CN107629009A - A kind of synthetic method of the dimethoxypyridin of 2 amino of a system 4,6 - Google Patents
A kind of synthetic method of the dimethoxypyridin of 2 amino of a system 4,6 Download PDFInfo
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- CN107629009A CN107629009A CN201711088636.6A CN201711088636A CN107629009A CN 107629009 A CN107629009 A CN 107629009A CN 201711088636 A CN201711088636 A CN 201711088636A CN 107629009 A CN107629009 A CN 107629009A
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- amidine
- alkali lye
- malononitrile
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- 0 COC(C=C(N)OC)=* Chemical compound COC(C=C(N)OC)=* 0.000 description 1
- LVFRCHIUUKWBLR-UHFFFAOYSA-N COc1nc(N)nc(OC)c1 Chemical compound COc1nc(N)nc(OC)c1 LVFRCHIUUKWBLR-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention provides a kind of synthetic method of the dimethoxypyridin of 2 amino of a system 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, directly heating, steaming solvent, distillation obtain the dimethoxypyridin of 2 amino 4,6.The synthetic method 1 of the present invention, the synthesis technique and equipment of the amidine dihydrochloride of 3- dimethyl propylenes two are simple, and the control of system moisture is extremely low, and product quality is stable, high income.Using a system method synthesis technique, synthesis cost is reduced, vacuum distillation obtains the dimethoxypyridin of 2 amino 4,6, and product purity is up to 99.99%.
Description
Technical field
The present invention relates to a kind of synthetic method of system 2- amino-4,6-dimethoxy pyrimidines, belong to organic synthesis skill
Art field.
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 hydrochloric acid of two amidine of first step 1,3- dimethyl propylenes two
After salt end of synthesis, separate in dissolving agent process, equipment is cumbersome, and product contact wetting and air have gone bad, and influences product receipts
Rate and quality；In 3- amino -3- methoxyl group-N- itrile groups the third amidines of -2- retake closed loop process, prior art will obtain 3- ammonia
After base -3- methoxyl group-N- itrile groups the third amidines of -2-, filtering, washing, dry, be further dissolved in heating closed loop in organic solvent and retake
To 2- amino-4,6-dimethoxy pyrimidines, technique is relative complex, and equipment is cumbersome.
The content of the invention
The invention provides a kind of system method with malononitrile, methanol, chloroacetic chloride, cyanamide, alkali lye raw material synthesis road
Line, chloroacetic chloride is added dropwise in malononitrile and methanol system, directly obtains the amidine dihydrochloride of 1,3- dimethyl propylenes two, afterwards and alkali
Liquid, cyanamide react to obtain 3- amino -3- methoxyl groups the third amidines of-N- itrile groups -2- and directly heat closed loop without filtering, washing and retake
To 2- amino -4,6- dimethoxypyridins.
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
The hydrogen chloride in solvent is extracted in continuous insulation reaction 0.5-4 hours, decompression out, obtains the mixing of the amidine dihydrochloride of 1,3- dimethyl propylenes two
Liquid；
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
The cyanamide solution of alkali lye and concentration for 50wt% is added into the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two,
Malononitrile：Alkali lye：The mol ratio of cyanamide is 1:1-2:1-2, reaction temperature are -5-10 DEG C, and pH value in reaction is in 5-8, and feed intake knot
Shu Hou, toluene layer is separated, aqueous phase is to slowly warm up to 10-30 DEG C, is incubated 6-15 hours, obtains 3- amino -3- methoxyl group-N- nitriles
Base -2- the third amidine mixed liquors；
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl group-N- itrile groups -2- the third amidine mixed liquors are warming up to 60-110 DEG C, are incubated 4-10 hours, reaction
After end, 100-105 DEG C of normal pressure steams water, continues 80-130 DEG C of vacuum distillation product, it is phonetic to obtain 2- amino -4,6- dimethoxys
Pyridine；
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.
