CN101781222A - Method for preparing enamine ketone compound - Google Patents
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- CN101781222A CN101781222A CN201010103100A CN201010103100A CN101781222A CN 101781222 A CN101781222 A CN 101781222A CN 201010103100 A CN201010103100 A CN 201010103100A CN 201010103100 A CN201010103100 A CN 201010103100A CN 101781222 A CN101781222 A CN 101781222A
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Abstract
The invention discloses a method for preparing an enamine ketone compound, wherein the enamine ketone compound with two substituents on a nitrogen atom is prepared through an enolate intermediate. A formylation reaction is carried out by using a ketone compound with alpha-methyl or alpha-methylene as a substrate to obtain enolate; and a dehydration-condensation reaction of the enolate and dimethylamine hydrochloride is further carried out to obtain the enamine ketone compound. A reaction formula is as shown in the figure. The raw materials adopted by the method are all ordinary and easily obtained materials, and the method has simple preparation process and mild reaction condition, does not need large expensive equipment and is adaptable to industrialized large-scale production; moreover, the reaction selectivity is high, and the prepared enamine ketone has high yield, is easy to separate and purify and has broad application prospect.
Description
Technical field
The invention belongs to the field of chemical synthesis, relate in particular to a kind of method for preparing enamine ketone compound.Specifically, be by the method for two substituent enamine ketone compounds is arranged on the enolate intermediate preparation nitrogen-atoms about a kind of.
Background technology
Enamine ketone compound is meant and contains the alpha, beta-unsaturated ketone compounds that amido replaces that it is the electrophilic center that a class had both had carbonyl, and the multifunctional chemical reaction intermediate of the nucleophilic center with amido is arranged.They are at the synthetic Tetrahedron of nitrogen-containing heterocycle compound, 2003,59:8463-8480; J.Chem.Rev., 2004,104:2433-2480.; All there is very important application polyhedron the preparation aspect of metal complexes, 2004,23:15-21, in addition, some documents have in recent years also been reported anti-inflammatory, antiviral physiologically active: the CN 00816675.7 of enamine ketone compound, CN 99813208.X, CN 200580021414.1.
Because enamine ketone compound is with a wide range of applications, very many both at home and abroad to the research of the synthetic method of enamine ketone compound, and having obtained some very effective synthetic methods, these synthetic method classification mainly comprise: condensation reaction, addition reaction, substitution reaction and decomposition reaction.
U.S. Pat P 4579675 discloses a kind of beta-diketon and has replaced amine and prepare the method for enamine ketone by the ketoamine condensation reaction, will use toluene or benzene azeotropic band water in the reaction process, and the reaction times is longer, the productive rate of reaction be subjected to substituent influence bigger.Process modification in recent years adopts Lewis acid or the condensation reaction of organic acid catalysis ketoamine more, Lewis acid is not only made catalyzer but also do water-retaining agent, improved the transformation efficiency of condensation reaction, shortened the reaction times, but this also relates to the problem of the recovery and the recycling of catalyzer.
U.S. Pat P 7019094B2 discloses the ketone with active methyl or methylene radical and the method for acetal prepared in reaction enamine ketone, and reaction process also will be used toluene or dimethylbenzene azeotropic band water, and the use of lewis acid catalyst can reduce temperature of reaction.
Synthesis, 2003,18:2815-2826. middlely reported a kind of method that adopts addition reaction to prepare enamine ketone compound, this method by one kettle way can high yield preparation a series ofly have the substituent enamine ketone compound of big steric hindrance, but because used raw material end group alkynes, the Pd (PPh of reaction
3)
2Cl
2Relatively expensive, severe reaction conditions, industrial prospect is also little.
Tetrahedron, 2006,62:611-618.; Catal.Comm, 2009,10:1514-1517., the employing isoxazole compounds of middle report thermal degradation under Raney-Ni catalysis becomes enamine ketone compound, reaction product is subjected to the influence of reaction conditions bigger, and different reaction conditionss can obtain different cleavage reaction product down.
