CN102311394B - Preparation method for 5-ethyl-5-phenyl barbituric acid - Google Patents
Preparation method for 5-ethyl-5-phenyl barbituric acid Download PDFInfo
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- CN102311394B CN102311394B CN201010211476.1A CN201010211476A CN102311394B CN 102311394 B CN102311394 B CN 102311394B CN 201010211476 A CN201010211476 A CN 201010211476A CN 102311394 B CN102311394 B CN 102311394B
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- ethyl
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- barbituric acid
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- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- DDBREPKUVSBGFI-UHFFFAOYSA-N Phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 title abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 20
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000004202 carbamide Substances 0.000 claims abstract description 6
- WRLGYAWRGXKSKG-UHFFFAOYSA-M phenobarbital sodium Chemical compound [Na+].C=1C=CC=CC=1C1(CC)C(=O)NC([O-])=NC1=O WRLGYAWRGXKSKG-UHFFFAOYSA-M 0.000 claims abstract description 3
- 239000012043 crude product Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 5
- -1 α-ethyl-α-phenyl ethyl Chemical group 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000005712 crystallization Effects 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 230000000630 rising Effects 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000002699 waste material Substances 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 2
- KDEAZJJSARLKAO-UHFFFAOYSA-L 2-ethyl-2-phenylpropanedioate Chemical compound CCC(C([O-])=O)(C([O-])=O)C1=CC=CC=C1 KDEAZJJSARLKAO-UHFFFAOYSA-L 0.000 abstract 1
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000020477 pH reduction Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- 239000002912 waste gas Substances 0.000 abstract 1
- 239000002351 wastewater Substances 0.000 abstract 1
- 229960004756 ethanol Drugs 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N Sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- 235000013877 carbamide Nutrition 0.000 description 4
- CGMMPMYKMDITEA-UHFFFAOYSA-N 2-ethylbenzoic acid Chemical compound CCC1=CC=CC=C1C(O)=O CGMMPMYKMDITEA-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 230000000087 stabilizing Effects 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 229960000935 Dehydrated Alcohol Drugs 0.000 description 1
- KQJQICVXLJTWQD-UHFFFAOYSA-N N-methylthiourea Chemical compound CNC(N)=S KQJQICVXLJTWQD-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000005039 chemical industry Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N o-xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 230000001131 transforming Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Abstract
The invention provides a preparation method for 5-ethyl-5-phenyl barbituric acid. The method comprises the following steps of: A, adding ethyl acetate into methanol solution of sodium methylate and heating to reflow, then adding a compound diethyl alpha-ethyl-alpha-phenylmalonate, and acting with urea to prepare sodium 5-ethyl-5-phenylbarbiturate; and performing hydrochloric acidification to prepare a rough product of the 5-ethyl-5-phenyl barbituric acid; and B, re-crystallizing the rough product of the 5-ethyl-5-phenyl barbituric acid in ethanol aqueous solution to obtain a finished product of the 5-ethyl-5-phenyl barbituric acid. Compared with the prior art, the preparation method has the advantages of stable process, mild reaction conditions, easiness in control, stable product quality, high yield, easiness and convenience in post-treatment, few three wastes (waste water, waste gas and industrial residues), low production cost and adaptability to industrial production.
Description
Technical field
The present invention relates to chemical synthesis process, particularly the new synthetic process of luminal.
Background technology
Document U.S.Pat, the synthetic methods of 2358072 reports are mainly taking ethyl benzoic acid and thiocarbamide as raw material, condensation under sodium ethylate catalysis and obtain, but due to a large amount of by products generations, cause yield lower, and very difficult suitability for industrialized production.Anhui chemical industry, the 33rd volume, the study on the synthesis of the paper phenylethyl barbituric acid of the 2nd phase report, its synthetic method is 52.8g(0.1998mol in 50ml dehydrated alcohol) ethyl benzoic acid and 14g(0.2333mol) carbonyl diamine reflux (80 DEG C), in 4 hours, drip 85.8g, 6.7%(w/w) (0.0845mol) newly prepares alcohol sodium solution, but be the sodium salt of phenylethyl barbituric acid due to what first generate in reaction process, and the sodium ethylate that this paper uses is all converted into the sodium salt of phenylethyl barbituric acid, the transformation efficiency of α-ethyl-α-phenyl ethyl malonate at most also only has 42%, and this reaction is just can carry out under the catalysis of sodium ethylate, therefore the shortcoming of the method technique is, product yield is low, efficiency is low, by product needs by xylene extraction more, energy consumption is high, and the content requirement to sodium ethylate in ethanol is also higher, the three wastes are many, cost is high.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of preparation method of luminal, process stabilizing, and reaction conditions is easy to control, and simple to operate, the three wastes are few, and yield is high, and production cost is low.
