CN107619393A - The synthetic method of the dimethoxypyridin of 2 amino 4,6 - Google Patents
The synthetic method of the dimethoxypyridin of 2 amino 4,6 Download PDFInfo
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- CN107619393A CN107619393A CN201711088637.0A CN201711088637A CN107619393A CN 107619393 A CN107619393 A CN 107619393A CN 201711088637 A CN201711088637 A CN 201711088637A CN 107619393 A CN107619393 A CN 107619393A
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- dimethyl propylenes
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Abstract
The invention provides a kind of synthetic method of the dimethoxypyridin of 2 amino 4,6, belong to technical field of organic synthesis.The invention provides it is a kind of with malononitrile, methanol, chloroacetic chloride, cyanamide, alkali lye raw material synthetic route, chloroacetic chloride is added dropwise in malononitrile and methanol system, directly obtain 1, the amidine dihydrochloride of 3- dimethyl propylenes two, react to obtain the amidine of 3 amino, 3 methoxyl group N itrile groups 2 third with alkali lye, cyanamide afterwards, further reset to obtain the dimethoxypyridin of 2 amino 4,6 through closed loop.The synthetic method of the present invention saves the cumbersome synthesis technique of the amidine dihydrochloride of 1,3- dimethyl propylenes two and equipment, and chloroacetic chloride is added into malononitrile and in methanol, one-step method directly obtains the amidine dihydrochloride of 1,3- dimethyl propylenes two.The control of the amidine dihydrochloride synthetic route moisture of 1,3- dimethyl propylenes two is extremely low in the present invention, and product quality is stable, high income.
Description
Technical field
The present invention relates to a kind of synthetic method of 2- amino-4,6-dimethoxy pyrimidines, belong to technical field of organic synthesis.
Background technology
In the development of agricultural chemicals, heterocyclic compound has turned into the main flow of novel pesticide research and development.Pyrimidines are
A kind of important bioactive substance, is widely used in Insecticides (tech) ＆ Herbicides (tech), bactericide and medicine intermediate and enjoys people
Concern.In the production of sulfonylurea herbicide, 2- amino-4,6-dimethoxy pyrimidines are the important intermediates of its synthesis,
Have much using it as sulfonylurea herbicide kind prepared by raw material.
The existing documents and materials of 2- amino-4,6-dimethoxy pyrimidines report its structure and synthetic route, at present 2- amino -4,
6- dimethoxypyridins are using the synthesis of the raw material routes such as guanidine nitrate, dimethyl malenate, POCl3, sodium methoxide, POCl3
Larger to environmental hazard during transport, use, there is the disagreeableness problem of environment in technique；2- amino -4,6- dimethoxys
Another route is relatively low and environment-friendly as cost of material using malononitrile in the synthetic method of pyrimidine, using malononitrile, methanol, anhydrous
Hydrogen chloride, toluene, cyanamide, sodium acid carbonate raw material, intermediate 1, in the amidine dihydrochloride building-up process of 3- dimethyl propylenes two definitely
Anhydrous, wherein anhydrous hydrogen chloride gas is one of indispensable raw material, but the preparation of anhydrous hydrogen chloride, drying equipment complexity, fortune be present
Row cost is high, anhydrous hydrogen chloride the problems such as directly affecting product yield of poor quality.
The content of the invention
The invention provides it is a kind of with malononitrile, methanol, chloroacetic chloride, cyanamide, alkali lye raw material synthetic route, by acetyl
Chlorine is added dropwise to malononitrile with methanol system, directly obtaining the amidine dihydrochloride of 1,3- dimethyl propylenes two, anti-with alkali lye, cyanamide afterwards
3- amino -3- methoxyl group-N- itrile groups the third amidines of -2- should be obtained, further reset to obtain 2- amino -4,6- dimethoxys through closed loop phonetic
Pyridine.
Technical scheme：
The synthetic method of 2- amino-4,6-dimethoxy pyrimidines, step are as follows：
(1) synthesis of the amidine dihydrochloride of 1,3- dimethyl propylenes two
Malononitrile and absolute methanol are put into reactor, then chloroacetic chloride is slowly added dropwise, wherein, malononitrile, absolute methanol
Mol ratio with chloroacetic chloride three is 1:4-8:2-5；Under -10-20 DEG C of temperature conditionss, chloroacetic chloride is added dropwise, after completion of dropwise addition, after
Continuous insulation reaction 0.5-4 hours, nitrogen protection filtering, obtain the amidine dihydrochloride of 1,3- dimethyl propylenes two；
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
The amidine dihydrochloride of 1,3- dimethyl propylenes two and alkali lye are added into reactor, controls the mol ratio of malononitrile and alkali lye
For 1:1-2, reaction temperature are -5-10 DEG C, then the cyanamide solution that concentration is 50wt%, control are slowly added into above-mentioned reaction solution
The mol ratio of malononitrile and cyanamide processed is 1:1-2, pH value in reaction are to slowly warm up to 10-30 DEG C after 5-8, the end that feeds intake, protected
Warm 6-15 hours, filter, wash, dry, obtain 3- amino -3- methoxyl group-N- itrile groups the third amidines of -2-；
(3) synthesis of 2- amino -4,6- dimethoxypyridins
Input 3- amino -3- methoxyl groups the third amidines of-N- itrile groups -2- and solvent into reactor, control malononitrile and solvent
Mass ratio is 1:3-30, temperature rising reflux 4-10 hours, reaction terminate after, distilling off solvent, solid through be recrystallized to give 2- amino-
4,6- dimethoxypyridins；
Described solvent is that one or both of toluene, methanol, methyl acetate, ethyl acetate, water are mixed above.
