CN106905179A - The method that reaction prepares ɑ carbonyl butyramides in water phase - Google Patents
The method that reaction prepares ɑ carbonyl butyramides in water phase Download PDFInfo
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Abstract
The invention discloses a kind of method that reaction prepares ɑ carbonyl butyramides in water phase, the method is with water as solvent, dimethyl sulfoxide (DMSO) is as cosolvent, with iodine or salt compounded of iodine as catalyst, situation about existing in alkali makes butanone, ammonium chloride and oxidant reaction directly generate ɑ carbonyl butyramides.The present invention is directly synthesized compound ɑ carbonyl butyramides by raw material of butanone and ammonium chloride, and the method can be carried out under relatively low low temperature, and reaction condition is gentle, and simple to operate, pollution-free, environment-friendly, and post processing is simple, can significantly reduce production cost.The method overcome in existing process using high poison, have contaminative, relatively costly chemical raw material deficiency, with good technology application and industrialization prospect.
Description
Technical field
Reacted in aqueous phase system the present invention relates to a kind of method for being directly synthesized ɑ-carbonyl butyramide, more particularly to one kind
The method of ɑ-carbonyl butyramide is directly synthesized, belongs to chemosynthesis technical field.
Background technology
ɑ-carbonyl butyramide compounds are a kind of amide compounds with double carbonyls, special because having in its molecular structure
Double carbonyl structures, thus in vivo have critically important bioactivity, be widely used for synthesizing the suppression of various biology enzymes
Preparation and biological tissue's albumen.Additionally, most of all, ɑ-carbonyl butyramide compounds are a series of complex structure medicines of synthesis
Precursor compound.ɑ-carbonyl butyramide（Structural formula shown in Formulas I）It is mainly used as synthetic drug, the inhibitor of synthesising biological enzyme.
It is mainly used in synthesizing anti-hyperlipidemia class medicine --- statins as synthetic drug intermediate（bestatin
analoges）, and some cancer therapy drugs, anti-AIDS（HIV）Medicine biostatic agent and biologically active peptide etc..
Statins is HMG CoA（HMG-CoA）Reductase inhibitor, is to commonly use in the world at present
One of anti-hyperlipidemia medicine.The whole world is all undergo the torment of chronic disease, increasing people's Hyperlipidemia, according to statistics, in
State brings the further lifting of the incidence of disease and patient assessment leads with the quickening of living-pattern preservation and aging process
Improve, China's blood lipid-lowering medicine market scale rises to 201.81 hundred million in 2014 from 92.28 hundred million yuan of 2009
Unit, annual compound growth rate is about 16.94%.Because statins has, effect for reducing fat is strong, determined curative effect, vdiverse in function, pair
The characteristics of acting on less, occupies the share of absolute predominance in blood lipid-lowering medicine market at present.From 2010 to 2014,
The ratio that statins accounts for reducing blood lipid totality medication market is respectively 81.07%, 83.34%, 87.02%, 88.43% and
89.73%, in ascendant trend year by year.It is contemplated that following blood lipid-lowering medicine will keep the growing trend of quick dilatation, Statins
Medicine will keep lasting high growth.ɑ-carbonyl acid amides is the potent HMG CoA of synthesis（HMG-CoA）Reductase
The important intermediate of inhibitor, therefore demand to ɑ-carbonyl acid amides also can be more and more.
At present, the main production process of production ɑ-carbonyl butyramide is both at home and abroad:Alkylidene cyan-acetic ester in alkali and
Hydrolyze the corresponding acid of generation in the presence of oxidant after generation epoxideamides again, then heating divides in the presence of a small amount of water again
The corresponding product of solution generation.The method many unfavorable conditions such as have many production stages, low production efficiency, environmental pollution big.
Also there are some other reports prepared on ɑ-amide carbonyl class compound, for example, patent
CN200710046005.8 discloses a kind of synthetic method of alpha-amide carbonyl class compound, the method with acid amides as raw material, with
Cesium carbonate is alkali, with quaternary ammonium salts phase transfer catalyst as catalyst, with DMF as solvent, with air as oxidant, 100 ~
Reaction prepares alpha-carbonyl acid amides at a high temperature of 120 DEG C.The acid amides is the alpha-carbonyl acid amides with phenyl ring or pyridine ring.The method
React in organic solvent, reaction temperature is high and high cost of product.Again for example, patent CN200910241813.9 is disclosed
A kind of alpha-amide carbonyl class compound and its derivative and synthetic method, the method is with aryl acetylene compound and aryl amine
Compound is raw material, with air or oxygen as oxidant, with mantoquitas such as copper chloride, cupric iodide, copper carbonate, Kocide SD, copper bromides
It is catalyst, with toluene etc. as organic solvent, is obtained by oxidative coupling reaction under the mixed system of pyridine and organic solvent
Alpha-amide carbonyl class compound and its derivative are planted, aryl acetylene compound and Amines mol ratio are 1:10-10:
1, preferably 5:1.With arylalkyne and arylamine as raw material, aryl substituent reduces the difficulty of reaction to the method, but for straight
The alkynes of chain and the raw material of Inorganic Ammonium cannot be reacted using this kind of method.
