MXPA97007526A - Process for the preparation of a compound of dihidropir - Google Patents

Abstract

Provide a simple process for economically preparing a dihydropyran compound at high productivity and high reaction production. Using a compound selected from the group consisting of a base and a compound (VIII) having a weak coordination power for the Lewis acid that the aldehyde compound and having an activity for dissolving the Lewis acid, coordinated by the compound (VIII ), in a solvent as a co-catalyst in the reaction of the aldehyde with a diene compound in the presence of a Lewis acid to prepare a 5,6-dihydro-2H-pyran compound represented by the formula (III): wherein R1 represents a hydrogen atom, an alkyl group having from 1 to 12 carbon atoms, an aryl group which can be substituted with the alkyl group, having from 6 to 12 total carbon atoms; R2 and R3 represents a hydrogen atom or an alkyl group having from 1 to 6 carbon atoms

Description

PROCESS FOR THE PREPARATION OF A COMPOUND OF OIHID OPIRANO Field of the Invention The present invention relates to a high selective process for the preparation of a dihydropyran compound. More especially, the invention relates to a process for the preparation of a dihydropyran compound at a high selectivity and a high reaction production.

Techniques in the background A dihydropyran compound is an important industrial raw material for perfumes. For example, alpha-phenyl-dihydro pyran can be converted to 5-phenylpentanol which is particularly important as a perfume by opening the ring -reductive of the pyran ring (Swiss Patent 655932). In addition, dihydropyran compounds such as 6-phenyl-4-methyl-5, -dihydro-2H-pyran, 6-phenyl-2,4-dimethyl-5,6-dihydro-2H-pyran are also useful. and 6-butyl-2,4-dimethyl-5,6-dihydro-2H-pyran (US-A 3681263 and Arm. Khm. Zh (1976), 29 (3), page 276 a - Ref. 25764 As described in the literatures discussed above, these dihydropyran compounds can be obtained in the form of a mixture of the double-ligation isomers by reaction of the aldehyde compounds such as benzaldehyde and valeraldehyde (pentanal) with 3-buten-1-ol compounds such as isoprenol in the presence of a catalytic amount of an acid. However, the 3-buten-1-ol compounds are expensive, and therefore a method for the preparation of these dihydropyran compounds with inexpensive and readily available materials has been desired.

Such a method is known as a method by a hetero-Diels-Alder reaction of the aldehyde compounds with the conjugated diene compounds. In this case, conjugated diene compounds such as isoprene and 2-methylpentadiene are readily available. In general, however, in this hetero-Diels-Alder reaction type, the products have been able to achieve a practical reaction production only when the high reactivity aldehyde compounds such as the glyoxylic ester and the trichloroacetaldehyde are used (Comprehensible Organic Synthesis, Vol 5, p 431 Pergamon Press 1991).

A reaction of the aldehyde compounds with the diene compounds using a Lewis acid - as a catalyst is provided as an improved method thereof. For example, a method in which aluminum chloride or tin tetrachloride is used as a Lewis acid catalyst and in addition an aromatic or aliphatic nitro compound is used as a co-catalyst, is known from ( JP-A 1-238578). In this method, however, waste is produced in large quantities after the reaction, and the reaction production is so low-about 501. Therefore, this method has not yet been sufficiently satisfactory from the point of view of reaction production and -productivity. In recent years, as is known, a method in which the rare alkaline earth metal of perfluoroalkanesulfonate such as scandium perfluoro is used as a catalyst to carry out the hetero-Dieder-Alder reaction (New Joujr nal of Chemistry, 1995, vol 19, 707). However, this method uses an expensive catalyst and therefore not economical and industrially inappropriate Tetrahedron Letters vol. 38, No. 14, pages 2569-2572, published in, Apr. 7th, 1997, discloses the reaction of an aromatic aldehyde with an excess amount of a diene with a tri fluorometanesulfonic acid catalyst.

Accordingly, an object of the invention is to provide a simple process for the preparation of a dihydropyran compound by. the Diels-Alder hetero reaction of an aldehyde compound with a diene compound, in view of a high productivity, a high production of -reaction and an economic saving.

Description of the invention The intensive investigations continued by the present inventors to solve the problems described above have resulted in the discovery that a dihydropyran compound can be easily prepared at a high yield and a high reaction yield by using a specific compound as a catalyst in the preparation. - removing the dihydropyran compound from an aldehyde compound and a diene compound in the presence of a Lewis acid catalyst, and thus completing the present invention.

