CN1927842A - Synthesis technology of 1,3-dimethyl-2-chloroimidazoline chloride - Google Patents
Synthesis technology of 1,3-dimethyl-2-chloroimidazoline chloride Download PDFInfo
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- CN1927842A CN1927842A CN 200610046909 CN200610046909A CN1927842A CN 1927842 A CN1927842 A CN 1927842A CN 200610046909 CN200610046909 CN 200610046909 CN 200610046909 A CN200610046909 A CN 200610046909A CN 1927842 A CN1927842 A CN 1927842A
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- climiqualine
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Abstract
The present invention belongs to the field of fine chemical producing technology, and is especially preparation process of chloro-1, 3-dimethyl-2-chloro imidazoline. The preparation process includes dissolving solid phosgene, which is used to replace gaseous phosgene and liquid phosgene, in inert solvent; dropping the solid phosgene solution into inert solution of 1, 3-dimethyl-2-imidazolidone to react at 25-65 deg.c for 2-8 hr to prepare white chloro-1, 3-dimethyl-2-chloro imidazoline. The inert solvent may be benzene, toluene, methylene chloride, chloroform, carbon tetrachloride or chlorobenzene, and is preferably methylene chloride or carbon tetrachloride. The preparation process is safe, pollutionless and simple, and has high product yield and high product purity.
Description
Technical field
The invention belongs to the production field of fine chemical product, particularly a kind of chloro 1, the preparation technology of 3-dimethyl-2-climiqualine.
Background technology
Chloro 1,3-dimethyl-2-climiqualine has the chemical structure of be shown below (1).(American Chemical Society, CAS) the CAS registration number of this compound of Fa Hang summary magazine " " chemical abstracts " (Chemical Abstracts, CA) " is: " [37091-73-9] " in American Chemical Society.
Chloro 1,3-dimethyl-2-climiqualine, the synthetic of organic compound as: in the processes such as ester, acid anhydrides, acid amides, nitrile and polypeptide and polyester, as a kind of good new chemical reaction reagent, important use (J.Org.Chem., 1999 are arranged at chemical industry and field of medicaments, 64,6984; J.Org.Chem., 1999,64,6989; J.Org.Chem., 1999,64,5832).
The preparation of this reagent is with 1, and 3-dimethyl-2-imidazolone (2) is a raw material, realizes by following chemical reaction process under suitable chlorination reagent effect:
As existing preparation method; it is that chlorination reagent prepares chloro 1 that United States Patent (USP) in early days (US3959258) has been introduced with the phosgene, the method for 3-dimethyl-2-climiqualine, and this method yield is low; and owing to have the use of strong toxicity phosgene, making does not have the possibility of large-scale production.
Disclosing a kind of at Japanese Patent (JP59-25375) is that chlorination reagent prepares chloro 1 with the oxalyl chloride, the method for 3-dimethyl-2-climiqualine, and product yield is 69% in the method.But oxalyl chloride is a strongly corrosion liquid, brings inconvenience for transportation and use, and has a large amount of byproduct hydrogen chlorides to produce in reaction, therefore exists significantly not enough as large-scale method for producing.
Disclosing a kind of at Japanese Patent (JP59-39851) in addition is that chlorination reagent prepares chloro 1 with the trichloromethylchloroformate, the method for 3-dimethyl-2-climiqualine, and product yield is 90% in the method.But trichloromethylchloroformate is in a liquid state, and transportation and use still exist certain dangerous, still are restricted in the use.
In above-mentioned patent, introduced simultaneously and prepared chloro 1 with chlorination reagents such as phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, the possibility of 3-dimethyl-2-climiqualine, but the use of this type of reagent makes reaction system be the two-phase state, and the existence of by product phosphoric acid in the reaction, to making reaction be difficult to fully carry out, and very difficult when product separation, the product that obtains is difficult to meet the requirement of medicine, Chemical Manufacture.
Summary of the invention
The present invention aims to provide a kind of high yield, chloro 1 safe, pollution-free, easy and simple to handle, and the synthesis technique of 3-dimethyl-2-climiqualine is to satisfy requirement of massive production.
The object of the present invention is achieved like this: chloro 1, the synthesis technique of 3-dimethyl-2-climiqualine, can carry out as follows:
(1) solid phosgene is dissolved in the inert solvent, reaction mixture keeps below 5 ℃;
(2) step (1) products therefrom is slowly dropped to 1, in the solution of the inert solvent of 3-dimethyl-2-imidazolone;
(3) step (2) gained reaction solution is at room temperature stirred, heats up, promptly get final product through cooling, filtration, washing.
In the step of the present invention (3) step (2) gained reaction solution at room temperature can be stirred 0.5～1.5 hour, be warming up to 40 ℃～65 ℃ again, and under this temperature, keep 2～8 hours.
Solid phosgene of the present invention and 1, the mol ratio that 3-dimethyl-2-imidazolone carries out chlorination reaction is: 1: 3～6; Be preferably 1: 3～4.
