JPH10338687A - Production of dihydropyran derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To economically obtain a dihydropyran derivative in high productivity and yield by reacting aldehydes with a diene compound in the presence of a Lewis acid catalyst and a specific cocatalyst. SOLUTION: An aldehyde of the formula, R<1> -CHO (R<1> is H, 1-12C alkyl, 6-12C aryl or the like which may be substituted with an alkyl) is reacted with a diene compound of formula I (R<2> and R<3> are each H, a 1-6C alkyl or alkenyl) in the presence of a Lewis acid catalyst and a cocatalyst without any solvent or in a solvent at -30 to 100 deg.C to provide the objective 5,6-dihydro-2H-pyran derivative of formula II. A compound (excluding a nitro compound) having weaker coordination force to Lewis acid than the aldehyde and having action dissolving the Lewis acid into a solvent by coordinating to Lewis acid is used as the cocatalyst and, e.g. one or two or more kinds of compounds selected from aliphatic or aromatic esters, chloroacetic esters, ethers, ketones and carbonates are used in an amount of 0.1-10 mol based on 1 mol Lewis acid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a highly selective method for producing a dihydropyran derivative. More specifically, the present invention relates to a method for producing a 5,6-dihydro-2H-pyran derivative with high selectivity and high yield.

[0002]

BACKGROUND OF THE INVENTION Dihydropyran derivatives are important industrial raw materials for perfumes. For example, α-phenyl-dihydropyran can be converted by reductive opening of the pyran ring to 5-phenylpentanol, which is of particular importance as a perfume (Swiss Patent 6555932).
issue). Also, 6-phenyl-4-methyl-5,6-dihydro-2H-pyran, 6-phenyl-2,4-dimethyl-5,6-dihydro-2H-pyran and 6-butyl-
Dihydropyran derivatives such as 2,4-dimethyl-5,6-dihydro-2H-pyran are themselves useful as perfumes (US Pat. No. 3,681,263 and Arm. Khm. Zh.
(1976), 29 (3), pp. 276-277).

[0003] As described in the above literature, these dihydropyran derivatives generally comprise an aldehyde such as benzaldehyde and valeraldehyde (pentanal) and a 3-buten-1-ol such as isoprenol in a catalytic amount of an acid. The reaction can be effected to give a mixture of double bond isomers. However, the desired 3-butene-1-
Since alls are expensive, there has been a demand for a method for producing these dihydropyran derivatives from easily available and inexpensive raw materials.

As such a production method, there has been known a method based on a heterodiels-Alder reaction between an aldehyde and a conjugated diene compound. In this case, isoprene or 2-
Conjugated diene compounds such as methylpentadiene are readily available, but in general, this type of heterodiels-Alder reaction is only practical if a highly reactive aldehyde such as glyoxylate or trichloroacetaldehyde is used. Product could not be obtained at a high rate (Comprehensive Organic Synthesis, Vol. 5, p. 43
1, Pergamon Press 1991).

As an improved method, there is a reaction between an aldehyde and a diene using a Lewis acid as a catalyst. For example, aluminum chloride or tin tetrachloride is used as a Lewis acid catalyst, and an aliphatic or aromatic nitro compound is used as a cocatalyst. The method used (Japanese Patent Publication No. 6-99419) is known. However, this method generates a large amount of waste after the reaction, and the yield is as low as about 50%, which is still not sufficiently satisfactory in terms of yield and productivity. Recently, a heterodiels-Alder reaction using a rare earth metal perfluoroalkanesulfonate such as scandium perfluorate as a catalyst (New Journal
of Chemistry, 1995, vol 19, 707). However, this method is not economical and industrially unsuitable because the catalyst used is expensive.

Accordingly, an object of the present invention is to provide a simple and economical method for producing a dihydropyran derivative by a heterodiels-Alder reaction between an aldehyde and a diene compound with high productivity and high yield. It is in.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, when producing a dihydropyran derivative from an aldehyde and a diene compound in the presence of a Lewis acid catalyst, a co-catalyst was used. The present inventors have found that a dihydropyran derivative can be easily prepared with high productivity and high yield by using a specific compound, and thus completed the present invention.