Described alkali lye is more than one or both of sodium hydroxide, sodium acid carbonate, sodium carbonate, wet chemical mixed
Close.
Beneficial effects of the present invention：
(1) synthetic method of the invention saves the cumbersome synthesis technique of the amidine dihydrochloride of 1,3- dimethyl propylenes two and set
Standby, chloroacetic chloride is added to malononitrile with methanol, directly obtaining the amidine dihydrochloride of 1,3- dimethyl propylenes two by one-step method.
(2) control of the amidine dihydrochloride synthetic route moisture of 1,3- dimethyl propylenes two is extremely low in the present invention, and product quality is stable,
High income.
Embodiment
Below in conjunction with technical scheme, embodiment of the invention is further illustrated.
Embodiment one
The synthetic method of 2- amino-4,6-dimethoxy pyrimidines, step are as follows：
(1) synthesis of the amidine dihydrochloride of 1,3- dimethyl propylenes two
Malononitrile 66g, absolute methanol 176g are put into reactor, chloroacetic chloride 235.5g is slowly added dropwise into kettle, is controlled
Reaction temperature time for adding 5 hours, after completion of dropwise addition, continues insulation reaction 1 hour at 0-5 DEG C, nitrogen protection filtering, obtains
The amidine dihydrochloride wet product of 1,3- dimethyl propylenes two.
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
The amidine dihydrochloride of 1,3- dimethyl propylenes two and alkali lye (sodium acid carbonate 20g, sodium hydroxide 30g, water are added to reactor
500g), -5-0 DEG C of controlling reaction temperature, 50% cyanamide solution 110g is slowly added into solution, pH value in reaction is in 5-6, throwing
Material mol ratio is slowly increased to 18 DEG C for temperature in the kettle after the end that feeds intake, and is incubated 10 hours, filtering, washing, be dried to obtain 3- amino-
3- methoxyl group-N- itrile groups the third amidines of -2- 131g.
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl group-N- itrile groups -2- the third amidine 131g and methanol 500g are put into reactor, temperature rising reflux 6 is small
When, after reaction terminates, methanol is distilled out, solid is through being recrystallized to give 2- amino-4,6-dimethoxy pyrimidines 125g.
It is 99.2% through liquid-phase chromatographic analysis purity, product yield 80.6%.
Embodiment two
The synthetic method of 2- amino-4,6-dimethoxy pyrimidines, step are as follows：
(1) synthesis of the amidine dihydrochloride of 1,3- dimethyl propylenes two
Malononitrile 66g, absolute methanol 204.8g are put into reactor, chloroacetic chloride 353.25g is slowly added dropwise into kettle, is controlled
Reaction temperature processed time for adding 8 hours, after completion of dropwise addition, continues insulation reaction 2 hours at 10-15 DEG C, nitrogen protection filtering,
Obtain the amidine dihydrochloride wet product of 1,3- dimethyl propylenes two.
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
The amidine dihydrochloride of 1,3- dimethyl propylenes two and alkali lye (sodium acid carbonate 20g, sodium hydroxide 30g, water are added to reactor
500g), 0-3 DEG C of controlling reaction temperature, is slowly added to 50% cyanamide solution 101g into solution, and pH value in reaction feeds intake in 7-8
Mol ratio is slowly increased to 26 DEG C for temperature in the kettle after the end that feeds intake, and is incubated 10 hours, filtering, washing, is dried to obtain 3- amino -3-
Methoxyl group-N- itrile groups the third amidines of -2- 122.4g.
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl group-N- itrile groups -2- the third amidine 122.4g and toluene 600g, temperature rising reflux 4 are put into reactor
Hour, after reaction terminates, distilling off solvent toluene, solid is through being recrystallized to give 2- amino-4,6-dimethoxy pyrimidines 121.2g.
It is 99.8% through liquid-phase chromatographic analysis purity, product yield 78%.
