CN101323595A - Synthetic method 1,2-dimethyl-1,4,5,6-tetrahydrochysene pyrimidine - Google Patents
Synthetic method 1,2-dimethyl-1,4,5,6-tetrahydrochysene pyrimidine Download PDFInfo
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- CN101323595A CN101323595A CNA2008100208752A CN200810020875A CN101323595A CN 101323595 A CN101323595 A CN 101323595A CN A2008100208752 A CNA2008100208752 A CN A2008100208752A CN 200810020875 A CN200810020875 A CN 200810020875A CN 101323595 A CN101323595 A CN 101323595A
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Abstract
The invention relates to a method for synthesizing 1,2-dimethyl-1,4,5,6-tetrahydro-pyrimidine, which comprises steps as follows: an ethyl acetoacetate solution is dissolved in toluene, then N-methylaminopropylamine is dripped into and reaction temperature is controlled; after the dripping of the N-methylaminopropylamine is completed, the reaction solution is subjected to thermal retardation, decompression and dehydration; catalysts are added into the reaction solution after dehydration and the reaction solution is heated up to thermal retardation; the catalysts are aluminum muriate, zinc chloride, cupric chloride or iron trichloride; the obtained reaction solution is distilled to obtain the ethyl acetoacetate; the reaction solution is cooled, depressurized and distilled to obtain the finished product. The invention has the advantages of simple reaction, no extreme conditions, high yield (over 90 percent), less three wastes and being easy and stable for industrial production.
Description
One, technical field
The present invention relates to a kind of 1,2-dimethyl-1,4,5, the synthetic method of 6-tetrahydropyrimidine belongs to chemical technology field.
Two, background technology
1,2-dimethyl-1,4,5,6-tetrahydropyrimidine are faint yellow to colourless liquid, and it is the intermediate of insect repellent pyrantel, hydroxyl pyrimidine; Present 1,2-dimethyl-1,4,5, the synthetic method of 6-tetrahydropyrimidine is mainly: 1, that the imidoether of N-methyl-prop diamines and open chain or amidine reaction is synthetic 1,2-dimethyl-1,4,5, the 6-tetrahydropyrimidine, but its byproduct of reaction is many, and yield is lower than 70%; 2, N-methyl-prop diamines and tosic acid and cyanogen carboxylic acid is synthetic 1 210 ℃ of reactions, 2-dimethyl-1,4,5, the 6-tetrahydropyrimidine, the temperature of reaction height of this synthetic method can not be applied in the industrial production.
And U.S. Pat 4001232 introductions synthesize 1 with N-methyl-prop diamines and methyl aceto acetate reaction, 2-dimethyl-1,4,5, and the 6-tetrahydropyrimidine, but its reaction yield is also only 75%～85%.
Three, technology contents
At above-mentioned shortcoming, the object of the present invention is to provide a kind of reaction yield high 1,2-dimethyl-1,4,5, the synthetic method of 6-tetrahydropyrimidine.
Technology contents of the present invention is: a kind of 1, and 2-dimethyl-1,4,5, the synthetic method of 6-tetrahydropyrimidine, its step is as follows:
(1), with the methyl aceto acetate stirring and dissolving in toluene, the weight ratio of methyl aceto acetate and toluene is 1: 1～1.5; Drip 25～30 ℃ of N-methyl-prop diamines and control reaction temperature again, the add-on of N-methyl-prop diamines is 0.6～0.8 times of methyl aceto acetate weight; After N-methyl-prop diamines dropwises, with reaction soln insulation 2～6 hours, again reaction soln is carried out decompression dehydration, the temperature of decompression dehydration is 45～50 ℃, pressure is 2.0～3.5KPa;
(2), add catalyzer in the reaction soln after above-mentioned dehydration, be warming up to 130～140 ℃ again, and be incubated 1～3 hour; Catalyzer is aluminum chloride, zinc chloride, cupric chloride or iron trichloride, and its add-on is 0.02-0.20 a times of methyl aceto acetate weight;
(3), reaction soln that step (2) is made distills, and distillates methyl aceto acetate, reaction soln is cooled to 50～60 ℃ again;
(4), the reaction soln after the cooling in the step (3) being carried out the step-down distillation gets product.
Above-mentioned 1,2-dimethyl-1,4,5, in the synthetic method of 6-tetrahydropyrimidine, in step (1), reaction soln carried out decompression dehydration after, the toluene in the reclaim under reduced pressure solution again so that this toluene is recycled, pressure is 2.0～3.5KPa.