Org.Lett., 2007, carry out the method that substitution reaction prepares big sterically hindered substituted enaminones with the aryl trimethyl silicane after having reported a kind of active methylene group among the 9:1029-1032. with negative ionization reagent such as sec.-propyl lithium, n-Butyl Lithium activation enamine ketone compound.This method all more than 90%, still owing to the use of catalyzer such as its harsh reaction conditions, sec.-propyl lithium, n-Butyl Lithium, makes this route applications be restricted for the very effective productive rate of the preparation of some big sterically hindered enamine ketone.
Because above these existing methods all exist shortcomings such as severe reaction conditions, raw material costliness, treating processes trouble, fail to adapt to the production demand of present enamine ketone compound.Therefore, develop a kind of method of synthetic enamine ketone compound newly, have important practical significance.
Summary of the invention
The objective of the invention is to synthesize the problem that faces, provide a kind of synthetic route simple, reaction conditions gentleness, the new synthetic method that raw material cheaply is easy to get at present existing enamine ketone compound.
The present invention realizes above-mentioned purpose by following scheme:
With the ketone with Alpha-Methyl, alpha-methylene is raw material, obtains enamine ketone compound through formylation and dehydrating condensation two-step reaction.
Ketone compounds with Alpha-Methyl, alpha-methylene, be aliphatics and the aromatic ketone that the carbonyl ortho position has active methyl or methylene radical, comprise: acetone, butanone, 2 pentanone, propione, methyl-n-butyl ketone, methyln-hexyl ketone, 2-heptanone, hexone, 2,6-dimethyl-propione, methyl phenyl ketone, p-methoxy-acetophenone, p-methyl aceto phenone.This compounds is carried out formylation reaction as substrate and basic metal, can obtain the basic metal enolate; The basic metal enolate further carries out dehydration condensation with dimethylamine hydrochloride and obtains enamine ketone compound.In this reaction, the mol ratio of substrate ketone compounds and dimethylamine hydrochloride is 1: 1-1: 3.
Specifically, method of the present invention comprises the steps: that (1) is mixed into suspension liquid with basic metal or its compound and organic solvent; In suspension liquid, drip Alpha-Methyl or alpha-methylene ketone compounds and ethyl formate at a certain temperature and react, obtain the basic metal enolate.(2) the basic metal enolate that is obtained mixes with organic solvent, becomes basic metal enolate suspension, drips dimethylamine hydrochloride solution at a certain temperature and react in basic metal enolate suspension, obtains enamine ketone compound.
As alkali-metal representative, its reaction formula is expressed as follows with sodium:
Basic metal in the step (1) or its compound, be sodium Metal 99.5, sodium ethylate, sodium methylate, sodium amide, sodium hydride, potassium metal, potassium ethylate, potassium tert.-butoxide, potassium amide, metallic lithium, trimethyl carbinol lithium, Virahol lithium etc., basic metal or its compound are mixed with organic solvent, the solvent of the organic solvent that is adopted for dissolving each other with ethyl formate, such as benzene,toluene,xylene, trimethylbenzene, ether, n-butyl ether, methyl alcohol, ethanol or Virahol, the existence of organic solvent can be played the effect that disperses reactant and lysate, and reaction can steadily be carried out; The volumetric molar concentration of sodium is 0.5-5mol/L in the suspension liquid that is obtained, and is preferably 2-3mol/L;
The mol ratio of the Alpha-Methyl that is dripped in the step (1) or the ketone compounds of alpha-methylene and ethyl formate is 1: 1-1: 10, and both are added drop-wise in the suspension liquid after mixing.The mol ratio of ketone and ethyl formate is preferably 1: 3.
The temperature of reaction of step (1) is 0-50 ℃, and the reaction times is 4-24h; Preferred temperature of reaction is 20-30 ℃, and the reaction times is 5-10h.
In step (2), the organic solvent of employing can be most common organic solvent, comprising: benzene,toluene,xylene, ether, n-butyl ether.The existence of this organic solvent can be played the effect that disperses reactant and lysate equally; Simultaneously, the dimethylamine hydrochloride solution that step (2) is adopted is the aqueous solution of dimethylamine hydrochloride, and the two phase reaction between water and the organic solvent can make reaction gentle more.