The content of the invention
It is an object of the invention to provide a kind of method that reaction prepares ɑ-carbonyl butyramide in water phase, the method is with butanone
It is raw material with ammonium chloride, is synthesized ɑ-carbonyl butyramide under lower temperature in water phase, reaction condition is gentle, environment-friendly,
Low cost, with good industrial applications prospect.
The present invention can be directly synthesized ɑ-carbonyl butyryl with butanone and ammonium chloride as raw material by oxidative amination coupling reaction
Amine.Present invention process has the low advantage of simple to operate, gentle, environment-friendly, cost, with larger industrialization prospect and society
Meeting, economic benefit.
Concrete technical scheme of the present invention is as follows：
A kind of method that reaction prepares ɑ-carbonyl butyramide in water phase, the method is with water as solvent, dimethyl sulfoxide (DMSO) is as hydrotropy
Agent, with iodine or salt compounded of iodine as catalyst, situation about existing in alkali makes butanone, ammonium chloride and oxidant reaction directly generate ɑ-carbonyl fourth
Acid amides.
The reaction equation of the above method of the present invention can be expressed as follows：
In the above method, the ratio between amount of material of butanone and ammonium chloride is 1：1.2-1：4.0.Wherein, ammonium chloride preferably excessively adds
Enter, to increase yield.
In the above method, the catalyst is I2, CuI, tetrabutylammonium iodide, one or more in KI, preferably
It is tetrabutylammonium iodide.The consumption of catalyst is generally the 2-4% of the amount of the material of butanone.
In the above method, the alkali is Na2CO3、K2CO3、NaHCO3、CaCO3、SeCO3, NaOH, triethylamine or DBU.Alkali
Effect be for reaction alkaline environment is provided, various alkalescence can be similar to, it is preferred to use lower-cost Na2CO3、NaHCO3.Alkali
Consumption is generally 1.0-1.5 times of the amount of the material of ammonium chloride.
In the above method, the oxidant is air, O2、H2O2And TBHP（Tertbutanol peroxide）In one or more,
Preferably H2O2。
In the above method, water is main solvent, and dimethyl sulfoxide (DMSO) is cosolvent, adds slightly cosolvent to promote butanone
Dissolving, makes reaction be carried out under homogeneous system.The volume ratio of water and dimethyl sulfoxide (DMSO) is 7-10:1, the consumption of water meets each material
Can sufficiently react, the consumption of cosolvent meets butanone can sufficiently be dissolved, and the consumption of water and butanone can be according to reality
Needs are selected.
The present invention by raw material and catalyst, alkali, solvent selection, can be reacted at a lower temperature, react
Temperature is 25-70 DEG C, such as 25 DEG C, 30 DEG C, 40 DEG C, 50 DEG C, 60 DEG C, can be reacted at 70 DEG C.In course of reaction
Controlling reaction temperature fluctuating range is ± 5 DEG C.It is too high or too low for temperature to influence product yield.
In the above method of the present invention, following steps are specifically included：
（1）By in the mixed liquor of butanone addition water and dimethyl sulfoxide (DMSO), stir；
（2）In step（1）Mixture in add ammonium chloride, alkali and catalyst, first react 30-40min, be subsequently adding oxidant
Continue to react, until butanone disappears, extractive reaction liquid after reaction obtains ɑ-carbonyl butyramide.
Above-mentioned steps（2）In, after adding ammonium chloride, alkali and catalyst, control temperature to be reacted for 25-70 DEG C, control
Reaction temperature fluctuating range is ± 5 DEG C.
Above-mentioned steps（2）In, oxidant be air or oxygen when, during the course of the reaction continue to be passed through in system air or
Oxygen, until reaction is complete；Oxidant is H2O2When, in being added drop-wise to system in the form of the aqueous hydrogen peroxide solution, time for adding is
30-120min, H2O2It is 1.25-5 with the ratio between the amount of material of butanone:1；It is directly disposable to add system when oxidant is TBHP
In, the ratio between amount of material of TBHP and butanone is 1.25-5:1.