That is, the present invention relates to a compound represented by the general formula (I) R ¹ -CHO (I) wherein R ¹ is substituted with a hydrogen atom, an alkyl or alkenyl group having 1 to 12 carbon atoms, or an alkyl group. A total of 6 to 12 carbon atoms which may be substituted by a cycloalkyl group having 3 to 12 carbon atoms, or an alkyl group or an alkoxy group;
Represents an aryl group. ) And an aldehyde represented by the general formula (II)

[0009]

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(Wherein R ² and R ³ are the same or different and each represent a hydrogen atom, an alkyl group or an alkenyl group having 1 to 6 carbon atoms) and a diene compound represented by the following formula: Under the general formula (III)

[0011]

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In the production of the 5,6-dihydro-2H-pyran derivative represented by the formula (I) wherein R ¹ , R ² and R ³ have the same meanings as above, a general formula (I) )
A compound having a lower coordination force to a Lewis acid than the aldehyde represented by the formula and having a function of coordinating to the Lewis acid and dissolving the Lewis acid in a solvent (excluding nitro compounds)
And a process for producing a dihydropyran derivative.

[0013]

Embodiments of the present invention will be described below in detail.

The general formula (I) used in the production method of the present invention
In the aldehyde represented by R ¹ is a hydrogen atom, an alkyl or alkenyl group having 1 to 12 carbon atoms, a cycloalkyl group having a total of 3 to 12 carbon atoms which may be substituted with an alkyl group, or an alkyl group or An aryl group having a total of 6 to 12 carbon atoms which may be substituted with an alkoxy group is shown, preferably an alkyl group having a carbon number of 3 to 12 or a total of 6 to 12 carbon atoms which may be substituted with an alkyl group. An aryl group, particularly an aryl group having a total of 6 to 10 carbon atoms, more preferably a phenyl group, an o-, m-, or p-tolyl group is preferred.

Specific examples of the aldehyde represented by the general formula (I) include benzaldehyde, o-, m-, p-tolualdehyde, naphthaldehyde, butyraldehyde, valeraldehyde, caproaldehyde, heptaldehyde, capryaldehyde. , Capric aldehyde, laurin aldehyde and the like.

Further, in the diene compound represented by the general formula (II) used in the production method of the present invention, R ² and R ³ are the same or different and are a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or It represents an alkenyl group, preferably a hydrogen atom or a methyl group.

Specific examples of the diene compound represented by the general formula (II) include isoprene, 2-methyl-1,3-pentadiene, butadiene and 1,3-pentadiene. 1,3-pentadiene is particularly preferred.

In the present invention, the reaction ratio of the aldehyde to the diene compound is diene / aldehyde = 5 / molar ratio.
1 to 1/5 is preferable, and 2/1 to 1/2 is particularly preferable.

In the present invention, the Lewis acid used as a catalyst is not particularly limited, but aluminum chloride, tin tetrachloride, iron trichloride, titanium trichloride, titanium tetrachloride and boron trifluoride are preferred. The Lewis acid catalyst is used in an amount of 0.001 mol or more, preferably 0.005 to
Used in a ratio of 0.4 mol.

In the present invention, the compound used as a cocatalyst has a weaker coordination force to the Lewis acid than the aldehyde represented by the general formula (I), and further coordinates to the Lewis acid to dissolve the Lewis acid in the solvent. (Excluding nitro compounds), for example, one or two selected from the group consisting of aliphatic or aromatic esters, chloroacetates, ethers, ketones and carbonates Species or more.

In the present invention, the coordination force to the Lewis acid can be estimated from the magnitude of the heat of complex formation with the Lewis acid. The heat of formation was determined by JAOlah's "Friedel-Cr
aftsand Related Reaction ", Volume 1, 601 (1963)
The actual measurement values described can be used, or the calculation may be performed using the AM1 method of the MOPAC 93 semi-empirical molecular orbital method package.

Specific examples of the aliphatic or aromatic esters used as a promoter in the present invention include methyl acetate, ethyl acetate, propyl acetate, octyl acetate, phenyl acetate, methyl benzoate, ethyl benzoate, and propyl benzoate. , Diethyl terephthalate, ethyl p-chlorobenzoate and the like. Specific examples of the chloroacetates include methyl monochloroacetate, ethyl monochloroacetate,
Examples include methyl dichloroacetate, ethyl dichloroacetate, methyl trichloroacetate, and ethyl trichloroacetate. Specific examples of ethers include anisole and diphenyl ether. Specific examples of ketones include acetophenone and benzophenone. Specific examples of the carbonates include dimethyl carbonate, ethylene carbonate and the like. Among these, lower alkyl benzoate, lower alkyl acetate,
Particularly preferred are lower alkyl monochloroacetic acid esters, anisole, benzophenone, and ethylene carbonate.

