JP4386977B2 - Method for producing ketones methylated at α-position - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing ketones having a methyl group at the α-position of a carbonyl group (hereinafter, abbreviated as α-methyl ketones). The α-methyl ketones obtained by the production method of the present invention are useful as synthetic intermediates for solvents, fragrances or cationic dyes, pharmaceuticals, agricultural chemicals and the like.
[0002]
[Prior art]
Methods for synthesizing α-methyl ketones by introducing a methyl group into the α-position of the carbonyl group of the ketones are known. For example, a ketone is a derivative of an enol that is a tautomer thereof, and a halogen is added thereto. A method of reacting methyl iodide (4th edition, New Experimental Chemistry Course (Maruzen Co., Ltd.), Vol. 21, p. 298; see US Pat. No. 3,668,255, etc.) is known.
[0003]
[Problems to be solved by the invention]
However, in the above method, it is generally necessary to use a basic substance (for example, an alkali metal, an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal amide, or the like) equivalent to or more than ketones to make an enol derivative. As a result, a salt such as alkali halide or ammonium halide is produced in a large amount (equal molar amount with the starting ketones) after reacting with methyl halide, and the treatment is carried out on an industrial scale. It becomes a big problem.
As a method capable of solving such a problem, an α, β-unsaturated carbonyl compound obtained by a dehydration reaction from a hydroxymethylated product obtained by reacting a ketone with formaldehyde (see JP-A-2-149537, etc.) ) Is subjected to a normal hydrogenation reaction, and a carbon-carbon double bond of the α, β-unsaturated carbonyl compound is hydrogenated to produce α-methyl ketones. Manufacturing requires three steps, and it is difficult to say that it is industrially advantageous because it is necessary to handle a highly reactive α, β-unsaturated carbonyl compound in the step. .
Therefore, an object of the present invention is to provide a method by which α-methyl ketones can be produced industrially advantageously in a short process.
[0004]
[Means for Solving the Problems]
According to the present invention, the above problem is solved by the formula (2)
[0005]
[Chemical 3]
R ¹ COCH ₂ R ² (2)
[0006]
(In the formula, R ¹ represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an aryl group or an aralkyl group, and R ² represents a carbon atom which may have a hydrogen atom or a substituent. Represents an alkyl group, an aryl group or an aralkyl group having a number of 1 to 8. R ¹ and R ² may be one and represent a C 3-16 alkylene group which may have a substituent. Good.)
Formula (1) comprising reacting a ketone represented by the formula, formaldehyde and hydrogen in the presence of a basic substance and a hydrogenation catalyst.
[0007]
[Formula 4]
R ¹ COCH (R ² ) CH ₃ (1)
[0008]
(Wherein R ¹ and R ² are the same as defined above)
It solves by providing the manufacturing method of (alpha) -methyl ketone shown by these.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
The production method of α-methyl ketones of the present invention is characterized in that hydrogen, a ketone represented by the above formula (2) and formaldehyde are reacted in the presence of a basic substance and a hydrogenation catalyst.
[0010]
In the above formula (2), the alkyl group having 1 to 8 carbon atoms represented by R ¹ and R ^2, for example, a methyl group, an ethyl group, n- propyl group, i- propyl, n- butyl, i -Butyl group, sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, and the like. Examples of the aryl group include phenyl group, tolyl group, naphthyl group, and the like. Examples of the aralkyl group include a benzyl group.
Further, the alkylene group of R ¹ and R ² are carbon atoms which may represent become one 3-16, for example, trimethylene group, tetramethylene group, 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, the substituent must be inert under basic conditions. Examples of such a substituent include an alkoxy group, a formyl group protected by an acetal type, and a hydroxyl group.
[0011]
Specific examples of the ketones represented by the formula (2) are 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-methylheptan-2-one, 3-octanone, 4-octanone, cyclopentanone, cyclohexanone, 4-methylcyclohexanone, 4-t-butylcyclohexanone, Examples include cycloheptanone, acetophenone, propiophenone, and the like.
[0012]
In addition, as the formaldehyde used in the present invention, any one of an aqueous solution (formalin), gaseous formaldehyde, solid form such as paraformaldehyde and trioxane may be used. However, ease of handling and production of α-methyl ketones may be used. From the viewpoint of cost and the like, it is preferably used as an aqueous solution. When used as an aqueous solution, the concentration is preferably 50% by weight or less, and more preferably 20 to 45% by weight from the viewpoint of ease of handling, volumetric efficiency of the reaction, and the like.
[0013]
The ratio of the ketones represented by formula (2) and formaldehyde is not particularly limited, but the ketones represented by formula (2) are usually 0.5 to 10 mol, preferably 0.8 to 1 mol per mol of formaldehyde. It is used within a range of 3 mol, more preferably 1.0 to 1.2 mol.
[0014]
Examples of the basic substance used in the present invention include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as barium hydroxide and calcium hydroxide. Can do. One kind of these may be used, or two or more kinds may be mixed and used.