Above-mentioned steps（2）In, after reaction, reaction solution is extracted with extractant, and extractant is recovered under reduced pressure after extraction, obtain ɑ-
Carbonyl butyramide；The extractant is ether, toluene, chlorobenzene, ethyl acetate, isopropyl ether, n-hexane, Ethyl formate or hexamethylene
Alkane.The extractant of recovery can repeat to apply mechanically after simple process.
Above-mentioned steps（2）In, monitor reaction using TLC silica gel plate tracking and monitoring extent of reactions or using high performance liquid chromatography
Progress, reacts after butanone disappears and reaches home.Typically, reaction 8-24h is that can reach reaction end after adding oxidant.With
TLC silica gel plates（TLC TLCs）During tracking and monitoring extent of reaction, solvent be ethyl acetate with n-hexane volume ratio be 1 ~
2：5 mix reagent, reaction end is judged by monitoring the concentration of point and the concentration of remaining point of new generation in reaction.With
During high performance liquid chromatography monitoring extent of reaction, by monitor in liquid chromatogram ɑ-formation of carbonyl butyramide and the disappearance of butanone come
Judge reaction end.
The present invention is directly synthesized compound ɑ-carbonyl butyramide by raw material of butanone and ammonium chloride, and the method can be relatively low low
Carried out under temperature, reaction condition is gentle, and simple to operate, pollution-free, environment-friendly, post processing is simple, can significantly reduce production
Cost.The method overcome in existing process using high poison, have contaminative, relatively costly chemical raw material deficiency, have
Good technology application and industrialization prospect.
Specific embodiment
Technical scheme is explained in detail below by way of specific embodiment, the description below is only exemplary
, the scope of the present invention is not limited.
All reactants and reagent involved by following embodiments are market purchase gained.
Embodiment 1
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the NaHCO of 2mmol of 2mmol3, add
The tetrabutylammonium iodide of 0.01mmol, the condensing reflux reaction half an hour at 50 DEG C.Then in three neck round bottom flask dropwise
Instill hydrogen peroxide solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.The condensing reflux at 50 DEG C again after dripping off
Reaction 16 hours, period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, 20 mL acetic acid second are added
Ester is extracted, and then ethyl acetate is removed under reduced pressure, and obtains yellow solid.Gained yellow solid is purified, is then tied
Structure identifies that its nuclear magnetic data is as follows：1H NMR (400 MHz, CDCl3): δ 0.64（t, J = 7.2 Hz, 3H）, 2.44
(d, J = 4.0Hz, 2H), 16.17 (s, 2H), 13C NMR (100 MHz, CDCl3): δ 7.9, 24.9,
165.5, 199.2.
From nuclear magnetic data it was determined that products therefrom is ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide yield is
82%, HPLC test product purity are 99%.
Embodiment 2
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the NaHCO of 2mmol of 2mmol3, add
The tetrabutylammonium iodide of 0.01mmol, the condensing reflux reaction half an hour at 70 DEG C.Then in three neck round bottom flask dropwise
Instill hydrogen peroxide solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.The condensing reflux at 70 DEG C again after dripping off
Reaction 16 hours, period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, 20 mL acetic acid second are added
Ester is extracted, and then ethyl acetate is removed under reduced pressure, and obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl fourth
Acid amides yield is that 80%, HPLC test products purity is 99%.
Embodiment 3
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the K of 2mmol of 2mmol2CO3, add
The CuI of 0.01mmol, the condensing reflux reaction half an hour at 70 DEG C.Then to dropwise instilling hydrogen peroxide in three neck round bottom flask
Solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.Condensing reflux reaction 14 is small at 70 DEG C again after dripping off
When.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, the extraction of 20 mL ethyl acetate is added,
Then ethyl acetate is removed under reduced pressure, obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide is received
Rate is that 73%, HPLC test products purity is 97%.
Embodiment 4
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.15ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the NaHCO of 2mmol of 2mmol3, add
The tetrabutylammonium iodide of 0.01mmol, the condensing reflux reaction half an hour at 50 DEG C.Then in three neck round bottom flask dropwise
Instill hydrogen peroxide solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.The condensing reflux at 50 DEG C again after dripping off
Reaction 16 hours.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, 20 mL acetic acid second are added
Ester is extracted, and then ethyl acetate is removed under reduced pressure, and obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl fourth
Acid amides yield is that 82%, HPLC test products purity is 99%.