The present invention provides a process for the preparation of a dihydropyran compound (III) having the formula (III): wherein R represents a hydrogen atom, an alkyl group or an alkenyl group having from 1 to up to 12 carbon atoms, a cycloalkyl group which can be substituted with an alkyl group, having from 3 to 12 carbon atoms; carbon or an aryl group which can be substituted with an alkyl group or an alkoxy group, having from 6 to 12 total carbon atoms; R 2 and R 3 may be the same or different and each represents a hydrogen atom or an alkyl group or an -alkenyl group having from 1 to 6 carbon atoms, which comprises the reaction step of an aldehyde compound ( I) that has the formula (I): R ^ CHO (I) in which R is defined above, with a diene com position (II) having the formula (IT): R? I CH2 = C-CH = CH-R- (II) wherein R 2 and R 3 are defined above, in the presence of a Lewis acid and at least one co-catalyst selected from the group consisting of a base and a compound (VIII) having a weak coordination power for the Lewis acid which is the aldehyde compound (I) and which has an activity to dissolve the Lewis acid, coordinated by the compound (VIII), in a solvent, since -the compound (VIII) is used only, This is not any nitro compound.

The present invention provides a process in which the cocatalyst is a compound - (VIII), or a process in which the cocatalyst is a combination of a base with a compound - (VIII), so as to is carried out.

Preferably, the co-catalyst is a compound (VIII) selected from the group consisting of an aromatic or aliphatic ester compound, a chloroacetic ester compound, and an ether compound, a ketone compound and a carbonate compound .

Preferably, the Lewis acid is selected from the group consisting of aluminum chloride, tin tetrachloride, iron trichloride, titanium trichloride, titanium tetrachloride, and boron trifluoride.

Preferably, the base is used in a cavity of 0.01 to 1 mol per mole of Lewis acid.

Preferably, the compound (VIII) is used in an amount of 0.1 to 10 moles per mole of the Lewis acid.

Preferably, the base is used in a box of 0.01 to 1 mol per mole of Lewis acid, the compound (VIII) is used in an amount of 0.1 to 10 moles per mole of Lewis acid, Preferably, the co-catalyst is a combination of a base with a nitro compound such as compound (VIII).

Preferably, the Lewis acid is boron tri-fluoride and the co-catalyst is an amine compound as the base.

Preferably, the Lewis acid is the aluminum chloride and the co-catalyst is the methyl benzoate as the compound (VIII).

The invention defined above is a -progress of the Diels-Alder hetero reaction, which is obtained by the use of a combined catalyst and 2 co-catalators, in view of high reaction production, high productivity and economic savings. .

Mode for carrying out the invention The embodiment of the present invention will be explained below in detail, In the aldehyde compound represented by the formula (I) used in the preparation process of the present invention, R represents a hydrogen atom, an alkyl group or an alkenyl group having from 1 to 12 carbon atoms, cycloalkyl group which can be substituted with the alkyl group, having from 3 to -12 total carbon atoms or an aryl group which can be substituted with the alkyl group or the alkoxy group, having from 6 to 12 carbon atoms , preferably an alkyl group having from 3 to 12 carbon atoms or an aryl group which can be substituted with the acyl group, having from 6 to 12 total carbon atoms, particularly preferably an aryl group having 6 to 10 carbon atoms, and more particularly a phenol group or an o-, m- p p-tolyl group is preferable.

Specific compounds of the aldehyde compound represented by the formula (I) include benzaldehyde, o-, m- or p-tolualdehyde, naphthoaldehyde, butyraldehyde, valeraldehyde, caproaldehyde, heptaldehyde, caprylic aldehyde, the nonyl aldehyde and the lauraldehyde.

In the di-ene compound represented by the formula (II) which is used in the pre-process of the present invention, R and R can be the same or different and. each represents a hydrogen atom or an alkyl group or an alkenyl group having from 1 to 6 carbon atoms, preferably a hydrogen atom or a methyl group.

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

In the present invention, the reaction ratio of the aldehyde compound to the diene compound is preferably 5/1 to 1/5, particularly preferably 2/1 to 1/2 in terms of the molar ratio of diene / aldehyde.

In the present invention, the Le-wis acid that is used as the catalyst specifically will not be restricted. 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, suitably 0.005 to 0.8 mol, or 0.005 to 0.4 mol, per 1 mol of the aldehyde compound.

