JPH1129564A - Production of dihyropyrane derivatives - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply obtain the subject compounds in high productivity, high yield by carrying out the hetero Diels Alder reaction of aldehydes and dienes using a specific compounds as a cocatalyst. SOLUTION: The 5,6-dihydro-2H-pyrane derivatives of formula II is obtained by carrying out the reaction of aldehydes of the formula, R<1> -CHO (R<1> is H, an 1-12C alkyl, alkylneyl or the like) and diene compounds of formula I (R<2> and R<3> are each H, an 1-6C alkyl or alkenyl) in the presence of a Lewis acid as the catalyst and the cocatalyst using a compound (i) having lower coordinating force to Lewis acid than the aldehydes of the formula, function dissolving the Lewis acid into solvents by coordinating to the Lewis acid (for example, aliphatic or aromatic esters, ethers, etc.), and (ii)a base(preferably, aliphatic amine, pyridine). The component (i) is preferably used in amount of 0.1-10 mole and 0.01-1 mole of the component (ii) per 1 mole of 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 dihydropyran derivative comprising a compound having a weaker coordination force to a Lewis acid than the aldehyde represented by the formula, and further having a function of coordinating to the Lewis acid to dissolve the Lewis acid in a solvent, and a base. Is provided.

[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
Use at 0.8 mole ratio.

In the present invention, the co-catalyst has a weaker coordinating power to the Lewis acid than the aldehyde represented by the general formula (I), and further functions to coordinate with the Lewis acid to dissolve the Lewis acid in the solvent. (Hereinafter, simply referred to as a compound having a weak coordination force) and a base.

The compound having a weak coordination force used in the present invention is selected, for example, from the group consisting of aliphatic or aromatic esters, chloroacetates, ethers, ketones, carbonates and nitro compounds. One or two
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 the compound having a weak coordination force in the present invention include methyl acetate, ethyl acetate, propyl acetate, octyl acetate, phenyl acetate, methyl benzoate, ethyl benzoate. Propyl benzoate, diethyl terephthalate, ethyl p-chlorobenzoate, and the like. Specific examples of chloroacetates include methyl monochloroacetate, ethyl monochloroacetate, methyl dichloroacetate, ethyl dichloroacetate, methyl trichloroacetate, Ethyl trichloroacetate and the like, specific examples of ethers include anisole,
Specific examples of ketones include acetophenone and benzophenone. Specific examples of carbonates include dimethyl carbonate and ethylene carbonate. Specific examples of nitro compounds include nitromethane. , Nitroethane,
Nitropropane, nitrobenzene, nitrocyclohexane and the like can be mentioned. Among these, lower alkyl esters of benzoic acid, lower alkyl esters of acetic acid, lower alkyl esters of monochloroacetic acid, anisole, benzophenone, ethylene carbonate, nitropropane, and nitromethane are particularly preferred.

In the present invention, the amount of the compound having a weak coordination force is preferably 0.1 to 10 mol, more preferably 0.5 to 2.0 mol, per 1 mol of the Lewis acid.

The base used as a cocatalyst in the present invention may be any base having a property capable of capturing an acidic substance. Examples thereof include amines, strong alkali salts of weak acids such as organic carboxylic acids and phosphoric acid (sodium acetate). , Alkali metal or alkaline earth metal oxides, hydroxides, carbonates, bicarbonates (calcium oxide, magnesium oxide, sodium hydroxide, sodium carbonate, sodium bicarbonate, etc.), etc. But amines are preferred from the viewpoint of solubility in raw materials and the like. Specific examples of the amines include ammonia, aliphatic amines, alicyclic amines, aromatic amines, and heterocyclic compounds having a nitrogen atom, and are preferably aliphatic amines or pyridine. These amines include primary, secondary and tertiary amines.
Preferred are tertiary amines. In addition, these amines
Either a monoamine or a polyamine may be used, but a monoamine is preferred. Further, the total number of carbon atoms in these amines is preferably 30 or less (including 0 ammonia), particularly preferably 3 to 20 carbon atoms, more preferably 6 to 12 carbon atoms.

The following are specific examples of these amines. Aliphatic primary amine: methylamine, ethylamine, propylamine, isopropylamine, butylamine, amylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, dodecylamine, etc. Aliphatic secondary amine: dimethyl Amines, diethylamine, dipropylamine, diisopropylamine, dibutylamine, diamylamine, etc. Aliphatic tertiary amines: trimethylamine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, diethylmethylamine, diethylmethylamine, diethylpropylamine, diisopropylmethylamine, etc. Cyclic amine: cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, etc. Aromatic amine: aniline , Methylaniline, dimethylaniline, ethylaniline, diethylaniline, toluidine, benzylamine, diphenylamine, naphthylamine and other heterocyclic compounds: pyridine and the like polyamines: ethylenediamine, diethylenetriamine, propylenediamine, dipropylenetriamine, etc. The amount is preferably from 0.01 to 1 mol, more preferably from 0.01 to 0.4 mol, per mol of the Lewis acid.

