JPH10168006A - Method for producing phyton and isophytol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially and advantageously produce the subject compound useful as a synthetic raw material for biologically active substances such as vitamin E by efficiently and simply producing 6-methyl-2-heptanone from isovaleral and acetone and using the compound as a raw material. SOLUTION: Isovaleral is subjected to cross aldol condensation with acetone while continuously each adding isovaleral and an aqueous alkali solution to acetone to form 6-methyl-3-hepten-2-one and the compound is hydrogenated to form 6-methyl-2-heptanone and 6-methyl-2-heptanone is used as a raw material to finally form 6,10,14-trimethyl-5,9-pentadecadien-2-one, which is then hydrogenated to provide the objective phytone and the phytone is further reacted with a Grignard reagent to vinylate or ethynylate the phytone and the treated phytone is partially hydrogenated to provide the objective isophytol.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing 6-methyl-2-heptanone efficiently and industrially easily from isovaleral and acetone, which are industrially produced and available at low cost, and using the same as a raw material. The present invention relates to a method for industrially advantageously producing phyton and isophytol.

[0002]

2. Description of the Related Art It is known that phyton and isophytol, which are useful as raw materials for synthesizing a physiologically active substance such as vitamin E, can be produced by various routes, but from the viewpoint of industrial implementation, the following formula (I) )

[0003]

Embedded image A ketone containing 8 carbon atoms represented by the formula (dotted lines indicate that one or two double bonds are present or absent so as to satisfy the carbon valency at the positions indicated by the Has been evaluated (hereinafter the ketone represented by the formula (I) is referred to as C8 terpene ketone).

[0004] The following scheme outlines the total synthesis process of phyton and isophytol when 6-methyl-5-hepten-2-one is used as the C8 terpene ketone.

[0005]

Embedded image Thus, in the process of producing phyton or isophytol from C8 terpene ketone, the carbonyl group of C8 terpene ketone is used to repeatedly extend 5 carbons corresponding to the isoprene unit, and then to form a double bond in the molecule. Hydrogenation is the basic flow, and the basic flow is the same regardless of the presence or absence of the unsaturated bond in the starting C8 terpene ketone and the position thereof. Thus, in the process for producing phyton or isophytol from C8 terpene ketone, how to produce the intermediate C8 terpene ketone easily and inexpensively determines the superiority of the process. It is one of the important factors.

In this connection, for example, the following method is known as a method for forming a skeleton of C8 terpene ketone in a conventional method for producing phyton and isophytol.

[0007] Using acetone as a starting material, an ethynylation reaction with acetylene is carried out in the presence of an alkali catalyst to give 3-methyl-1-butyn-3-ol, which is partially hydrogenated with a Lindlar catalyst. After acetoacetic esterification with diketene, the resulting ester is further subjected to Carroll rearrangement to produce 6-methyl-5-hepten-2-one (for example, J. Org. Chem.,
23, 153 (1958); Zh. Obsch. Chi
m. , 28, 1444 (1958)).

The method comprises reacting isobutene, acetone and formalin at high temperature and high pressure to give 6-methyl-
A method for producing 6-hepten-2-one (see, for example, German Patent Nos. 1,259,876, 1,268,135 and 16,180,98).

Method Prenyl chloride obtained from the reaction of isoprene with hydrogen chloride is reacted with acetone in the presence of an equimolar amount of alkali to give 6-methyl-
A method for producing 5-hepten-2-one (see, for example, U.S. Pat. Nos. 3,983,175 and 3,984,475).

A method for producing 6-methyl-2-heptanone by condensing isoamyl halide and acetoacetate under alkaline conditions, followed by hydrolysis and decarboxylation (for example, "SYNT by WAGNER")
HETIC ORGANIC CHEMISTRY ", 3
27 pages, JOHN WILEY & SONS, IN
C. reference).

Method 6-Methyl-2-heptanone is obtained by reacting isovaleral with acetone in a hydrogen stream using a catalyst in which a rare earth metal oxide and a group VIII metal are supported on a carrier such as γ-alumina. (See JP-B-61-41612).

However, these methods of forming a skeleton of C8 terpene ketone have the following problems.

For example, in the case of the method, there is a problem that the reaction steps are longer than those of other methods, and the production cost is high. In the case of the method, there is a problem that a special production facility is required to cause the reaction under high temperature and high pressure conditions. In the case of the method, there is a problem that a large amount of salt is generated because the alkali is used in an equimolar amount with respect to prenyl chloride, and the treatment requires a great deal of labor. Also in the case of the method, since an equimolar amount of the base is required with respect to the acetoacetate, there is a problem that a large amount of labor is required for treating a large amount of the generated salt and the production cost is increased. And in the case of the method, as in the case of the method, high temperature,
There is a problem that special production equipment is required to carry out the reaction under high pressure conditions.

[0014]

Therefore, the present inventors have proposed a compound other than C8 terpene ketone obtained by the above-mentioned method (1) and which can be used as a raw material for synthesizing phyton and isophytol. -Heptene-
We focused on 2-one. Since this compound has an unsaturated bond at the α, β-position with respect to the carbonyl group, it is difficult to extend the 5-carbon corresponding to the isoprene unit at a high selectivity. By doing
It can be converted to 6-methyl-2-heptanone, a kind of C8 terpene ketone, which is a raw material for producing phyton and isophytol.

As a method for producing 6-methyl-3-hepten-2-one, for example, a method based on a crossed aldol reaction between isovaleral and acetone is known. For example, the Chemical Society of Japan, vol. 59, p. 224 (1938) discloses an example in which isovaleral and acetone are reacted in equimolar amounts. Also, Bull. Soc. Chi
m. Fr. , P. 112 (1957) describes an example in which 4 mol of acetone is used per 1 mol of isovaleral.

In addition to these, a method of reacting isovaleral and acetone at a high temperature (300 ° C.) and a high pressure (270 atm) without using a catalyst (Japanese Patent Publication No. 47-62)
No. 81) and a method in which isovaleral and acetone are reacted in the presence of zinc oxide under conditions of high temperature (180 ° C.) and high pressure (35 atm) (US Pat. No. 4,0051,147).

However, The Chemical Society of Japan, 59, 2
In the case of the method shown on page 24 (1938), there is a problem that the yield of the target compound, 6-methyl-3-hepten-2-one, is only 35 to 40%.

Further, Bull. Soc. Chim. F
r. , P. 112 (1957), there is a problem that the use of an excess amount of acetone is industrially disadvantageous in terms of acetone recovery and volumetric efficiency of the reaction. Moreover, the compound mainly obtained under these conditions is 6
-Methyl-4-hydroxyheptan-2-one,
A further dehydration reaction is required to convert to 6-methyl-3-hepten-2-one. There is also a problem that the yield of 6-methyl-3-hepten-2-one thus obtained is as low as 51% based on isovaleral.

In the methods described in Japanese Patent Publication No. 47-6281 and US Pat. No. 4,0051,147, the reaction conditions are high temperature and high pressure. There is a problem that it is necessary.

Thus, 6-methyl-3-heptene-
Many methods for producing 2-one are known, but there are problems to be solved in terms of raw material prices, production equipment, and the like.

The present invention is intended to solve the above-mentioned problems of the prior art, and is efficient and industrially simple.
An object of the present invention is to provide a method for producing phyton and isophytol including a step for producing -methyl-2-heptanone.

[0022]

Means for Solving the Problems The present inventor has found that when aldol condensation of isovaleral and acetone in the presence of an aqueous alkali solution to form 6-methyl-3-hepten-2-one is carried out, isovaleral and acetone are mixed in acetone. 6-Methyl-3-hepten-2-one can be formed efficiently and industrially easily by reacting while continuously adding an aqueous alkali solution, respectively, and further obtained in this manner. By hydrogenating 6-methyl-3-hepten-2-one, 6-ethyl-2-heptanone, a kind of C8 terpene ketone, which is a raw material for producing phyton or isophytol, can be industrially advantageously produced. As a result, the present invention has been completed.