Specifically, the Lewis acid that is used as a catalyst will not be restricted. Aluminum chloride, tin tetrachloride, and boron trifluoride are preferred. The Lewis acid of the catalyst is used in an amount of 0.001 mole or more, conveniently 0.005 to 0.4 mole per -1 mole of the aldehyde compound.

In the present invention, the compound (VIII) having a weak coordination power, for the Lewis acid, the aldehyde compound represented by the formula (I) and having an activity to dissolve the Lewis acid, coordinated by the compound (VIII), in a solvent it is used in combination with the base, as the co-catalyst.

The compound (VIII) which is used in the present invention is at least one compound selected from the group consisting of an aromatic or aliphatic ester compound, a ketone compound, a carbonate compound and a n compound.

In the present invention, the power of co-ordination for the Lewistic acid can be estimated by the amount of heat of formation of a com pound with the Lewis acid. The measured values described in Friedel-Crafts and Related Reaction, vol. 1, 601 (1963) by J. A. Olah can be used -like the heat of formation. 0. It can be used to calculate this an AM1 method which is a semi-empirical molecular-orbit method MOPAC 93 package.

Specific examples of the aromatic or aliphatic ester compounds which are used as the compound (VIII) in the present invention include methyl acetate, ethyl acetate, propyl acetate, octyl acetate, phenyl acetate, methyl benzoate, ethyl benzoate, propyl benzoate, diethyl terephthalate and ethyl p-chlorobenzoate. Specific examples of the chloroacetic ester compounds include methyl monochloroacetate, monochloro-ethyl acetate, methyl dichloroacetate, ethyl dichloroacetate, methyl trichloroacetate and ethyl trichloroacetate. Specific examples of the ether compounds include anisole and diphenyl ether. Specific examples of the ketone compounds include acetophenone and benzophenone. Specific examples of the carbonate compounds include dimethyl carbonate and ethylene carbonate. Specific examples of n compounds include nmethane, nethane, npropane, nbenzene and n- > cyclohexane. Among them, a lower alkyl benzoate, a lower alkyl acetate, a lower alkyl roacetate monoclonal, the anisole, the benzophenone, the ethylene carbonate, the npropane and the nmethane are particularly preferred.

In the present invention, the amount which is used of the compound (VIII) is preferably 0. 1 to 10 moles, still preferably 0.5 to 2.0 moles per 1 mole of Lewis acid.

The base or a basic compound that is used as the co-catalyst in the present invention may be any onas as long as they have a property capable of capturing the acidic compounds and include, for example, the amine compounds, -the strong alkali salts of weak acids such as organic carboxylic acids and phosphoric acid (sodium acetate, disodium acid phosphate and the like), and oxides, hydroxides, carbonates and bicarbonates of metals at alkaline and alkaline earth metals ( calcium oxide, magnesium oxide, sodium hydroxide, sodium carbonate, sodium bicarbonate and the like) .- -amine compounds are preferred from pun. in view of the solubility in raw materials. To be specific, amine compounds include ammonia, amine-aliphatic compounds, alicyclic amine compounds, aromatic amine compounds, and heterocyclic compounds having hydrogen atoms, preferably aliphatic amine compounds or pyridine. These amine compounds include the primary, secondary and tertiary amine compounds. Among them, the amine-tertiary compounds are preferred. In addition, these amine compounds can be either monoamine compounds and polyamine compounds. Among them, monoamine compounds are preferred. In addition, the total number of carbon atoms contained in these amine compounds is preferably 30 or less (including ammonia having zero carbon atoms), more preferably from 3 to 20, and particularly - preferably from 6 to 12. .

Specific examples of these amine compounds include the following onas.

Aliphatic primary amine compounds: methylamine, ethylamine, propylamine, isopropylamine, butylamine, amylamine, hexylamine, heptylamine, octylamine, non-nylamine, decylamine, undecylamine, dodecyl amine, and the like.

The secondary aliphatic amine compounds: dimethylamine, diethylamine, dippropylamine, diisopropylamine, dibutylamine, diamylamine, and the like.

The tertiary aliphatic amine compounds: trimethylamine, triethylamine, tri-propylamine, tributylamine, dipropylethylamine, diethylmethylamine, diethylpropylamine, diisopropylmethylamine, and the like.

The alicyclic amine compounds: Cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, and the like before.

The aromatic amine compounds: Aniline, methylaniline, dimethylaniline, ethylaniline, diethylaniline, toluidine, benzylamine, diphenylamine, naphthylaprine, and the like.

Heterocyclic amine compounds Pyridine and the like.

The polyamine compounds: Ethylenediamine, diethylenetriamine, propylenediamine, dipropylenetriamine, and the like.

In the present invention, the amount - which is used of the base is preferably 0.01 to 1 mol, more preferably 0.01 to 0.4 mol per 1 mol of Lewis acid.

In the present invention, the reaction yield can be increased from 10 to 20 - compared with, for example, the case where only the compound (VIII) is used because it uses the above compound (VIII) in combination with the ba , as the co-catalyst.

In the present invention, only the compound (VIII) described above, only the base, or a combination of the compound (VIII) with the base can be used as the co-catalyst.

In the present invention, when only the compound (VIII) is used, this is not any nitro compound.

The reaction of the present invention can be carried out either without using a solvent or using a solvent. The base hydrocarbon solvents and the chlorine base solvents are preferred as the solvent used in the present invention. Hydrocarbon base solvents - include benzene, toluene, xylene, pentane, hexane, cyclohexane and petroleum ether. Chlorine based solvents include chlorobenzene, dichloromethane and tetrachloroethylene. These solvents can be used either alone or in a mixture of 2 or more types thereof, preferably they are used in an amount of 50% by weight or more, particularly preferably 100% by weight or more based on the weight of the composed of -aldehyde.

In the present invention, the optimal reaction temperature depends on the reactivity of the aldehyde compound with the di-ene compound, the types of catalyst and co-catalyst used, the amounts thereof and the presence and the property of the solvent. In general, this is -30 to 100 ° C, particularly convenient from -20 to 70 ° C.

In the present reaction, when using only a compound (VIII) or a combination of a base with a compound (VIII) as a co-catalator, especially a method for mixing the aldehyde compound, the compound will not be restricted. of diene, the catalyst and the co-catalyst, and a conventional method which can be used advantageously is a method in which a mixture of the aldehyde compound, the di-ene compound and the solvent are added dropwise to the a mixture of the catalyst, the co-catalyst and the soya while maintaining the desired temperatures. The reaction is preferably carried out in the absence of water and oxygen.

In the present reaction, when only one base is used as a co-catalyst, especially a method for mixing the aldehyde compound, the diene compound, the catalyst and the cocatalyst will not be restricted, and a method can be used. conventional method which is a method in which a mixture of the catalyst and the co-catlizer is added dropwise to a mixture of the aldehyde compound, the diene compound and the solvent while maintaining the desired temperatures under strong stirring. The reaction is preferably carried out in the absence of water - and oxygen.

The present invention will be explained below in more detail with reference to the examples, but the present invention will not be restricted to these examples.

Example 1 Preparation of 6-phenyl-4-methyl-5,6-dihydro-2H-pyran represented by the following formula (IV): were fed into a 30 ml glass pressure vessel replaced with 4.66 g (44.0 mmoles) of benzaldehyde, 3.00 g (44.1 mmoles) of isoprene and 5 ml of dry toluene, and then a mixture of 0.90 was added dropwise. g (6.3 mmoles) of BFg-0 (C2H5) 2, 0.18 g (1.4 mmoles) of N, N-diisopropylethylamine and 5 ml of non-dried tolue in 30 minutes while vigorously stirring at about 0 ° C. After stirring the mixture for 8.5 hours, it is cooled and then poured into ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium acid carbonate and then with a saturated saline solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby obtaining 5.99 g (yield: 78%) of the desired dihydropyran compound.

Example 2 Preparation of 6-phenyl-4-methyl-, -dihydro-2H-pyran -represented by the formula (IV) described above: were fed into a 30 ml glass pressure vessel replaced with 4.66 -g (44.0 mmoles) of benzaldehyde, 3.00 g (44.1 mmoles) of isoprene and 5 ml of dry toluene, and then a mixture of 0.94 was added dropwise. g (6.6 'immoles) of BFg-0 (C2H5) 2, 0.11 g (1.3 mmoles) of sodium acetate and 5 ml of dry toluene in 30 minutes while vigorously stirring at about 0 ° C. After stirring the mixture for 4.5 hours, cool it and then see it in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium acid carbonate and then with a saturated saline solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby obtaining 4.62 g (yield: 60%) of the desired dihydropyran compound.

Example Preparation of the 6-pheny1-4-methy1-5,6-dihydro-2H-pyran represented by the formula (IV) described above: ml 4.66 g (44.0 mmoles) of benzaldehyde, 3.00 g (44.1 mmoles) of isoprene and 5-ml of dry toluene replaced with nitrogen were fed into a glass vessel and then a 0.94 g mixture was added dropwise. (6.6 mmoles) of RF3 '(C2H5) 2, 0.10 g (1.3 mmoles) of pyridine and 5 ml of dry toluene in 30 minutes while vigorously stirring at about 0 ° C. After stirring the mixture for 8 hours, it is cooled and then it is seen in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium acid carbonate and then with a saturated saline solution. the solvents were distilled, and the residue was distilled under reduced pressure, thereby 5.36 g (yield: 70%) of the desired dihydropyran compound was obtained.

Example 4 Preparation of the 6-frenyl-4-methyl-5,6-dihydro-2H-picrane represented by the formula (IV) described above: 4.66 g (44.0-mmol) of benzaldehyde were fed into a glass pressure vessel replaced with nitrogen. 3.00 g (44.1 mmoles) of -isoprene and 5 ml of dry toluene, and then a mixture of 0.36 g (2.2 mmoles) of A1C13, 0.057 g (0.44 mmoles) of N, N-diisopropylethylamine and 5 ml are added dropwise. of dry toluene in 30 minutes while vigorously stirring at about 0 ° C. After stirring the mixture for 15 hours, cool it and then see it in water and ice. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed - with an aqueous solution of acid carbonate of sodium and then with a saturated saline solution. The solvents were distilled, and the residue was distilled -under reduced pressure, therefore 5.36 g was obtained. (yield: 70%) of the dried dihydropyran compound.

Example Preparation of 6-phenyl-2,4-dimemethyl-5,6-dihydro-2H-pyra not represented by the following formula (V): they were fed to a glass vessel at the pressure of 30 ml replaced, with nitrogen 4.66 -g (44.0 mmoles) of benzaldehyde, 3.57 g (44.1 min) - of 2-methyl-l, 3-pentadiene and 5 ml of toluene dry, and then a mixture of 0.90 g (6.3 mmoles) of BF3 * 0 (C2H5) 2, 0.18 g (1.4 mmoles) of N, N-diisopropylethylamine and 5 ml of non-dry tolue in 30 minutes is added while vigorously stir at about 0 ° C. After stirring the mixture for 12 hours, it is ampriated and then seen in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby 5.96 g (yield: 72%) of the desired dihydropyran compound was obtained.

Example 6 Preparation of 6-p-tolyl-4-methyl-5,6-dihydro-2H-pyran represented by the following formula (VI): were fed into a 30 ml glass pressure vessel replaced with nitrogen 5.28 g (44.0 mmoles) of p-tolualdehyde, 3.00 g (44.1 mmoles) of isoprene and 5 ml of dry toluene, and then a mixture of 0.90 g (6.3 mmoles) of BF3 • 0 (C2H, -) 2, 0.18 g (1.4 mmoles) of N, N-diisopropylethylamine and 5 ml of dry toluene in 30 minutes while stirring vigorously at about 0 ° C. After stirring the mixture for 15 hours, cool it and then see it in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous sodium carbonate acid solution and then with a saturated saline solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby 6.20 g (yield: 75%) of the desired dihydropyran compound was obtained.

Example 7 Preparation of 6-n-butyl-4-methyl-5,6-dihydro-2H-picrane represented by the following formula (VII): were fed into a 30 ml glass pressure vessel replaced with nitrogen 3.39 g (44.0 mmol) of valeraldehyde, 3.00 g (44.1 mmol) of isoprene and 5 ml of dry toluene, and then a mixture of 0.90 g was added dropwise. (6.3 mmoles) of BF3 «0 (C2H5) 2, 0.18 g (1.4 mmoles) of N, N-dipropyllethalamine and 5 ml of dry toluene in 30 minutes while stirring vigorously at -about 0 ° C. After stirring the mixture - for 15 hours, it is cooled and then it is seen in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer which is collected is washed with an aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby obtaining 4.66 g (yield: 73%) of the desired dihydropyran compound.

Example 8 Preparation of 6-phenyl-4-methyl-5, -dihydro-2H-pyran - represented by the formula (IV) described above - 2ndly: it is fed into a 4-neck 200 ml flask equipped with a condenser, a thermometer and a stirrer 3.20 g (24 mmol) of aluminum chloride and, this container is replaced with nitrogen. In addition, 40 ml of toluene and -3.27 g (24 mmoles) of methyl benzoate are added at room temperature. This mixture is cooled to 0 ° C, and a mixed solution of 12.70 g (120 mmol) of benzaldehyde, 1Q.00 g (280 mmol) of isoprene and 50 ml of toluene is added dropwise in-one hour while maintaining the temperatures from 0 to 5 ° C. After the addition is complete, the mixture is stirred for 10 minutes. Then, it gets cold and you see yourself in ice and water. The layers are separated, and the aqueous layer is washed with a few drops of toluene. The organic layer that is collected is washed with an aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The solvent is distilled, and the residue is distilled under reduced pressure, thereby obtaining 15. Q g ( production: 76%) of the dried dihydropyran compound.

Example- 9 Preparation of 6-phenyl-4-methyl-, 6-dihydro-2H-pyran - represented by the following formula (IV) described above: feed into a 200-ml 4-neck flask equipped with a condenser, a thermometer, and a stirrer 3.20 g (24 mmol) of aluminum chloride and then this vessel is replaced with nitrogen. 40 ml of toluene and 3.27 g (24 mmoles) of methyl benzoate were further added at room temperature. This mixture is cooled to 0 ° C, and a mixed solution of 12.70 g (120 mmol) of benzaldehyde, 10.7 g (156 mmol) of isoprene and 50 ml of toluene is added in one hour while maintaining the temperatures of the mixture. 0 to 5 ° C. After the addition is complete, the mixture is stirred for 10 minutes. Then, cool down and see yourself in ice and water. The layers were separated, and the aqueous layer washed with a few toluene amounts. The organic layer that is washed is washed with an aqueous solution of carbon to sodium acid and then with a saturated saline solution. The solvent is distilled, and the residue is distilled under reduced pressure, thereby obtaining 14.4 g (yield: 70%) of the desired dihydropyran compound.

Examples 10 to 14 The 6-phenyl-4-methyl-5,6-dihydro-2H-pyran represented by the formula (IV) described above was obtained at the productions shown in -Table 1 respectively in the same manner as in example 8, except that the catalyst was changed as shown in Table 1.

Table 1 co-catalyst production (%) Example 10 Methyl monochloroacetate 79 Example 11 anisole 88 Example 12 Methyl acetate 60 Example 13 Benzophenone 65 Example 14 Ethylene carbonate 68 Example 15 Preparation of 6-phenyl-2,4-dimethyl-1-5,6-dihydro-2H-pyra not represented by formula (V) described above: The reaction is carried out in the same manner as in Example 8, except that 23 g (280 mmol) of 2-methyl-1,3-pentadiene are sub-divided by isoprene, thereby obtaining 16.1 g (yield: 72%) of the desired dihydropyran.

Example 16 Preparation of 6-p-totl1-4-methyl-1-5,6-dihydro-2H-pyran represented by formula (VI) described above: The reaction is carried out in the same manner as in Example 8, except that 14.4 g - (120 mmoles) of p-tolualdehyde were replaced by benzaldehyde, hence 16.8 g (yield: 75%) of the desired dihydropyran was obtained.

Example 17 Preparation of 6-n-butyl-4-methyl-5,6-dihydro-2H-picine represented by the formula (VII) described above: The reaction is carried out in the same manner as in Example 8, except 10.3 g (120 mmol) of valeraldehyde are replaced by benzaldehyde, thereby obtaining 13.5 g (yield: 73%) of the desired dihydropyran.

Example 18 Preparation of the 6-pheny1-4-methy1-5,6-dihydro-2H-pyran represented by the formula (IV) described above: were fed into a 2Q0 ml 4-necked flask equipped with a condenser, a thermometer and a - stirrer 6.40 g (48 mmoles) of aluminum chloride and then this vessel is replaced with nitrogen. 80 ml of toluene and 3.27 g (24 mmoles) of methyl-benzoate were further added at room temperature. This mixture is cooled to 0 ° C, and 0.76 g (9.6 mmol) of pyridine are added. Then, it is added. drip a mixed solution of 6.35 g (60 mmoles) of benzaldehyde, 5.35 g (79 mmoles) of isoprene and 25 ml of toluene in 3 hours while maintaining the temperatures from 0 to 5 ° C. After the addition is complete, the mixture is further stirred for 10 minutes. Then, to see yourself in ice and water until the reaction stops, and the organic layer is recovered. The aqueous layer was extracted with toluene, and the organic layer that is collected is washed with an aqueous sodium hydrogen carbonate solution and then with a saturated saline solution. The solvent is distilled, and the residue is distilled under reduced pressure, thereby obtaining 8.77 g (yield: 84%) of the undesired dihydripira.

Example 19 Preparation of 6-phenyl-4-methyl-5, 6-dihydro-2H-pyran -represented by the formula (IV) described above: it is fed into a 4-neck flask -of 200 ml equipped with a condenser, a thermometer and a stirrer 3.20 g (24 mmol) of chloride of aluminum and then this container is replaced - with nitrogen. 40 ml of toluene and 2.14 g (24 mmoles) of 2-nitropropane were also added at room temperature. This mixture is cooled to 0 ° C, and a mixed solution of 7.11 g (67 mmol) of benzaldehyde, 10.7 g (156 mmoles) of isoprene and 50 ml of toluene is added in 1.5 hours while maintaining the temperatures from 0 ° C to 5 ° C. After the addition is complete, the mixture is also stirred for 10 minutes. Then, see yourself in ice and water until the reaction stops, and the organic layer is recovered. The organic layer was extracted with toluene, and the organic layer which is collected is washed with an aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The solvent is distilled, and the residue is distilled under reduced pressure, thereby obtaining 9.21 g (yield: 79%) of the dried dihydropyran.

Example 20 Preparation of 6-phenyl-4-methyl-5,6-dihydro-2H-pyran -represented by the formula (IV) described above: it is fed into a 4-neck flask of 200 ml equipped with a condenser, a terpometro and an agitator 6.40 g (48 mmol) of aluminum chloride and then this vessel is replaced - with nitrogen. 80 ml of toluene and 3.27 g (24 mmoles) of methyl benzoate were further added at room temperature. This mixture is cooled to 0 ° C, and then a mixed solution of 6.35 g (60 mmol) of benzaldehyde, 5.35 g (79 mmol) of ioprene and 25 ml of toluene is added in 3 hours while maintaining the Tempura ratios from 0 to 5 ° C. After the addition is complete, the mixture is also stirred for 10 minutes. Then, '- see yourself in ice and water until the reaction stops, and the organic layer recovers. The organic layer was extracted with toluene, and the organic layer that is collected is washed with an aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The solvent is distilled, and the residue is distilled under reduced pressure, thereby 6.79 g (yield: 65%) of the unwanted dihydropyra was obtained.

Comparative Example 1 Preparation of 6-phenyl-4-methyl-5,6-dihydro-2H-pyran represented by the formula (IV) described above: were fed into a 200 ml 4-necked flask equipped with a condenser, a thermoset and a stirrer 6.4 g (47 mmol) of aluminum chloride and 60 g of toluene. This mixture is cooled to about 5 ° C, and 3.8 g (36 mmol) of benzaldehyde are added in 5 minutes. Then, a mixture of 8.9 g (84 mmoles) of benzaldehyde, 17.6 g (260 mmoles) -of isoprene and 25 ml of toluene in 30 minutes is added dropwise after it is stirred well at 5 ° C. Also after stirring the mixture for 10 minutes at 15 ° C, it is cooled and then it is seen in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium acid carbonate and then with a saturated dalina solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby obtaining 10.1 g (yield: 48%) of the desired dihydropyran, Comparative Example 2 Preparation of the 6-pheny1-4-methy1-5,6-dihydro-2H-picine represented by the formula (IV) described above: were fed into a 100-ml 4-neck flask equipped with a condenser, a thermometer and a stirrer 4.74 g (44.6 mmoles) of benzal ^ dehyde, 1.53 g (22.3 mmoles) of isoprene and 10 ml of dry toluene. Then, 0.32 g (2.23 mmoles) of F3 * 0 (C2H5) 2 were added, and the stirring is continued at room temperature. Also after shaking the mixture for 8 hours, it is cooled and then it is seen in ice and water. The organic layer is separated, and the aqueous layer is washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The solvents were distilled, and the residue was distilled under reduced pressure, thereby obtaining 1.99 g (yield: 51%) of the desired dihydropyran compound.

Comparative Example 3 Preparation of 6-phenyl-4-methyl-5,6-dydro-2H-pyran represented by the formula (IV) described above: were fed into a 200-ml 4-neck flask equipped with a condenser, a thermometer and an agitator 5.3 g (40 mmol) of aluminum chloride and 40 ml of n-hexane. This mixture is cooled to about -5 ° C, and then 3.56 g (40 mmol) of 2-nitropropane are added at this temperature in 10 minutes. Then, a mixture of 10.6 g (100 mmol) of -benzaldehyde, 14.9 g (220 mmol) of ioprene and -30 mL of n-hexane is added dropwise in 30 minutes while being perfectly stirred at -5 ° C. In addition, stir the mixture for 10 minutes at -5 ° C and then pour into ice and water. The layers were separated, and the aqueous layer washed with hexane. The organic layer that is collected is washed with an aqueous solution of sodium acid carbonate and then with a saturated saline solution. The solvent is distilled, and the residue is distilled under reduced pressure, through which 9.38 g (production: 54%) of the desired dichloride was obtained.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. having described the invention as above, the content of the following is claimed as property.

Claims (11)

1. A process for the preparation of a dihydropyran compound (III) having the formula (III): characterized in that R represents a hydrogen atom, an alkyl group or an alkenyl group having from 1 to 12 carbon atoms, a cycloalkyl group which can be substituted with the alkyl group, having from 3 to 12 total carbon atoms or an aryl group which can be substituted with the alkyl group or the alkoxy group, having from 6 to 12 carbon atoms; R -2 'and R3 may be the same or different and each represents a hydrogen atom or an alkyl group or an alkenyl group having from 1 to 6 carbon atoms, which comprises the reaction step of a compound of aldehyde - (I) having the formula (I): R1-CHO (I) wherein R is defined above, with a diene compound (II) having the formula (II): CH2 = C-CH = CH-R- (ID wherein R 2 and R 3 ~ are defined above, in the presence of a Lewis acid and at least one co-catalyst selected from the group consisting of a base and a compound (VIII) having a coordination power weak for the Lewistic acid that the aldehyde compound (I) and having an activity for dissolving the Lewis acid, coordinated by the compound (VIII), in a given solvent - that when the compound (VIII) is used only, - this is not any nitro compound.

2. The process according to claim 1, characterized in that the co-catalyst is a base.

3. The process according to claim 1, characterized in that the co-catalyst is a compound (VIII)

4. The process according to claim 3, characterized in that the co-catalyst is a compound (VIII) selected from the group, which is composed of an aromatic or aliphatic ester compound, a chloroacetic ester compound, a compound of ether, a ketone compound and a carbonate compound.

5. The process according to claim 1, characterized in that the co-catalyst is a combination of a base with a compound (VIII).

6. The process according to claim 1, characterized in that the Lewis acid is selected from the group consisting of the aluminum chloride, the tin tetrachloride, the iron trifluoride, the titanium trichloride, the titanium tetrachloride and boron trifluoride.

7. The process according to claim 2, characterized in that the base is used in an amount of 0.01 to 1 mole per 1 mole of Lewistic acid

8. The process according to claim 3, characterized in that the compound (VIII) is used in an amount of 0.1 to 10 moles - per 1 mole of the Lewis acid.

9. The process according to claim 5, characterized in that the base is used in an amount of 0.01 to 1 mole per 1 mole of Lewis acid and the compound (VIII) is used in an amount of 0.1 to 10 mole per 1 mole of Lewis acid.

10. The process according to claim 1, characterized in that the co-catalyst is a combination of a base with a nitro compound such as the compound (VIII).

11. The process according to claim 1, characterized in that the Lewis acid - is the boron trifluoride and the co-catalyst is an amine compound as the base. 12 The process according to claim 1, characterized in that the Lewis acid is aluminum chloride and the co-catalyst is methyl benzoate as the compound (VIII). SUMMARY A simple process is provided to economically prepare a dihydropyran compound at high productivity and high reaction production. A compound selected from the group consisting of a base and a compound (VIII) - having a weak coordinating power for the Lewistic acid is used as the aldehyde compound and having an activity for dissolving the Lewis acid, coordinated by the compound (VIII), in a solvent as a co-catalyst in the reaction of the aldehyde with a diene compound in the presence of a Lewis acid to prepare a 5,6-dihydro-2H-picine compound represented by the formula (III): wherein R represents a hydrogen atom, an alkyl group having from 1 to 12 carbon atoms, an aryl group which can be substituted by the alkyl group, having from 6 to 2 3 12 atoms. of total carbon; R and R represents a hydrogen atom or an alkyl group having from 1 to 6 carbon atoms.