JP2008120759A - Process for producing β-diketone compound having ether group - Google Patents

Abstract

Provided is a process for producing an industrially suitable β-diketone compound having an ether group, which obtains a β-diketone compound having an ether group in a high yield by a simple method.
A process for producing a β-diketone compound having an ether group, which comprises reacting a ketone compound with a carboxylic acid ester in the presence of an alkali metal alkoxide. For example, 2-methyl-6-methyl-3,5-heptanedione is obtained by reacting 3-methylbutanone with methyl 2-chloropropionate in the presence of sodium methoxide.
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Description

  The present invention relates to a method for producing a β-diketone compound having an ether group useful as a ligand for synthesis of a metal complex for forming a metal-containing thin film, for example, as a synthetic intermediate or raw material for pharmaceuticals and agricultural chemicals.

Conventionally, as a method for producing a β-diketone compound having an ether group, for example, 3-methoxy-3-methyl-1-butyne is synthesized and isolated by reacting acetylene, acetone, potassium hydroxide and dimethyl sulfate. The first step followed by reaction with 2,2-dimethylpropionyl chloride in the presence of copper (I) chloride to synthesize 2-methoxy-2,6,6-trimethyl-3-heptin-5-one In the second step to be isolated later, 2-methoxy-2,6,6-trimethyl-3-heptin-5-one is reacted with aniline to give 3-N-anilino-2-methoxy-2,6 , 6-Trimethyl-3-hepten-5-one is synthesized after the third step, and finally, 3-N-anilino-2-methoxy-2,6,6-trimethyl-3-heptene-5- A method for producing 2-methoxy-2,6,6-trimethyl-3,5-heptadione by reacting ON with hydrochloric acid has been reported (for example, see Non-Patent Document 1).
Alternatively, after reacting methyl 2-bromopropionate with sodium methoxide to synthesize methyl 2-methoxypropionate, it was isolated once and then in the presence of sodium amide or potassium t-butoxide, A method for producing 2-methoxy-6-methyl-3,5-heptanedione by reacting with -butanone is disclosed (for example, see Patent Document 1).
However, these methods are reactions over a plurality of steps, and must be isolated for each step, resulting in a low yield of the target product, which is not desirable as an industrial production method.
Polyhedron, 15 (24), 4521 (1996) International Publication No. PCT / JP2005 / 087697 Pamphlet

  The object of the present invention is to solve the above-mentioned problems and obtain a β-diketone compound having an ether group in a high yield by a simple method. It is to provide a manufacturing method.

  General formula (1)

(In the formula, R ¹ represents a linear or branched alkyl group having 1 to 5 carbon atoms, and M represents an alkali metal.)
In the presence of an alkali metal alkoxide represented by the general formula (2)

(In the formula, R ² represents a linear or branched alkyl group having 1 to 8 carbon atoms, or a general formula (2-1)

(In the formula, Ra represents ^a linear or branched alkylene group having 1 to 7 carbon atoms, and X represents a halogen atom.)
A linear or branched halogenated alkyl group having 1 to 7 carbon atoms, and R ³ represents a linear or branched alkyl group having 1 to 5 carbon atoms. )
A ketone compound represented by the general formula (3)

(Wherein, ^{R 4} has the same meaning as ^{R 2.} Among the ^{R 2} and ^{R 4,} at least one is, it must include a halogenated alkyl group represented by the general formula (2-1) .)
And a carboxylic acid ester represented by the general formula (4)

(In the formula, A represents the general formula (4-1)

(In the formula, R ^a and R ¹ are as defined above.)
C is an ether group represented by the general formula (4-1) or a linear or branched alkyl group having 1 to 8 carbon atoms, and B is a hydrogen atom or 1 to 1 carbon atoms. 4 represents an alkyl group. )
This is solved by a method for producing a β-diketone compound having an ether group represented by the formula:

  An object of the present invention is to provide an industrially suitable method for producing a β-diketone compound having an ether group, which provides a β-diketone compound having an ether group in a high yield by a simple method.

The alkali metal alkoxide used in the reaction of the present invention is represented by the general formula (1). In the general formula (1), R ¹ is a straight chain having 1 to 5 carbon atoms such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a t-butyl group, or a pentyl group. A chain or branched alkyl group is shown. M represents an alkali metal atom such as a lithium atom, a sodium atom, or a potassium atom. These alkali metal alkoxides may be used alone or in combination of two or more, or may be used as a corresponding alcohol solution.

