CN102250018B - Preparation method of 2-ehtyoxyl-4,6-dyhydroxypyrimidine - Google Patents
Preparation method of 2-ehtyoxyl-4,6-dyhydroxypyrimidine Download PDFInfo
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- CN102250018B CN102250018B CN201110130501.8A CN201110130501A CN102250018B CN 102250018 B CN102250018 B CN 102250018B CN 201110130501 A CN201110130501 A CN 201110130501A CN 102250018 B CN102250018 B CN 102250018B
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- oxyethyl group
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Abstract
The invention discloses a preparation method of 2-ehtyoxyl-4,6-dyhydroxypyrimidine. The preparation method comprises the following steps: (1) dissolving O-ethylisothiourea bisulfate into absolute methanol so as to obtain a methanol solution containing O-ethylisothiourea bisulfate, then cooling the methanol solution containing O-ethylisothiourea bisulfate to minus 10 DEG C-10 DEG C, dropwise adding 27wt% sodium methanol solution under the condition of stirring and reacting for 20 minutes-60 minutes after dropwise adding; (2) slowly adding diethyl malonate at the temperature of minus 10 DEGC-10 DEG C, and then stirring and reacting for 5 hours-10 hours at the temperature of 15 DEG C-25 DEG C; and (3) after reaction is finished, carrying out postprocessing so as to obtain 2-ethyoxyl-4,6-dyhydroxypyrimidine. The method has the advantage of high yield.
Description
Technical field
The present invention relates to a kind of preparation method of herbicide intermediate, particularly relate to a kind of preparation method of 2-oxyethyl group-4,6-dihydroxy-pyrimidine.
Background technology
2-oxyethyl group-4,6-dihydroxy-pyrimidine is a kind of important pyrimidines, is also the important intermediate of synthesis triazolopyrimidine sulfonamides herbicide diclosulam etc.
American documentation literature US5463055A discloses one and prepares 2-oxyethyl group-4, the method of 6-dihydroxy-pyrimidine, the method is that the ethanolic soln containing O-ethyl isourea hydrosulfate is cooled to-10 DEG C, stir lower dropping 21% alcohol sodium solution, drip off rear reaction 5min, slowly diethyl malonate is added, afterwards heating reflux reaction 4 hours at-10 DEG C.React after terminating, the ethanol in distillation removing reaction system, adds enough water dissolution, is cooled to less than 15 DEG C, drip the salt acid for adjusting pH about 2 ~ 3 of 32%, separate out solid in system, and filtration, washing, drying obtain 2-oxyethyl group-4,6-dihydroxy-pyrimidine.Its reaction equation is as follows:
The deficiency of the method is: obtained product is yellow solid, and yield only has 54%.
Summary of the invention
The object of the invention is to overcome the problems referred to above, the preparation method of 2-oxyethyl group-4, the 6-dihydroxy-pyrimidine providing a kind of yield higher.
The technical scheme realizing the object of the invention is as follows: a kind of 2-oxyethyl group-4, the preparation method of 6-dihydroxy-pyrimidine, there are following steps: 1. O-ethyl isourea hydrosulfate is dissolved in anhydrous methanol the methanol solution obtained containing O-ethyl isourea hydrosulfate, then the methanol solution this being contained O-ethyl isourea hydrosulfate is cooled to-10 DEG C ~ 10 DEG C, stirring lower dropping concentration is the sodium methoxide solution of 27wt%, drips off rear reaction 20min ~ 60min; 2. at-10 DEG C ~ 10 DEG C, slowly diethyl malonate is added, then stirring reaction 5h ~ 10h at 15 DEG C ~ 25 DEG C; 3., after reaction terminates, 2-oxyethyl group-4,6-dihydroxy-pyrimidine is obtained through aftertreatment.
Above-mentioned steps 1. described in O-ethyl isourea hydrosulfate and the weight ratio of anhydrous methanol be 1: 2 ~ 1: 5.
Above-mentioned steps 1. described in O-ethyl isourea hydrosulfate and concentration be the mol ratio of 27wt% sodium methoxide solution be 1: 1 ~ 1: 5.
Above-mentioned steps 1. described in O-ethyl isourea hydrosulfate and step 2. described in the mol ratio of diethyl malonate be 1: 1 ~ 1: 2.
Above-mentioned steps 3. described in aftertreatment be: Distillation recovery methyl alcohol, adds water, and is then cooled to 0 DEG C ~ 10 DEG C, drips hydrochloric acid, by the solid filtering, washing, dry of separating out.
Above-mentioned steps 1. described in O-ethyl isourea hydrosulfate and step 3. described in the mol ratio of hydrochloric acid be 1: 0.5 ~ 1: 1.5.
The positively effect that the present invention has: (1) the present invention adopts methyl alcohol-sodium methylate to replace ethanol-sodium ethylate, and adopt concentration to be the sodium methylate of 27wt%, control at room temperature (15 DEG C ~ 25 DEG C) it is crucial that temperature of reaction is changed into by reflux temperature, the product finally obtained is white crystal, purity reaches more than 99%, and yield reaches more than 80%.(2) the recyclable recycling of solvent methanol used in process of the present invention, saves production cost.
Embodiment
(embodiment 1)
1. in the reaction flask of 500mL, add 39g purity is O-ethyl isourea hydrosulfate (0.2mol) of 95wt% and the anhydrous methanol of 120g, then the methanol solution this being contained O-ethyl isourea hydrosulfate is cooled to-5 DEG C ~ 0 DEG C, stir the sodium methoxide solution (0.6mol) that lower dropping 120g concentration is 27wt%, drip off rear reaction 30min.