In the enol sodium salt suspension that is obtained, the volumetric molar concentration of sodium alkoxide is: 0.1-5mol/L is preferably 2-3mol/L;
The aqueous solution of the dimethylamine hydrochloride that step (2) is adopted, volumetric molar concentration is 1-10mol/L, is preferably 3-5mol/L.Temperature of reaction is 0-60 ℃, and the reaction times is 1-5h; Preferred temperature of reaction is 20-30 ℃, and the reaction times is 1.5-3h.
Exist in solution as crude product through the above-mentioned resulting enamine ketone compound of method,, obtain purified enamine ketone through further separation and purification.Specifically, reaction solution is realized the separation of product through separatory, extraction, concentrated; By recrystallization or underpressure distillation enamine ketone compound is made with extra care.Used recrystallization solvent system is the mixture of sherwood oil and acetone, and its volume ratio is 1000: 1-10: 1.
Compared with prior art, the present invention has following beneficial effect:
(1) raw material of the present invention is the common material that is easy to get, and raw materials cost is low, helps reducing the production cost of product;
(2) preparation technology of the present invention is simple, and the reaction conditions gentleness does not need large-scale expensive device, is adapted to industrialized production;
(3) method reaction preference height provided by the present invention, prepared enamine ketone productive rate height, and separate easily purifying have further improved the productive efficiency of this method, have huge economic benefit and wide prospect.
Embodiment
Embodiment 1
The preparation of 1-dimethylamino-1-butylene-3-ketone:
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 14.7ml (0.2mol) acetone and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Dripping concentration under the room temperature in resulting enol sodium salt suspension is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leaves standstill separatory, and water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, and the oil pump underpressure distillation gets (101-102 ℃ of weak yellow liquid 17.5ml, 5mmHg), productive rate 74.5%.MS：m/z?114.0943；
1H-NMR(CD
3OD，500MHz)δ：2.104(s，3H，CH
3)，2.878-3.158(d，6H，N(CH
3)
2)，4.967-5.005(d，1H，＝CH
a)，7.383-7.426(d，1H，＝CH
b)。
Embodiment 2
The preparation of 1-dimethylamino-2-methyl-1-butene-3-one
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 18ml (0.2mol) butanone and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Dripping concentration under the room temperature in resulting enol sodium salt suspension is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leaves standstill separatory, and water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, and the oil pump underpressure distillation gets (80-82 ℃ of weak yellow liquid 15ml, 5mmHg), productive rate 47.5%.MS：m/z?127.0832；
1H-NMR(CD
3OD，500MHz)δ：1.952(s，3H，CH
3a)，2.200(s，3H，CH
3b)，3.172(s，6H，N(CH
3)
2)，7.449(s，1H，＝CH
b)。
Embodiment 3
The preparation of 1-dimethylamino-2-methyl isophthalic acid-hexene-3-one
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 21.5ml (0.2mol) propione and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Dripping concentration under the room temperature in resulting enol sodium salt suspension is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leaves standstill separatory, and water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, and the oil pump underpressure distillation gets (102-106 ℃ of weak yellow liquid 24ml, 5mmHg), productive rate 76.1%.MS：m/z?142.1225，164.1097；
1H-NMR(CD
3OD，500MHz)δ：1.113(s，3H，CH
3a)，1.967(s，3H，CH
3b)，3.068(s，6H，N(CH
3)
2)，7.278(s，1H，＝CH
b)。
Embodiment 4
The preparation of 1-dimethylamino-5-methyl isophthalic acid-hexene-3-one
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 21.5ml (0.2mol) hexone and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Dripping concentration under the room temperature in resulting enol sodium salt suspension is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leaves standstill separatory, and water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, and the oil pump underpressure distillation gets (126 ℃ of weak yellow liquid 24.5ml, 5mmHg), productive rate 71.3%.MS：m/z?156.1431，178.1257；