That is, the present invention comprises the following steps: Step a) While continuously adding isovaleral and an aqueous alkali solution to acetone, cross-aldol condensation of isovaleral and acetone is carried out to form 6-methyl-3.
Step of forming hepten-2-one; Step b , 6-methyl-3-heptene obtained in Step a.
Hydrogenation of 2-one to form 6-methyl-2-heptanone; step c, by reacting 6-methyl-2-heptanone obtained in step b with a vinyl Grignard reagent to vinylate; or steps to form a 3,7-dimethyl-1-octen-3-ol by adding partial hydrogenation after ethynylation the 6-methyl-2-heptanone; obtained in step d step c 3,7 By reacting diketene or acetoacetate with the hydroxyl group of dimethyl-1-octen-3-ol to give acetoacetate of 3,7-dimethyl-1-octen-3-ol, the resulting ester is subjected to Carroll rearrangement. Or the 3,7
-Dimethyl-1-octen-3-ol is reacted with isopropenyl ether to give 3,7-dimethyl-
Step of forming 6,10-dimethyl-5-undecene-2-one by converting the resulting ether into Claisen rearrangement as isopropenyl ether of 1-octen-3-ol; Step e, Step 6 , 10-Dimethyl-5-undecene-2-one is reacted with a vinyl Grignard reagent for vinylation, or is partially hydrogenated after ethynylation of the 6,10-dimethyl-5-undecene-2-one. 3,7,11-trimethyl-
Forming 1,6-dodecadien-3-ol; step f , 3,7,11-trimethyl- obtained in step e.
The hydroxyl group of 1,6-dodecadien-3-ol is reacted with diketene or acetoacetate to give 3,7,11
The acetoacetic ester of trimethyl-1,6-dodecadien-3-ol and Carol rearrangement of the resulting ester, or the hydroxyl group of the 3,7,11-trimethyl-1,6-dodecadien-3-ol Was reacted with isopropenyl ether to give isopropenyl ether of 3,7,11-trimethyl-1,6-dodecadien-3-ol, and the resulting ether was Claisen rearranged to give 6,10,14-trimethyl-5. , 9-
Forming pentadecadien-2-one; and hydrogenation of 6,10,14-trimethyl-5,9-pentadecadien-2-one obtained in step g, step f, to form phyton (6,10 , 14-Trimethylpentadecane-
(2) forming a phyton.

In the present invention, following the above-mentioned step g, step h is carried out by reacting a phyton obtained by the above-mentioned method for producing phyton of the present invention with a vinyl Grignard reagent, or by ethynylating the phyton. Isophytol (3,7,11,
15-tetramethyl-1-hexadecene-2-one).

[0025]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

The process for producing phyton and isophytol according to the present invention comprises, in particular, a step a in which a cross aldol reaction of isovaleral and acetone is carried out, and
By hydrogenating -methyl-3-hepten-2-one, 6-methyl-, a kind of C8 terpene ketone, is obtained.
B) forming 2-heptanone.

In general, the condensation of carbonyl compounds such as aldehydes and ketones in the presence of a basic catalyst to form aldol or ketol has long been known as the aldol reaction. For example, isovaleral or acetone readily undergoes self-aldol condensation in the presence of a basic catalyst to convert to the corresponding aldol or ketol, respectively, and then, by intramolecular dehydration, yields α, β-unsaturated carbonyl as an aldol condensation product. To provide the compound (eg, “ORGANIC REACTIONS Vol.
16 ", pages 88 and 112, JOHN WILEY
& Sons, Inc. reference). Such α, β-unsaturated carbonyl compounds are liable to be changed into higher-order condensates by the aldol reaction.

The aldol reaction between two different carbonyl compounds is known as a crossed aldol reaction. In the crossed aldol reaction, a wide variety of reaction products are often generated, and an aldol condensate in which two carbonyl compounds are condensed one-to-one (hereinafter sometimes referred to as a one-to-one condensate) is selected. It is generally difficult to obtain a target. Therefore, in the crossed aldol reaction, in order to increase the selectivity of a one-to-one condensate based on one of the two carbonyl compounds, the other carbonyl compound is generally used in excess. However, in the conventional aldol condensation, a basic catalyst is charged into the reaction system from the beginning, and the formation of a self-condensation product of an excessively used carbonyl compound is inevitable. There are problems such as a decrease in the yield of the one-to-one condensate, difficulty in isolating it, and further contamination with impurities.

Therefore, in the step a of the present invention, in performing the cross-aldol reaction between isovaleral and acetone, isovaleral and an aqueous alkali solution are continuously added to acetone. As a result, 6-
Methyl-3-hepten-2-one can be produced, contamination of impurities can be suppressed, and isolation of the target compound becomes easy. The reason that such an effect is obtained is that the reaction is carried out while adding isovaleral in acetone, so that acetone is present in a large excess with respect to isovaleral in the reaction system during most of the reaction in step a. As a result, the selectivity of 6-methyl-3-hepten-2-one based on isovaleral is increased. In addition, by continuously adding an alkaline aqueous solution as a catalyst, the alkali concentration in the reaction system is controlled to a very small amount immediately after the start of the reaction to suppress the self-condensation of acetone, while the addition of isovaleral proceeds. However, the reaction between isovaleral and acetone progresses, and as the concentration of acetone in the reaction system decreases, the alkali concentration increases, so that the reaction can be driven.As a result, selectivity due to runaway of the reaction is reduced. The drop can be prevented.

Further, 6-methyl-3- obtained in step a)
Hepten-2-one is obtained by the hydrogenation reaction in step b.
It can be quantitatively converted to 6-methyl-2-heptanone. Thus, C8 obtained in step a and the subsequent step b
6-Methyl-2-heptanone, which is a kind of terpene ketone, is produced from inexpensive and easily available raw materials under mild production conditions compared to C8 terpene ketone obtained by the above-mentioned conventional method for producing C8 terpene ketone. As a result, phyton and isophytol can be industrially advantageously produced.

The method for producing phyton and isophytol according to the present invention will be described below in the order of steps.

Step a First, in step a of the present invention, isovaleral and acetone are cross-aldol-condensed with acetone while continuously adding isovaleral and an aqueous alkali solution to acetone, respectively, to give 6-methyl-3-heptene-2. Forming ON.

The amount of acetone used is not particularly limited.
In order to enhance the selectivity on the basis of the more expensive isovaleral, preferably 0.5 to 3 to 1 mol of isovaleral is used.
From the viewpoint of further increasing the volumetric efficiency of the reaction, it is more preferably in the range of 0.8 to 2 mol per mol of isovaleral, particularly preferably 0.9 to 2 mol per mol of isovaleral. １．２1.2 mol.

Examples of the alkaline compound for preparing an aqueous alkaline solution by dissolving in water used in step a include alkali metal hydroxides represented by sodium hydroxide and potassium hydroxide; barium hydroxide, calcium hydroxide Alkaline earth metal hydroxides represented by the following formulas; alkali metal carbonates such as potassium carbonate; amine compounds such as 1,5-diazabicyclo [5.4.0] undecene-5 (DBU) and piperidine; However, it is preferable to use an alkali metal hydroxide or an alkaline earth metal hydroxide. These alkaline compounds may be used alone or in combination of two or more.

The concentration of the alkaline compound in the aqueous alkaline solution is usually 1 to 50% by weight, preferably 1 to 5% by weight.

The amount of the alkaline compound to be used is generally 0.001 to 0.2 mol per mol of isovaleral, preferably 0.01 to 0.2 mol per mol of isovaleral, from the viewpoint of reaction rate and production cost. 0.1 mol.

In step a, there is no particular need to use an organic solvent, but an organic solvent may be used as long as it does not adversely affect the cross-aldol condensation reaction. Examples of usable organic solvents include lower aliphatic alcohols such as methanol, ethanol, propanol, isopropanol, n-butanol, s-butanol and t-butanol; tetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl Cyclic or chain ethers such as ether and dibutyl ether; and aliphatic or aromatic hydrocarbons such as hexane, heptane, octane, benzene, toluene and xylene.

