CN102050754B - Method for preparing alpha-amino-dialkyl substituted acetamide - Google Patents
Method for preparing alpha-amino-dialkyl substituted acetamide Download PDFInfo
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- CN102050754B CN102050754B CN 200910236171 CN200910236171A CN102050754B CN 102050754 B CN102050754 B CN 102050754B CN 200910236171 CN200910236171 CN 200910236171 CN 200910236171 A CN200910236171 A CN 200910236171A CN 102050754 B CN102050754 B CN 102050754B
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Abstract
The invention relates to a method for preparing alpha-amino-dialkyl substituted acetamide. In the method, the alpha-amino-dialkyl substituted acetamide is prepared by performing a hydrogen peroxide oxidation hydrolysis reaction on alpha-amino-dialkyl substituted acetonitrile serving as a raw material under the catalytic action of ketone substances or amide substances. The reaction yield is high and the product quality is high.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to the preparation method that a kind of alpha-amino group-dialkyl group replaces ethanamide.
Background technology
The alpha-amino group acid amides is usually used in the synthetic higher a-amino acid of purity, all has a wide range of applications in medicine, agricultural chemicals and perfume industry.Wherein the intermediate of widespread use alpha-amino group-dialkyl group replaces ethanamide in imidazolinone herbicide, and structure is suc as formula shown in (I):
(I), R in the formula
1And R
2Be selected from identical or different C
1-C
4Alkyl.
Alpha-amino group-dialkyl group replaces ethanamide and belongs to the fats acid amides, and the disclosed preparation method of prior art can adopt following two kinds of methods preparation.First kind is to have disclosed some alpha-amino group acid amides among the GB1548032A can pass through corresponding nitriles substance, in containing the water of letones, reacts under the condition of pH=12-14, and product obtains corresponding alpha-amino group acid amides after vitriolization.Another kind of preparation method is disclosed in US4460776 and GB2174395: replace acetonitrile through vitriol oil oxidation by alpha-amino group-dialkyl group, preparation alpha-amino group-dialkyl group replaces ethanamide.First kind of preparation method's mechanism it be unclear that, and applies in the synthetic process of this research purpose product and can not obtain expected effect.Though second kind of preparation method is used widely,, quantity of three wastes is big thereby disposal of three wastes cost is very high, and equipment corrosion is serious simultaneously, and operational danger is higher.
Summary of the invention
The object of the present invention is to provide a kind of high yield, high quality to prepare the novel method that alpha-amino group-dialkyl group replaces ethanamide, with a guardian technique difficult problem such as solve that the raw materials consumption height, the three wastes discharge amount that exist in the existing synthesis technique are big, equipment corrosion is serious and plant factor is low.By further investigation, the contriver successfully selects a kind of suitable catalyzer to be used for the reaction that the alkaline hydrogen peroxide oxydrolysis prepares alpha-amino group-dialkyl group replacement ethanamide, obtains satisfied effect.
Using preparation method provided by the invention can prepare structure and replace acetamide compound suc as formula the alpha-amino group of (I)-dialkyl group:
Technical scheme provided by the invention is as follows:
A kind of alpha-amino group-dialkyl group replaces the preparation method of ethanamide, replacing acetonitrile with alpha-amino group-dialkyl group is raw material, in alkaline medium, under the katalysis of letones or amide substance, hydrolysis makes alpha-amino group-dialkyl group replacement ethanamide through hydrogen peroxide oxidation.
Experiment shows, adds an amount of amide substance and can promote the carrying out that react greatly, no matter is that fatty amide or aromatic amides can be as catalyst for reaction.Suitable amides catalyzer is selected from and does not contain alpha-amino amide substance, and preferred amide substance is selected from phenylacetamide, Acetanilide or DMF etc.Letones as catalyzer among the present invention then requires must contain methyl on its structure, so preferred aliphat ketone is as catalyzer, and preferred acetone or methylethylketone are comparatively ideal catalyzer.
Concrete reaction conditions is as follows: every mole of alpha-amino group-dialkyl group replaces acetonitrile and adds 2.1-2.5 mole hydrogen peroxide, 0.005-0.1 mol catalyst, reaction medium pH=9-10; Temperature of reaction 5-30 ℃, reaction times 6-8 hour.
Because added suitable catalyzer, reaction is finished after causing easily, and obtains yield and quality level preferably.Infer from reaction result, amide substance has stabilization to hydrogen peroxide, and the lone-pair electron in the acid amides on the N or methyl ketone all can effectively receive the hydrogen positive ion that forms in the oxydrolysis process at the carbanion that alkaline condition generates, and promote constantly finishing of reaction.What deserves to be explained is, though target product of the present invention also is a kind of acid amides, but owing to have alpha-amino group on its structure, lone-pair electron on the nitrogen change the Cloud Distribution of compound, do not having under the initiation catalysis situation of other amide substances or letones, autocatalysis can not obtain effect as scheduled.
