CN101190898B - Preparation method for 1.3-dimethylbarbituric acid - Google Patents
Preparation method for 1.3-dimethylbarbituric acid Download PDFInfo
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- CN101190898B CN101190898B CN2006101189228A CN200610118922A CN101190898B CN 101190898 B CN101190898 B CN 101190898B CN 2006101189228 A CN2006101189228 A CN 2006101189228A CN 200610118922 A CN200610118922 A CN 200610118922A CN 101190898 B CN101190898 B CN 101190898B
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- dimethyl
- solvent
- solid
- barbituric acid
- lower aliphatic
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- 238000002360 preparation method Methods 0.000 title claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000007787 solid Substances 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- -1 aliphatic alcohols Chemical class 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 7
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical group [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 claims description 3
- VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 abstract description 10
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 abstract description 3
- 239000011734 sodium Substances 0.000 abstract description 3
- 229910052708 sodium Inorganic materials 0.000 abstract description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract description 2
- 239000013078 crystal Substances 0.000 abstract description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 abstract 2
- 229940057054 1,3-dimethylurea Drugs 0.000 abstract 1
- MGJKQDOBUOMPEZ-UHFFFAOYSA-N N,N'-dimethylurea Chemical compound CNC(=O)NC MGJKQDOBUOMPEZ-UHFFFAOYSA-N 0.000 abstract 1
- 241000577218 Phenes Species 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- BDFJWKALVSRGSR-UHFFFAOYSA-N butan-1-ol;sodium Chemical compound [Na].CCCCO BDFJWKALVSRGSR-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- LMHHRCOWPQNFTF-UHFFFAOYSA-N s-propan-2-yl azepane-1-carbothioate Chemical compound CC(C)SC(=O)N1CCCCCC1 LMHHRCOWPQNFTF-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method to prepare 1, 3-dimethyl barbituric acid through the reaction of malonic ester and 1, 3-dimethylurea. The method adopts sodium alcoholate as catalyst and lower aliphatic alcohol or the mixture of the lower aliphatic alcohol and phene, toluene or dimethyl benzene as solvent, wherein, the catalyst and the solvent are blended in a reactor to a raised temperature of 60-120 DEG C and done with reflux reaction for 9-10 hours; after the completion of the reaction, the reacted product is cooled to precipitate solid which is then filtered and then dissolved in water; then the pH of the solution is adjusted to 1-2 by adding hydrochloric acid and cooled to precipitate crystal, which is filtered again and crystallized again to obtain the 1, 3-dimethyl barbituric acid.The invention has low-cost raw materials, simple operation and high product yield.
Description
One, technical field
The present invention relates to a kind of preparation method of 1,3-dimethyl barbituric acid, relate to a kind ofly by malonic ester and 1 or rather, the 3-dimethyl urea is a raw material, with the sodium alkoxide be catalyzer synthetic 1,3-dimethyl barbituric acid method.
Two, background technology
1,3-dimethyl barbituric acid is white or faint yellow crystallization, is dissolved in ethanol, and 121～123 ℃ of fusing points are a kind of important chemical intermediates, extensively use what chemical industry, pharmaceutical industries.According to 1 of document (Beil 24 IV1875) (E471 EI 270) disclosure, the conventional preparation method of 3-dimethyl barbituric acid is a propanedioic acid, 1, the 3-dimethyl urea is made solvent at Glacial acetic acid, and aceticanhydride is that dewatering agent reacts generation 1,3-dimethyl barbituric acid down at 60～90 ℃, desolvate and excessive aceticanhydride through distilling to remove, add ethanol again and separate out crude product, crude product obtains finished product 1,3-dimethyl barbituric acid through decolouring, recrystallization process.The prior art has only about 50% because raw materials cost height, yield are lower, and product appearance is yellow crystal, and fusing point is 119～120 ℃, this be need improved.
