JP2000026360A - Production of alpha-methylated ketones - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a process for producing α-methyl ketones via shortened steps with industrial advantage. SOLUTION: A ketone represented by formula II, R1COCH2R2 (R1 is a 1-8C alkyl which may be substituted, an aryl or aralkyl group, R2 is H or a 1-8C alkyl which may be substituted, an aryl or aralkyl group or R1 and R2 may be bound to form a 3-16C alkylene which may be substituted) is allowed to react with formaldehyde and hydrogen in the presence of a basis substance and a hydrogenation catalyst to produce a ketone that bears a methyl group in the α-position to the carbonyl represented by formula I, R1COCH(R2)CH3 (R1 and R2 are indentical to the definitions in the formula II).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a carbonyl group having an α
The present invention relates to a method for producing ketones having a methyl group at the -position (hereinafter, these are abbreviated as α-methyl ketones). The α-methyl ketones obtained by the production method of the present invention are useful as a synthetic intermediate for solvents, fragrances, cationic dyes, medicines, agricultural chemicals and the like.

[0002]

2. Description of the Related Art A method for synthesizing α-methyl ketones by introducing a methyl group into the α-position of a carbonyl group of ketones is known. For example, ketones are derivatives of enols which are tautomers thereof. And a method of reacting it with a methyl halide (4th Edition, New Experimental Chemistry Course (Maruzen Co., Ltd.), vol. 21, p. 298; US Pat. No. 3,663).
No. 8,255, etc.) are known.

[0003]

However, in the above-mentioned method, however, a basic substance (e.g., alkali metal, alkali metal alcoholate,
It is necessary to use an alkali metal hydroxide, an alkali metal amide, or the like) to make an enol derivative. As a result, after reacting with a methyl halide, a large amount of a salt such as an alkali halide or an ammonium halide is used (as a raw material). (Equimolar amount to ketones), and the treatment is a serious problem in production on an industrial scale. As a method that can solve this problem, an α, β-unsaturated carbonyl compound obtained by a dehydration reaction from a hydroxymethylated product obtained by reacting a ketone with formaldehyde (see Japanese Patent Application Laid-Open No. 2-14937) )
Is subjected to a normal hydrogenation reaction to hydrogenate the carbon-carbon double bond of the α, β-unsaturated carbonyl compound to produce α-methyl ketones. Requires three steps for the production of α, β-polymerizable and reactive α, β-
Since it is necessary to handle unsaturated carbonyl compounds, it is difficult to say that it is industrially advantageous. Thus, the present invention
It is an object of the present invention to provide a method capable of industrially and advantageously producing α-methyl ketones in a short process.

[0004]

According to the present invention, the above object is achieved by the following equation (2).

[0005]

Embedded image R ¹ COCH ₂ R ² (2)

(Wherein, R ¹ represents an alkyl group having 1 to 8 carbon atoms, an aryl group or an aralkyl group which may have a substituent, and R ² represents a hydrogen atom or a substituent Represents an alkyl group, an aryl group, or an aralkyl group having 1 to 8 carbon atoms, and R ¹ and R ² are a single alkylene group having 3 to 16 carbon atoms which may have a substituent. A) reacting a ketone represented by the formula (1) with formaldehyde and hydrogen in the presence of a basic substance and a hydrogenation catalyst.

[0007]

Embedded image R ¹ COCH (R ² ) CH ₃ (1)

The problem is solved by providing a process for producing α-methyl ketones represented by the formula (wherein R ¹ and R ² are the same as defined above).

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
The method for producing α-methyl ketones of the present invention comprises the step of reacting hydrogen with the above formula (2) in the presence of a basic substance and a hydrogenation catalyst.
Characterized by reacting a ketone represented by (1) with formaldehyde.

In the above formula (2), examples of the alkyl group having 1 to 8 carbon atoms represented by R ¹ and R ² include a methyl group, an ethyl group, an n-propyl group, an i-propyl group and an n-propyl group.
-Butyl group, i-butyl group, sec-butyl group, ter
t-butyl group, n-pentyl group, n-hexyl group and the like. Examples of the aryl group include a phenyl group,
Examples include a tolyl group and a naphthyl group, and examples of the aralkyl group include a benzyl group.
Further, R ¹ and R ² may be represented by one and have 3 to 3 carbon atoms.
Examples of the 16 alkylene groups include a trimethylene group, a tetramethylene group, and a hexamethylene group. R ¹ and R ² may have a substituent, but in view of the fact that the reaction is carried out in the presence of a basic substance, it is necessary that the substituent be an inert substituent under basic conditions. Examples of such a substituent include an alkoxy group, a formyl group protected in an acetal type, and a hydroxyl group.