Inert solvent of the present invention is a kind of in benzene, toluene, methylene dichloride, chloroform, tetracol phenixin, the chlorobenzene, is preferably methylene dichloride or tetracol phenixin.
The consumption of inert solvent of the present invention is 1 by percentage to the quality, 5～30 times of 3-dimethyl-2-imidazolone, preferred 10～20 times.
The chloridization process that adopts solid phosgene to substitute phosgene or liquid phosgene in the technology of the present invention can thoroughly solve product yield and toxicity and pollute conflicting problem.
The present invention compares with conventional art has following remarkable advantage:
1) solid phosgene is easy to use as solid, and accurately weighing has avoided excessive use to produce side reaction;
2) be compared to use phosgene, liquid phosgene and other chlorinating agents, use the chloro-product yield height of solid phosgene;
3) solid phosgene discharges carbonic acid gas in chlorination, and is pollution-free, reduced in the technology waste gas treatment process and to the harsh requirement of equipment;
4) chloro 1 that makes of technology of the present invention, 3-dimethyl-2-climiqualine is a pure white crystallinity product, the purity height can satisfy the requirement of chemical industry, field of medicaments.
Embodiment
The present invention will describe by following specific embodiment, but not be subjected to the restriction of the following example.
Embodiment 1
In three mouthfuls of reaction flasks of 1000ml, add 1,3-dimethyl-2-imidazolone (34.2 grams, 0.3 mole), tetracol phenixin (400 milliliters) stirs the carbon tetrachloride solution that slowly drips solid phosgene (two trichloromethyl carbonate) down and (contains solid phosgene 30 grams, 0.1 mole, 100 milliliters in tetracol phenixin), reaction mixture keeps below 5 ℃, vigorous stirring 0.5 hour, and room temperature reaction is after 1 hour, be warming up to 50 ℃, kept 4 hours.The question response product is cooled to room temperature, and filtration, a small amount of tetracol phenixin washing obtain the white crystalline product, and be dry in the moisture eliminator through having Vanadium Pentoxide in FLAKES, obtains lily crystalline product chloro 1,3-dimethyl-2-climiqualine 49 grams, yield 96.6%.
Fusing point: 85～86 ℃
IR(KBr)：γ＝1632，1541，1415，1344，1301，1230，1142，960cm
-1
1H-NMR(CDCl
3)：δ＝3.36(s，6H，CH
3×2)，4.39(s，4H，CH
2CH
2)ppm
Embodiment 2
In three mouthfuls of reaction flasks of 1000ml, add 1,3-dimethyl-2-imidazolone (34.2 grams, 0.3 mole), methylene dichloride (400 milliliters) stirs the dichloromethane solution that slowly drips solid phosgene down and (contains solid phosgene 30 grams, 0.1 mole, 100 milliliters of methylene dichloride), reaction mixture keeps below 5 ℃, vigorous stirring 0.5 hour, and room temperature reaction is after 0.5 hour, be warming up to 40 ℃, kept 4 hours.The question response product is cooled to room temperature, and filtration, a small amount of tetracol phenixin washing obtain the white crystalline product, and be dry in the moisture eliminator through having Vanadium Pentoxide in FLAKES, obtains lily crystalline product 48 grams, yield 95%, and fusing point, IR reach
1It is all consistent with embodiment 1 that H-NMR absorbs situation.
Embodiment 3
In three mouthfuls of reaction flasks of 500ml, add 1,3-dimethyl-2-imidazolone (34.2 grams, 0.3 mole), chlorobenzene (350 milliliters) stirs the chlorobenzene solution that slowly drips solid phosgene down and (contains solid phosgene 30 grams, 0.1 mole, 50 milliliters of chlorobenzenes), reaction mixture keeps below 5 ℃, vigorous stirring 0.5 hour, and room temperature reaction is after 2 hours, be warming up to 60 ℃, kept 3 hours.The question response product is cooled to room temperature, and filtration, a small amount of washed with dichloromethane obtain the white crystalline product, and be dry in the moisture eliminator through having Vanadium Pentoxide in FLAKES, obtains lily crystalline product 41.5 grams, yield 82%.
Fusing point, IR reach
1It is all consistent with embodiment 1 that H-NMR absorbs situation.
Comparative example:
In three mouthfuls of reaction flasks of 500ml, add 1,3-dimethyl-2-imidazolone (22.4 grams, 0.2 mole), tetracol phenixin (250 milliliters) stirs adding phosphorus oxychloride (30.6 grams, 0.2 mole) down, under the vigorous stirring fast, behind the room temperature reaction 2 hours, be warming up to 50 ℃, kept 6 hours.The question response product is cooled to room temperature, filters, a small amount of tetracol phenixin washing, obtains having solid product 15.9 grams of viscosity, and yield 47% is dry in the moisture eliminator through having Vanadium Pentoxide in FLAKES, and the product that obtains is toughness slightly still.