In the present invention, the amount of the cocatalyst used is preferably 0.1 to 10 mol, and more preferably 0.5 to 2.0 mol per mol of the Lewis acid.
Mole is more preferred.

The reaction in the present invention can be carried out without a solvent or with a solvent. As the solvent used in the present invention, hydrocarbon solvents and chlorine solvents are preferable.Examples of the hydrocarbon solvents include benzene, toluene, xylene, pentane, hexane, cyclohexane, petroleum ether, and the like. Include chlorobenzene, dichloromethane, tetrachloroethylene and the like. These solvents may be used alone or as a mixture of two or more kinds, and are preferably used in an amount of 50% by weight or more, particularly 100% by weight or more based on the aldehyde.

The optimum reaction temperature in the present invention is determined based on the reactivity between the aldehyde and the diene compound, the catalyst and cocatalyst used,
Although it depends on the amount used, and also on the presence or absence and properties of the solvent, a temperature of -30 ° C to 100 ° C is generally used, and particularly preferably -20 ° C to 70 ° C.

The method of mixing the aldehyde, the diene compound, the catalyst and the co-catalyst in the present reaction is not particularly limited, but a conventional method that can be advantageously used is to mix the catalyst, the co-catalyst and the solvent at a desired temperature. This is a method in which a mixture of an aldehyde, a diene compound and a solvent is added dropwise while maintaining the mixture. The reaction is preferably performed in the absence of water and oxygen.

[0027]

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

Example 1 6-phenyl-4-methyl- represented by the following formula (IV)
Production of 5,6-dihydro-2H-pyran

[0029]

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3.20 g (24 mmol) of aluminum chloride was charged into a 200 ml four-necked flask equipped with a cooling tube, a thermometer, and a stirrer, followed by purging with nitrogen. To this, 40 ml of toluene and 3.27 g (24 mmol) of methyl benzoate were added at room temperature. The mixture was cooled to 0 ° C, and a mixed solution of 12.70 g (120 mmol) of benzaldehyde, 19.00 g (280 mmol) of isoprene and 50 ml of toluene was added dropwise over 1 hour while maintaining the temperature at 0 to 5 ° C. After completion of the dropwise addition, the mixture was stirred for 10 minutes, cooled, and then poured into ice water. The layers were separated, the aqueous layer was washed with some toluene, and the combined organic layers were washed with aqueous sodium bicarbonate then saturated brine. The solvent was distilled off and the residue was distilled under reduced pressure to obtain the desired dihydropyran in 15.9.
g (yield: 76%).

Example 2 6-phenyl-4-methyl- represented by the above formula (IV)
Production of 5,6-dihydro-2H-pyran 3.20 g (24 mmol) of aluminum chloride was charged into a 200 ml four-necked flask equipped with a condenser, a thermometer, and a stirrer, followed by purging with nitrogen. Here, 40 ml of toluene and 3.27 g of methyl benzoate
(24 mmol) was added at room temperature. This was cooled to 0 ° C., and 12.70 g (120 mmol) of benzaldehyde and 10.7 g of isoprene were added.
(156 mmol) and a mixed solution of toluene (50 ml) were added dropwise over 1 hour while maintaining the temperature at 0 to 5 ° C. After completion of the dropwise addition, the mixture was stirred for 10 minutes, cooled, and then poured into ice water.
The layers were separated, the aqueous layer was washed with some toluene, and the combined organic layers were washed with aqueous sodium bicarbonate then saturated brine. The solvent was distilled off, and the residue was distilled under reduced pressure to obtain 14.4 g (yield: 70%) of a desired dihydropyran.

Examples 3 to 7 The procedure of Example 1 was repeated except that the cocatalyst was changed to the one shown in Table 1. 6-phenyl-4-methyl-5,6-dihydro-2H represented by the above formula (IV) -Pyran was obtained in the yields shown in Table 1, respectively.

[0033]

[Table 1]

Example 8 Preparation of 6-phenyl-2,4-dimethyl-5,6-dihydro-2H-pyran represented by the following formula (V)

[0035]

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Instead of isoprene, 2-methyl-1,3
Example 1 except that 23 g (280 mmol) of pentadiene were used
The desired dihydropyran was obtained by the reaction
6.1 g (yield: 72%) was obtained.

Example 9 6-p-tolyl-4-methyl- represented by the following formula (VI)
Production of 5,6-dihydro-2H-pyran

[0038]

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The reaction was carried out in the same manner as in Example 1 except that 14.4 g (120 mmol) of p-tolualdehyde was used instead of benzaldehyde, and 16.8 g of desired dihydropyran was obtained.
(Yield: 75%).