Here, specific examples of the ketones represented by the formula (2) include acetone, 2-butanone (methyl ethyl ketone), 2-pentanone, 3-pentanone (diethyl ketone), methyl isopropyl ketone, 2-hexanone,
3-hexanone, pinacolone, 2-heptanone, 3-heptanone, 2-octanone, 6-methylheptane-2-
On, 3-octanone, 4-octanone, cyclopentanone, cyclohexanone, 4-methylcyclohexanone, 4-t-butylcyclohexanone, cycloheptanone, acetophenone, propiophenone and the like can be mentioned.

As the formaldehyde used in the present invention, any of an aqueous solution (formalin), gaseous formaldehyde, and solid forms such as paraformaldehyde and trioxane may be used. It is preferable to use it as an aqueous solution from the viewpoint of the production cost of the products. When used as an aqueous solution, the concentration is preferably 50% by weight or less, and more preferably from 20 to 45% by weight from the viewpoints of easy handling, reaction volume efficiency, and the like.

The ratio of the ketone of the formula (2) to formaldehyde is not particularly limited, but the ketone of the formula (2) is usually added in an amount of 0.5 to 10 mol, preferably 0 to 1 mol of formaldehyde. It is used in the range of 0.8 to 3 mol, more preferably 1.0 to 1.2 mol.

The basic substance used in the present invention includes, for example, hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide; hydroxides of alkaline earth metals such as barium hydroxide and calcium hydroxide. Can be mentioned. These may use one kind,
You may mix and use two or more types. The basic substance can be used as it is, but usually 0.5 to 5
It is used as a 0% by weight aqueous solution, preferably a 1 to 30% by weight aqueous solution.

The amount of the basic substance used is usually from 0.01 to 0.3 mol per mol of formaldehyde, but from the viewpoint of the reaction rate and the production cost, from 0.02 to 0.1 mol per mol of formaldehyde. The amount is preferably 2 mol.

The hydrogenation catalyst used in the present invention includes:
Generally, catalysts used for catalytic hydrogenation reactions,
A catalyst used for selectively hydrogenating a carbon-carbon double bond of an α, β-unsaturated carbonyl compound can be used. For example, a catalyst containing palladium, rhodium, nickel, platinum or the like as an active component can be used. Can be mentioned. Examples of the form of the hydrogenation catalyst include metals themselves; metal oxides and alloys with other metals; activated carbon, alumina,
Any of those supported on a carrier such as silica gel or diatomaceous earth may be used. Among these, palladium carbon, palladium alumina, Raney nickel, platinum carbon and the like are preferable, and palladium carbon, palladium alumina and the like are more preferable.

The amount of the hydrogenation catalyst used is usually 0.0005 to 0.1 part by weight based on 1 part by weight of formaldehyde, but from the viewpoint of the reaction rate and the production cost of α-methyl ketones, 1 part by weight of formaldehyde is used. For 0.
It is preferably from 001 to 0.03 parts by weight.

In the present invention, the use of a solvent is not always necessary, but a solvent may be used as long as the reaction is not adversely affected. Examples of usable solvents include ether solvents such as tetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl ether and dibutyl ether; hydrocarbon solvents such as hexane, heptane, octane, benzene, toluene and xylene; methanol , Ethanol, 2-propanol, butanol and the like; and water.

Specific reaction procedures of the production method of the present invention include, for example, formaldehyde, ketones represented by the formula (2) in a predetermined reaction temperature range and under a hydrogen atmosphere.
An operation in which a basic substance and a hydrogenation catalyst are mixed by a general operation using a general-purpose device can be mentioned. In this case, there is no particular limitation on the mixing order and mixing speed of each component to be subjected to the reaction. It is preferable to continuously add formaldehyde to the suspension. Here, "continuously adding" includes adding a component to be added in plural times.

The reaction temperature is usually in the range of 20 to 180 ° C., but in order to make the reaction rate practical, 4
The temperature is preferably in the range of 0 to 140 ° C.