Embodiment 5
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the triethylamine of 2mmol of 1.5mmol, is added
The KI of 0.01mmol, the condensing reflux reaction half an hour at 60 DEG C.Then it is double to dropwise being instilled in three neck round bottom flask
The oxygen aqueous solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.The condensing reflux reaction 16 at 60 DEG C again after dripping off
Hour.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, 20 mL ethyl acetate extraction is added
Take, then ethyl acetate is removed under reduced pressure, obtain yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide
Yield is that 70%, HPLC test products purity is 97%.
Embodiment 6
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the NaHCO of 2mmol of 2mmol3, add
The I of 0.01mmol2, the condensing reflux reaction half an hour at 70 DEG C.Then to dropwise instilling hydrogen peroxide in three neck round bottom flask
Solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.Condensing reflux reaction 16 is small at 70 DEG C again after dripping off
When.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, the extraction of 20 mL ethyl acetate is added,
Then ethyl acetate is removed under reduced pressure, obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide is received
Rate is that 76%, HPLC test products purity is 98%.
Embodiment 7
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the NaHCO of 2mmol of 2mmol3, add
The tetrabutylammonium iodide of 0.01mmol, the condensing reflux reaction half an hour at 50 DEG C.Then oxygen ball is taken, three mouthfuls of round bottoms are placed on
On flask, then condensing reflux reacts 20 hours at 50 DEG C.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.
After completion of the reaction, the extraction of 20 mL ethyl acetate is added, then ethyl acetate is removed under reduced pressure, obtain yellow solid, as ɑ-carbonyl
Base butyramide.In terms of butanone, ɑ-carbonyl butyramide yield is that 70%, HPLC test products purity is 97%.
Embodiment 8
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the CaCO of 2mmol of 2mmol3, add
The tetrabutylammonium iodide of 0.01mmol, the condensing reflux reaction half an hour at 25 DEG C.Then in three neck round bottom flask dropwise
Instill hydrogen peroxide solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.The condensing reflux at 25 DEG C again after dripping off
Reaction 24 hours.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, 20 mL acetic acid second are added
Ester is extracted, and then ethyl acetate is removed under reduced pressure, and obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl fourth
Acid amides yield is that 75%, HPLC test products purity is 98%.
Embodiment 9
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, the fourth of 2mmol is measured afterwards
Ketone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the SeCO of 3mmol of 2.5mmol3, add
The I of 0.01mmol2, the condensing reflux reaction half an hour at 60 DEG C.Then to dropwise instilling hydrogen peroxide in three neck round bottom flask
Solution（H containing 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.Condensing reflux reaction 16 is small at 60 DEG C again after dripping off
When.Period TLC silica gel plate or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, the extraction of 20 mL ethyl acetate is added,
Then ethyl acetate is removed under reduced pressure, obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide is received
Rate is that 75%, HPLC test products purity is 98%.
Embodiment 10
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the DBU of 2mmol of 2mmol, adds 0.02mmol
CuI, at 50 DEG C condensing reflux reaction half an hour.Then to dropwise instilling hydrogen peroxide solution in three neck round bottom flask（Contain
The H of 2.5mmol2O2, 1ml water）, it was added dropwise to complete at 2 hours.Condensing reflux reacts 16 hours at 50 DEG C again after dripping off.Period
TLC silica gel plates or high performance liquid chromatography monitoring extent of reaction.After completion of the reaction, the extraction of 20 mL ethyl acetate is added, then by second
Acetoacetic ester is removed under reduced pressure, and obtains yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide yield is 70%,
HPLC test products purity is 97%.
Embodiment 11
In the three neck round bottom flask of 25ml, the water of 1.5ml is added, add the DMSO of 0.2ml, measure 0.5mmol's afterwards
Butanone is added in round-bottomed flask, is stirred, and is subsequently adding ammonium chloride, the NaHCO of 2mmol of 2mmol3, add
The tetrabutylammonium iodide of 0.01mmol, the condensing reflux reaction half an hour at 50 DEG C.Then the TBHP of 2.5mmol is taken again, directly
Connect and be disposably added in round-bottomed flask, condensing reflux reacts 16 hours at 50 DEG C again after addition.Period TLC silica gel plate or height
Effect liquid phase chromatogram monitors extent of reaction.After completion of the reaction, the extraction of 20 mL ethyl acetate is added, then ethyl acetate decompression is removed
Go, obtain yellow solid, as ɑ-carbonyl butyramide.In terms of butanone, ɑ-carbonyl butyramide yield is 73%, HPLC test products
Purity is 97%.
Comparative example 1
Method according to embodiment 1 prepares ɑ-carbonyl butyramide, unlike, reflux condensation mode temperature is maintained at 95-105 DEG C.With
Butanone meter, the yield of gained ɑ-carbonyl butyramide is that 53%, HPLC test products purity is 97%.
