KR830002391B1 - Synthesis of , -unsaturated ketones - Google Patents

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Description

Synthesis method of α, β-unsaturated ketones

The present invention relates to a novel method for synthesizing α, β-unsaturated ketones. The ketones are useful intermediates for the manufacture of medicines and pesticides, in particular 6-ethylthio-3-hepten-2-one being used for the preparation of herbicides.

In a conventionally known method for producing the above-mentioned ketones, aldehydes have been used as one of the raw materials. However, this method is not suitable for use in industrial manufacturing because it has some drawbacks.

Ber. According to 40, 4764 (1907), the ketones are synthesized by aldol condensation with aldehydes and acetone. However, in this method, the desired ketones are obtained at low yield without using aldehydes having no α-position hydrogen atom, and an excess of acetone must be used.

Indian J. Chem. Vol. According to 16B, 970-972 (1978), the ketones are synthesized by condensation with aldehydes and acetone in the presence of piperidine-acetic acid as a catalyst. In this method, a large amount of expensive catalyst and excess acetone are used. Furthermore, in the case of using easily dissociated aldehydes such as 3-ethylthiobutanol, the desired ketone is obtained in low yield by its decomposition.

Ber. According to 103, 2077 (1970), the ketone is synthesized by reacting an aldehyde with a witting reagent produced by reacting mono-chloroacetone or mono-bromoacetone with tri-phenylphosphine. In this method, the witting reagents are very expensive, and treatment with phosphine-containing waste is very difficult.

Acta. Chem. Scand. According to 17, 2216-2220 (1963), the ketones are obtained by thermal decomposition of α, β'-unsaturated-β'-ketosan esters using P-toluene sulfonic acid as a catalyst at high temperature, where α, β Unsaturated-β'-ketosan esters are synthesized by reacting aldehydes with tert-butylaceto acetate. However, in this method, the production reaction of the above β-ketosan ester takes a long time while the yield is low. In addition, when aldehydes such as 3-ethylthiobutanol are easily dissociated, the desired compound is hardly obtained due to its decomposition.

According to US Pat. No. 2,108,427, the ketones are synthesized by reacting aldehydes with di-ketones. However, the reaction time is long, and the yield of the desired ketone is low.

It is an object of the present invention to provide a novel synthesis method of α, β-unsaturated ketones, which can be used for industrial production because of the high yield of the desired ketone under mild reaction conditions.

These and other objects of the present invention will become more apparent in the foregoing description and in the examples which follow.

The present invention is a method for synthesizing α, β-unsaturated ketones, wherein the ketone is an aliphatic secondary amine in a mixture of an aldehyde having an α-position hydrogen atom and an alkali metal salt of acetoacetic acid in an inhomogeneous solvent forming an oil layer and a water layer. It is synthesized by reacting in the presence.

In the present invention, the desired α, β-unsaturated ketone by synthesis is represented by the following general structural formula (I),

3-alkene-2-ones, wherein R represents an aldehyde residue of alkylaldehydes used as raw material. The alkyl aldehydes have an α-position hydrogen atom, the following general structural formula (II),

R · CHO (Ⅱ)