Control is reflected under certain pH value condition to be carried out, and can reduce the decomposition of hydrogen peroxide, and guarantees the catalytic effect of letones or amide substance.PH value preferably is 9.2-9.5.
According to preparation method provided by the invention, adopt letones or amide substance as catalyst for reaction, use hydrogen peroxide as oxydrolysis reagent, by alpha-amino group-dialkyl group replace the desirable preparation of acetonitrile alpha-amino group-dialkyl group replace ethanamide, obtain the amide product of high purity, high yield.Can reduce three waste discharge significantly in the production, reduce preparation cost, reduce equipment corrosion, guarantee operational safety, practical application has obtained significant effect.
Embodiment
Following specific embodiment and reference examples are used for further specifying the present invention.
Embodiment 1
Add 2-amino-2 in 250 milliliters of there-necked flasks, 3-methylbutyronitrile 23 grams (0.2 mole), 30 milliliters in water, phenylacetamide 0.2 gram, stirring is cooled to 5 ℃, drips 30% sodium hydroxide, 20 grams (about 0.22 mole) and 25% hydrogen peroxide, 60 grams (0.44 mole) under 5-10 ℃ of condition simultaneously, and control pH value is between 9-10, added in about 1 hour, in 5-10 ℃ of insulation reaction 4 hours, be warming up to 20-25 ℃ afterwards naturally, and kept 1 hour, chromatogram tracking is analyzed to feedstock conversion complete, and reaction finishes.Reaction solution dichloromethane extraction 3 times, each consumption 100 grams.Combining extraction liquid is also deviate from methylene dichloride and is obtained 2-amino-2,3-methylbutyryl amine 25.3 grams, and white solid, GC analyzes content 97.8%, fusing point: 73-76 ℃, yield 95.2%.
The chemical structure of product is identified as follows through nuclear-magnetism and infrared analysis.
Nuclear-magnetism:
1H-NMR (CDCI
3, 300MHz) δ 0.887 (q 6H J=6.6,12.6), 1.271 (s 3H), 2.189 (m 1H).Infrared: IR (KBr) 3240,3220,3120,2880,2670,1660,1580,1440,880,580cm
-1
Embodiment 2
Add 2-amino-2 in 250 milliliters of there-necked flasks, 3-methylbutyronitrile 23 grams (0.2 mole), 30 milliliters in water, acetone 1.0 grams, stirring is cooled to 5 ℃, drips 30% sodium hydroxide, 20 grams (about 0.22 mole) and 25% hydrogen peroxide, 65 grams (0.48 mole) under 5-10 ℃ of condition simultaneously, and control pH value is between 9-10, added in about 1 hour, kept 4 hours under the uniform temp, be warming up to 20-25 ℃ afterwards naturally, and kept 1 hour, chromatogram tracking is analyzed to feedstock conversion complete, and reaction finishes.Aftertreatment obtains 2-amino-2 with example 1,3-methylbutyryl amine 25.1 grams, and white solid, GC analyzes content 98.0%, fusing point: 74-76 ℃, yield 94.6%.
Embodiment 3
Add 2-amino-2 in 250 milliliters of there-necked flasks, 3-methylbutyronitrile 23 grams (0.2 mole), 30 milliliters in water, Acetanilide 0.5 gram, stirring is cooled to 5 ℃, drips 30% sodium hydroxide, 20 grams (about 0.22 mole) and 25% hydrogen peroxide, 60 grams (0.44 mole) under 5-10 ℃ of condition simultaneously, and control pH value is between 9-10, added in about 1 hour, kept 4 hours under the uniform temp, be warming up to 20-25 ℃ afterwards naturally, and kept 1 hour, chromatogram tracking is analyzed to feedstock conversion complete, and reaction finishes.Aftertreatment obtains 2-amino-2 with example 1,3-methylbutyryl amine 26 grams, and white solid, GC analyzes content 97.1%, fusing point: 74-76 ℃, yield 97.1%.
Product chemistry results of structural analysis is with embodiment 1.