  The amount of the alkali metal alkoxide to be used is preferably 0.1 to 10 mol, more preferably 0.5 to 5 mol, per 1 mol of the ketone compound.

The ketone compound used in the reaction of the present invention is represented by the general formula (2). In the general formula (2), R ² is methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, pentyl group, hexyl group, heptyl group, octyl group. A linear or branched alkyl group having 1 to 8 carbon atoms, or the general formula (2-1)

(R ^a is a methylene group, ethylene group, trimethylene group, propylene group, methylmethylene group, dimethylmethylene group, ethylmethylene group, ethylmethylmethylene group, tetramethylene group, ethylethylene group, pentamethylene group, hexamethylene group, A linear or branched alkylene group having 1 to 7 carbon atoms such as a heptamethylene group, and X represents a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.) 1 to 7 halogenated alkyl groups, R ³ is a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, pentyl group, etc. A linear or branched alkyl group is shown.

  The amount of the ketone compound used is preferably 0.1 to 50 mol, more preferably 0.5 to 10 mol, relative to 1 mol of the carboxylic acid ester.

The carboxylic acid ester used in the reaction of the present invention is represented by the general formula (3). In the general formula (3), R ⁴ has the same meaning as R ² , and R ¹ is the same as that shown in the general formula (1).

Note that at least one of R ² and R ⁴ must contain a halogenated alkyl group represented by the general formula (2-1).

  The reaction of the present invention is carried out in the presence or absence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction. For example, aliphatic hydrocarbons such as hexane, heptane, octane, cyclohexane, methylcyclohexane, and ethylcyclohexane; aromatic carbonization such as toluene and xylene Hydrogens; ethers such as diethyl ether, dibutyl ether, dimethoxyethane, tetrahydrofuran and dioxane; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methylpyrrolidone; 1,3-dimethyl-2 -Ureas such as imidazolidinone; alcohols corresponding to the metal alkoxides represented by general formula (1) (methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, t-butyl alcohol, Pentyl alcohol, etc.) That is, preferably aliphatic hydrocarbons, ethers are used. In addition, you may use these solvents individually or in mixture of 2 or more types.

  The amount of the solvent used is appropriately adjusted depending on the uniformity of the reaction solution, the stirring ability, etc., but is preferably 0 to 100 g, more preferably 1 to 50 g based on 1 g of the carboxylic acid ester.

  The reaction of the present invention is performed by, for example, a method of mixing a ketone compound, a carboxylic acid ester, an alkali metal alkoxide, and a solvent and reacting them while stirring. The reaction temperature at that time is preferably −20 to 100 ° C., more preferably 0 to 80 ° C., and the reaction pressure is not particularly limited.

  In addition, as a preferable aspect of the reaction of the present invention, after the alkali metal alkoxide and the ketone compound are stirred in the solvent, the method of adding the carboxylic acid ester or after the alkali metal alkoxide and the carboxylic acid ester are stirred in the solvent. And a method of adding a ketone compound.

  A β-diketone compound having an ether group can be obtained by the reaction of the present invention. This can be performed after the reaction, for example, neutralization, extraction, filtration, concentration, distillation, recrystallization, crystallization, column chromatography, etc. However, after the reaction is complete, a method of adding an acid to liberate a β-diketone compound having an ether group and obtaining it is preferably used. Examples of acids used in this case include carboxylic acids such as acetic acid, propionic acid, butyric acid, succinic acid, and succinic acid; mineral acids such as phosphoric acid, sulfuric acid, hydrochloric acid, and nitric acid, p-toluenesulfonic acid, methanesulfonic acid, etc. Of these, carboxylic acids are preferably used. In addition, you may use these acids individually or in mixture of 2 or more types.

  The amount of the acid used is preferably 0.05 to 10 mol, more preferably 0.1 to 5 mol, per 1 mol of the alkali metal alkoxide.

The β-diketone compound having an ether group obtained by the reaction of the present invention is represented by the general formula (4). In the general formula (4), A is a group represented by the general formula (4-1) (R ^a and R ¹ are as defined above), B is a hydrogen atom or a methyl group, A linear or branched alkyl group having 1 to 4 carbon atoms such as ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, etc., and C is the above general formula ( 4-1) or a group such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, pentyl group, hexyl group, heptyl group, octyl group, etc. A linear or branched alkyl group having 1 to 8 carbon atoms is shown.

  Specific examples of the β-diketone compound having an alkoxyalkyl group obtained by the reaction of the present invention include, for example, formulas (5) to (41).

