CN103319420A - Method for preparing 4,6-dihydroxypyrimidine - Google Patents
Method for preparing 4,6-dihydroxypyrimidine Download PDFInfo
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- CN103319420A CN103319420A CN2013102356942A CN201310235694A CN103319420A CN 103319420 A CN103319420 A CN 103319420A CN 2013102356942 A CN2013102356942 A CN 2013102356942A CN 201310235694 A CN201310235694 A CN 201310235694A CN 103319420 A CN103319420 A CN 103319420A
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- malonic ester
- alkali
- solvent
- dihydroxypyrimidine
- dihydroxy
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Abstract
The invention discloses a method for preparing 4,6-dihydroxypyrimidine, relates to the method for preparing the 4,6-dihydroxypyrimidine, and belongs to the technical field of a medicine. The method comprises the following steps: firstly, feeding formamidine hydrochloride, malonic ester and alkali to a solvent to reflux, agitate and react for 1-12 hours; washing by acid water until the solvent is neutral; adding water, cooling, agitating and filtering so as to obtain pale yellow crystal after recovering the solvent at reduced pressure; finally re-crystallizing the pale yellow crystal by acetone to obtain the white crystal 4,6-dihydroxypyrimidine. According to the method, the 4,6-dihydroxypyrimidine is prepared from formamidine hydrochloride and malonic ester as materials in a cyclization manner; the used materials are cheap; the reaction yield can be up to over 90%; the content of the 4,6-dihydroxypyrimidine after re-crystallization is greater than 98%.
Description
Technical field
The present invention relates to a kind of preparation 4, the method for 6-dihydroxy-pyrimidine belongs to medical technical field.
Background technology
4,6-dihydroxy-pyrimidine, English name are 4,6-Dihydroxypyrimidine, and molecular formula is: C
4H
4N
2O
2, structural formula is as follows:
4,6-dihydroxy-pyrimidine is the key intermediate of preparation sulfamonomethoxine.
At present domestic 4 according to the literature, the 6-dihydroxy-pyrimidine be by methane amide and propionic acid diethyl ester in alcohol sodium alcohol solution 60 ℃ react 4h and make, yield only has about 78%.
Summary of the invention
The object of the invention is to propose the high preparation of a kind of yield 4, the method for 6-dihydroxy-pyrimidine.
Technical scheme of the present invention is: earlier amitraz hydrochloride, malonic ester and alkali are dropped into backflow stirring reaction 1～12h in the solvent, extremely neutral with acid rinsing then, behind the decompression and solvent recovery, add the water cooling agitation and filtration and get faint yellow xln, at last with the described faint yellow xln of acetone recrystallization, get white crystals 4, the 6-dihydroxy-pyrimidine.
Of the present invention provide 4, the preparation process reaction formula of 6-dihydroxy-pyrimidine is as follows:
In the following formula, R is-C
2H
5, or-CH
3, or-Bn.
The present invention is that raw material and malonic ester cyclization make 4,6-dihydroxy-pyrimidine with the amitraz hydrochloride, and the raw material of use is cheap, and reaction yield is up to more than 90%, behind recrystallization, and the content of 4,6-dihydroxy-pyrimidine＞98%.
In addition, the molar ratio of amitraz hydrochloride of the present invention and malonic ester, alkali is 1 ︰, 1～5 ︰ 1～4.
The molar ratio of described amitraz hydrochloride and malonic ester, alkali is 1 ︰, 1～3 ︰ 1～3, and the stirring reaction time is 2～10h.
Described malonic ester is selected from any one in dimethyl malonate, diethyl malonate or the propanedioic acid dibenzyl ester.
Described malonic ester is selected from dimethyl malonate or diethyl malonate.
Described alkali is any one in sodium hydroxide, potassium hydroxide, sodium methylate, sodium ethylate or the triethylamine.
Described solvent be in ethanol, methyl alcohol, water, methylene dichloride, trichloromethane, ethyl acetate, benzene or the toluene at least any one.
Embodiment
Below in conjunction with the time implement example the present invention will be further described, but this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment, all technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
20g amitraz hydrochloride, 40g diethyl malonate, 12g sodium hydroxide are dropped in the methyl alcohol, temperature rising reflux 9h, reaction finishes to be cooled to 40 ℃, dripping hydrochloric acid is regulated about PH=7, reclaim under reduced pressure methyl alcohol adds the water cooling agitation and filtration after recovery finishes and gets faint yellow crystallization, gets 4 with acetone recrystallization, 6-dihydroxy-pyrimidine 25.3g, content 98.9%.
Embodiment 2
20g amitraz hydrochloride, 60g diethyl malonate, 25g potassium hydroxide are dropped in the ethanol, temperature rising reflux 4h, reaction finishes to be cooled to 40 ℃, dripping hydrochloric acid is regulated about PH=7, decompression recycling ethanol adds the water cooling agitation and filtration after recovery finishes and gets faint yellow crystallization, gets 4 with acetone recrystallization, 6-dihydroxy-pyrimidine 27.4g, content 99.2%.