Further, the aldol reaction in the step a is carried out by nitrogen,
It is desirable to carry out in an atmosphere of an inert gas such as argon.

In step a, isovaleral and an aqueous alkali solution are separately and continuously added to a reaction vessel equipped with a stirrer generally charged with acetone. The term “continuously added” as used herein means that isovaleral and an aqueous alkali solution are fed, but as long as the spirit of the invention is not impaired, isovaleral and the aqueous alkali solution are divided into several portions. The embodiment of adding is included. The addition of isovaleral and the aqueous alkali solution are usually started at the same time, but if the amount is about 1/6 mol of acetone, there is no great effect on the yield of the target compound. It may be added. On the other hand, if an excessively large amount of the aqueous alkali solution is added prior to isovaleral, the amount of by-products due to the self-aldol condensation of acetone itself increases, and the selectivity of 6-methyl-3-hepten-2-one increases. Although it is reduced, it may be added to acetone prior to isovaleral in an amount of about 1 mol% based on acetone. Also, if isovaleral and an aqueous alkali solution are added after mixing rather than separately, it is not preferable because self-aldol condensation of isovaleral itself occurs and the selectivity to 6-methyl-3-hepten-2-one decreases.

The time required for the addition of isovaleral and the aqueous alkali solution varies depending on the type and concentration of the alkaline compound, but is usually 0.5 to 10 hours.

The reaction temperature in step a is usually from -20 ° C to 1
Although it is in the range of 00 ° C., it is set in the range of 40 ° C. to 80 ° C. in order to make the reaction rate practical and increase the yield of 6-methyl-3-hepten-2-one. Is preferred.

The aldol reaction in step a as described above proceeds simultaneously with the addition of isovaleral and an aqueous alkali solution, and is usually completed within 5 hours after the addition.

After completion of the reaction, the desired compound, 6-methyl-3-, is extracted from the reaction mixture by a conventional method such as distillation or extraction.
Hepten-2-one can be isolated.

Step b Next, in step b, the 6-methyl-3- obtained in step a
Hepten-2-one is hydrogenated to give 6-methyl-2-
Form heptanone.

6 obtained by the aldol reaction of step a
-Methyl-3-hepten-2-one has a carbon-carbon double bond at the α, β-position with respect to the carbonyl group. It is difficult to elongate. Thus, prior to the subsequent step from an industrial point of view, the above carbon-carbon double bond is hydrogenated and converted to 6-methyl-2-heptanone.

The hydrogenation can be carried out by a known method capable of converting a carbon-carbon double bond into a saturated carbon-carbon bond. For example, a common hydrogenation catalyst such as palladium, platinum, Raney nickel, Raney cobalt (preferably 5% Pd
/ C) in the absence of a solvent or in a solvent such as a hydrocarbon, an alcohol, an ether, a ketone, an ester or a carboxylic acid, under a hydrogen pressure of 1 to 100 kg / cm ² , preferably 1 to 20 kg / cm ² , At a reaction temperature of 15 to 150 ° C, preferably 30 to 130 ° C, 6-methyl-3-heptene-
The 2-one can be hydrogenated. The reaction time can be appropriately set depending on the catalyst used, the hydrogen pressure, and the like.

After completion of the reaction, the target compound, 6-methyl-2-heptanone, can be isolated from the reaction mixture by a conventional method, for example, distillation.

Step c In this step c, the 6-methyl-2 obtained in step b
- from heptanone, by adding a vinyl group (-CH ₂ = CH ₂₎ to form a 3,7-dimethyl-1-octen-3-ol the carbon chain is extended to the carbonyl group of the terminal. As a formation method, a method of reacting 6-methyl-2-heptanone with a vinyl Grignard reagent, or 6
Ethynylation of -methyl-2-heptanone followed by partial hydrogenation is selected. For industrial implementation, a method of partial hydrogenation after ethynylation is more advantageous.

In the former method of reacting 6-methyl-2-heptanone with a vinyl Grignard reagent, for example,
In a solvent such as tetrahydrofuran or diethyl ether, vinyl chloride such as vinyl chloride or vinyl bromide is reacted with metal magnesium, and vinylmagnesium halide obtained by reacting 0.5 to 6-methyl-2-heptanone with respect to 1 mol thereof is used. 2 mol, usually at a temperature of -10 to 55 ° C,
Preferably, the reaction is carried out at a temperature of 0 to 40 ° C., followed by hydrolysis with a dilute sulfuric acid aqueous solution, a saturated ammonium chloride aqueous solution, or the like, to give the target compound 3,7-dimethyl-1-
Octen-3-ol can be obtained.

In the latter method of partial hydrogenation after ethynylation, first, 6-methyl-2-heptanone is ethynylated by a conventional method to obtain 3,7-heptanone having 10 carbon atoms and having a triple bond at a terminal. Dimethyl-1-octyne-3-
Manufacture oars. Here, the ethynylation can be carried out by a method known per se as a method for producing a compound having a propargyl alcohol structure by ethynylation of a ketone (US Pat. Nos. 3,082,260 and 3,496,240; Kaisho 50-5930
No. 8, etc.). When the ethynylation reaction is carried out on a small scale, a method using an acetylide of an alkali metal such as lithium, sodium or potassium or an alkaline earth metal such as calcium (see Org. Synth., 3 , 416 (1955))
Or a method using an ethynyl Grignard reagent (Org. Synt
h., 4 , 792 (1963)). When performing the ethynylation reaction on an industrial scale,
As described below, a method of directly ethinylating with acetylene in the presence of a strong basic catalyst is suitable in that a propargyl-type alcohol having a triple bond at a terminal can be produced at low cost and the post-treatment is easy. ing. This method is carried out under the conditions in which a strongly basic compound of an alkali metal such as sodium or potassium (eg, a hydroxide of an alkali metal, an alkali metal alcoholate, an alkali metal amide, etc.) is present in a pressure vessel under a catalytic amount. N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, tetrahydrofuran, dimethyl ether, diethyl ether, methyl ethyl ether, anisole, an organic solvent that does not inhibit the reaction of dioxane, etc. 2-Heptanone and 1 mol of acetylene are usually used for 1 mol thereof.
The reaction was carried out at −30 to 30 ° C. for 1 to 20 hours, and then acetylene was discharged out of the pressure-resistant container.
This is a method for obtaining 7-dimethyl-1-octin-3-ol.

Next, the 3,7-dimethyl-
1-Octin-3-ol was partially hydrogenated to 3,7
-Convert to dimethyl-1-octen-3-ol. The purpose of this partial hydrogenation is to selectively reduce a carbon-carbon triple bond to a carbon-carbon double bond, and the method itself is known. As a method for selectively reducing a carbon-carbon triple bond to a carbon-carbon double bond, for example, a method using a hydrogenating agent such as lithium aluminum hydride (see J. Chem. Soc., 1854 (1954)) , N-hexane, n-heptane, octane, benzene, toluene, xylene, methanol, ethanol, propanol and the like using a hydrogenation catalyst in a solvent such as alcohol and a solvent to catalytically reduce a propargyl alcohol (Org. Synth., 5 , 880 (1973)).

The latter method is industrially preferable, and the hydrogenation is carried out, for example, at a temperature of 0 to 130 ° C., preferably 20 to 130 ° C.
80 ° C., normal pressure to 50 kg / cm ² , preferably 2 to 20
It can be performed in a hydrogen atmosphere at a pressure of kg / cm ² . As the hydrogenation catalyst, metals such as nickel, cobalt, palladium, platinum, rhodium, and iridium or compounds thereof can be used. They are,
It may be used by being supported on a carrier such as activated carbon, barium sulfate, and calcium carbonate. Above all, in the present invention, a Lindlar catalyst in which palladium is supported on calcium carbonate can be particularly preferably used.

After completion of the reaction, the desired compound can be isolated from the reaction mixture by a conventional method, for example, distillation.