Three, summary of the invention
The objective of the invention is for a kind of preparation method of with low cost, easy and simple to handle, 1,3-dimethyl barbituric acid that yield is high, superior in quality is provided.
The present invention is achieved in that in the preparation process that it is characterized in that described 1,3-dimethyl barbituric acid and may further comprise the steps:
(1) add malonic ester and 1 in reaction vessel, the 3-dimethyl urea adds solvent, catalyzer again, is warmed up to 60～120 ℃ under stirring, and back flow reaction 9～10 hours after reaction finishes, with the reactant cooling, is separated out solid;
(2) filtration obtains solid, and solid is soluble in water, adds hydrochloric acid and regulates pH value to 1～2, after the cooling, separates out crystallization, refilters to such an extent that the crude product recrystallization obtains 1,3-dimethyl barbituric acid.
The chemical equation of whole process of preparation is as follows:
Wherein, the malonic ester and 1 in the step (1), the mol ratio of 3-dimethyl urea is (1.0～1.3): (1.0～1.2); Malonic ester is propanedioic acid two formicesters or diethyl malonate; Catalyzer then is selected from one or more in sodium methylate, sodium ethylate, sodium isopropylate, the propyl carbinol sodium, and catalyst consumption is malonic ester and 1,25～30% of 3-dimethyl urea raw material gross weight; Solvent is selected from the mixture of lower aliphatic alcohols or lower aliphatic alcohols and benzene,toluene,xylene; Lower aliphatic alcohols then is selected from one or more in methyl alcohol, ethanol, Virahol, the propyl carbinol; Temperature of reaction is 60～120 ℃, can carry out under normal pressure; If during as solvent, solvent load is malonic ester and 1,300～400% of the gross weight of 3-dimethyl urea with the mixture of lower aliphatic alcohols and toluene.
In sum, the present invention compared with prior art, it is low to have material cost, easy and simple to handle, good quality of product and yield are than characteristics such as height.
Four, embodiment
In order to implement the present invention better, especially exemplified by following embodiment, but enforcement is not limitation of the present invention.
Embodiment 1
Add 1.1mol dimethyl malonate and 1.0mol1 in reactor, the 3-dimethyl urea adds solvent, n-butanol and toluene 900 grams and catalyzer sodium ethylate 58 grams again, is warming up to 90～110 ℃, back flow reaction 10 hours under stirring.After reacting end reactant is cooled off, separate out solid, solid is soluble in water, and adding hydrochloric acid adjusting pH value is 1-2, and crystallization is separated out in cooling, filters to such an extent that crude product 132 restrains, and recrystallization gets pure product 119 and restrains, fusing point 121.4-123.2 ℃, and yield 76%, content 99.7%.
Embodiment 2
In reactor, add 1.2mol diethyl malonate and 1.1mol1, the 3-dimethyl urea, add solvent, n-butanol and toluene 1150 grams again, catalyzer sodium ethylate 72 grams, be warming up to 100～120 ℃ under stirring, back flow reaction 9 hours, reaction after finishing is cooled off reactant, separate out solid, solid collected by filtration, solid is soluble in water, and adding hydrochloric acid adjusting PH is 1-2, the cooling precipitation and crystallization, filter to such an extent that crude product 144 restrains, recrystallization gets pure product 130 grams, fusing point 121.3-123.1 ℃, yield is 75%, and content is 99.6%.
Embodiment 3
In reactor, add 1.3mol dimethyl malonate and 1.2mol1, the 3-dimethyl urea, add solvent, n-butanol and toluene 1100 grams, catalyzer sodium ethylate 70 grams again, be warming up to 100～120 ℃ under stirring, back flow reaction 10 hours with the reactant cooling, is separated out solid after reaction finishes, solid collected by filtration, solid is soluble in water, add in the hydrochloric acid and regulate pH value 1-2, cooling separate out crystallization filter crude product, get 157 grams, recrystallization gets pure product 141 grams, and yield is 75%, fusing point 121.3-123.1 ℃, yield is 75%, and content is 99.6%.