Embodiment 3
20g amitraz hydrochloride, 35g dimethyl malonate, 15g sodium methylate are dropped in the methyl alcohol, temperature rising reflux 8h, reaction finishes to be cooled to 40 ℃, dripping hydrochloric acid is regulated about PH=7, reclaim under reduced pressure methyl alcohol adds the water cooling agitation and filtration after recovery finishes and gets faint yellow crystallization, gets 4 with acetone recrystallization, 6-dihydroxy-pyrimidine 26.7g, content: 99%.
Embodiment 4
20g amitraz hydrochloride, 53g dimethyl malonate, 25g sodium ethylate or triethylamine are dropped in the ethanol, temperature rising reflux 4h, reaction finishes to be cooled to 40 ℃, dripping hydrochloric acid is regulated about PH=7, decompression recycling ethanol adds the water cooling agitation and filtration after recovery finishes and gets faint yellow crystallization, gets 4 with acetone recrystallization, 6-dihydroxy-pyrimidine 27.2g, content: 99.4%.
Claims (7)
1. one kind prepares 4, the method of 6-dihydroxy-pyrimidine, it is characterized in that earlier amitraz hydrochloride, malonic ester and alkali being dropped into backflow stirring reaction 1～12h in the solvent, extremely neutral with acid rinsing then, behind the decompression and solvent recovery, add the water cooling agitation and filtration and get faint yellow xln, at last with the described faint yellow xln of acetone recrystallization, get white crystals 4, the 6-dihydroxy-pyrimidine.
2. according to the described method of claim 1, the molar ratio that it is characterized in that described amitraz hydrochloride and malonic ester, alkali is 1 ︰, 1～5 ︰ 1～4.
3. according to the described method of claim 2, the molar ratio that it is characterized in that described amitraz hydrochloride and malonic ester, alkali is 1 ︰, 1～3 ︰ 1～3, and the stirring reaction time is 2～10h.
4. according to claim 1 or 2 or 3 described methods, it is characterized in that described malonic ester is selected from any one in dimethyl malonate, diethyl malonate or the propanedioic acid dibenzyl ester.
5. according to the described method of claim 4, it is characterized in that described malonic ester is selected from dimethyl malonate or diethyl malonate.
6. according to claim 1 or 2 or 3 described methods, it is characterized in that described alkali is any one in sodium hydroxide, potassium hydroxide, sodium methylate, sodium ethylate or the triethylamine.
7. according to claim 1 or 2 or 3 described methods, it is characterized in that described solvent be in ethanol, methyl alcohol, water, methylene dichloride, trichloromethane, ethyl acetate, benzene or the toluene at least any one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102356942A CN103319420A (en) | 2013-06-15 | 2013-06-15 | Method for preparing 4,6-dihydroxypyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102356942A CN103319420A (en) | 2013-06-15 | 2013-06-15 | Method for preparing 4,6-dihydroxypyrimidine |
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|---|---|
| CN103319420A true CN103319420A (en) | 2013-09-25 |
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|---|---|---|---|
| CN2013102356942A Pending CN103319420A (en) | 2013-06-15 | 2013-06-15 | Method for preparing 4,6-dihydroxypyrimidine |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107868057A (en) * | 2017-12-25 | 2018-04-03 | 中山市榄商置业发展有限公司 | A kind of synthetic method of 4,6 dihydroxy-pyrimidines |
| WO2020136130A1 (en) | 2018-12-28 | 2020-07-02 | Saltigo Gmbh | Improved process for preparing 4,6-dihydroxypyrimidine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002038550A1 (en) * | 2000-11-08 | 2002-05-16 | Sumitomo Chemical Takeda Agro Company, Limited | Pyrimidine derivatives and herbicides containing the same |
| US20030060628A1 (en) * | 2001-08-16 | 2003-03-27 | Degussa Ag | Process for preparing 4,6-dihydroxypyrimidine (DHP) |
| CN102060783A (en) * | 2010-12-06 | 2011-05-18 | 张家港市蓝迪森新材料科技有限公司 | Method for preparing 2-substituted-5-nitro-4,6-dichloropyrimidine |
-
2013
- 2013-06-15 CN CN2013102356942A patent/CN103319420A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002038550A1 (en) * | 2000-11-08 | 2002-05-16 | Sumitomo Chemical Takeda Agro Company, Limited | Pyrimidine derivatives and herbicides containing the same |
| US20030060628A1 (en) * | 2001-08-16 | 2003-03-27 | Degussa Ag | Process for preparing 4,6-dihydroxypyrimidine (DHP) |
| CN102060783A (en) * | 2010-12-06 | 2011-05-18 | 张家港市蓝迪森新材料科技有限公司 | Method for preparing 2-substituted-5-nitro-4,6-dichloropyrimidine |
Non-Patent Citations (1)
| Title |
|---|
| 张国富等: "4,6-二羟基-5-氯嘧啶的合成", 《4,6-二羟基-5-氯嘧啶的合成》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107868057A (en) * | 2017-12-25 | 2018-04-03 | 中山市榄商置业发展有限公司 | A kind of synthetic method of 4,6 dihydroxy-pyrimidines |
| WO2020136130A1 (en) | 2018-12-28 | 2020-07-02 | Saltigo Gmbh | Improved process for preparing 4,6-dihydroxypyrimidine |
| CN113227058A (en) * | 2018-12-28 | 2021-08-06 | 赛拓有限责任公司 | Improved process for preparing 4, 6-dihydroxypyrimidine |
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Application publication date: 20130925 |