1H-NMR(CD
3OD，500MHz)δ：0.950-0.963(d，6H，CH(CH
3)
2)，2.059-2.114(m，1H，CH(CH
3)
2)，2.237-2.251(d，2H，CH
2)，2.750-2.898(d，6H，N(CH
3)
2)，5.145(d，1H，＝CH
a)，7.643-7.668(d，1H，＝CH
b)。
Embodiment 5
The preparation of 1-dimethylamino-5-methyl-2-sec.-propyl-1-hexene-3-one
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, Dropwise 35 ml (0.2mol) 2 under the room temperature, the solution that 6-dimethyl dipropyl ketone and 32ml (0.4mol) ethyl formate is formed, about 30min dropwises, and room temperature continues to stir 5h.Dripping concentration under the room temperature in resulting enol sodium salt suspension is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leaves standstill separatory, and water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, and the oil pump underpressure distillation gets (130-136 ℃ of weak yellow liquid 20ml, 5mmHg), productive rate 46%.MS：m/z?198.1885，220.1695；
1H-NMR(CD
3OD，500MHz)δ：0.878-0.909(m，6H，CH(CH
3)
2)，1.634-1.663(m，1H，CH(CH
3)
2)，2.057-2.079(m，6H，CH(CH
3)
2)，1.250-1.264(m，1H，CH(CH
3)
2)，2.088-2.122(d，2H，CH
2)，3.018-3.035(d，6H，N(CH
3)
2)，7.505-7.530(s，1H，＝CH)。
Embodiment 6
The preparation of 1-dimethylamino-1-nonene-3-ketone
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 25ml (0.2mol) methyln-hexyl ketone and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Dripping concentration under the room temperature in resulting enol sodium salt suspension is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leaves standstill separatory, and water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, and the oil pump underpressure distillation gets (140-141 ℃ of weak yellow liquid 28ml, 5mmHg), productive rate 68.8%.MS：m/z?184.1570，206.1404；
1H-NMR(CD
3OD，500MHz)δ：0.864-0.878(m，3H，CH
3)，1.295-1.359，1.595-1.618(m，8H，(CH
2)
4)，2.380-2.410(m，2H，CH
2)，2.840-3.070(m，6H，N(CH
3)
2)，5.054-5.060(d，H，＝CH
a)，7.512-7.533(d，1H，＝CH
b)。
Embodiment 7
The preparation of 3-dimethylamino-1-phenyl-2-propylene-ketone
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 24g (0.2mol) methyl phenyl ketone and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Suction filtration, the dry faint yellow solid salt 35.6g that gets.
Become suspension in the 35g enol sodium salt adding 100ml anhydrous diethyl ether, dripping concentration under the room temperature is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, and room temperature continues to stir 2h, leaves standstill separatory, water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolves to steam to remove to desolvate, the yellow solid that obtains gets faint yellow needle-like crystal 34g (m.p.91-92 ℃), productive rate 86.2% with sherwood oil-acetone mixing solutions recrystallization.MS：m/z?198.0909；
1H-NMR(CD
3OD，500MHz)δ：2.978-3.182(d，6H，N(CH
3)
2)，5.825-5.850(d，H，＝CH
a)，7.853-7.879(d，H，＝CH
b)，7.429-7.516(m，3H，Ph)，7.879-7.828(d，2H，Ph)。
Embodiment 8
The preparation of 3-dimethylamino-1-(4-p-methoxy-phenyl)-2-propylene-ketone
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution of 30.2g (0.2mol) to methoxyl group and 32ml (0.4mol) ethyl formate composition under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Suction filtration, the dry faint yellow solid salt 43.8g that gets.
43.8g joining in the 100ml anhydrous diethyl ether, the enol sodium salt becomes suspension, dripping concentration under the room temperature is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leave standstill separatory, water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolve to steam to remove and desolvate, the yellow solid that obtains with sherwood oil-acetone mixing solutions recrystallization get faint yellow needle-like crystal 38g (94-96 ℃, 5mmHg), productive rate 93.1%.MS：m/z206.1226，228.1039；
1H-NMR(CD
3OD，500MHz)δ：3.005-3.208(d，6H，N(CH
3)
2)，3.866(s，3H，OCH
3)，5.843-5.867(d，H，CH
a)，7.819-7.843(d，H，CH
b)，6.965-6.995(m，2H，Ar)，7.884-7.908(m，2H，Ar)。
Embodiment 9
The preparation of 3-dimethylamino-1-(4-aminomethyl phenyl)-2-propylene-ketone
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 24.4g (0.2mol) p-methyl aceto phenone and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Suction filtration, the dry faint yellow solid salt 38.6g that gets.