Etc.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Example 1 (Synthesis of 2-methoxy-6-methyl-3,5-heptanedione)
To an internal volume 5000 ml flask equipped with a stirrer, thermometer and dropping funnel, 450 g (8.33 mol) of sodium methoxide and 1500 ml of methylcyclohexane were added under argon atmosphere, and the liquid temperature was kept at 55 ° C. 408 g (3.33 mol) of methyl chloropropionate was slowly added dropwise, then 750 ml of methylcyclohexane and 287 g (3.33 mol) of 3-methyl-2-butanone were added in this order, followed by reaction at 60 ° C. for 1 hour with stirring. It was. After completion of the reaction, 1500 ml of water was added to the reaction solution, and then the aqueous layer was separated. Thereafter, 750 ml of methylcyclohexane and 400 ml of acetic acid were added to separate the organic layer, and the organic layer was washed with water. After concentrating the obtained organic layer, the concentrate was distilled under reduced pressure (82 ° C., 1.60 kPa) to obtain 344 g of 2-methoxy-6-methyl-3,5-heptanedione as a colorless liquid (simple (Separation yield; 60%).
The physical properties of 2-methoxy-6-methyl-3,5-heptanedione were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 1.17 (6H, d), 1.30 (0.15H, d), 1.36 (2.85H, d), 2.48 to 2.57 (0.95H, m), 2.59 to 2.73 (0.05H, m), 3.36 (0.15H, s), 3.37 (2.85H, s), 3.71-3.78 (1H, m), 3.78 (0.1H, s), 5.81 (0.95H, s), 15.4 ( 0.95H, s)
IR (neat (cm ^-1 )); 2976, 2936, 1607 (br), 1462, 1366, 1328, 1210, 1120, 910, 805
(The peak at 1607 cm ^-1 is unique to β-diketones)
MS (m / e); 142, 113, 59, 43

Example 2 (Synthesis of 2-methoxy-6-methyl-3,5-heptanedione)
To an internal volume 5000 ml flask equipped with a stirrer, a thermometer and a dropping funnel, 450 g (8.33 mol) of sodium methoxide and 1500 ml of methylcyclohexane were added under an argon atmosphere, and the liquid temperature was kept at 30 ° C. Slowly add 556 g (3.33 mol) of methyl bromopropionate dropwise, then add 750 ml of methylcyclohexane and 287 g (3.33 mol) of 3-methyl-2-butanone in this order, and then react at 60 ° C. for 1 hour with stirring. It was. After completion of the reaction, 1500 ml of water was added to the reaction solution, and then the aqueous layer was separated. Thereafter, 750 ml of methylcyclohexane and 400 ml of acetic acid were added to separate the organic layer, and the organic layer was washed with water. After concentrating the obtained organic layer, the concentrate was distilled under reduced pressure (82 ° C., 1.60 kPa) to obtain 384 g of 2-methoxy-6-methyl-3,5-heptanedione as a colorless liquid (simple (Separation yield; 67%).

Example 3 (Synthesis of 2-methoxy-3,5-heptanedione)
To an internal volume 5000 ml flask equipped with a stirrer, thermometer and dropping funnel, 450 g (8.33 mol) of sodium methoxide and 1500 ml of methylcyclohexane were added under argon atmosphere, and the liquid temperature was kept at 55 ° C. 408 g (3.33 mol) of methyl chloropropionate was slowly added dropwise, and then 750 ml of methylcyclohexane and 240 g (3.33 mol) of 2-butanone were sequentially added, followed by reaction at 60 ° C. for 1 hour with stirring. After completion of the reaction, 1500 ml of water was added to the reaction solution, and then the aqueous layer was separated. Thereafter, 750 ml of methylcyclohexane and 400 ml of acetic acid were added to separate the organic layer, and the organic layer was washed with water. After concentrating the obtained organic layer, the concentrate was distilled under reduced pressure (81 ° C., 1.60 kPa) to obtain 300 g of 2-methoxy-3,5-heptanedione as a colorless liquid (isolation yield; 57%).
The physical properties of 2-methoxy-3,5-heptanedione were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 1.08 (0.48H, t), 1.16 (2.52H, t), 1.30 (0.48H, d), 1.36 (2.52H, d), 2.3 (1.68H) , q), 2.56 (0.32H, q), 3.37 (3H, s), 3.45 (0.32H, s), 3.71 to 3.81 (1H, m), 2.59 to 2.73 (0.05H, m), 3.36 (0.15H) , s), 3.37 (2.85H, s), 3.71 to 3.78 (1H, m), 5.80 (0.84H, s), 15.3 (0.84H, s)
IR (neat (cm ^-1 )); 2984, 2939, 2828, 1610 (br), 1458, 1328, 1210, 1119, 1063, 882, 814
(The peak at 1610 cm ^-1 is unique to β-diketones)
MS (m / e); 128, 99, 59, 43, 29