In the present invention, by using a compound having a weak coordination force and a base together as a cocatalyst as described above, for example, the yield can be reduced as compared with a case where only a compound having a weak coordination force is used. It can be increased by about 10 to 20%.

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.

In the present invention, the optimum reaction temperature is determined by 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 adjust the desired temperature while mixing the catalyst, the co-catalyst and the solvent. This is a method in which a mixture of an aldehyde, a diene compound, and a solvent is added dropwise while keeping the mixture. The reaction is preferably performed in the absence of water and oxygen.

[0031]

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

[0033]

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6.40 g (48 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, 80 ml of toluene and 3.27 g (24 mmol) of methyl benzoate were added at room temperature. This was cooled to 0 ° C., and 0.76 g (9.6 mmol) of pyridine was added. Then, 6.35 g (60 mmol) of benzaldehyde and 5.35 g (79%) of isoprene were added.
mmol) and 25 ml of toluene were added dropwise over 3 hours while maintaining the temperature at 0 to 5 ° C. After completion of the dropwise addition, the mixture was stirred for 10 minutes, then poured into ice water to stop the reaction, and the organic layer was recovered. The aqueous layer was extracted with toluene, and the collected organic layer was washed with an aqueous sodium hydrogen carbonate solution and then with a saturated saline solution. The solvent was distilled off, and the residue was distilled under reduced pressure to obtain 8.77 g (yield: 84%) of a desired dihydropyran.

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 2-nitropropane 2.
14 g (24 mmol) were added at room temperature. Cool it to 0 ° C,
After adding 0.12 g (1.2 mmol) of triethylamine, 7.11 g (67 mmol) of benzaldehyde and 10.7 g (156 m2) of isoprene are added.
mol) and toluene (50 ml) were added dropwise over 1.5 hours while maintaining the temperature at 0 to 5 ° C. After completion of the dropwise addition, the mixture was stirred for 10 minutes, then poured into ice water to stop the reaction, and the organic layer was recovered. The aqueous layer was extracted with toluene, and the collected organic layer was washed with an aqueous sodium hydrogen carbonate solution and then with a saturated saline solution. The solvent was distilled off, and the residue was distilled under reduced pressure to obtain 9.21 g (yield: 79%) of a desired dihydropyran.

Comparative Example 1 6-phenyl-4-methyl- represented by the above formula (IV)
Production of 5,6-dihydro-2H-pyran 6.40 g (48 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. Here 80 ml of toluene and 3.27 g of methyl benzoate
(24 mmol) was added at room temperature. After cooling this to 0 ° C,
6.35 g (60 mmol) of benzaldehyde, 5.35 g of isoprene
(79 mmol) and a mixed solution of 25 ml of toluene were added dropwise over 3 hours while maintaining the temperature at 0 to 5 ° C. After completion of the dropwise addition, the mixture was stirred for 10 minutes, then poured into ice water to stop the reaction, and the organic layer was recovered. The aqueous layer was extracted with toluene, and the collected organic layer was washed with an aqueous sodium hydrogen carbonate solution and then with a saturated saline solution. The solvent was distilled off, and the residue was distilled under reduced pressure to obtain 6.79 g (yield: 65%) of a desired dihydropyran.

Claims (6)

[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), Production of a dihydropyran derivative, characterized by using a compound having a lower coordination force to a Lewis acid than the aldehyde to be produced and having a function of coordinating to the Lewis acid to dissolve the Lewis acid in a solvent, and a base. Method. 2. A compound having a weak coordination force used as a cocatalyst selected from the group consisting of aliphatic or aromatic esters, chloroacetates, ethers, ketones, carbonates and nitro compounds. Or two or more, the base is an amine, a strong alkali salt of an organic carboxylic acid or phosphoric acid, an oxide of an alkali metal or an alkaline earth metal,
The method according to claim 1, wherein the method is a hydroxide, a carbonate or a bicarbonate. 3. The method according to claim 1, wherein the base is an aliphatic amine or pyridine. 4. A compound having a weak coordination force is used in an amount of 0.1 to 10 mol per mol of Lewis acid, and a base is added in an amount of 0.1 to 10 mol per mol of Lewis acid.
The production method according to any one of claims 1 to 3, wherein 01 to 1 mol is used. 5. The method according to claim 1, wherein the Lewis acid is aluminum chloride, tin tetrachloride, iron trichloride, titanium trichloride, titanium tetrachloride or boron trifluoride. 6. 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 any one of claims 1 to 5, wherein the production method is a hydrogen atom or a methyl group.