl imidazole from imidazole and hexamethyldisilazane and reacting N-trimethylsilyl imidazole and diphenyl carbonate to obtain carbonyl diimidazole. Compared with the prior art, the preparation method has the advantages that diphenyl carbonate is adopted as a carbonylation reagent, the carbonyl diimidazole product is obtained in the presence of a complex catalyst, namely, aluminum chloride and sodium methoxide, the conversion rate and yield of the product are increased and the entire process is more environment-friendly and is simple and convenient to operate.
Description
Technical field
The invention belongs to the technical field of technique of organic chemistry, be specifically related to a kind of synthetic method of carbonyl dimidazoles.
Background technology
Carbonyl dimidazoles is a kind of important medicine intermediate, is widely used as enzyme and casco, and antibiotics synthetic drugs intermediate, particularly as the linking agent of improvement on synthesis compound.In recent years, carbonyl dimidazoles is as activator, and reaction process low toxicity, to the selectivity that different functional groups has height, thus has very important significance in biochemistry synthesis, organic synthesis, field of polymer technology.Along with the develop rapidly in these fields, carbonyl dimidazoles oneself enjoy market to favor, domestic and international market demand increases day by day.
The method mainly phosgenation of current production carbonyl dimidazoles, mutters as solvent mainly with benzene, toluene, Si Qing Misaki, and by phosgene reaction, with excessive imidazoles as acid binding agent, yield is low, and product purity is not high, need be further purified, raw materials recovery difficulty.Few base reagent is widely used although phosgene is one, and there is higher reactive behavior, but it is hypertoxicity chemical, and the by product that phosgene brings comprises hydrochloric acid and other muriates, severe contamination can be caused to environment, also can cause serious corrosion and aftertreatment problem.Carbonic ether is emerging low toxicity, the free of contamination green chemical of a class, methylates and carbonylation agent as one is eco-friendly, and the cruel photoreactive gas of dimethyl sulfate of severe toxicity can be replaced to carry out suitability for industrialized production.In recent years because problem of environmental pollution is day by day for various countries pay close attention to, the industrialized reagent that environmental pollution is few more and more receives the concern of people.
Summary of the invention
Technical problem to be solved by this invention is to provide that a kind of yield is high, purity is high and the preparation method of the carbonyl dimidazoles of Environmental Safety.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
A preparation method for carbonyl dimidazoles, it comprises the steps:
(1) salt of wormwood is added after imidazoles being dissolved in hexamethyldisilazane, at 100 ~ 110 DEG C after stirring reaction 5 ~ 6h, be cooled to 45 ~ 70 DEG C of underpressure distillation, collect the cut of 75 ~ 78 DEG C/1.03kPa (under namely collecting 1.03kPa pressure, cut when 75 ~ 78 DEG C), obtain N-TSIM;
(2) after diphenyl carbonate being dissolved in dimethylbenzene, pass into nitrogen protection, add the N-TSIM of gained in aluminum chloride, sodium methylate and step (1), react 4 ~ 5h at 140 ~ 150 DEG C, obtain carbonyl dimidazoles reaction solution;
(3) the carbonyl dimidazoles reaction solution of gained in step (3) is cooled to 50 ~ 60 DEG C, concentrating under reduced pressure, gets solid part vacuum-drying after filtration, obtain carbonyl dimidazoles.
In step (1), the mol ratio of imidazoles and hexamethyldisilazane is 1:0.5 ~ 0.65, and preferred molar ratio is 1:0.6 ~ 0.61.
In step (1), add that quality is imidazoles quality 0.5 ~ 1% of salt of wormwood, preferably 0.7 ~ 1%.
In step (2), the mass ratio of diphenyl carbonate and N-TSIM is 1:1.3 ~ 2, and preferred mass is than being 1:1.4 ~ 1.5.
In step (2), the mass ratio of combination catalyst aluminum chloride and sodium methylate is 1:1.6 ~ 2, and preferred mass is than being 1:1.6 ~ 1.7.
In step (2), combination catalyst aluminum chloride and sodium methylate total mass are 1.5 ~ 3% of diphenyl carbonate quality, preferably 2%.
In step (2), preferable reaction temperature is 145 DEG C.
In step (3), described concentrating under reduced pressure, temperature is 65 DEG C ~ 75 DEG C, is concentrated into 1/5 of original volume.
In step (3), described vacuum-drying, temperature is 65 DEG C ~ 75 DEG C.
The chemical equation of the inventive method is as follows:
Beneficial effect: compared with prior art, the present invention has following advantage:
The present invention's diphenyl carbonate substitutes phosgene and the TSIM Reactive Synthesis carbonyl dimidazoles of severe toxicity, while improving conversion rate of products and yield, and the environmental protection more of whole technique, easy and simple to handle.