Wherein the alkyl aldehydes are 2, such as ethanal, propanal, i-butanal, TT-butanal, n-hexanal, n-octanal, n-caprylaldehyde, n-caprinaldehyde, etc. Linear or branched alkylaldehydes having from 10 to 10 carbon atoms, methylthioethanal, ethylthioethanal, propylthioethanal, 3-ethylthiopropanal, 3-butyl-thiopropanal, 2-methylthiopropane Alkylthioalkylaldehydes and methylsulfinylethanal, such as eggs, 2-propylthiopropanal, 3-ethylthiobutanal, 3-butylthiobutanal, 2-methylthiobutanal, 2-propylthiobutanal, and the like, Ethylsulfinylethanal, 3-ethylsulfinylpropanal, 3-propylsulfinylpropanal, 2-propylsulfinylpropanal, 2-butylsulfinylpropanal, 3-methylsulfinylbutanal, 3-ethylsul Alkyl sulfinyl alkyl aldehydes, such as pinyl butanal, 2-ethyl sulfinyl butanal, 2-propyl sulfinyl butanal, etc., methyl sulfation Alkylsulfonyl aldehydes, such as a nil ethanal, 3-ethylsulfonyl propanal, 2-propylsulfonyl propanal, 3-ethylsulfonyl butanal, 3-butylsulfonyl butanal, 2-methylsulfonyl butanal, etc. With benzylaldehyde, 2- (4'-ethylphenyl) ethanal, 2- (4'-methoxyphenyl) ethanal, 3- (4'-methylphenyl) propanal, 3- (2 ', 5'-dimethyl Phenyl) propanal, 3- (4'-chlorophenyl) propanal, 2- (4'-ethylphenyl) propanal, 2- (4'-methoxyphenyl) propanal, 2- (2 ', 4' -Dichlorophenyl) propanal, 3- (4'-methylphenyl) butanal, 3- (2 ', 5'-dimethylphenyl) butanal, 3- (4'-chlorophenyl) butanal, 2- (4' Phenyl- or substituted phenylalkylaldehydes such as -ethylphenyl) butanal, 2- (4'-methoxyphenyl) butanal, 2- (2 ', 4'-dichlorophenyl) butanal and the like, and phenylthio Bullet, (2 ', 5'-dimethylphenylthio) ethanal, 3- (4'-methylphenylthio) propanal, 3- (4'-methoxy-phenylthio) propanal, 2- (4'-ethyl Phenylthio) propanal, 2- (4'-chlorophenylthio) prop Ropanal, 3- (4'-ethylphenylthio) butanal, 3- (2 ', 4'-dichlorophenylthio) butanal, 2- (4'-methylphenylthio) butanal, 2- (4'- Phenylthio- or substituted phenylthio aldehydes such as chlorophenylthio) butanal and the like, 3- (4'-chlorophenylsulfinyl) propanal, 3-phenylsulfonylpropanal, 3- (4'-chlorophenyl Phenylsulfinylalkylaldehydes such as sulfonyl) butanal or the like, or phenylsulfonylalkylaldehydes and benzylthioalkylaldehydes such as 3-benzinethiopropanal.

Another material used as a raw material is the following general structural formula (III),

는 나트륨, 칼륨 등과 같은 알칼리금속을 나타낸다. 상기의 아세토아세트산의 알칼리금속염은 가성소오다, 가성칼리 등과 같은 가성알칼리를 사용하는 디케톤 또는 아세토아세테이트의 가수분해에 의해서 수용액으로서 용이하게 얻어지는데, 얻어진 아세토아세트산 수용액의 알칼리금속염이 본 발명에 사용된다.Alkali metal salts of acetoacetic acid with

Represents an alkali metal such as sodium, potassium or the like. The alkali metal salt of acetoacetic acid is easily obtained as an aqueous solution by hydrolysis of diketone or acetoacetate using caustic alkali such as caustic soda, caustic alkali and the like. The alkali metal salt of acetoacetic acid aqueous solution obtained is used in the present invention. do.

The reaction between the aldehyde and the alkali metal salt of acetoacetic acid is represented by the following reaction scheme in the presence of aliphatic amine in a mixture of heterogeneous solvent which produces a water layer and an oil layer,

Proceeding as follows, the alkali metal salt of the desired ketone and hydrogen carbonate is produced.

In the above reaction, an aliphatic secondary amine group, for example, pyrrolidine and morpholine, piperazine piperidine, 3-methylpiperidine, 3-ethylpiperidine, 4-methylpiperidine, 4-ethylpiperi Cycloaliphatic secondary amines such as dine, substituted piperidine exemplifying 1,3-di-piperidylpropane, and the like, di-methylamine, di-ethylamine, di-n-propylamine, di-n-butyl Amine, N-methyl-n-butylamine, N-ethyl-n-butylamine, N-methyl-n-amylamine, N-methyl-n-hexylamine, N-methyl-n-heptylamine, N-methyl An amine selected from N-alkyl-n-alkylamines such as -n-octylamine, N-ethyl-n-laurylamine and the like is used as the catalyst. These amines selectively react aldehydes with alkali metal salts of acetoacetic acid. However, it is not preferred to use aliphatic secondary amines such as di-iso-propylamine, dicyclohexylamine due to steric hindrance.

The reaction is carried out in a mixture of heterogeneous solvents producing a water layer and an oil layer. The oil layer is produced by using organic solvents insoluble or slightly soluble in water, such as chlorinated hydrocarbons such as di-chloromethyl, chloroform, di-chloromethane, etc., and aromatic hydrocarbons such as benzene, toluene, xylene, and the like. .

Ketones desired in the present invention are obtained by the following examples.