Comparative example 2
Method according to embodiment 1 prepares ɑ-carbonyl butyramide, unlike, used catalyst is the tetrabutyl bromine of 0.01mmol
Change ammonium.In terms of butanone, the yield of gained ɑ-carbonyl butyramide is that 43%, HPLC test products purity is 95%.
Comparative example 3
Method according to embodiment 1 prepares ɑ-carbonyl butyramide, unlike, used catalyst is the copper chloride of 0.01mmol.
In terms of butanone, the yield of gained ɑ-carbonyl butyramide is that 40%, HPLC test products purity is 93%.
Comparative example 4
Method according to embodiment 1 prepares ɑ-carbonyl butyramide, unlike, the consumption of butanone is 3mmol.In terms of ammonium chloride,
The yield of gained ɑ-carbonyl butyramide is that 65%, HPLC test products purity is 97%.
Comparative example 5
Method according to embodiment 1 prepares ɑ-carbonyl butyramide, unlike, ammonium chloride is changed to formamide.In terms of butanone, institute
The yield of ɑ-carbonyl butyramide is obtained for 15%, HPLC test products purity is 90%.
Comparative example 6
Method according to embodiment 1 prepares ɑ-carbonyl butyramide, unlike, butanone is changed to butine.In terms of butanone, gained ɑ-
The yield of carbonyl butyramide is 0%.
Claims (10)
1. it is a kind of that the method for preparing ɑ-carbonyl butyramide compounds is reacted in water phase, it is characterized in that：With water as solvent, dimethyl
Sulfoxide is cosolvent, and with iodine or salt compounded of iodine as catalyst, situation about existing in alkali makes butanone, ammonium chloride and oxidant reaction directly give birth to
Into ɑ-carbonyl butyramide.
2. method according to claim 1, it is characterized in that：The catalyst is I2, CuI, tetrabutylammonium iodide, KI
In one or more, preferably tetrabutylammonium iodide.
3. method according to claim 1 and 2, it is characterized in that：The ratio between amount of material of butanone and ammonium chloride is 1：1.2-
1：4.0；The consumption of the catalyst is the 2-4% of the amount of the material of butanone.
4. method according to claim 1 and 2, it is characterized in that：The alkali is Na2CO3、K2CO3、CaCO3、NaHCO3、
SeCO3, NaOH, triethylamine or DBU；The oxidant is air, O2、H2O2With one or more in TBHP, preferably H2O2。
5. the method according to claim 1 or 4, it is characterized in that：The consumption of alkali is the 1.0-1.5 of the amount of the material of ammonium chloride
Times；The volume ratio of water and dimethyl sulfoxide (DMSO) is 7-10:1.
6. method according to claim 1 and 2, it is characterized in that：Reaction temperature is 25-70 DEG C.
7. the method according to any one of claim 1-6, it is characterized in that comprising the following steps：
（1）By in the mixed liquor of butanone addition water and dimethyl sulfoxide (DMSO), stir；
（2）In step（1）Mixture in add ammonium chloride, alkali and catalyst, first react 30-40min, be subsequently adding oxidant
Continue to react, until butanone disappears, extractive reaction liquid after reaction obtains ɑ-carbonyl butyramide.
8. method according to claim 7, it is characterized in that：When oxidant is air or oxygen, continue during the course of the reaction
To air or oxygen is passed through in system, until reaction is complete；Oxidant is H2O2When, it is added dropwise in the form of aqueous hydrogen peroxide solution
To in system, time for adding is 30-120min, H2O2It is 1.25-5 with the ratio between the amount of material of butanone:1；Oxidant is TBHP
When, directly in disposable addition system, the ratio between amount of material of TBHP and butanone is 1.25-5:1.
9. method according to claim 7, it is characterized in that：Step（2）In, react 10-24h under oxidant effect.
10. method according to claim 7, it is characterized in that：After reaction, reaction solution is extracted with extractant, after extraction
Extractant is recovered under reduced pressure, ɑ-carbonyl butyramide is obtained；The extractant be ether, toluene, chlorobenzene, ethyl acetate, isopropyl ether, just oneself
Alkane, Ethyl formate or hexamethylene.
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| CN102924319A (en) * | 2011-08-11 | 2013-02-13 | 成都地奥制药集团有限公司 | Method for preparing alpha-ketoamide compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102924319A (en) * | 2011-08-11 | 2013-02-13 | 成都地奥制药集团有限公司 | Method for preparing alpha-ketoamide compounds |
| CN102603552A (en) * | 2012-03-22 | 2012-07-25 | 苏州大学 | Preparation method of alpha-keto amide |
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