Example 4 (Synthesis of 2-methoxy-3,5-octanedione)
To an internal volume 5000 ml flask equipped with a stirrer, thermometer and dropping funnel, 450 g (8.33 mol) of sodium methoxide and 1500 ml of methylcyclohexane were added under argon atmosphere, and the liquid temperature was kept at 55 ° C. 408 g (3.33 mol) of methyl chloropropionate was slowly added dropwise, and then 750 ml of methylcyclohexane and 287 g (3.33 mol) of 2-pentanone were sequentially added, followed by reaction at 60 ° C. for 1 hour with stirring. After completion of the reaction, 1500 ml of water was added to the reaction solution, and then the aqueous layer was separated. Thereafter, 750 ml of methylcyclohexane and 400 ml of acetic acid were added to separate the organic layer, and the organic layer was washed with water. After concentrating the obtained organic layer, the concentrate was distilled under reduced pressure (90 ° C., 1.33 kPa) to obtain 332 g of 2-methoxy-3,5-octanedione as a colorless liquid (isolation yield; 58%).
The physical properties of 2-methoxy-3,5-octanedione were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 0.94 to 0.99 (3H, m), 1.35 (3H, d), 1.60 to 1.70 (2H, m), 2.29 to 2.34 (1.7H, m), 2.51 (0.3H, m), 3.36 (3H, s), 3.60 (0.3H, s), 3.74 (1H, q), 5.79 (0.85H, s), 15.3 (0.85H, s)
^{IR (neat (cm -1))} ; 2967,2936,2877,2827,1608 (br), 1458,1332,1210,1119,802 ( peak of 1608 cm ^-1 is β- diketone specific peak)
MS (m / e); 142, 113, 59, 28

  The present invention relates to a method for producing a β-diketone compound having an ether group useful as a ligand for synthesis of a metal complex for forming a metal-containing thin film, for example, as a synthetic intermediate or raw material for pharmaceuticals and agricultural chemicals.

Claims (4)

General formula (1)

(In the formula, R ¹ represents a linear or branched alkyl group having 1 to 5 carbon atoms, and M represents an alkali metal.)
In the presence of an alkali metal alkoxide represented by the general formula (2)

(In the formula, R ² represents a linear or branched alkyl group having 1 to 8 carbon atoms, or a general formula (2-1)

(In the formula, Ra represents ^a linear or branched alkylene group having 1 to 7 carbon atoms, and X represents a halogen atom.)
A linear or branched halogenated alkyl group having 1 to 7 carbon atoms, and R ³ represents a linear or branched alkyl group having 1 to 5 carbon atoms. )
A ketone compound represented by the general formula (3)

(Wherein, ^{R 4} has the same meaning as ^{R 2.} Among the ^{R 2} and ^{R 4,} at least one is, it must include a halogenated alkyl group represented by the general formula (2-1) .)
And a carboxylic acid ester represented by the general formula (4)

(In the formula, A represents the general formula (4-1)

(In the formula, R ^a and R ¹ are as defined above.)
C is an ether group represented by the general formula (4-1) or a linear or branched alkyl group having 1 to 8 carbon atoms, and B is a hydrogen atom or 1 to 1 carbon atoms. 4 represents an alkyl group. )
A method for producing a β-diketone compound having an ether group represented by the formula: At least one of R ² and R ⁴ is represented by the general formula (2-2) or (2-3)

(In the formula, R ^b represents a linear or branched alkylene group having 1 to 5 carbon atoms, and X represents a halogen atom.)
And A in the general formula (4) is represented by the general formula (4-2)

(Wherein R ^b and R ¹ are as defined above.)
The method for producing a β-diketone compound having an ether group according to claim 1, which is an alkoxyalkylmethyl group represented by the formula:   The ether group according to claim 1, which is obtained by reacting a ketone compound with a carboxylic acid ester in the presence of an alkali metal alkoxide, and then adding an acid to liberate a β-diketone compound having an ether group. A method for producing a β-diketone compound.   4. The process for producing a β-diketone compound having an ether group according to claim 1, wherein the alkali metal alkoxide is at least one alkali metal alkoxide selected from the group consisting of sodium methoxide and potassium methoxide.