The time required for the reaction varies depending on the type, concentration, reaction temperature and the like of the basic substance used, but as described above, the hydrogenation catalyst is suspended in the ketone and the basic substance represented by the formula (2). When formaldehyde is continuously added to the resulting suspension, the time required for the addition of formaldehyde is usually 0.5 to 10 hours, and the addition time after completion of the addition is 0 to 20 hours. During the addition of formaldehyde and the driving of the reaction, it is desirable to sufficiently stir the reaction mixture.

In the present invention, hydrogen may be brought into contact with the surface of a mixture of formaldehyde, a ketone represented by the formula (2), a basic substance and a hydrogenation catalyst, and hydrogen is introduced (bubbled) into the mixture. You may. The pressure of hydrogen in the reaction system is usually in the range of 1 to 100 atm.
The pressure is preferably in the range of 10 to 10 atm.

After completion of the reaction, the target compound α-methyl ketones are separated from the reaction mixture, for example, by filtering or centrifuging the hydrogenation catalyst from the reaction mixture, separating the aqueous layer from the reaction mixture, and separating the remaining organic layer. A method of distillation, a hydrogenation catalyst is filtered off from the reaction mixture, and the desired α-
Methyl ketones can be extracted with an organic solvent and separated and obtained from the obtained organic layer by a general method such as a method of distilling the organic solvent under normal pressure or reduced pressure. In addition, examples of the organic solvent used in the above extraction include hydrocarbon solvents such as toluene, benzene, hexane, and cyclohexane; and halogenated hydrocarbon solvents such as methylene chloride, chloroform, carbon tetrachloride, and dichloroethane.

The α- represented by the formula (1) thus obtained is
The purity of methyl ketones can be further increased by conventional methods such as distillation under reduced pressure and silica gel column chromatography.

[0025]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 A 1-liter autoclave equipped with a stirrer contains 198.0 g (2.75 mol) of methyl ethyl ketone and 20.0 g (0.05 mol of sodium hydroxide) of a 10% aqueous sodium hydroxide solution. ) And 5% palladium carbon (hydrogenation catalyst) 0.30 under a nitrogen atmosphere
g was added, and the internal temperature of the autoclave was raised to 60 ° C. Thereafter, hydrogen was introduced into the autoclave, and the pressure inside the autoclave was increased to 0.45 MPa (4.59 Kg / c).
m ² , gauge pressure, hydrogen partial pressure therein: 0.4 MPa), 214.3 g of 35% aqueous formaldehyde solution (2.
(Containing 5 moles of formaldehyde) was added continuously to the mixture obtained above using a feed pump over a period of 2 hours and 45 minutes. During the addition, the liquid temperature of the reaction mixture was maintained at 60 ° C., and hydrogen consumed in the reaction was supplied to the autoclave, and the pressure in the autoclave was maintained at 0.45 MPa (gauge pressure). After the completion of the addition of the aqueous formaldehyde solution, the temperature of the reaction mixture was raised to 100
The temperature was raised to 0 ° C., stirring was further continued for 1 hour to drive the reaction, and then cooled to room temperature. The palladium carbon was removed from the reaction mixture by filtration, and 218.9 g of the organic layer was separated from the filtrate separated into two layers. This organic layer was subjected to gas chromatography [capillary column: CBP-10 (trade name, manufactured by Shimadzu Corporation), column length: 50 m, column inner diameter: 0.25 mm, column temperature: 70 ° C → 240
° C (at a rate of 5 ° C / min up to 170 ° C and 170 ° C
And the temperature was raised at a rate of 10 ° C./min.)].
5.8 g of methyl isopropyl ketone having a methyl group introduced into the α-position of the carbonyl group of methyl ethyl ketone is 1
It was found that 57.0 g, 4.6 g of diethyl ketone, and 13.2 g of methyl isopropyl ketone or 13.2 g of ethyl isopropyl ketone having a methyl group introduced into the α-position of the carbonyl group of diethyl ketone were contained. The yield of methyl isopropyl ketone based on formaldehyde is 73.0%. Organic layer 21 obtained above
Distilling 8.9 g under normal pressure gives a boiling point of 94-95.
As a fraction at 20 ° C., 203.6 g were obtained. This fraction contained 98.3% of methyl isopropyl ketone.