Aqueous solution containing from 1.0 to 1.5 moles, preferably from 1.1 to 1.3 moles of acetoacetic acid alkali metal salt of acetoacetic acid, obtained by the above-mentioned method in which the amine as a catalyst of at least 0.005 moles per mole of aldehyde, preferably 0.02 to 0.08 moles, is obtained. The resulting solution is added to an inorganic acid such as hydrochloric acid to adjust the pH range to 6.0 to 8.0.

Raw material aldehyde and 100-500 ml of organic solvent per mol of this aldehyde are added to the above solution containing acetoacetic acid and a catalyst.

The resulting mixture is then stirred for 2-7 hours under atmospheric pressure and 10-50 ° C., preferably 20-40 ° C. conditions. While the reaction is in progress, an inorganic acid such as hydrochloric acid is added dropwise to maintain the pH range of 6.0 to 8.0.

The reaction conditions described above vary somewhat with the type and amount of aldehydes, amines and organic solvents used. However, the reaction using the numerical value without the above-mentioned limitation is not preferable because the yield of the desired ketones is low.

After the reaction, when crystals of alkali metal salts of bicarbonate are found, an inorganic acid such as hydrochloric acid is added to dissolve the crystals, and the prepared inorganic compounds are dissolved in a water layer, followed by lean or filtration. The reaction mixture is separated into an oil layer containing the desired ketone prepared and a water layer containing the prepared organic compound. The desired ketone can be obtained by concentrating and then sorting the oil layer separated above.

In the method according to the present invention, the synthesized α, β-unsaturated ketones include 3-penten-2-one, 3-hexen-2-one, 5-methyl-3-hexen-2-one, 3-heptene-2- Straight or branched chain 3-alkenes having from 5 to 12 carbon atoms such as on, 3-octen-2-one, 3-nonen-2-one, 3-undeken-2-one, 3-trideken-2-one and the like 2-ones, 5-methylthio-3-penten-2-one, 5-ethylthio-3-penten-2-one, 5-propylthio-3-penten-2-one, 6-ethylthio- 3-hexen-2-one, 6-propylthio-3-hexen-2-one, 6-butylthio-3-hexen-2-one, 5-methylthio-3-hexen-2-one, 5-propyl Thio-3-hexen-2-one, 6-ethylthio-3-hepten-2-one, 6-butylthio-3-hepten-2-one, 5-methylthio-3-hepten-2-one, 5 Alkylthio-3-alkene-2-ones such as -butylthio-3-hepten-2-one and the like, 6-methylsulfinyl-3-hexen-2-one and 6-propylsulfinyl-3-hexene-2 -One, 5-ethylsulfinyl-3-hexen-2-one, 5-butylsulfinyl-3-hexen-2-one, 6-ethylsulfinyl-3-hepten-2-one, 6-butylsulfinyl -3-hepten-2-one, 5-methylsulfinyl-3-hepten-2-one, 5-propyl Sulfinyl-3-hepten-2-one, 6-ethylsulfonyl-3-hexen-2-one, 5-propylsulfonyl-3-hexen-2-one, 6-methylsulfonyl-3-hepten-2 Alkylsulfinyl-3-alken-2-ones and alkylsulfonyl-3-alken-2-ones such as -one, 5-butylsulfonyl-3-hepten-2-one and the like, and 5-phenyl-3-pentene 2-one, 5- (2 ', 4'-dimethylphenyl) -3-hexen-2-one, 5- (4'-ethylphenyl) -3-hexen-2-one, 5- (4'- Chlorophenyl) -3-hexen-2-one, 6- (4'-methylphenyl) -3-hepten-2-one, 6- (2 ', 4'-dichlorophenyl) -3-hepten-2-one Phenyl-3-alkene-2-ones such as 5- (4'-ethylphenyl) -3-hepten-2-one, 5- (4'-chlorophenyl) -3-hepten-2-one and the like; Phenylthio-3-penten-2-one, 5- (4'-ethylphenylthio) -3-penten-2-one, 5- (4'-chlorophenylthio) -3-penten-2-one, 6 -(4'-methylphenylthio) -3-hexen-2-one, 6- (2 ', 5'-dimethylphenylthio) -3-hexen-2-one, 6- (2', 4'-dichlorophenyl Thio) -3-hexen-2-one, 5- (4'-methoxyphenylthio) -3-hexen-2-one, 5- (4'-chlorophenylthio) -3-hexen-2-one, 6- (4'-ethylphenylthio) -3-hepten-2-one, 6- (4'-chloro Phenylthio) -3-hepten-2-one, 5- (2 ', 5'-dimethyl-phenylthio) -3-hepten-2-one, 5- (2', 4'-dichlorophenylthio) -3 Phenylthio-3-alkene-2-ones such as -hepten-2-one, etc., and 6- (4'-chlorophenylsulfinyl) -3-hexen-2-one, 6-phenylsulfonyl-3-hexene-2 Phenylsulfinyl-3-alkenes such as -one, 6- (4'-methylsulfonyl) -3-hepten-2-one, 6- (4'-chlorophenylsulfonyl) -3-hepten-2-one -2-ones and phenylsulfonyl-3-alkene-2-ones, and benzylthio-3-alkene-2-ones such as 6-benzylthio-3-penten-2-one and the like.