The preparation method of a kind of luminal of the present invention, is characterized in that: the method comprises two steps:
A, in the methanol solution of sodium methylate, first add ethyl acetate to be warming up to backflow, then add compound α-ethyl-α-phenyl ethyl malonate, make luminal sodium with urea effect, then make the crude product of luminal through hcl acidifying;
B, the above-mentioned crude product recrystallization in aqueous ethanolic solution that obtains luminal is obtained to the finished product of luminal.
The preparation method of described luminal, the wherein methanol solution of sodium methylate: sodium methylate=1:29%～31%(w/w).
The preparation method of described luminal, wherein the mol ratio of A step reaction thing is: α-ethyl-α-phenyl ethyl malonate: sodium methylate: urea=1:1.5～2.5:1.8～2.8; Reaction is to complete in the process of distilling alcohols, and distillation temperature is controlled at 85～110 DEG C.
The preparation method of described luminal, after wherein A step steaming alcohol finishes, after adding water or mother liquor to dissolve, then acidifying crystallization, pH=2～5.Water (or mother liquor) amount: α-ethyl-α-phenyl ethyl malonate=3～6:1(mol ratio).
The preparation method of described luminal, the wherein crude product of luminal in B step: ethanol=1:4～8(mol ratio); The volume ratio of ethanol and water is: 1:1～2.
The preparation method of described luminal, wherein the recrystallization described in B step is that the crude product of luminal is added in aqueous ethanolic solution, then adds gac, temperature rising reflux decolouring, press filtration, crystallization, centrifugal, dry.
The present invention and prior art tool have the following advantages: this process stabilizing, reaction conditions gentleness, be easy to control, whole reaction is to complete in steaming alcohol process, simple to operate, the three wastes are few, and for luminal compound crude product provides a kind of good purification process, products obtained therefrom quality good (HPLC purity >99.9%), yield is high, production cost is low, is more suitable for suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the present invention is further elaborated:
Embodiment 1:
Steps A: the methanol solution of 351.7kg sodium methylate (29%, w/w) is joined in reaction flask, then add 3.5kg ethyl acetate to be warming up to backflow (85 DEG C) elimination free alkali.Then add urea 108.0kg and 264.3kg α-ethyl-α-phenyl ethyl malonate, intensification Distillation recovery first, ethanol is to 105 DEG C of interior temperature, then evaporated under reduced pressure.Be cooled to below 40 DEG C, add 1056.0kg water dissolution, filter, filtrate, is filtered to PH=3 with hcl acidifying, the crude product 211.2kg of washing, dry the compounds of this invention luminal.
Step B: the crude product that steps A is made to luminal joins in reaction flask, then add 422.4kg ethanol, 633.6kg purified water and gac, temperature rising reflux decolouring 0.5 hour, filter, crystallization, filters, and is dried to obtain 196.4kg5-ethyl-5-phenyl barbituric acid finished product.
Embodiment 2:
Steps A: the methanol solution of 438.7kg sodium methylate (31%, w/w) is joined in reaction flask, then add 4.3kg ethyl acetate to be warming up to backflow (87 DEG C) elimination free alkali.Then add urea 138.0kg and 264.3kg α-ethyl-α-phenyl ethyl malonate, intensification Distillation recovery first, ethanol is to 110 DEG C of interior temperature, then evaporated under reduced pressure.Be cooled to below 40 DEG C, add 1056kg water dissolution, filter, filtrate, is filtered to PH=4 with hcl acidifying, the crude product 215.6kg of washing, dry luminal.
Step B: the crude product that steps A is made to luminal joins in reaction flask, then add 359.3kg ethanol, 718.7kg purified water and gac, temperature rising reflux decolouring 0.5 hour, filter, crystallization, filters, and is dried to obtain 205.2kg5-ethyl-5-phenyl barbituric acid finished product.
Embodiment 3:
The methanol solution of 586.2kg sodium methylate (29%, w/w) is joined in reaction flask, then add 5.8kg ethyl acetate to be warming up to backflow (85 DEG C) elimination free alkali.Then add urea 168.0kg and 264.3kg α-ethyl-α-phenyl ethyl malonate, intensification Distillation recovery first, ethanol is to 105 DEG C of interior temperature, then evaporated under reduced pressure.Be cooled to below 40 DEG C, add 1056.0kg water dissolution.Add refining useless carbon decoloring, filter, hcl acidifying is to PH=3, filters, the crude product 209.8kg of washing, dry luminal.