The present invention is that raw material synthesizes 1,2-dimethyl-1,4 with methyl aceto acetate and N-methyl-prop diamines, 5, the 6-tetrahydropyrimidine is when dripping N-methyl-prop diamines, heat release in the reaction process, the content of middle control N-methyl-prop diamines by the control rate of addition is with finishing of guaranteeing to react; The temperature of controlling decompression dehydration again is 45～50 ℃, guarantees to react single, and subsequent reactions does not react in this temperature; The dehydration back that finishes adds catalyzer, guarantees that annulation carries out fast, and reaction produces a large amount of ethyl acetate, again 130～140 ℃ of insulations, guarantees that the ethyl acetate that generates all collects.
Reaction formula of the present invention is as follows:
The advantage that the present invention is compared with prior art had is: reaction is simple, no severe condition, and the yield height is more than 90%, the three wastes are few, be easy to suitability for industrialized production and suitability for industrialized production is stablized.
Four, concrete enforcement
The present invention is further detailed explanation below in conjunction with embodiment.
Embodiment 1,
(1), 496g methyl aceto acetate, 400g toluene are dropped into reaction flask, stirring and dissolving drips the suction of 243gN-methyl-prop diamines in the bottle again, splash into reactor, 25～30 ℃ of control reaction temperature are dripped Bi Baowen 3h, and middle control GC measures N-methyl-prop diamines≤0.5 weight %, 50 ℃ of control decompression temperature, pressure 2.5KPa, decompression divides water, and moisture≤0.5% is decided in middle detection, reclaim under reduced pressure 375g toluene, pressure 2.5KPa;
(2), add catalyzer 18g in the reaction soln after above-mentioned dehydration, catalyzer is a zinc chloride, reaction soln is warming up to 135 ℃ and be incubated 2 hours again,
(3), reaction soln that step (2) is made distills, and distillates ethyl acetate 235g, reaction soln is cooled to 55 ℃ again,
(4), the reaction soln after the cooling in the step (3) is transferred to still kettle, 1 of 20mmHg/110～112 ℃ are collected in underpressure distillation, 2-dimethyl-1,4,5, and 6-tetrahydropyrimidine 296g, it is a colourless transparent liquid, yield 96%.
Example 2,496g methyl aceto acetate, 400g toluene are dropped into reaction flask, stirring and dissolving drips the suction of 243gN-methyl-prop diamines in the bottle again, splash into reactor, 25～30 ℃ of control reaction temperature are dripped Bi Baowen 3h, and middle control GC measures N-methyl-prop diamines≤0.5 weight %, 50 ℃ of control decompression temperature, decompression divides water, pressure 2.5KPa, and moisture≤0.5% is decided in middle detection, reclaim under reduced pressure 375g toluene, pressure 2.5KPa;
(2), add catalyzer 18g in the reaction soln after above-mentioned dehydration, catalyzer is a nickelous chloride, reaction soln is warming up to 135 ℃ and be incubated 2 hours again,
(3), reaction soln that step (2) is made distills, and distillates ethyl acetate 238, reaction soln is cooled to 55 ℃ again,
(4), the reaction soln after the cooling in the step (3) is transferred to still kettle, 1 of 20mmHg/110～112 ℃ are collected in underpressure distillation, 2-dimethyl-1,4,5, and 6-tetrahydropyrimidine 282g, it is a colourless transparent liquid, yield 91.5%.
Example 3,496g methyl aceto acetate, 400g toluene are dropped into reaction flask, stirring and dissolving drips the suction of 243gN-methyl-prop diamines in the bottle again, splash into reactor, 25～30 ℃ of control reaction temperature are dripped Bi Baowen 3h, and middle control GC measures N-methyl-prop diamines≤0.5 weight %, 50 ℃ of control decompression temperature, decompression divides water, pressure 2.5KPa, and moisture≤0.5% is decided in middle detection, reclaim under reduced pressure 375g toluene, pressure 2.5KPa;
(2), add catalyzer 18g in the reaction soln after above-mentioned dehydration, catalyzer is an aluminum chloride, reaction soln is warming up to 135 ℃ and be incubated 2 hours again,
(3), reaction soln that step (2) is made distills, and distillates ethyl acetate 229g, reaction soln is cooled to 55 ℃ again,
(4), the reaction soln after the cooling in the step (3) is transferred to still kettle, 1 of 20mmHg/110～112 ℃ are collected in underpressure distillation, 2-dimethyl-1,4,5, and 6-tetrahydropyrimidine 287g, it is a colourless transparent liquid, yield 93%.