Step d In this step d, 3,7-dimethyl-1-octen-3-ol obtained in step c is chain-lengthened by 3 carbon atoms by utilizing the terminal allylic alcohol portion. Form extended 6,10-dimethyl-5-undecene-2-one. As a forming method, 3,7-dimethyl-1
A method of reacting a hydroxyl group of -octen-3-ol with diketene or acetoacetate to form an acetoacetate of 3,7-dimethyl-1-octen-3-ol, and subjecting the obtained ester to Carol rearrangement, and 3, A method for reacting the hydroxyl group of 7-dimethyl-1-octen-3-ol with isopropenyl ether to give isopropenyl ether of 3,7-dimethyl-1-octen-3-ol, and subjecting the resulting ether to Claisen rearrangement. Choose one method.

In the former method involving Carol rearrangement, diketene is usually added in an amount of 0.8 to 2 mol, preferably 0.9 to 1 mol, per 1 mol of 3,7-dimethyl-1-octen-3-ol. React to form the acetoacetic ester of 3,7-dimethyl-1-octen-3-ol. In this case, formation of the acetoacetate ester is performed by simply contacting 3,7-dimethyl-1-octen-3-ol with diketene in a solvent-free or organic solvent that does not hinder the reaction of hydrocarbons or ethers. 50 to 100 ° C. if necessary.
May be heated. Further, when amines such as triethylamine and pyridine are present in a catalytic amount in the reaction system, the esterification reaction rate is increased, and the yield of the desired acetoacetic ester of 3,7-dimethyl-1-octen-3-ol is increased. Is improved.

Next, the obtained acetoacetic ester of 3,7-dimethyl-1-octen-3-ol was added to a mixture of usually 13
Carol rearrangement reaction (rearrangement reaction and decarboxylation reaction) proceeds by heating to 0 to 180 ° C, preferably 150 to 180 ° C, thereby obtaining 6,10-dimethyl-5-undecene-2-one. At this time, if an aluminum alkoxide such as aluminum isopropoxide is present in the reaction system in a catalytic amount, the yield of the target 6,10-dimethyl-5-undecene-2-one is improved.

If the reactants necessary for the above two-stage reaction (acetoacetic esterification reaction and Carroll rearrangement reaction) are charged at a time, the reaction temperature is controlled to adjust 3,7-dimethyl-1- 6,10-Dimethyl-5-undecene-2-one can be obtained from octen-3-ol and diketene in one pot.

In the above, when acetoacetate is used in place of diketene, the operation can be performed under the same reaction conditions, and the same result as in the case of using diketene can be obtained. These reactions and mechanisms are described, for example, in J. Am. Chem. Soc. 704 (1940),
This is described in Japanese Patent Publication Nos. 32-8616 and 49-25251, British Patent No. 907142, and the like.

On the other hand, in the latter method involving Claisen rearrangement, isopropenyl ether 0.5 to 10 is used per mole of 3,7-dimethyl-1-octen-3-ol.
Mol, preferably 0.8 to 3 mol, in the presence of an acid catalyst such as phosphoric acid, sulfuric acid, oxalic acid, and trichloroacetic acid.
By heating to a temperature of 200 ° C., preferably 100 to 200 ° C., the hydroxyl group of 3,7-dimethyl-1-octen-3-ol is isopropenyl-etherified,
The resulting ether is subjected to Claisen rearrangement to give 6,10-dimethyl-5-undecene-2-one (see, for example, Japanese Patent Publication No. 40-23328).

After completion of the reaction, the reaction mixture is subjected to a conventional method,
For example, the target compound can be isolated by distillation.

Step e In this step e, a carbon group is extended from 6,10-dimethyl-5-undecene-2-one obtained in step d by adding a vinyl group to the terminal carbonyl group. 3,7,11-trimethyl-1,6-dodecadiene-
Forming 3-ols. 6, 10
-Dimethyl-5-undecene-2-one by reacting a vinyl Grignard reagent or 6,10-dimethyl-
Either the 5-undecen-2-one ethynylation followed by partial hydrogenation is selected.

In industrial practice, a method of partial hydrogenation after ethynylation is more advantageous.

This step e can be carried out according to the operation described in step c.

That is, in the former method of reacting 6,10-dimethyl-5-undecene-2-one with a vinyl Grignard reagent, for example, in a solvent such as tetrahydrofuran or diethyl ether, a solvent such as vinyl chloride or vinyl bromide is used. A vinyl magnesium halide obtained by reacting a vinyl halide with metallic magnesium was added to 0.5 mol of 6,10-dimethyl-5-undecene-2-one per mol thereof.
The reaction is carried out usually at a temperature of -10 to 55C, preferably at a temperature of 0 to 40C, and then the target compound 3 is hydrolyzed with a dilute sulfuric acid aqueous solution, a saturated ammonium chloride aqueous solution or the like. , 7,11-trimethyl-
1,6-dodecadien-3-ol can be obtained.

In the latter method of partial hydrogenation after ethynylation, first, 6,10-dimethyl-5-
Undecene-2-one is ethynylated by a conventional method to produce 3,7,11-trimethyl-6-dodecene-1-yn-3-ol having 15 carbon atoms and having a terminal triple bond. Here, ethynylation can be carried out by a method known per se as a method for producing a compound having a propargyl alcohol structure by ethynylating ketones. When the ethynylation reaction is carried out on a small scale, a method using an acetylide of an alkali metal such as lithium, sodium, or potassium or an alkaline earth metal such as calcium, or a method using an ethynyl Grignard reagent can also be used.

When the ethynylation reaction is carried out on an industrial scale, as will be described below, a propargyl-type alcohol having a triple bond at a terminal can be produced at low cost and post-treatment is easy. A method in which ethynylation is carried out directly with acetylene in the presence of a basic catalyst is suitable. This method is carried out under conditions where a strongly basic compound of an alkali metal such as sodium or potassium (eg, an alkali metal hydroxide, an alkali metal allate, an alkali metal amide, etc.) is present in a pressure-resistant container in a catalytic amount. N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, tetrahydrofuran, dimethyl ether, diethyl ether, methyl ethyl ether, anisole,
6,10-dimethyl-5-undecene-2-one and 1 mol thereof in an organic solvent or liquid ammonia which does not inhibit the reaction such as dioxane or a mixed solvent thereof,
Usually, 1 to 10 mol of acetylene is added at -30 to 30 ° C. for 1 hour.
Acetylene was discharged out of the pressure vessel, and 3,7,11-trimethyl-6 was left as a residue.
-Dodecene-1-yn-3-ol.

Next, the 3,7,11-trimethyl-6-dodecene-1-yn-3-ol obtained above was partially hydrogenated to give 3,7,11-trimethyl-1,6-dodecadiene. Convert to -3-ol. The purpose of this partial hydrogenation is to selectively reduce a carbon-carbon triple bond to a carbon-carbon double bond, and the method itself is known. As such a method, for example, a method using a hydrogenating agent such as lithium aluminum hydride,
Methods for catalytically reducing propargyl alcohol using a hydrogenation catalyst in a solvent such as hydrocarbons such as n-hexane, n-heptane, octane, benzene, toluene, xylene, methanol, ethanol, and propanol and alcohols, and the like. Can be.

The latter method is industrially preferable, and the hydrogenation is carried out, for example, at a temperature of 0 to 130 ° C., preferably 20 to 130 ° C.
80 ° C., normal pressure to 50 kg / cm ² , preferably 2 to 20
It can be performed in a hydrogen atmosphere at a pressure of kg / cm ² . As the hydrogenation catalyst, metals such as nickel, cobalt, palladium, platinum, rhodium, and iridium or compounds thereof can be used. They are,
It may be used by being supported on a carrier such as activated carbon, barium sulfate, and calcium carbonate. Above all, in the present invention, a Lindlar catalyst in which palladium is supported on calcium carbonate can be particularly preferably used.

After completion of the reaction, the target compound can be isolated from the reaction mixture by a conventional method, for example, distillation.