38.6g the enol sodium salt join in the 100ml anhydrous diethyl ether and become suspension, dripping concentration under the room temperature is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leave standstill separatory, water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolve to steam to remove and desolvate, the yellow solid that obtains with sherwood oil-acetone mixing solutions recrystallization get faint yellow needle-like crystal 34g (94-96 ℃, 5mmHg), productive rate 89.6%.MS：m/z190.1124；
1H-NMR(CD
3OD，500MHz)δ：2.924-2.182(d，6H，N(CH
3)
2)，2.388(s，3H，OCH
3)，5.705-5.780(d，H，CH
a)，7.817-7.821(d，H，CH
b)，7.205-7.221(m，2H，Ar)，7.78-7.814(m，2H，Ar)。
Embodiment 10
The preparation of 3-dimethylamino-1-phenyl-2-vinyl cyanide
4.6g (0.2mol) sodium Metal 99.5 bar is suspended in the 100ml anhydrous diethyl ether, drips the solution that 23.4g (0.2mol) benzyl cyanide and 32ml (0.4mol) ethyl formate are formed under the room temperature, about 30min dropwises, and room temperature continues to stir 5h.Suction filtration, the dry faint yellow solid salt 30.9g that gets.
30.9g joining in the 100ml anhydrous diethyl ether, the enol sodium salt becomes suspension, dripping concentration under the room temperature is 3.5mol/L dimethylamine hydrochloride aqueous solution 70ml (0.245mol), about 30min dropwises, room temperature continues to stir 2h, leave standstill separatory, water layer washs with the ether of 3 * 30ml, merge organic layer, organic layer spends the night with anhydrous magnesium sulfate drying, revolve to steam to remove and desolvate, the yellow solid that obtains with sherwood oil-acetone mixing solutions recrystallization get faint yellow needle-like crystal 30g (78-80 ℃, 5mmHg), productive rate 85.9%.MS：m/z173.1098；
1H-NMR(CD
3OD，500MHz)δ：3.211(s，6H，N(CH
3)
2)，7.198(s，H，＝CH)，7.088-7.119，7.264-7.325(m，5H，Ar)。
Claims (10)
1. a method for preparing enamine ketone compound is characterized in that adopting the ketone compounds with Alpha-Methyl or alpha-methylene to carry out formylation reaction as substrate and obtains enolate; Enolate further carries out dehydration condensation with dimethylamine hydrochloride and obtains enamine ketone compound.
2. the method for preparing enamine ketone compound as claimed in claim 1, the mol ratio that it is characterized in that described substrate ketone compounds and dimethylamine hydrochloride is 1: 1-1: 3.
3. the method for preparing enamine ketone compound as claimed in claim 1, it is characterized in that described ketone compounds is acetone, butanone, 2 pentanone, propione, methyl-n-butyl ketone, methyln-hexyl ketone, 2-heptanone, hexone, 2,6-dimethyl-propione, methyl phenyl ketone, p-methoxy-acetophenone or p-methyl aceto phenone.
4. as the described method for preparing enamine ketone compound of the arbitrary claim of claim 1～3, it is characterized in that may further comprise the steps:
(1) basic metal or its compound and organic solvent are mixed into suspension liquid; In suspension liquid, drip Alpha-Methyl or alpha-methylene ketone compounds and ethyl formate at a certain temperature and react, obtain the basic metal enolate.
(2) the basic metal enolate that is obtained mixes with organic solvent, becomes basic metal enolate suspension, drips dimethylamine hydrochloride solution at a certain temperature and react in basic metal enolate suspension, obtains enamine ketone compound.