The present invention provides a novel synthesis of α, β-unsaturated ketones suitable for use in industrial production.

That is, in this process the desired ketone is obtained at least 80% of the yield under mild reaction conditions such as atmospheric pressure and room temperature, and the desired ketone can be easily separated from the reaction mixture.

Accordingly, the present invention is described in more detail by the following examples, which are intended to illustrate the present invention and should not be construed as limiting the scope of the invention.

Example 1

Preparation of Sodium Acetoacetic Acid Solution

In a reactor having a volume of 30 ml, 0.39 mol of methyl acetoacetate and 54.6 gr of water are added, and then 54.6 gr of 30% aqueous sodium hydroxide solution is added to the mixture. During the addition of caustic soda, operation in the water bath keeps the temperature below 35 ° C.

The mixture is stirred at 30-35 ° C. for 6 hours while undergoing a hydrolysis reaction. By adjusting the pH of the reaction mixture to 8.3 by addition of concentrated hydrochloric acid, an aqueous sodium-acetoacetic acid solution is obtained.

Preparation of α, β-unsaturated ketones

1.4555에서 106 내지 112℃의 비등점을 갖는 무색의 기름상의 생성물 51.8gr이 얻어진다.0.0225 mole of di-n-butylamine is added to the aqueous sodium-acetoacetic acid solution thus obtained, and then concentrated hydrochloric acid is added to adjust the pH of the mixture to 6.0. 60 ml of toluene and 0.3 mol of n-caphrinealdehyde are added to the resulting mixture, which is stirred for 4 hours while maintaining at 30 ° C. After the reaction has taken place, concentrated hydrochloric acid is slowly added dropwise to the mixture to decompose the crystallized sodium bicarbonate. The oil and water layers are then separated from the mixture by tilting. The oil layer is concentrated and then distilled under vacuum. Then 0.8torr. (MmHga) and

51.8 gr of a colorless oily product with a boiling point of 106 to 112 ° C. were obtained at 1.4555.

The oily product is identified as 3-trideken-2-one by gas-chromatography. The purity of 3-trideken-2-one is 97.9% and the yield from aldehyde is 86.2%.

Example 2-16

Example 1 is repeated with varying aldehydes, amines and other conditions according to Table 1.

The results, including Example 1, are shown in Table 1.

TABLE 1

Note: ^{* In} Examples 1, 9, 10 and 13, toluene was used as the organic solvent, and in other examples chloroform was used.

^** Confirmed by gas chromatography.

Claims (1)

A heterogeneous solvent mixture of water and organic solvents, wherein the aldehyde of the general formula (II) having an α-position hydrogen atom and the acetoacetic acid alkali metal salt of the general formula (III) can be separated into an oil layer and a water layer by decanting. A method for synthesizing α, β-unsaturated ketones of the following general formula (I), which is reacted at atmospheric pressure and 10 to 50 ° C., preferably 20 to 40 ° C., in the presence of an aliphatic secondary amine.

Of the above formulas R is a straight or branched chain alkyl group, alkylthioalkyl group, alkylsulfinylalkyl group, alkylsulfonylalkyl group, phenyl- or substituted phenylalkyl group, phenylthio- or substituted phenylthioalkyl group, phenylsulfinyl- having 1 to 9 carbon atoms, or Substituted phenylsulfinylalkyl group, phenylsulfonyl- or substituted phenylsulfonylalkyl group, or benzylthioalkyl group, M ⁺ is sodium ions or potassium ions.)