Step f In this step f, the 3,7,11-
6,10,14-trimethyl-5,9 having a carbon number extended by 3 using the part of the allylic alcohol at the end of trimethyl-1,6-dodecadien-3-ol.
-To form pentadecadien-2-one. As a formation method, 3,7,11-trimethyl-1,6-dodecadien-3-ol is reacted with diketene or acetoacetate to react with a hydroxyl group of 3,7,11-trimethyl-1-ol.
A method of converting 1,6-dodecadien-3-ol to an acetoacetate ester and subjecting the obtained ester to Carol rearrangement,
Alternatively, isopropenyl ether is reacted with the hydroxyl group of 3,7,11-trimethyl-1,6-dodecadien-3-ol to give isopropenyl ether of 3,7,11-trimethyl-1,6-dodecadien-3-ol. And any one of methods for Claisen rearrangement of the obtained ester.

This step f can be carried out according to the operation described in step d.

That is, in the former method involving the Carroll rearrangement, diketene is usually added in an amount of usually 0.8 to 2 mol, preferably 1 to 3,7,11-trimethyl-1,6-dodecadien-3-ol. Reacts 0.9-1.2 moles to form acetoacetic ester of 3,7,11-trimethyl-1,6-dodecadien-3-ol. In this case, formation of acetoacetate ester is carried out by dissolving 3,7,11-trimethyl-1,6-dodecadien-3-ol and diketene without using a solvent or an organic solvent that does not inhibit the reaction of hydrocarbons or ethers. It can be carried out simply by contacting, but if necessary, it may be heated to 50 to 100 ° C. Also, when amines such as triethylamine and pyridine are present in a catalytic amount in the reaction system, the esterification reaction speed is increased, and the desired acetoacetic acid of 3,7,11-trimethyl-1,6-dodecadien-3-ol is increased. The ester yield is improved.

Next, the obtained acetoacetic ester of 3,7,11-trimethyl-1,6-dodecadien-3-ol is treated usually at 130 to 180 ° C., preferably 160 to 180 ° C.
By heating to 80 ° C. and the Carroll rearrangement (rearrangement and decarboxylation) proceed,
0,14-trimethyl-5,9-pentadecadiene-2
-Get on. At this time, when an aluminum alkoxide such as aluminum isopropoxide is present in the reaction system in a catalytic amount, the desired 6,10,14-trimethyl-
The yield of 5,9-pentadecadien-2-one is improved.

The reactants necessary for the above two-stage reaction system (acetoacetic esterification reaction and Carroll rearrangement reaction) are charged all at once, and the reaction temperature is adjusted to adjust the 3,7,11-trimethyl- 1,6-dodecadien-
6,10,1 in one pot from 3-ol and diketene
4-trimethyl-5,9-pentadecadien-2-one can be obtained.

In the above, when acetoacetate is used instead of diketene, the operation can be carried out under the same reaction conditions, and the same result as in the case of using diketene can be obtained.

In the latter method involving the Claisen rearrangement, 0.5 to 10 mol, preferably 0 to 10 mol of isopropenyl ether per mol of 3,7,11-trimethyl-1,6-dodecadien-3-ol is used. 0.8 to 3 moles
In the presence of an acidic catalyst such as phosphoric acid, sulfuric acid, oxalic acid, and trichloroacetic acid, at a temperature of 50 to 200 ° C, preferably 100 to 200 ° C.
By heating to a temperature of 200 ° C, 3,7,11-
The hydroxy group of trimethyl-1,6-dodecadien-3-ol is isopropenyl-etherified, and the resulting ether is Claisen rearranged to obtain 6,10,14-trimethyl-5,9-pentadecadien-2-one. .

After completion of the reaction, the reaction mixture is subjected to a conventional method,
For example, the target compound can be isolated by distillation.

Step g In this step g, the 6,10,14 obtained in step f
-Trimethyl-5,9-pentadecadien-2-one is hydrogenated to give phyton (6,
10,14-trimethylpentadecane-2-one).

This step g can be carried out according to the operation described in step b.

That is, this hydrogenation can be carried out by a known method capable of converting a carbon-carbon double bond into a saturated carbon-carbon bond. For example, generally in an autoclave, palladium, platinum, Raney nickel,
A conventional hydrogenation catalyst such as Raney cobalt (preferably 5
% Pd / C) in the absence of a solvent or in a solvent such as hydrocarbons, alcohols, ethers, ketones, esters, carboxylic acids, etc. under a hydrogen pressure of 1 to 100 kg / cm ² , preferably 1 to 20 kg / cm. ² , reaction temperature 15-150
6,10,14-Trimethyl-5,9-pentadecadien-2-one can be hydrogenated at a temperature of preferably from 30 to 130 ° C. The reaction time can be appropriately set depending on the catalyst used, the hydrogen pressure, and the like.

After completion of the reaction, the target compound phyton (6,10,1) was obtained from the reaction mixture by a conventional method, for example, distillation.
4-trimethylpentadecane-2-one) can be isolated.

Step h In this step h, isophytol, another target compound of the present invention, is formed from the phyton obtained in step g. As the formation method, either a method of reacting phyton with a vinyl Grignard reagent or a method of partially hydrogenating phyton after ethynylation is selected. For industrial implementation, a method of partial hydrogenation after ethynylation is more advantageous.

This step h can be carried out according to the operation described in step c.

That is, in the former method of reacting phyton with a vinyl Grignard reagent, for example, it is obtained by reacting a vinyl halide such as vinyl chloride or vinyl bromide with metal magnesium in a solvent such as tetrahydrofuran or diethyl ether. 0.5 to 2 mol of phytone is added to 1 mol of vinyl magnesium halide,
The reaction is carried out at a temperature of 10 to 55 ° C., preferably at a temperature of 0 to 40 ° C., followed by hydrolysis with a dilute sulfuric acid aqueous solution, a saturated ammonium chloride aqueous solution or the like to thereby give the target compound isophytol (3, 7, 11, 15). -Tetramethyl-1
-Hexadecene-3-ol).

In the latter method of partial hydrogenation after ethynylation, first, phyton is ethynylated by a conventional method to have 20 carbon atoms and a triple bond at the terminal.
7,11,15-tetramethyl-1-hexadecine-3
-Produce all. Here, ethynylation can be carried out by a method known per se as a method for producing a compound having a propargyl alcohol structure by ethynylating ketones. When the ethynylation reaction is carried out on a small scale, a method using an acetylide of an alkali metal such as lithium, sodium or potassium or an alkaline earth metal such as calcium or a method using an ethynyl Grignard reagent can be used.

When the ethynylation reaction is carried out on an industrial scale, a strong base such as a propargyl alcohol having a triple bond at a terminal can be produced at a low cost and the post-treatment is easy as described below. Suitable is a method of direct ethynylation with acetylene in the presence of a neutral catalyst. In this method, a strong basic compound of an alkali metal such as sodium or potassium (for example, an alkali metal hydroxide, an alkali metal alcoholate, an alkali metal amide, or the like) is contained in a pressure-resistant container under a catalytic amount. N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, tetrahydrofuran, dimethyl ether,
Phytone in an organic solvent or liquid ammonia or a mixed solvent thereof that does not inhibit the reaction of diethyl ether, methyl ethyl ether, anisole, dioxane, etc.
Usually, 1 to 10 moles of acetylene are added to 1 mole thereof,
The reaction is usually carried out at 30 to 30 ° C. for 1 to 20 hours, after which acetylene is discharged out of the pressure vessel, and 3,7,
It is intended to obtain 11,15-tetramethyl-1-hexadecin-3-ol.

Next, the obtained 3,7,11,15-tetramethyl-1-hexadecin-3-ol is partially hydrogenated to obtain isophytol. This partial hydrogenation
The purpose is to selectively reduce a carbon-carbon triple bond to a carbon-carbon double bond, and the method itself is known. Examples of such a method include a method using a hydrogenating agent such as lithium aluminum hydride, n-
A method of catalytically reducing a propargyl-type alcohol using a hydrogenation catalyst in a solvent such as a hydrocarbon such as hexane, n-heptane, octane, benzene, toluene, xylene, methanol, ethanol, or propanol and an alcohol can be used. .