Although the basic substance can be used as it is, it is usually used as an aqueous solution of 0.5 to 50% by weight, preferably 1 to 30% by weight.
[0015]
The amount of the basic substance used is usually 0.01 to 0.3 mol per mol of formaldehyde, but from the viewpoint of reaction rate and production cost, it is 0.02 to 0.2 mol per mol of formaldehyde. Is preferred.
[0016]
The hydrogenation catalyst used in the present invention is generally a catalyst used in a catalytic hydrogenation reaction, and particularly used for selectively hydrogenating a carbon-carbon double bond of an α, β-unsaturated carbonyl compound. A catalyst can be used, for example, a catalyst having palladium, rhodium, nickel, platinum or the like as an active component.
The form of the hydrogenation catalyst may be any of metal itself; metal oxide or alloy with other metal; and supported on a support such as activated carbon, alumina, silica gel or diatomaceous earth. 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.
[0017]
The amount of the hydrogenation catalyst used is usually 0.0005 to 0.1 parts by weight with respect to 1 part by weight of formaldehyde, but from the viewpoint of reaction rate and production cost of α-methyl ketones, 1 part by weight of formaldehyde. It is preferable that it is 0.001-0.03 weight part.
[0018]
In the present invention, it is not always necessary to use a solvent, but a solvent may be used as long as it does not adversely affect the reaction. Usable solvents include, for example, ether solvents such as tetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl ether, dibutyl ether; hydrocarbon solvents such as hexane, heptane, octane, benzene, toluene, xylene; methanol Alcohol solvents such as ethanol, 2-propanol and butanol; water and the like.
[0019]
As a specific reaction operation of the production method of the present invention, for example, formaldehyde, a ketone represented by the formula (2), a basic substance, and a hydrogenation catalyst are widely used within a predetermined reaction temperature range and in a hydrogen atmosphere. And mixing by a normal operation using a typical apparatus. In this case, there is no particular limitation on the mixing order and mixing speed of each component to be subjected to the reaction, but from the viewpoint of suppressing the reaction runaway, the hydrogenation catalyst is changed to the ketones and basic substances represented by the formula (2). It is preferable to continuously add formaldehyde to the suspended suspension. Here, “continuously added” includes adding the components to be added in multiple portions.
[0020]
The reaction temperature is usually in the range of 20 to 180 ° C, but in order to make the reaction rate practical, it is preferably in the range of 40 to 140 ° C.
[0021]
The time required for the reaction varies depending on the type, concentration, reaction temperature, etc. of the basic substance to be used. As described above, the hydrogenation catalyst is suspended in the ketones and basic substance represented by the formula (2). When formaldehyde is continuously added to the suspension, the time required for the addition of formaldehyde is usually 0.5 to 10 hours and the follow-up time after completion of the addition is 0 to 20 hours.
In addition, it is desirable to sufficiently stir the reaction mixture during addition of formaldehyde and driving of the reaction.
[0022]
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, but may be introduced (bubbled) into the mixture. .
The pressure of hydrogen in the reaction system is usually in the range of 1 to 100 atm, but preferably in the range of 1 to 10 atm.
[0023]
After completion of the reaction, the target compound α-methyl ketone is obtained by, for example, separating the aqueous layer from the reaction solution after removing the hydrogenation catalyst from the reaction mixture by filtration or centrifugation, and distilling the remaining organic layer. Or by filtering the hydrogenation catalyst from the reaction mixture, extracting the desired α-methyl ketones from the filtrate with an organic solvent, and distilling the organic solvent from the resulting organic layer under normal pressure or reduced pressure. Separation can be obtained by a general method. Examples of the organic solvent used for extraction in the above include hydrocarbon solvents such as toluene, benzene, hexane, and cyclohexane; halogenated hydrocarbon solvents such as methylene chloride, chloroform, carbon tetrachloride, and dichloroethane.
[0024]
The α-methyl ketones represented by the formula (1) thus obtained can be further improved in purity by conventional methods such as vacuum distillation and silica gel column chromatography.
[0025]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to this Example.
[0026]
Example 1
A 1 liter autoclave equipped with a stirrer was charged with 198.0 g (2.75 mol) of methyl ethyl ketone and 20.0 g of a 10% aqueous sodium hydroxide solution (containing 0.05 mol of sodium hydroxide) in a nitrogen atmosphere. The lower 5% palladium carbon (hydrogenation catalyst) 0.30 g was added, and the internal temperature of the autoclave was raised to 60 ° C. Thereafter, hydrogen was introduced into the autoclave, the pressure inside the autoclave was set to 0.45 MPa (4.59 Kg / cm ² , gauge pressure, hydrogen partial pressure: 0.4 MPa), and 214.3 g of 35% formaldehyde aqueous solution ( (Containing 2.5 moles of formaldehyde) was continuously added to the mixture obtained above using a feed pump over 2 hours 45 minutes. During the addition, while maintaining the liquid temperature of the reaction mixture at 60 ° C., the 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 completion of the addition of the aqueous formaldehyde solution, the temperature of the reaction mixture was raised to 100 ° C., and stirring was further continued for 1 hour to cool the reaction. 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. (up to 170 ° C. Was increased at a rate of 5 ° C./min, and after exceeding 170 ° C., the temperature was increased at a rate of 10 ° C./min)]. As a result, 25.8 g of methyl ethyl ketone, which is an unreacted raw material, 157.0 g of methyl isopropyl ketone having a methyl group introduced at the α-position and 4.6 g of diethyl ketone, and ethyl isopropyl ketone having a methyl group introduced at the α-position of the carbonyl group of methyl isopropyl ketone or diethyl ketone It was found to contain 13.2 g. The yield of methyl isopropyl ketone based on formaldehyde is 73.0%.