Claims (1)
1. the preparation method of a 3-dimethyl barbituric acid is characterized in that may further comprise the steps in this preparation process:
(1) add dimethyl malonate and 1 in reaction vessel, the 3-dimethyl urea adds solvent, catalyzer again, is warming up to 60-120 ℃ under stirring, and back flow reaction 9～10 hours after the end, with the reactant cooling, is separated out solid;
(2) filter and to obtain solid, solid is soluble in water, add hydrochloric acid and regulate pH value to 1～2, separate out crystallization after the cooling, refilter crude product, recrystallization obtains 1, the 3-dimethyl barbituric acid;
Dimethyl malonate and 1, the mol ratio of 3-dimethyl urea are 1.0～1.3: 1.0～1.2;
Used catalyzer is a sodium ethylate, and catalyst consumption is propanedioic acid two formicesters and 1,25～30% of 3-dimethyl urea raw material gross weight;
Used solvent is the mixture of lower aliphatic alcohols and toluene in the preparation process; Described lower aliphatic alcohols is a propyl carbinol.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101189228A CN101190898B (en) | 2006-11-30 | 2006-11-30 | Preparation method for 1.3-dimethylbarbituric acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101189228A CN101190898B (en) | 2006-11-30 | 2006-11-30 | Preparation method for 1.3-dimethylbarbituric acid |
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| Publication Number | Publication Date |
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| CN101190898A CN101190898A (en) | 2008-06-04 |
| CN101190898B true CN101190898B (en) | 2011-09-14 |
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| CN2006101189228A Expired - Fee Related CN101190898B (en) | 2006-11-30 | 2006-11-30 | Preparation method for 1.3-dimethylbarbituric acid |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102432549B (en) * | 2011-09-28 | 2014-09-03 | 南通市华峰化工有限责任公司 | Preparation method of drug intermediate 1,3-dicyclohexyl barbituric acid for inhibiting angiogenesis, tumorigenesis and proliferative diseases |
| CN103012288B (en) * | 2012-12-24 | 2015-06-17 | 济南圣泉唐和唐生物科技有限公司 | Preparation method of 6-chloro-1,3-dimethyluracil |
| CN104151254A (en) * | 2014-07-25 | 2014-11-19 | 南通市华峰化工有限责任公司 | Method for preparing 1,3-bicyclo hexyl barbituric acid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999061427A1 (en) * | 1998-05-26 | 1999-12-02 | Rimma Iliinichna Ashkinazi | N-substituted derivatives of 5-oxyiminobarbituric acid |
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2006
- 2006-11-30 CN CN2006101189228A patent/CN101190898B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999061427A1 (en) * | 1998-05-26 | 1999-12-02 | Rimma Iliinichna Ashkinazi | N-substituted derivatives of 5-oxyiminobarbituric acid |
Non-Patent Citations (7)
| Title |
|---|
| .Purines, pyrimidines, and condensed systems based on them.2. Synthesis of 1-methyl-9-aminoxanthine and 9-aminotheophylline.Khimiya Geterotsiklicheskikh Soedinenii 6.1987,(6),836-44，特别是694页Ia和Ib化合物的制备. * |
| Aleksandrov, G. G. * |
| JP昭63-121828A 1988.05.25 * |
| Kuz＇menko, T. A. * |
| Kuz＇menko, V. V. * |
| Kuz＇menko, V. V.;Kuz＇menko, T. A.;Aleksandrov, G. G.;Pozharskii, A. F.;.Purines, pyrimidines, and condensed systems based on them.2. Synthesis of 1-methyl-9-aminoxanthine and 9-aminotheophylline.Khimiya Geterotsiklicheskikh Soedinenii 6.1987,(6),836-44,特别是694页Ia和Ib化合物的制备. * |
| Pozharskii, A. F. * |
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