2. at-5 DEG C ~ 0 DEG C, the diethyl malonate (0.22mol) of 35g is slowly added, then stirring reaction 5h under room temperature (15 DEG C ~ 25 DEG C).
3. after reaction terminates, solvent methanol in Distillation recovery reaction system, subsequently to adding enough water dissolution in system, be cooled to less than 5 DEG C, dropping 14g concentration is that the hydrochloric acid (0.14mol) of 36.5wt% regulates pH about 2 ~ 3, separates out solid, filter, washing, drying obtain the 2-oxyethyl group-4 of 27g, 6-dihydroxy-pyrimidine white crystal, purity is 99.2%, and yield is 85.7%.
(embodiment 2 ~ embodiment 6)
Each embodiment is substantially the same manner as Example 1, and difference is in table 1.
Note: the anhydrous methanol adopted in embodiment 3 is that embodiment 2 reclaims.
Claims (6)
1. the preparation method of 2-oxyethyl group-4, a 6-dihydroxy-pyrimidine, is characterized in that having following steps:
1. O-ethyl isourea hydrosulfate is dissolved in anhydrous methanol the methanol solution obtained containing O-ethyl isourea hydrosulfate, then the methanol solution this being contained O-ethyl isourea hydrosulfate is cooled to-10 DEG C ~ 10 DEG C, stirring lower dropping concentration is the sodium methoxide solution of 27wt%, drips off rear reaction 20min ~ 60min;
2. at-10 DEG C ~ 10 DEG C, slowly diethyl malonate is added, then stirring reaction 5h ~ 10h at 15 DEG C ~ 25 DEG C;
3., after reaction terminates, 2-oxyethyl group-4,6-dihydroxy-pyrimidine is obtained through aftertreatment.
2. the preparation method of 2-oxyethyl group-4,6-dihydroxy-pyrimidine according to claim 1, is characterized in that: step 1. described in O-ethyl isourea hydrosulfate and the weight ratio of anhydrous methanol be 1: 2 ~ 1: 5.
3. the preparation method of 2-oxyethyl group-4,6-dihydroxy-pyrimidine according to claim 1, is characterized in that: step 1. described in O-ethyl isourea hydrosulfate and concentration be the mol ratio of 27wt% sodium methoxide solution be 1: 1 ~ 1: 5.
4. the preparation method of 2-oxyethyl group-4,6-dihydroxy-pyrimidine according to claim 1, is characterized in that: step 1. described in O-ethyl isourea hydrosulfate and step 2. described in the mol ratio of diethyl malonate be 1: 1 ~ 1: 2.
5. the preparation method of 2-oxyethyl group-4,6-dihydroxy-pyrimidine according to claim 1, is characterized in that: step 3. described in aftertreatment be: Distillation recovery methyl alcohol, add water, then be cooled to 0 DEG C ~ 10 DEG C, drip hydrochloric acid, by the solid filtering of precipitation, washing, drying.
6. the preparation method of 2-oxyethyl group-4,6-dihydroxy-pyrimidine according to claim 5, is characterized in that: step 1. described in O-ethyl isourea hydrosulfate and step 3. described in the mol ratio of hydrochloric acid be 1: 0.5 ~ 1: 1.5.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110130501.8A CN102250018B (en) | 2011-05-19 | 2011-05-19 | Preparation method of 2-ehtyoxyl-4,6-dyhydroxypyrimidine |
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| CN201110130501.8A CN102250018B (en) | 2011-05-19 | 2011-05-19 | Preparation method of 2-ehtyoxyl-4,6-dyhydroxypyrimidine |
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| CN102250018A CN102250018A (en) | 2011-11-23 |
| CN102250018B true CN102250018B (en) | 2015-01-14 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111303045A (en) * | 2019-11-25 | 2020-06-19 | 温州大学 | Production process of 2-ethoxy-4, 6-difluoropyrimidine |
| CN114262300A (en) * | 2021-12-15 | 2022-04-01 | 浙江伟锋药业有限公司 | Preparation method of 2-ethoxy-4, 6-difluoropyrimidine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5463055A (en) * | 1992-12-24 | 1995-10-31 | Skw Trostberg Aktiengesellschaft | Process for the production of 2-ethoxy-4,6-dihydroxypyrimidine or its alkali salts |
| US5552546A (en) * | 1994-07-28 | 1996-09-03 | Dowelanco | Process for the preparation of 2-ethoxy-4,6-dihydroxypyrimidine |
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2011
- 2011-05-19 CN CN201110130501.8A patent/CN102250018B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5463055A (en) * | 1992-12-24 | 1995-10-31 | Skw Trostberg Aktiengesellschaft | Process for the production of 2-ethoxy-4,6-dihydroxypyrimidine or its alkali salts |
| US5552546A (en) * | 1994-07-28 | 1996-09-03 | Dowelanco | Process for the preparation of 2-ethoxy-4,6-dihydroxypyrimidine |
Non-Patent Citations (3)
| Title |
|---|
| 2-乙氧基-4,6-二氯嘧啶的合成;马亚团,等;《西北农业学报》;20071231;第16卷(第5期);195-198 * |
| 杨新飞,等.农药中间体2-乙氧基-4,6-二氟嘧啶的合成研究.《山东建筑大学学报》.2006,第21卷(第5期),451-454. * |
| 穆学玲,等.二甲氧基嘧啶胺合成工艺改进研究.《江苏工业学院学报》.2005,第17卷(第3期),12-15. * |
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