By distilling 218.9 g of the organic layer obtained above under normal pressure, 203.6 g was obtained as a fraction having a boiling point of 94 to 95 ° C. This fraction contained 98.3% of methyl isopropyl ketone.
[0027]
Example 2
An autoclave with an internal volume of 300 ml equipped with a stirrer was charged with 47.3 g (0.55 mol) of diethyl ketone and 6.0 g of 10% aqueous sodium hydroxide solution (containing 0.015 mol of sodium hydroxide), and nitrogen. Under an atmosphere, 0.06 g of 5% palladium carbon (hydrogenation catalyst) 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 adjusted to 0.45 MPa (gauge pressure, hydrogen partial pressure: 0.37 MPa), and 42.9 g of 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 30 minutes. During the addition, the liquid temperature of the reaction mixture was maintained at 100 ° C., and hydrogen consumed by the reaction was supplied to the autoclave to maintain the pressure in the autoclave at 0.45 MPa (gauge pressure). After completion of the addition of the aqueous formaldehyde solution, the reaction was continued by further stirring for 1 hour at the same temperature, and then cooled to room temperature. Palladium carbon was removed from the reaction mixture by filtration, and 49.6 g of an organic layer was separated from the filtrate separated into two layers. This organic layer was analyzed by gas chromatography under the same conditions as in Example 1. As a result, 10.9 g of diethylketone as an unreacted raw material and ethyl having a methyl group introduced at the α-position of the carbonyl group of diethylketone. It was found that 31.1 g of isopropyl ketone and 8.3 g of diisopropyl ketone having a methyl group introduced at 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%.
[0028]
Example 3
A 1 liter autoclave equipped with a stirrer was charged with 220.5 g (2.25 mol) of cyclohexanone and 12.0 g of a 10% aqueous sodium hydroxide solution (containing 0.03 mol of sodium hydroxide) in a nitrogen atmosphere. The bottom 5% palladium carbon (hydrogenation catalyst) 0.18 g was added, and the internal temperature of the autoclave was raised to 100 ° C. Thereafter, hydrogen is introduced into the autoclave, the pressure in the autoclave is set to 0.45 MPa (gauge pressure), and 128.6 g of 35% aqueous formaldehyde solution (containing 1.5 mol of formaldehyde) is fed using a feed pump as described above. It was continuously added to the obtained mixture over 2 hours and 45 minutes. During the addition, the liquid temperature of the reaction mixture was maintained at 100 ° C., and hydrogen consumed by the reaction was supplied to the autoclave to maintain the pressure in the autoclave at 0.45 MPa (gauge pressure). After completion of the addition of the aqueous formaldehyde solution, the reaction was continued by further stirring for 1 hour at the same temperature, and then cooled to room temperature. Palladium carbon was removed from the reaction mixture by filtration, and 232.2 g of an organic layer was separated from the filtrate separated into two layers. This 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 and 2-methyl in which a methyl group was introduced into the α-position of the carbonyl group of cyclohexanone. It was found that 106.2 g of cyclohexanone and 8.3 g of 2,6-dimethylcyclohexanone having a methyl group introduced at the α-position of the carbonyl group of 2-methylcyclohexanone were contained. The yield of 2-methylcyclohexanone based on formaldehyde is 63.2%.
[0029]
【The invention's effect】
According to the present invention, formaldehyde, a ketone represented by the formula (2), and hydrogen are reacted in the presence of a basic substance and a hydrogenation catalyst, whereby α- Methyl ketones can be easily produced.

Claims (1)

Formula (2)

(Wherein R ¹ represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an aryl group or an aralkyl group, and R ² represents a hydrogen atom or an optionally substituted carbon. Represents an alkyl group, an aryl group or an aralkyl group having a number of 1 to 8. Further, R ¹ and R ² may be one to represent a C 3-16 alkylene group which may have a substituent. Good.)
Formula (1) comprising reacting a ketone represented by the formula, formaldehyde and hydrogen in the presence of a basic substance and a hydrogenation catalyst.

(Wherein R ¹ and R ² are as defined above), a method for producing a ketone having a methyl group at the α-position of the carbonyl group , wherein the basic substance is an alkali metal hydroxide And a method for producing a ketone having a methyl group at the α-position of a carbonyl group, which is at least one compound selected from the group consisting of an alkaline earth metal hydroxide.