Example 10 6-n-butyl-4-methyl- represented by the following formula (VII)
Production of 5,6-dihydro-2H-pyran

[0041]

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The reaction was carried out in the same manner as in Example 1 except that 10.3 g (120 mmol) of valeraldehyde was used instead of benzaldehyde, whereby 13.5 g of desired dihydropyran was obtained.
(Yield: 73%) was obtained.

Comparative Example 1 6-phenyl-4-methyl- represented by the above formula (IV)
Preparation of 5,6-dihydro-2H-pyran In a 200 ml four-necked flask equipped with a condenser, a thermometer, and a stirrer, 6.4 g (47 mmol) of aluminum chloride and toluene 60
g. The mixture was cooled to about 5 ° C. and 3.8 g (36 mmol) of benzaldehyde was added over 5 minutes. Then 8.9 g (84 mmol) of benzaldehyde, 17.6 of isoprene
g (260 mmol) and 25 g of toluene were added dropwise at 30 ° C. with thorough stirring at 30 ° C. The mixture was stirred at 15 ° C. for another 10 minutes, then cooled and poured into ice water. The layers were separated, the aqueous layer was washed with some hexane, and the combined organic layers were washed with aqueous sodium bicarbonate then saturated brine. The solvent was distilled off, and the residue was distilled under reduced pressure to obtain 10.1 g (yield: 48%) of a desired dihydropyran.

Comparative Example 2 6-phenyl-4-methyl- represented by the above formula (IV)
Production of 5,6-dihydro-2H-pyran 5.3 g (40 mmol) of aluminum chloride and 40 ml of n-hexane were charged into a 200 ml four-necked flask equipped with a condenser, a thermometer and a stirrer. After cooling the mixture to about -5 ° C., 3.56 g (40 mmol) of 2-nitropropane are added at this temperature.
Added in 10 minutes. Then 10.6 g of benzaldehyde (10
0 mmol), 14.9 g (220 mmol) of isoprene and n-hexane
30 ml of the mixture were added dropwise over 30 minutes with thorough stirring at -5 ° C. After the mixture was stirred at −5 ° C. for another 10 minutes,
After cooling, it was poured into ice water. The layers were separated, the aqueous layer was washed with some hexane, and the combined organic layers were washed with aqueous sodium bicarbonate then saturated brine. The solvent was distilled off, and the residue was distilled under reduced pressure to obtain 9.38 g (yield: 54%) of a desired dihydropyran.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Osamu Yamashita, Inventor 1334, Minato, Wakayama, Wakayama

Claims (5)

[Claims] 1. A compound of the general formula (I) R ¹ -CHO (I) wherein R ¹ is a hydrogen atom, an alkyl or alkenyl group having 1 to 12 carbon atoms, or a total carbon atom which may be substituted by an alkyl group. A total of 6 to 12 carbon atoms which may be substituted by a cycloalkyl group of the number 3 to 12, or an alkyl group or an alkoxy group;
Represents an aryl group. ) And an aldehyde represented by the general formula (II): (Wherein R ² and R ³ are the same or different and each represent a hydrogen atom, an alkyl group or an alkenyl group having 1 to 6 carbon atoms) in the presence of a Lewis acid catalyst. The compound of the general formula (III) (In the formula, R ¹ , R ² and R ³ have the same meanings as above.) In producing the 5,6-dihydro-2H-pyran derivative represented by the general formula (I), Using a compound having a lower coordination force to the Lewis acid than the aldehyde to be produced and having a function of coordinating to the Lewis acid and dissolving the Lewis acid in a solvent (excluding nitro compounds). A method for producing a pyran derivative. 2. The compound used as a co-catalyst is one or more compounds selected from the group consisting of aliphatic or aromatic esters, chloroacetic esters, ethers, ketones and carbonates. Item 10. The production method according to Item 1. 3. A co-catalyst is used in an amount of 0.1 to 1 mole of Lewis acid.
3. The method according to claim 1, wherein the amount is from 10 to 10 mol. 4. The production method according to claim 1, wherein the Lewis acid is aluminum chloride, tin tetrachloride, iron trichloride, titanium trichloride, titanium tetrachloride or boron trifluoride. 5. R ¹ is an alkyl group having 3 to 12 carbon atoms or an aryl group having a total of 6 to 12 carbon atoms which may be substituted with an alkyl group, wherein R ² and R ³ are the same or different, The production method according to claim 1, wherein the production method is a hydrogen atom or a methyl group.