Example 4,496g methyl aceto acetate, 400g toluene are dropped into reaction flask, stirring and dissolving drips the suction of 243gN-methyl-prop diamines in the bottle again, splash into reactor, 25～30 ℃ of control reaction temperature are dripped Bi Baowen 3h, and middle control GC measures N-methyl-prop diamines≤0.5 weight %, 50 ℃ of control decompression temperature, decompression divides water, pressure 2.5KPa, and moisture≤0.5% is decided in middle detection, reclaim under reduced pressure 375g toluene, pressure 2.5KPa;
(2), add catalyzer 18g in the reaction soln after above-mentioned dehydration, catalyzer is a cupric chloride, reaction soln is warming up to 135 ℃ and be incubated 2h again,
(3), reaction soln that step (2) is made distills, and distillates ethyl acetate 236g, reaction soln is cooled to 55 ℃ again,
(4), the reaction soln after the cooling in the step (3) is transferred to still kettle, 1 of 20mmHg/110～112 ℃ are collected in underpressure distillation, 2-dimethyl-1,4,5, and 6-tetrahydropyrimidine 294g, it is a colourless transparent liquid, yield 95.2%.
Claims (2)
1, a kind of 1,2-dimethyl-1,4,5, the synthetic method of 6-tetrahydropyrimidine, its step is as follows:
(1), with the methyl aceto acetate stirring and dissolving in toluene, the weight ratio of methyl aceto acetate and toluene is 1: 1～1.5; Drip 25～30 ℃ of N-methyl-prop diamines and control reaction temperature again, the add-on of N-methyl-prop diamines is 0.6～0.8 times of methyl aceto acetate weight; After N-methyl-prop diamines dropwises, with reaction soln insulation 2～6 hours, again reaction soln is carried out decompression dehydration, the temperature of decompression dehydration is 45～50 ℃, pressure is 2.0～3.5KPa;
(2), add catalyzer in the reaction soln after above-mentioned dehydration, be warming up to 130～140 ℃ again, and be incubated 1～3 hour; Catalyzer is aluminum chloride, zinc chloride, cupric chloride or iron trichloride, and its add-on is 0.02-0.20 a times of methyl aceto acetate weight;
(3), reaction soln that step (2) is made distills, and distillates methyl aceto acetate, reaction soln is cooled to 50～60 ℃ again;
(4), the reaction soln after the cooling in the step (3) being carried out the step-down distillation gets product.
2, described 1 according to claim 1,2-dimethyl-1,4,5, the synthetic method of 6-tetrahydropyrimidine is characterized in that after step (1) is carried out decompression dehydration to reaction soln, the toluene in the reclaim under reduced pressure solution again, its pressure is 2.0～3.5KPa.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664875A (en) * | 2013-12-21 | 2014-03-26 | 西北大学 | Novel method for synthesizing 1,4,5,6-tetrahydropyrimidine derivative |
| CN108822044A (en) * | 2018-07-12 | 2018-11-16 | 西安万德科技有限公司 | A kind of synthetic method of 1,2- dimethyl -1,4,5,6- tetrahydropyrimidine |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664875A (en) * | 2013-12-21 | 2014-03-26 | 西北大学 | Novel method for synthesizing 1,4,5,6-tetrahydropyrimidine derivative |
| CN103664875B (en) * | 2013-12-21 | 2016-01-13 | 西北大学 | Isosorbide-5-Nitrae, the synthetic method of 5,6-tetrahydropyrimidinederivatives derivatives |
| CN108822044A (en) * | 2018-07-12 | 2018-11-16 | 西安万德科技有限公司 | A kind of synthetic method of 1,2- dimethyl -1,4,5,6- tetrahydropyrimidine |
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Effective date of registration: 20160719 Address after: 2188 No. 213012 Jiangsu province Zhonglou District of Changzhou City Avenue Patentee after: Changzhou wintop Chemical Technology Co Ltd Address before: 213033, No. 8, South District Road, Shen Tong chemical District, Xinbei Town, Xinbei District, Jiangsu, Changzhou Patentee before: Changzhou Watson Fine Chemical Co., Ltd. |