Comparative examples 1
The reaction of catalyst-free: add 2-amino-2 in 250 milliliters of there-necked flasks, 3-methylbutyronitrile 23 grams (0.2 mole), 30 milliliters in water, stirring is cooled to 5 ℃, under 5-10 ℃ of condition, drip 30% sodium hydroxide, 67 grams (about 0.5 mole) and 25% hydrogen peroxide, 165 grams (1.21 moles) simultaneously, control pH value is between 9-10, added in about 2 hours, kept 4 hours under the uniform temp, naturally be warming up to 20-25 ℃ afterwards, and kept 2 hours, chromatogram tracking is analyzed to raw material and product ratio and is no longer changed termination reaction.Aftertreatment is with example 1, obtains oily matter 16 grams, 2-amino-2 wherein, 3-methylbutyryl amine content 57.8%, 2-amino-2,3-methylbutyronitrile content 38%; 2-amino-2,3-methylbutyryl amine yield 35.6%, feed stock conversion 73%.
Comparative examples 2
Sulfuric acid process: reference literature US4460776 and GB2174395 also optimize.
Add (1.0 moles of the vitriol oil 100 grams in 250 milliliters of there-necked flasks, 98%), be cooled to 5 ℃, under 5～10 ℃ of conditions, drip 2-amino-2,3-methylbutyronitrile 25 grams (0.2 mole), added in about 2 hours, rise to room temperature after adding and kept 1 hour, drip 20% ammoniacal liquor 1000 grams under the room temperature, reach pH=10, add under the room temperature of back and continue reaction 2 hours, chromatogram tracking is analyzed to feedstock conversion complete.Reaction solution dichloromethane extraction 3 times, each consumption 200 grams.Combining extraction liquid is also deviate from methylene dichloride and is obtained 2-amino-2,3-methylbutyryl amine 23.4 grams, and faint yellow solid, GC analyzes content 94.3%, fusing point: 68-74 ℃, yield 84.9%.Feed stock conversion 98%.
Claims (1)
1. the preparation method of alpha-amino group-dialkyl group replacement ethanamide is raw material with alpha-amino group-dialkyl group replacement acetonitrile, and in alkaline medium, under the katalysis of amide substance, hydrolysis makes alpha-amino group-dialkyl group replacement ethanamide through hydrogen peroxide oxidation; Described alkyl is selected from identical or different C
1-C
4Alkyl; Described catalyzer is selected from and does not contain alpha-amino amide substance on the structure; Every mole of alpha-amino group-dialkyl group replaces acetonitrile and adds 2.1-2.5 mole hydrogen peroxide, 0.005-0.1 mol catalyst, reaction medium pH=9-10; Temperature of reaction 5-30 ℃, reaction times 6-8 hour; Described catalyzer is selected from phenylacetamide, Acetanilide.
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| CN102746235B (en) * | 2012-07-20 | 2014-09-03 | 北京科莱博医药开发有限责任公司 | Improved method for preparing imidafenacin |
| CN103342654B (en) * | 2013-07-02 | 2015-07-15 | 扬州大学 | Novel method for hydrolyzing nitrile group to acylamino |
| CN108623491B (en) * | 2017-03-24 | 2020-12-22 | 联化科技股份有限公司 | Preparation method of halogenated benzamide compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1433397A (en) * | 1999-12-08 | 2003-07-30 | Dsm有限公司 | Method for the prepararation of enantiomerically enriched compounds |
| CN1867541A (en) * | 2003-08-12 | 2006-11-22 | 贝林格尔·英格海姆国际有限公司 | 1-carbamoylcycloalkylcarboxylic acid compounds, processes fro making and uses thereof |
| CN101503372A (en) * | 2009-03-18 | 2009-08-12 | 中国中化集团公司 | Preparation of fluoro benzamide compound |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1433397A (en) * | 1999-12-08 | 2003-07-30 | Dsm有限公司 | Method for the prepararation of enantiomerically enriched compounds |
| CN1867541A (en) * | 2003-08-12 | 2006-11-22 | 贝林格尔·英格海姆国际有限公司 | 1-carbamoylcycloalkylcarboxylic acid compounds, processes fro making and uses thereof |
| CN101503372A (en) * | 2009-03-18 | 2009-08-12 | 中国中化集团公司 | Preparation of fluoro benzamide compound |
Non-Patent Citations (1)
| Title |
|---|
| JP特开2001-163845A 2001.06.19 |
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Effective date of registration: 20160122 Address after: 110021 Liaodong Road, Tiexi District, Liaoning, No. 8-1, No. Patentee after: SHENYANG SINOCHEM PESTICIDE CHEMICAL RESEARCH AND DEVELOPMENT CO., LTD. Patentee after: Shenyang Sciencreat Chemicals Co., Ltd. Address before: 100031 Beijing, Xicheng District, the door of the revitalization of the main street, No. 28 Patentee before: Sinochem Corporation Patentee before: Shenyang Research Institute of Chemical Industry Patentee before: Shenyang Sciencreat Chemicals Co., Ltd. |