Claims (8)
1, chloro 1, and the synthesis technique of 3-dimethyl-2-climiqualine is characterized in that: carry out as follows:
(1) solid phosgene is dissolved in the inert solvent, reaction mixture keeps below 5 ℃;
(2) step (1) products therefrom is slowly dropped to 1, in the solution of the inert solvent of 3-dimethyl-2-imidazolone;
(3) step (2) gained reaction solution is at room temperature stirred, heats up, promptly get final product through cooling, filtration, washing.
2, chloro 1 according to claim 1, the synthesis technique of 3-dimethyl-2-climiqualine, it is characterized in that: in the described step (3) step (2) gained reaction solution was at room temperature stirred 0.5～1.5 hour, be warming up to 40 ℃～65 ℃ again, and under this temperature, kept 2～8 hours.
3, chloro 1 according to claim 1 and 2, the synthesis technique of 3-dimethyl-2-climiqualine is characterized in that: described solid phosgene and 1, the mol ratio that 3-dimethyl-2-imidazolone carries out chlorination reaction is: 1: 3～6; Be preferably 1: 3～4.
4, chloro 1 according to claim 1 and 2, the synthesis technique of 3-dimethyl-2-climiqualine, it is characterized in that: described inert solvent is a kind of in benzene, toluene, methylene dichloride, chloroform, tetracol phenixin, the chlorobenzene, is preferably methylene dichloride or tetracol phenixin.
5, chloro 1 according to claim 3, the synthesis technique of 3-dimethyl-2-climiqualine is characterized in that: described inert solvent is a kind of in benzene, toluene, methylene dichloride, chloroform, tetracol phenixin, the chlorobenzene, is preferably methylene dichloride or tetracol phenixin.
6, chloro 1 according to claim 1 and 2, the synthesis technique of 3-dimethyl-2-climiqualine is characterized in that: the consumption of described inert solvent is 1 by percentage to the quality, 5～30 times of 3-dimethyl-2-imidazolone, preferred 10～20 times.
7, chloro 1 according to claim 3, the synthesis technique of 3-dimethyl-2-climiqualine is characterized in that: the consumption of described inert solvent is 1 by percentage to the quality, 5～30 times of 3-dimethyl-2-imidazolone, preferred 10～20 times.
8, chloro 1 according to claim 4, the synthesis technique of 3-dimethyl-2-climiqualine is characterized in that: the consumption of described inert solvent is 1 by percentage to the quality, 5～30 times of 3-dimethyl-2-imidazolone, preferred 10～20 times.
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| CNB2006100469096A CN100427470C (en) | 2006-06-15 | 2006-06-15 | Synthesis technology of 1,3-dimethyl-2-chloroimidazoline chloride |
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| CNB2006100469096A CN100427470C (en) | 2006-06-15 | 2006-06-15 | Synthesis technology of 1,3-dimethyl-2-chloroimidazoline chloride |
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| CN1927842A true CN1927842A (en) | 2007-03-14 |
| CN100427470C CN100427470C (en) | 2008-10-22 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105367478A (en) * | 2015-06-03 | 2016-03-02 | 北京成宇药业有限公司 | Preparation process of zafirlukast |
| CN110845414A (en) * | 2019-11-27 | 2020-02-28 | 济宁康盛彩虹生物科技有限公司 | Preparation method and application of N-bis (dimethylamino) -1, 3-dimethylimidazoline |
| CN111517922A (en) * | 2020-04-28 | 2020-08-11 | 万华化学集团股份有限公司 | Method for preparing 4-chloro-3, 5-dimethylphenol |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5939851A (en) * | 1982-08-26 | 1984-03-05 | Shiratori Seiyaku Kk | Esterification |
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2006
- 2006-06-15 CN CNB2006100469096A patent/CN100427470C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105367478A (en) * | 2015-06-03 | 2016-03-02 | 北京成宇药业有限公司 | Preparation process of zafirlukast |
| CN105367478B (en) * | 2015-06-03 | 2019-01-04 | 北京成宇药业有限公司 | The preparation process of zafirlukast |
| CN110845414A (en) * | 2019-11-27 | 2020-02-28 | 济宁康盛彩虹生物科技有限公司 | Preparation method and application of N-bis (dimethylamino) -1, 3-dimethylimidazoline |
| WO2021103614A1 (en) * | 2019-11-27 | 2021-06-03 | 济宁康盛彩虹生物科技有限公司 | Preparation method for and use of n-bis(dimethylamino)-1,3-dimethylimidazoline |
| CN111517922A (en) * | 2020-04-28 | 2020-08-11 | 万华化学集团股份有限公司 | Method for preparing 4-chloro-3, 5-dimethylphenol |
| CN111517922B (en) * | 2020-04-28 | 2022-11-04 | 万华化学集团股份有限公司 | Method for preparing 4-chloro-3,5-dimethylphenol |
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