Step B: the crude product that steps A is made to luminal joins in treatment tank, then add 524.5kg ethanol, 524.5kg purified water and gac, temperature rising reflux decolouring 0.5 hour, press filtration, crystallization, centrifugal, be dried to obtain 189.5kg luminal finished product.
Claims (5)
1. a preparation method for luminal, is characterized in that: the method comprises two steps:
A, in the methanol solution of sodium methylate, first add ethyl acetate to be warming up to backflow, then add compound α-ethyl-α-phenyl ethyl malonate, make luminal sodium with urea effect, then make the crude product of luminal through hcl acidifying;
B, the above-mentioned crude product recrystallization in aqueous ethanolic solution that obtains luminal is obtained to the finished product of luminal.
2. it is characterized in that in accordance with the method for claim 1: in the methanol solution of described sodium methylate, the mass content of sodium methylate is 29%～31%.
3. in accordance with the method for claim 1, it is characterized in that: the mol ratio of A step reaction thing is: α-ethyl-α-phenyl ethyl malonate: sodium methylate: urea=1:1.5～2.5:1.8～2.8, reaction is to complete in the process of distilling alcohols, and distillation temperature is controlled at 85～110 DEG C.
4. in accordance with the method for claim 1, it is characterized in that: the crude product of luminal: ethanol=1mol:4～8mol in B step, the volume ratio of ethanol and water is: 1:1～2.
5. in accordance with the method for claim 1, it is characterized in that: the recrystallization described in B step is that the crude product of luminal is added in aqueous ethanolic solution, then adds gac, temperature rising reflux decolouring, press filtration, crystallization, centrifugal and dry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010211476.1A CN102311394B (en) | 2010-06-29 | 2010-06-29 | Preparation method for 5-ethyl-5-phenyl barbituric acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010211476.1A CN102311394B (en) | 2010-06-29 | 2010-06-29 | Preparation method for 5-ethyl-5-phenyl barbituric acid |
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| Publication Number | Publication Date |
|---|---|
| CN102311394A CN102311394A (en) | 2012-01-11 |
| CN102311394B true CN102311394B (en) | 2014-06-04 |
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| CN201010211476.1A Active CN102311394B (en) | 2010-06-29 | 2010-06-29 | Preparation method for 5-ethyl-5-phenyl barbituric acid |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105541731A (en) * | 2016-02-22 | 2016-05-04 | 山东新华制药股份有限公司 | Method for preparing 5-ethyl-5-(1-methylbutyl)malonylurea |
| CN105801490B (en) * | 2016-05-05 | 2019-08-23 | 傅晓倩 | A method of preparing Egelieting intermediate |
| CN106957271A (en) * | 2017-04-20 | 2017-07-18 | 山东新华制药股份有限公司 | The preparation method of the dimethyl barbituric acid of butalbital impurity 5,5 |
| CN109651204A (en) * | 2019-01-18 | 2019-04-19 | 山东新华制药股份有限公司 | A method of 2- phenyl butyryl urea is isolated and purified from phenobarbital production activated carbon waste residue |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO63385A2 (en) * | 1972-10-23 | 1978-06-15 | Medicamente Terapia Intreprind | PROCESS FOR PREPARING 5-ETHYL-5-PHENYLBARBITURIC ACID |
| CN1354170A (en) * | 2000-11-20 | 2002-06-19 | 西北合成药厂 | New process for synthesizing diethylbarbituric acid by using sodium methoxide as catalyst |
-
2010
- 2010-06-29 CN CN201010211476.1A patent/CN102311394B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO63385A2 (en) * | 1972-10-23 | 1978-06-15 | Medicamente Terapia Intreprind | PROCESS FOR PREPARING 5-ETHYL-5-PHENYLBARBITURIC ACID |
| CN1354170A (en) * | 2000-11-20 | 2002-06-19 | 西北合成药厂 | New process for synthesizing diethylbarbituric acid by using sodium methoxide as catalyst |
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| CN102311394A (en) | 2012-01-11 |
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| CB03 | Change of inventor or designer information |
Inventor after: Zhu Lianbo Inventor after: Liu Huailin Inventor after: Zhao Shuai Inventor after: Du Deqing Inventor before: Zhu Lianbo Inventor before: Liu Huailin Inventor before: Zhao Shuai |
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Free format text: CORRECT: INVENTOR; FROM: ZHU LIANBO LIU HUAILIN ZHAO SHUAI TO: ZHU LIANBO LIU HUAILIN ZHAO SHUAI DUDEQING |
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