Example 2 In a 300 ml-volume autoclave equipped with a stirrer, 47.3 g (0.55 mol) of diethyl ketone and 6.0 g (0.015 mol) of a 10% aqueous sodium hydroxide solution were added.
Mol of sodium hydroxide) and 5% palladium on carbon (hydrogenation catalyst) 0.0
6 g was added, and the internal temperature of the autoclave was raised to 100 ° C. Thereafter, hydrogen was introduced into the autoclave, the pressure in the autoclave was set to 0.45 MPa (gauge pressure, hydrogen partial pressure therein: 0.37 MPa), and 42.9 g of a 35% formaldehyde aqueous solution (0.5 mol of formaldehyde was added). Was continuously added to the mixture obtained above using a feed pump over 2 hours and 30 minutes.
During the addition, while keeping the liquid temperature of the reaction mixture at 100 ° C., the amount of hydrogen consumed in the reaction was supplied to the autoclave, and the pressure in the autoclave was increased to 0.45 MPa.
(Gauge pressure). After the addition of the aqueous formaldehyde solution was completed, stirring was continued at the same temperature for another hour to drive the reaction, and then the mixture was cooled to room temperature. The palladium carbon was removed from the reaction mixture by filtration, and 49.6 g of the organic layer was separated from the filtrate separated into two layers. The organic layer was analyzed by gas chromatography under the same conditions as in Example 1. As a result, 10.9 g of diethyl ketone, which was an unreacted raw material, was obtained by introducing a methyl group into the α-position of the carbonyl group of diethyl ketone. It was found that 31.1 g of isopropyl ketone and 8.3 g of diisopropyl ketone having a methyl group introduced into the α-position of the carbonyl group of ethyl isopropyl ketone were contained. The yield of ethyl isopropyl ketone based on formaldehyde is 62.1%.

Example 3 In a 1-liter autoclave equipped with a stirrer, 220.5 g (2.25 mol) of cyclohexanone and 1
12.0 g of an aqueous 0% sodium hydroxide solution (containing 0.03 mol of sodium hydroxide) was charged, and 0.18 g of 5% palladium carbon (hydrogenation catalyst) under a nitrogen atmosphere.
Was added, and the internal temperature of the autoclave was raised to 100 ° C. Thereafter, hydrogen was introduced into the autoclave, and the pressure in the autoclave was set to 0.45 MPa (gauge pressure).
128.6 g of a 35% aqueous formaldehyde solution (containing 1.5 moles of formaldehyde) were continuously added to the mixture obtained above using a feed pump over 2 hours and 45 minutes. During the addition, the temperature of the reaction mixture was raised to 1
While maintaining the temperature at 00 ° C., the amount of hydrogen consumed in the reaction was supplied to the autoclave, and the pressure in the autoclave was maintained at 0.45 MPa (gauge pressure). After the addition of the aqueous formaldehyde solution was completed, stirring was continued at the same temperature for another hour to drive the reaction, and then the mixture was cooled to room temperature. The palladium carbon was removed from the reaction mixture by filtration, and 232.2 g of the organic layer was separated from the filtrate separated into two layers. The organic layer was analyzed by gas chromatography under the same conditions as in Example 1. As a result, 48.9 g of cyclohexanone as an unreacted raw material was obtained, and α- of the carbonyl group of cyclohexanone was obtained.
106.2 g of 2-methylcyclohexanone having a methyl group introduced at the 2-position, and 2,6- having a methyl group introduced at the α-position of the carbonyl group of 2-methylcyclohexanone.
It was found that 8.3 g of dimethylcyclohexanone was contained. The yield of 2-methylcyclohexanone based on formaldehyde is 63.2%.

[0029]

According to the present invention, by reacting formaldehyde with a ketone represented by the formula (2) and hydrogen in the presence of a basic substance and a hydrogenation catalyst, the compound of the formula (1) can be obtained in one step. Can be easily produced.

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Claims (2)

[Claims] (1) R ¹ COCH ₂ R ² (2) (wherein R ¹ has ¹ to 5 carbon atoms which may have a substituent)
8 represents an alkyl group, an aryl group or an aralkyl group, and R ² represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, an aryl group or an aralkyl group which may have a substituent. Further, R ¹ and R ² may be one and represent an alkylene group having 3 to 16 carbon atoms which may have a substituent. A) reacting a ketone represented by the formula (1) with formaldehyde and hydrogen in the presence of a basic substance and a hydrogenation catalyst, wherein R ¹ COCH (R ² ) CH ₃ (1) Wherein R ¹ and R ² are the same as defined above), which has a methyl group at the α-position of the carbonyl group. 2. The method according to claim 1, wherein the basic substance is at least one compound selected from the group consisting of an alkali metal hydroxide and an alkaline earth metal hydroxide.