The latter method is industrially preferable, and the hydrogenation is carried out, for example, at a temperature of 0 to 130 ° C., preferably 20 to 130 ° C.
80 ° C., normal pressure to 50 kg / cm ² , preferably 2 to 20
It can be performed in a hydrogen atmosphere at a pressure of kg / cm ² . As the hydrogenation catalyst, metals such as nickel, cobalt, palladium, platinum, rhodium, and iridium or compounds thereof can be used. They are,
It may be used by being supported on a carrier such as activated carbon, barium sulfate, and calcium carbonate. Above all, in the present invention, a Lindlar catalyst in which palladium is supported on calcium carbonate can be particularly preferably used.

After completion of the reaction, the target compound can be isolated from the reaction mixture by a conventional method, for example, distillation.

As is evident from the above description, the present invention provides a method for preparing a 6-methyl-hydroxylated compound by continuously adding isovaleral and an aqueous alkali solution to acetone in a crossed aldol reaction between isovaleral and acetone.
By hydrogenating 3-hepten-2-one, 6-methyl-2, a kind of C8 terpene ketone, can be efficiently produced.
-Heptanone can be produced, and as a result, phyton and further isophytol can be produced industrially in terms of production cost and productivity.

[0091]

The present invention will be described below in more detail with reference to examples.

Example 1 (Step a (1)) After sufficiently replacing the inside of a stainless steel autoclave having an internal volume of 10 liters with nitrogen, acetone (1403.1 g (24.2 mol)) was charged, and jacket hot water was added. Was set to 72 ° C. The internal temperature of the autoclave is 68.0 ° C and the pressure is 1.9 kg / cm ² (gauge pressure).
, A 2.0% aqueous sodium hydroxide solution (addition rate 774 g / h) and isovaleral (addition rate 6
79 g / h) of acetone in the autoclave were each started. After the start of the addition, the internal temperature gradually increased, and the reaction was carried out in the range of 70 to 72 ° C. The addition of the aqueous sodium hydroxide solution and isovaleral was completed in 2 hours and 55 minutes. The total addition amount of the 2.0% sodium hydroxide aqueous solution was 2253.7 g (1.12 mol), and the total addition amount of isovaleral was 1979.4 g (2
2.99 mol).

Thereafter, stirring was continued at the same temperature for 1.5 hours to drive the reaction, followed by cooling. After extracting the reaction solution and separating the upper and lower layers, the upper layer was subjected to gas chromatography (column: silicon DC QF1 (Gascro Industry Co., Ltd., column length: 1 m, column temperature: 60 ° C. →
The analysis was performed at 200 ° C. (heating rate: 5 ° C./min). As a result, 2938.8 g of the upper layer (organic layer) contained 6-methyl-
1909.0 g of 3-hepten-2-one (yield: 6
6.0%). .

(Step a (2)) After sufficiently replacing the inside of a stainless steel autoclave having an internal volume of 10 liters with nitrogen, acetone (1470.0 g (25.3 mol)) was used.
And part of isovaleral (217.8 g (2.53
Mol)), and the jacket warm water was set to 60 ° C. Autoclave internal temperature is 57.7 ° C and pressure is 1.0K
g / cm ² (gauge pressure), the addition of 2.0% aqueous sodium hydroxide solution (addition rate 774 g / h) and isovaleral (addition rate 605 g / h) to acetone in the autoclave were started. did. Heat generation started about 3 minutes after the start of addition, the maximum temperature was 70.6 ° C. (5 minutes after the start of the addition), and the maximum pressure (gauge pressure) was 1.8 kg / cm.
² (4 minutes after the start of the addition). Thereafter, the temperature of the jacket hot water was set to 70 to 72 ° C., and the internal temperature was 63.4 to 7
The reaction was performed at 1.2 ° C. The addition of the aqueous sodium hydroxide solution and isovaleral was completed in 2 hours and 55 minutes. 2.0
% Aqueous sodium hydroxide solution is 225
6.2 g (1.128 mol), and the total amount of isovaleral added is 1764.1 g (20.49 mol).
Met.

Thereafter, stirring was continued at the same temperature for 1.5 hours to drive the reaction, followed by cooling. The reaction solution was withdrawn, the upper layer was separated from the lower layer, and the upper layer was analyzed by gas chromatography. As a result, in 2993.8 g of the upper layer (organic layer), 6-methyl-3-hepten-2-one contained 1926.
It was found that 1 g (yield: 66.5%) was contained.

(Step b) Into an autoclave having an internal volume of 5 liters, 6-methyl-3- obtained in step a (2) was obtained.
1816.4 g (14.4 mol) of hepten-2-one
The charged aldol reaction upper layer solution (2823.3 g) and 5% palladium / carbon catalyst (1.93 g) were charged, and the mixture was heated at a reaction temperature of 120 ° C. under hydrogen pressure (5 to 9 kg / cm ² ).
Allowed to react for hours.

Thereafter, the catalyst was filtered off, and the obtained filtrate was subjected to gas chromatography (capillary column: CBP-
10 (manufactured by Gaschrom Industry Co., Ltd.), column length: 50
m, column temperature: 70 → 240 ° C, heating rate 5 ° C / min)
As a result, it was found that 6-methyl-2-heptanone was 18
It was found that 90.4 g (yield: 100%) was contained.

Next, acetone was distilled off from the filtrate under normal pressure, and then a component having a boiling point of 33 to 132 ° C. was distilled off under a pressure of 300 mmHg. The obtained residue was purified by distillation (boiling point: 103 ° C./100 mmHg) to give a highly pure (99% or more) 6-methyl-2-heptanone (162%).
8.9 g).

(Step c) A 40% aqueous potassium hydroxide solution (31.0 g
(221.4 mmol)), and further, liquid ammonia (1.1 kg (64.7 mol)) and acetylene (0.18 kg (6.92 mol)) were introduced into the autoclave. Thereafter, the internal temperature is kept at 4 to 6 ° C.
6-methyl-2-heptanone (435.9 g) obtained in
(3.366 mol)) was introduced into the autoclave and the reaction was started.

After reacting at 4 to 6 ° C. for 2 hours, a 25% aqueous ammonium sulfate solution (69.8 g) was introduced into the autoclave to stop the reaction. Thereafter, the ammonia was discharged to the outside of the autoclave while gradually increasing the internal temperature to room temperature.

Next, hexane (220 g) and water (44
0g) was added to the reaction vessel, and the mixture was subjected to an extraction treatment and a water washing treatment to give 3,7-dimethyl-1-octyne-3-.
A hexane solution containing all was obtained. The same reaction was performed two more times (three times in total), and a total of 2280 g of 3,7-dimethyl-1-octyne-3 was obtained as a hexane solution for three times.
A hexane solution containing ol (680 g of hexane therein) was obtained. The conversion of 6-methyl-2-heptanone in the three reactions was determined by gas chromatography analysis (column: P
As a result of EG-20M (manufactured by Gaschrom Industry Co., Ltd.), column length: 3 m, column temperature: 140 ° C., each was 9
It was found to be 4.7%, 98.0% and 97.2%.

A hexane solution containing the above-obtained 3,7-dimethyl-1-octin-3-ol (1140 g)
And a palladium / Lindler catalyst (0.27 g) were charged into an autoclave having an internal volume of 3 liters, and the reaction temperature was set to 25 under hydrogen pressure (5 to 8 kg / cm ² (gauge pressure)).
The reaction was performed at -43 ° C for 4 hours. Then, the catalyst is filtered off,
The obtained filtrate was concentrated using a rotary evaporator to obtain crude 3,7-dimethyl-1-octen-3-ol. The same reaction was repeated once more, and the mixture was combined twice to give crude 3,7-dimethyl-1-octen-3-ol in 159.
0 g was obtained. Gas chromatography analysis (column: DC
-550 (manufactured by Gaschrom Industry Co., Ltd.), column length: 3
m, column temperature: 100 ° C. and column: PEG-HT
(Manufactured by Gaschrom Industry Co., Ltd.), column length: 3 m, column temperature: 130 ° C.).
The conversion of -dimethyl-1-octin-3-ol was 99.7% and 97.3%, respectively, and the selectivity to 3,7-dimethyl-1-octen-3-ol was 9% respectively.
It was found to be 5.0% and 95.8%.