Embodiment
According to following embodiment, the present invention may be better understood.But those skilled in the art will readily understand, the content described by embodiment only for illustration of the present invention, and should can not limit the present invention described in detail in claims yet.
Embodiment 1:
The preparation of N-TSIM: add 20g imidazoles and 28.5g hexamethyldisilazane in 250mL there-necked flask, 0.2g potassium carbonate catalyst is added after stirring and dissolving, stir 6 hours at 105 DEG C, cool to 45 DEG C of underpressure distillation, collect the cut of 75 ~ 78 DEG C/1.03kPa, obtain N-TSIM 37.6g.
The preparation of carbonyl dimidazoles reaction solution: add 24g diphenyl carbonate and 140mL dimethylbenzene in 250mL there-necked flask; 35.4gN-TSIM and catalysts aluminum chloride 0.18g and sodium methylate 0.3g is added in the condition passing into nitrogen protection after stirring and dissolving; 145 DEG C are warmed up to after material dissolution is complete; insulated and stirred makes it react completely in 5 hours, obtains carbonyl dimidazoles reaction solution.
The preparation of carbonyl dimidazoles: carry out after carbonyl dimidazoles reaction solution is cooled to 55 DEG C being evaporated to 1/5 of original volume at 65 DEG C, filters, and at 65 DEG C, vacuum-drying obtains carbonyl dimidazoles product 16.51g, and product yield reaches 95%, and purity is 96%.
Embodiment 2:
The preparation of N-TSIM: add 20g imidazoles and 28.5g hexamethyldisilazane in 250mL there-necked flask, 0.15g potassium carbonate catalyst is added after stirring and dissolving, stir 6 hours at 105 DEG C, cool to 45 DEG C of underpressure distillation, collect the cut of 75-78 DEG C/1.03kPa, obtain N-TSIM 37.6g.
The preparation of carbonyl dimidazoles reaction solution: add 24g diphenyl carbonate and 140mL dimethylbenzene in 250mL there-necked flask; open and stir and under the condition passing into nitrogen protection, add 35.4gN-TSIM and catalysts aluminum chloride 0.13g and sodium methylate 0.35; the complete rear raising temperature of material dissolution carries out insulated and stirred to 145 DEG C makes it react completely in 5 hours, obtains carbonyl dimidazoles reaction solution.
The preparation of carbonyl dimidazoles: carry out after carbonyl dimidazoles reaction solution is cooled to 50 DEG C being evaporated to 1/5 of original volume at 70 DEG C, filters, and at 70 DEG C, vacuum-drying obtains carbonyl dimidazoles product 15.81g, and product yield reaches 91%, and purity is 92%.
Embodiment 3:
The preparation of N-TSIM: add 20g imidazoles and 28.5g hexamethyldisilazane in 250mL there-necked flask, 0.15g potassium carbonate catalyst is added after stirring and dissolving, stir 6 hours at 105 DEG C, cool to 45 DEG C of underpressure distillation, collect the cut of 75-78 DEG C/1.03kPa, obtain N-TSIM 37.6g.
The preparation of carbonyl dimidazoles reaction solution: in the there-necked flask of 250mL; add 24g diphenyl carbonate and 140mL dimethylbenzene; open and stir and under the condition passing into nitrogen protection, add 35.4gN-TSIM and catalysts aluminum chloride 0.15g and sodium methylate 0.4; the complete rear raising temperature of material dissolution carries out insulated and stirred to 150 DEG C makes it react completely in 5 hours, obtains carbonyl dimidazoles reaction solution.
The preparation of carbonyl dimidazoles: carry out after carbonyl dimidazoles reaction solution is cooled to 60 DEG C being evaporated to 1/5 of original volume at 75 DEG C, filters, and at 75 DEG C, vacuum-drying obtains carbonyl dimidazoles product 16.17g, and product yield reaches 93%, and purity is 94%.
Embodiment 4
Implementation method is with embodiment 1, difference is the mol ratio of imidazoles and hexamethyldisilazane is 1:0.5, add that quality is imidazoles quality 0.5% of salt of wormwood, the mass ratio of diphenyl carbonate and N-TSIM is 1:1.3, the mass ratio of catalyst aluminum chloride and sodium methylate is 1:1.6, and combination catalyst aluminum chloride and sodium methylate total mass are 1.5% of diphenyl carbonate quality, in the preparation process of carbonyl dimidazoles reaction solution, temperature of reaction is 140 DEG C, and the reaction times is 4h.
Embodiment 5
Implementation method is with embodiment 1, difference is the mol ratio of imidazoles and hexamethyldisilazane is 1:0.65, add that quality is imidazoles quality 0.7% of salt of wormwood, the mass ratio of diphenyl carbonate and N-TSIM is 1:2, the mass ratio of catalyst aluminum chloride and sodium methylate is 1:2, and combination catalyst aluminum chloride and sodium methylate total mass are 3% of diphenyl carbonate quality.
Claims (8)
1. a preparation method for carbonyl dimidazoles, is characterized in that, comprises the steps:
(1) add salt of wormwood after imidazoles being dissolved in hexamethyldisilazane, at 100 ~ 110 DEG C after stirring reaction 5 ~ 6h, be cooled to 45 ~ 70 DEG C of underpressure distillation, collect the cut of 75 ~ 78 DEG C/1.03kPa, obtain N-TSIM;
(2) after diphenyl carbonate being dissolved in dimethylbenzene, pass into nitrogen protection, add the N-TSIM of gained in aluminum chloride, sodium methylate and step (1), react 4 ~ 5h at 140 ~ 150 DEG C, obtain carbonyl dimidazoles reaction solution;
(3) the carbonyl dimidazoles reaction solution of gained in step (3) is cooled to 50 ~ 60 DEG C, concentrating under reduced pressure, gets solid part vacuum-drying after filtration, obtain carbonyl dimidazoles.
2. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (1), the mol ratio of imidazoles and hexamethyldisilazane is 1:0.5 ~ 0.65.
3. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (1), and add that quality is imidazoles quality 0.5 ~ 1% of salt of wormwood.
4. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (2), the mass ratio of diphenyl carbonate and N-TSIM is 1:1.3 ~ 2.
5. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (2), the mass ratio of aluminum chloride and sodium methylate is 1:1.6 ~ 2.
6. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (2), aluminum chloride and sodium methylate total mass are 1.5 ~ 3% of diphenyl carbonate quality.
7. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (3), described concentrating under reduced pressure, temperature is 65 ~ 75 DEG C, is concentrated into 1/5 of original volume.
8. the preparation method of carbonyl dimidazoles according to claim 1, is characterized in that, in step (3), described vacuum-drying, temperature is 65 ~ 75 DEG C.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109030688A (en) * | 2018-07-13 | 2018-12-18 | 四川科伦药物研究院有限公司 | A method of detection N- trimethylsilylimidazole and its related substance |
| CN109232430A (en) * | 2018-08-16 | 2019-01-18 | 浙江胡涂硅科技有限公司 | A kind of preparation method of carbonyl dimidazoles |
| CN111747979A (en) * | 2020-07-07 | 2020-10-09 | 新乡海滨药业有限公司 | Preparation method of meropenem key intermediate N-trimethylsilylimidazole |
| CN114456067A (en) * | 2022-02-22 | 2022-05-10 | 石家庄圣泰化工有限公司 | Synthesis method of di (2,2, 2-trifluoroethyl) carbonate |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109030688A (en) * | 2018-07-13 | 2018-12-18 | 四川科伦药物研究院有限公司 | A method of detection N- trimethylsilylimidazole and its related substance |
| CN109030688B (en) * | 2018-07-13 | 2020-07-10 | 四川科伦药物研究院有限公司 | Method for detecting N-trimethylsilylimidazole and related substances thereof |
| CN109232430A (en) * | 2018-08-16 | 2019-01-18 | 浙江胡涂硅科技有限公司 | A kind of preparation method of carbonyl dimidazoles |
| CN111747979A (en) * | 2020-07-07 | 2020-10-09 | 新乡海滨药业有限公司 | Preparation method of meropenem key intermediate N-trimethylsilylimidazole |
| WO2022007347A1 (en) * | 2020-07-07 | 2022-01-13 | 新乡海滨药业有限公司 | Preparation method for meropenem key intermediate n-trimethylsilylimidazole |
| CN114456067A (en) * | 2022-02-22 | 2022-05-10 | 石家庄圣泰化工有限公司 | Synthesis method of di (2,2, 2-trifluoroethyl) carbonate |
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Effective date of registration: 20160831 Address after: 224000 Yancheng City Binhai Chemical Industrial Park, Binhai County, Zhongshan, China, No. three, Jiangsu Road Applicant after: Jiangsu Cale New Materials Co., Ltd. Address before: 224000 Yancheng City Binhai Chemical Industrial Park, Binhai County, Zhongshan, China, No. three, Jiangsu Road Applicant before: Jiangsu Cale New Materials Co., Ltd. Applicant before: SHANGHAI HAODENG MATERIAL SCIENCE & TECHNOLOGY CO., LTD. |
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