Claims (3)
1. a kind of synthetic method of 2- amino-4,6-dimethoxy pyrimidines, it is characterised in that step is as follows：
(1) synthesis of the amidine dihydrochloride of 1,3- dimethyl propylenes two
Malononitrile and absolute methanol are put into reactor, then chloroacetic chloride is slowly added dropwise, wherein, malononitrile, absolute methanol and second
The mol ratio of acyl chlorides three is 1:4-8:2-5；Under -10-20 DEG C of temperature conditionss, chloroacetic chloride is added dropwise, after completion of dropwise addition, continues to protect
Temperature reaction 0.5-4 hours, nitrogen protection filtering, obtain the amidine dihydrochloride of 1,3- dimethyl propylenes two；
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
Add the amidine dihydrochloride of 1,3- dimethyl propylenes two and alkali lye into reactor, the mol ratio of malononitrile and alkali lye is 1:1-2,
Reaction temperature is -5-10 DEG C, then the cyanamide solution that concentration is 50wt% is slowly added into above-mentioned reaction solution, controls malononitrile
Mol ratio with cyanamide is 1:1-2, pH value in reaction are to slowly warm up to 10-30 DEG C, insulation 6-15 is small after 5-8, the end that feeds intake
When, filter, wash, dry, obtain 3- amino -3- methoxyl group-N- itrile groups the third amidines of -2-；
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl groups the third amidines of-N- itrile groups -2- and solvent are put into reactor, controls the quality of malononitrile and solvent
Than for 1:3-30, temperature rising reflux 4-10 hours, after reaction terminates, distilling off solvent, solid is through being recrystallized to give 2- amino -4,6-
Dimethoxypyridin；
2. synthetic method according to claim 1, it is characterised in that described solvent be toluene, methanol, methyl acetate,
One or both of ethyl acetate, water are mixed above.
3. synthetic method according to claim 1 or 2, it is characterised in that described alkali lye is sodium hydroxide, bicarbonate
One or both of sodium, sodium carbonate, wet chemical are mixed above.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110903251A (en) * | 2019-12-27 | 2020-03-24 | 江苏丰山集团股份有限公司 | Preparation method of 2-amino-4, 6-dimethoxypyrimidine |
| CN112552243A (en) * | 2020-12-18 | 2021-03-26 | 营口昌成新材料科技有限公司 | Preparation method of 2-amino-4,6-dimethoxypyrimidine |
| CN113896637A (en) * | 2020-06-22 | 2022-01-07 | 昂吉(上海)环保新材料科技有限公司 | Preparation method of 3, 3-dimethoxy methyl propionate |
| CN115872903A (en) * | 2022-10-30 | 2023-03-31 | 江苏长青农化南通有限公司 | Synthetic method of acetamiprid intermediate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102491948A (en) * | 2011-12-12 | 2012-06-13 | 湖北志诚化工科技有限公司 | Preparation method for 2-amino-4, 6-dimethoxy pyrimidine |
| CN102898382A (en) * | 2012-11-07 | 2013-01-30 | 东南大学 | Method for synthesizing 2-amino-4,6-dimethoxypyrimidine |
| CN105377819A (en) * | 2013-07-09 | 2016-03-02 | Cj医药健康株式会社 | Method for preparation of benzimidazole derivatives |
-
2017
- 2017-11-08 CN CN201711088637.0A patent/CN107619393B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102491948A (en) * | 2011-12-12 | 2012-06-13 | 湖北志诚化工科技有限公司 | Preparation method for 2-amino-4, 6-dimethoxy pyrimidine |
| CN102898382A (en) * | 2012-11-07 | 2013-01-30 | 东南大学 | Method for synthesizing 2-amino-4,6-dimethoxypyrimidine |
| CN105377819A (en) * | 2013-07-09 | 2016-03-02 | Cj医药健康株式会社 | Method for preparation of benzimidazole derivatives |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110903251A (en) * | 2019-12-27 | 2020-03-24 | 江苏丰山集团股份有限公司 | Preparation method of 2-amino-4, 6-dimethoxypyrimidine |
| CN110903251B (en) * | 2019-12-27 | 2022-06-14 | 江苏丰山集团股份有限公司 | Preparation method of 2-amino-4, 6-dimethoxypyrimidine |
| CN113896637A (en) * | 2020-06-22 | 2022-01-07 | 昂吉(上海)环保新材料科技有限公司 | Preparation method of 3, 3-dimethoxy methyl propionate |
| CN112552243A (en) * | 2020-12-18 | 2021-03-26 | 营口昌成新材料科技有限公司 | Preparation method of 2-amino-4,6-dimethoxypyrimidine |
| CN115872903A (en) * | 2022-10-30 | 2023-03-31 | 江苏长青农化南通有限公司 | Synthetic method of acetamiprid intermediate |
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