A methanol solution of sodium methylate (concentration: 28%, 0.41 g) was added to the obtained crude 3,7-dimethyl-1-octen-3-ol (1590 g), and the mixture was heated at 150 ° C. for 1 hour. After decomposing the unreacted 3,7-dimethyl-1-octin-3-ol, the solution was subjected to simple evaporation under a pressure of about 50 mmHg, and the boiling point was 115 ° C.
1440 g of a nearby fraction was obtained. Further, while heating this fraction under reduced pressure, a low-boiling component (boiling point: about 80 ° C./about 20 mmHg) is distilled off, and the residue is separated by 1360.
g was obtained. Gas chromatography analysis (column: DC-
550 (manufactured by Gaschrom Industry Co., Ltd.), column length: 3
m, column temperature: 120 → 190 ° C., heating rate: 5 ° C. /
As a result, the residue contains 93.1% of 3,7-dimethyl-1-octen-3-ol (80.2% of isolated yield from 6-methyl-2-heptanone). I knew it was there.

(Step d) The 3,7-dimethyl-1-octen-3-ol (6) obtained in Step c was placed in a two-liter glass three-necked flask equipped with a reflux condenser.
80 g (4.05 mol)), triethylamine (2.2
3 g (22 mmol)) and aluminum isopropoxide (5.21 g (26 mmol)).
While heating to 80 ° C, diketene (328 g)
(3.905 mol)) was added dropwise over 1.5 hours, and further reacted for 1 hour. Thereafter, the temperature was raised to 170 ° C., and the reaction was performed for 3 hours. The same reaction was performed once again, and the mixture was combined twice to obtain 1650 g of a reaction mixture (crude 6,10-dimethyl-5-undecene-2-one). Gas chromatography analysis (column: DC-550 (manufactured by Gas Chromo Industry Co., Ltd.)), column length: 3 m, column temperature: 120
(→ 190 ° C., heating rate: 5 ° C./min), the conversion of 3,7-dimethyl-1-octen-3-ol in the two reactions is 93.1% and 92.7%, respectively. I understand.

The obtained reaction mixture (crude 6,10-dimethyl-5-undecene-2-one) (1650 g) was treated with 7 mmH
Single evaporation under a pressure of 1 g gave 1350 g of a fraction having a boiling point of 85 to 110 ° C. Further, the obtained fraction was purified and distilled (boiling point: about 120 ° C., 6 mmHg) to give 6,10-dimethyl-5-purity of 99.4%.
1100 g of undecene-2-one was obtained (isolation yield: 6
9.2%).

(Step e) A 40% aqueous potassium hydroxide solution (23.6 g) was placed in an autoclave having an internal volume of 3 liters.
(169 mmol)), and further, liquid ammonia (1.0 kg (58.8 mol)) and acetylene (0.
18 kg (6.92 mol)) were introduced into the autoclave. Thereafter, the internal temperature was maintained at 4 to 6 ° C, and the 6,10-dimethyl-5-undecene-2-one (5
50.0 g (2.784 mol)) were introduced into the autoclave and the reaction was started.

After reacting at 4-6 ° C. for 1.75 hours, 2
A 5% aqueous ammonium sulfate solution (53.3 g) was introduced into the autoclave to stop the reaction. Thereafter, the ammonia was discharged to the outside of the autoclave while gradually increasing the internal temperature to room temperature.

Next, hexane (280 g) and water (55 g)
0g) was added to the reaction vessel, and the mixture was subjected to an extraction treatment and a water washing treatment to obtain a hexane solution containing 3,7,11-trimethyl-6-dodecene-1-yn-3-ol.
The hexane was removed from this solution by a rotary evaporator to give crude 3,7,11-trimethyl-6-
Dodecene-1-yn-3-ol (630 g) was obtained.
Gas chromatography analysis (column: PEG-20M
(Gascro Industry Co., Ltd.), column length: 3 m, column temperature: 190 ° C.).
The conversion of undecene-2-one was found to be 98.0%.

The obtained 3,7,11-trimethyl-6-
Dodecene-1-yn-3-ol (630 g), hexane (270 g) and palladium / Lindler catalyst (0.
22 g) was charged into an autoclave having an internal volume of 3 liters, and under hydrogen pressure (5 to 8 kg / cm ² (gauge pressure)).
The reaction was performed at a reaction temperature of 25 to 43 ° C for 4 hours. Thereafter, the catalyst was filtered off, and the obtained filtrate was concentrated by a rotary evaporator to obtain crude 3,7,11-trimethyl-
1,6-Dodecadien-3-ol (630 g) was obtained. Gas chromatography analysis (column: DC-55
0 (manufactured by Gas Chromo Corporation), column length: 3 m, column temperature: 160 ° C. and PEG-20M (manufactured by Gas Chromo Industry Co., Ltd.), column length: 3 m, column temperature: 190
° C), the conversion of 3,7,11-trimethyl-6-dodecene-1-yn-3-ol was 95.5%,
3,7,11-trimethyl-1,6-dodecadien-3
-Selectivity to all was found to be 94.6%.

The resulting crude 3,7,11-trimethyl-
In 1,6-dodecadien-3-ol (630 g), a methanol solution of sodium methylate (concentration: 28%,
0.16 g), and heated at 150 ° C. for 1 hour to decompose unreacted 3,7,11-trimethyl-6-dodecene-1-yn-3-ol. Evaporation gave 520 g of a fraction with a boiling point of 120-135 ° C. As a result of gas chromatography analysis (column: DC-550 (manufactured by Gaschrom Industry Co., Ltd.), column length: 3 m, column temperature: 160 ° C.), this fraction was found to be 3,7,11-trimethyl-1,6- 93.7% of dodecadien-3-ol (isolation yield from 6,10-dimethyl-5-undecene-2-one: 78.0)
%).

(Step f) The 3,7,11-trimethyl-1,6-dodecadien-3-ol obtained in Step e was placed in a two-liter glass three-necked flask equipped with a reflux condenser. (520 g (2.17 mol)), triethylamine (1.56 g (15 mmol)) and aluminum isopropoxide (3.95 g (19 mmol))
And heated to 70 to 80 ° C., then diketene (18)
9.7 g (2.258 mol)) was added dropwise over 1.1 hours, and the mixture was further reacted for 1 hour. Thereafter, the temperature was raised to 170 ° C., and the reaction was performed for 3 hours. Thus, 590 g of a reaction mixture (crude 6,10,14-trimethyl-5,9-pentadecadien-2-one) was obtained. As a result of gas chromatography analysis (column: DC-550 (manufactured by Gaschrom Industry Co., Ltd.), column length: 3 m, column temperature: 210 ° C.), 3,7,11-trimethyl-1,6-dodecadien-3 was obtained. -All conversion was found to be 89.1%.

The resulting crude 6,10,14-trimethyl-
5,9-Pentadecadien-2-one (590 g) is evaporated under a pressure of 0.3 mmHg to a boiling point of about 110 ° C.
440 g of a fraction were obtained. Further, the obtained fraction is purified and distilled (boiling point: 113 ° C./0.1 mmHg).
To give 6,10,14-trimethyl-5,9-pentadecadien-2-one having a purity of 99.2% to 36.
0 g was obtained (isolation yield: 62.7%).

(Step g) Into an autoclave having an internal volume of 300 ml, the 6,10,14-
Trimethyl-5,9-pentadecadien-2-one (1
20 g (453.8 mmol)) and 10% palladium / carbon catalyst (0.1 g) were charged under hydrogen pressure (2
(0 kg / cm ² (gauge pressure)) at a reaction temperature of 180 ° C. for 4 hours. Thereafter, the catalyst was separated by filtration to obtain a filtrate. The same reaction was performed two more times (three times in total) to obtain a total of 340 g of the filtrate for the three times. As a result of gas chromatography analysis (column: DC-550 (manufactured by Gaschrom Industry Co., Ltd.), column length: 3 m, column temperature: 220 ° C.), the filtrate was 98.4% phyton (6,10,
14-trimethyl-2-pentadecanone).