(3) using system method synthesis 2- amino-4,6-dimethoxy pyrimidines, the amidine two of 1,3- dimethyl propylene two in the present invention
Cyanamide and alkali lye are directly added into after hydrochloride end of synthesis, process simplification, saves consersion unit, reduce product into
This, improves operating environmental condition.After the reaction of the third amidines of 3- amino -3- methoxyl group-N- itrile groups -2- terminates, directly heat up cyclization weight
Bat obtains 2- amino-4,6-dimethoxy pyrimidines, eliminates the washing of 3- amino -3- methoxyl group-N- itrile groups the third amidines of -2- material, mistake
Step is filtered, ring-closure reaction does not put into solvent additionally, reduces synthesis cost；Using vacuum distillation 2- amino -4,6- dimethoxys
Pyrimidine, product purity is up to 99.99%.
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, and the chlorine in solvent is extracted in decompression out
Change hydrogen, obtain the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two.
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
Alkali lye (sodium acid carbonate 20g, sodium hydroxide 30g, water are added into the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two
500g) and cyanamide solution 110g that concentration is 50wt%, -5-0 DEG C of controlling reaction temperature, pH value in reaction feed intake mole in 5-6
Than being slowly increased to 18 DEG C for temperature in the kettle after the end that feeds intake, 10 hours are incubated, obtains 3- amino -3- methoxyl group-N- itrile groups -2- third
Amidine mixed liquor.
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl group-N- itrile groups -2- the third amidine mixed liquors are warming up to 105 DEG C, are incubated 7 hours, reaction terminates
Afterwards, 105 DEG C of normal pressures steam water, continue 115 DEG C of vacuum distillation products, obtain 2- amino-4,6-dimethoxy pyrimidines 124g；
It is 100% through liquid-phase chromatographic analysis purity, product yield 80%.
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, and decompression is extracted out in solvent
Hydrogen chloride, obtain the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two.
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
Alkali lye (sodium acid carbonate 20g, sodium hydroxide 30g, water are added into the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two
500g) and cyanamide solution 101g that concentration is 50wt%, 0-3 DEG C of controlling reaction temperature, pH value in reaction feed intake mole in 6-7
Than being slowly increased to 27 DEG C for temperature in the kettle after the end that feeds intake, 10 hours are incubated, obtains 3- amino -3- methoxyl group-N- itrile groups -2- third
Amidine mixed liquor.
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl group-N- itrile groups -2- the third amidine mixed liquors are warming up to 80 DEG C, are incubated 10 hours, reaction terminates
Afterwards, 100 DEG C of normal pressures steam water, continue 120 DEG C of vacuum distillation products, obtain 2- amino-4,6-dimethoxy pyrimidines 120g；
It is 99.99% through liquid-phase chromatographic analysis purity, product yield 77.4%.
Claims (2)
1. a kind of synthetic method of system 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, decompression extract the hydrogen chloride in solvent out, obtain the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two；
(2) synthesis of 3- amino -3- methoxyl groups-N- itrile groups the third amidines of -2-
Add the cyanamide solution that alkali lye and concentration are 50wt% into the amidine dihydrochloride mixed liquor of 1,3- dimethyl propylenes two, the third two
The mol ratio of nitrile and alkali lye is 1:1-2:1-2, reaction temperature are -5-10 DEG C, and pH value in reaction separates first after 5-8, the end that feeds intake
Benzene layer, aqueous phase are to slowly warm up to 10-30 DEG C, are incubated 6-15 hours, obtain the mixing of the third amidines of 3- amino -3- methoxyl group-N- itrile groups -2-
Liquid；
(3) synthesis of 2- amino -4,6- dimethoxypyridins
3- amino -3- methoxyl group-N- itrile groups -2- the third amidine mixed liquors are continuously heating to 60-110 DEG C, are incubated 4-10 hours, reaction
After end, 100 DEG C of normal pressures steam water, continue 80-130 DEG C of vacuum distillation product, obtain 2- amino-4,6-dimethoxy pyrimidines；
2. synthetic method according to claim 1, it is characterised in that described alkali lye is sodium hydroxide, sodium acid carbonate, carbon
One or both of sour sodium, wet chemical are mixed above.
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Cited By (2)
| 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 |
Citations (3)
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| 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 |
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2017
- 2017-11-08 CN CN201711088636.6A patent/CN107629009B/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 |
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Cited By (3)
| 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 |
| 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 |
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