5. the method for preparing enamine ketone compound as claimed in claim 4 is characterized in that the described basic metal of step (1) or its compound; Described basic metal or its compound are sodium Metal 99.5, sodium ethylate, sodium methylate, sodium amide, sodium hydride, potassium metal, potassium ethylate, potassium tert.-butoxide, a kind of in potassium amide, metallic lithium, trimethyl carbinol lithium or the Virahol lithium.
6. the method for preparing enamine ketone compound as claimed in claim 4 is characterized in that the mol ratio of step (1) Alpha-Methyl that is dripped or the ketone compounds of alpha-methylene and ethyl formate is 1: 1-1: 10, and both are added drop-wise in the suspension liquid after mixing.
7. the method for preparing enamine ketone compound as claimed in claim 4 is characterized in that the described temperature of reaction of step (1) is 0-50 ℃, and the reaction times is 4-24h.
8. the method for preparing enamine ketone compound as claimed in claim 4 is characterized in that the described temperature of reaction of step (2) is 0-60 ℃, and the reaction times is 1-5h.
9. the method for preparing enamine ketone compound as claimed in claim 4 is characterized in that the solvent of the described organic solvent of step (1) for dissolving each other with ethyl formate; The volumetric molar concentration of sodium is 0.5-5mol/L in the suspension liquid that is obtained; In the enol sodium salt suspension that step (2) is obtained, the volumetric molar concentration of sodium alkoxide is: 0.1-5mol/L; The dimethylamine hydrochloride solution that step (2) is adopted is the aqueous solution of dimethylamine hydrochloride, and volumetric molar concentration is 1-10mol/L.
10. the method for preparing enamine ketone compound as claimed in claim 4 is characterized in that it is crude product that step (2) obtains described enamine ketone compound, obtains the purified enamine ketone compound through behind the purifying.
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Cited By (5)
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| CN101967207A (en) * | 2010-11-16 | 2011-02-09 | 南通新昱化工有限公司 | Composite macro-molecule polyfunctional group photoinitiator and preparation method thereof |
| CN103922947A (en) * | 2014-04-21 | 2014-07-16 | 江西师范大学 | New method for synthesizing N,N-disubstituted enaminone compound |
| WO2018074411A1 (en) * | 2016-10-19 | 2018-04-26 | 旭硝子株式会社 | Method for producing nitrogen-containing compound |
| CN109574862A (en) * | 2017-09-28 | 2019-04-05 | 宿迁市科莱博生物化学有限公司 | A kind of preparation method of compound |
| EP3521277A1 (en) | 2015-03-26 | 2019-08-07 | Agc Inc. | Method for producing a pyrazole-4-carboxylic acid derivative |
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2010
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101967207A (en) * | 2010-11-16 | 2011-02-09 | 南通新昱化工有限公司 | Composite macro-molecule polyfunctional group photoinitiator and preparation method thereof |
| CN103922947A (en) * | 2014-04-21 | 2014-07-16 | 江西师范大学 | New method for synthesizing N,N-disubstituted enaminone compound |
| CN103922947B (en) * | 2014-04-21 | 2015-06-17 | 江西师范大学 | New method for synthesizing N,N-disubstituted enaminone compound |
| EP3521277A1 (en) | 2015-03-26 | 2019-08-07 | Agc Inc. | Method for producing a pyrazole-4-carboxylic acid derivative |
| WO2018074411A1 (en) * | 2016-10-19 | 2018-04-26 | 旭硝子株式会社 | Method for producing nitrogen-containing compound |
| CN109863134A (en) * | 2016-10-19 | 2019-06-07 | Ａｇｃ株式会社 | The manufacturing method of nitrogenous compound |
| JPWO2018074411A1 (en) * | 2016-10-19 | 2019-08-08 | Ａｇｃ株式会社 | Method for producing nitrogen-containing compound |
| CN109863134B (en) * | 2016-10-19 | 2022-09-09 | Ａｇｃ株式会社 | Process for producing nitrogen-containing compound |
| CN115322152A (en) * | 2016-10-19 | 2022-11-11 | Ａｇｃ株式会社 | Process for producing nitrogen-containing compound |
| CN109574862A (en) * | 2017-09-28 | 2019-04-05 | 宿迁市科莱博生物化学有限公司 | A kind of preparation method of compound |
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