Example 2 (Step h) In an autoclave having an internal volume of 3 liters,
A 0% aqueous solution of potassium hydroxide (24.9 g (178 mmol)) was added, and further, liquid ammonia (1.1 kg (6 kg)) was added.
4.7 mol)) and acetylene (0.15 kg (6.2
5 mol)) were introduced into the autoclave. Thereafter, the internal temperature was maintained at 4 to 6 ° C., and the phyton obtained in step g of Example 1, that is, 6,10,14-trimethyl-2-pentadecanone (340.0 g (1.246 mol)) was placed in the autoclave. To start the reaction.

After reacting at 4 to 6 ° C. for 2.5 hours, 25
A 5% aqueous ammonium sulfate solution (56.3 g) was introduced into the autoclave to stop the reaction. Thereafter, the ammonia was discharged to the outside of the autoclave while gradually increasing the internal temperature to room temperature.

Next, hexane (330 g) and water (50
0g) was added to the reaction vessel, and the mixture was subjected to an extraction treatment and a water washing treatment to give 3,7,11,15-tetramethyl-1.
-A hexane solution containing hexadecyn-3-ol was obtained. Hexane was removed from this solution by a rotary evaporator to obtain crude 3,7,11,15-tetramethyl-1-hexadecin-3-ol (370 g). Gas chromatography analysis (column: PEG-
20M (Gascro Industry Co., Ltd.), Column length: 3
m, column temperature 220 ° C.), the phyton conversion was found to be 95.4%.

The obtained crude 3,7,11,15-tetramethyl-1-hexadecin-3-ol (93.4 g),
Hexane (55.6 g) and a palladium / Lindler catalyst (0.12 g) were charged into an autoclave having an internal volume of 300 ml, and were charged under hydrogen pressure (3 to 4 kg / cm ^2).
(Gauge pressure)), and reacted at a reaction temperature of 30 to 60 ° C. for 8 hours. The same reaction was repeated twice more (three times in total),
A total of 246.8 g of crude 3,7,11,15-tetramethyl-1-hexadecin-3-ol was hydrogenated.

The obtained reaction solutions were combined, the catalyst was filtered off, and hexane was removed from the obtained filtrate by a rotary evaporator to give crude 3,7,11,15-tetramethyl-1-hexadecene-3. -Ol, ie isophytol (262.8 g), was obtained. Gas chromatography analysis (column: DC-550 (manufactured by Gas Chromotech Co., Ltd.))
Column length: 3m, column temperature: 160 ° C and column:
As a result of PEG-20M (manufactured by Gaschrom Industry Co., Ltd.), column length: 3 m, column temperature: 215 ° C., 3,7,1
The conversion of 1,15-tetramethyl-1-hexadecin-3-ol was found to be 100%.

The obtained crude isophytol (262.8)
g), a methanol solution of sodium methylate (concentration: 28%, 0.06 g) was added, and the mixture was heated at 150 ° C. for 1 hour to obtain unreacted 3,7,11,15-tetramethyl-1.
-After decomposing hexadecin-3-ol,
Single evaporation under a pressure of 0.7 mmHg and a boiling point of 103 to 1
208.7 g of a 35 ° C. fraction were obtained. When this fraction was analyzed by gas chromatography under the same conditions as above, isophytol was found to be 186.3.
g (yield from phyton: 75.7%). Further, this fraction was purified and distilled (boiling point: 115 to 120 ° C./0.15 to 0.2 mmHg) to obtain 124.4 g of isophytol. Gas chromatography analysis (column: FFAP (manufactured by Gas Chromo Industry Co., Ltd.), column length: 4 m, column temperature:
195 ° C.), the purity of the obtained isophytol was 9
It turned out to be 9.0%.

Reference Example Different from step a of Example 1, an example in which acetone, isovaleral and a 2% aqueous sodium hydroxide solution were charged together in a reaction vessel is shown below.

That is, after sufficiently replacing the inside of a reactor having an internal volume of 300 ml with nitrogen, acetone (30.
5 g (525 mmol)), isovaleral (43.1)
g (500 mmol)) and a 2% aqueous sodium hydroxide solution (50.0 g (50 mmol)) were charged together, and the mixture was stirred at an internal temperature of 45 ° C. Thereafter, stirring was continued at an internal temperature of 55 to 65 ° C. for 3 hours.

After cooling to room temperature, the reaction solution was withdrawn,
After separating the upper and lower layers, the upper layer was analyzed by gas chromatography. As a result, 64.3 g of the upper layer (organic layer)
35.7 of 6-methyl-3-hepten-2-one is contained therein.
g (yield: 56.6%).
From this, acetone, isovaleral and a 2% aqueous sodium hydroxide solution were charged together to give 6-methyl-3.
It can be seen that the yield of -hepten-2-one decreases.

[0123]

According to the present invention, phyton and isophytol can be industrially advantageously produced.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Takashi Onishi 36 Towada, Kamisu-cho, Kashima-gun, Ibaraki Pref. Kuraray Co., Ltd. Inside the company Kuraray

Claims (3)

[Claims] 1. Step a : Step a While continuously adding isovaleral and an aqueous alkali solution to acetone, cross-aldol condensation of isovaleral and acetone is carried out to form 6-methyl-3.
Step of forming hepten-2-one; Step b , 6-methyl-3-heptene obtained in Step a.
Hydrogenation of 2-one to form 6-methyl-2-heptanone; step c, by reacting 6-methyl-2-heptanone obtained in step b with a vinyl Grignard reagent to vinylate; or steps to form a 3,7-dimethyl-1-octen-3-ol by adding partial hydrogenation after ethynylation the 6-methyl-2-heptanone; obtained in step d step c 3,7 By reacting diketene or acetoacetate with the hydroxyl group of dimethyl-1-octen-3-ol to give acetoacetate of 3,7-dimethyl-1-octen-3-ol, the resulting ester is subjected to Carroll rearrangement. Or the 3,7
-Dimethyl-1-octen-3-ol is reacted with isopropenyl ether to give 3,7-dimethyl-1
- and isopropenyl ether of octen-3-ol, the step of forming the 6,10-dimethyl-5-ene-2-one by Claisen rearrangement of the resulting ether; obtained in step e step d 6, By subjecting 10-dimethyl-5-undecene-2-one to vinylation by reacting it with a vinyl Grignard reagent, or by partially hydrogenating the 6,10-dimethyl-5-undecene-2-one after ethynylation. To give 3,7,11-trimethyl-
Forming 1,6-dodecadien-3-ol; step f , 3,7,11-trimethyl- obtained in step e.
3,7,11-Trimethyl-1,6-dodecadien-3 is obtained by reacting diketene or acetoacetate with the hydroxyl group of 1,6-dodecadien-3-ol.
All-acetoacetate, and the resulting ester is subjected to Carroll rearrangement, or the 3,7,11
-Reaction of the hydroxyl group of trimethyl-1,6-dodecadien-3-ol with isopropenyl ether to give 3,7,1
6-, 10,14-Trimethyl-5,9-pentadecadien-2-one is formed by isopropenyl ether of 1-trimethyl-1,6-dodecadien-3-ol and subjecting the resulting ether to Claisen rearrangement. And g) hydrogenating 6,10,14-trimethyl-5,9-pentadecadien-2-one obtained in step f to form phyton. How to make phyton. 2. The method according to claim 1, wherein in step a, the aqueous alkali solution is an aqueous solution of at least one hydroxide selected from the group consisting of an alkali metal hydroxide and an alkaline earth metal hydroxide. . 3. A phyton obtained by the production method according to claim 1 or 2 is reacted with a vinyl Grignard reagent to vinylate, or phyton is ethynylated and then partially hydrogenated to form isophytol. A process for producing isophytol, comprising the steps of: