JPH11279103A - Production of unsaturated carboxylic acid ester and production of beta-sinensal by using the unsaturated carboxylic acid ester as intermediate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily obtain the subject compound useful as a raw material or intermediate for various chemicals such as perfumery and pharmaceuticals in high efficiency by reacting a specific allyl alcohol compound with a specific trialkyl orthoacetate in the presence of an acid. SOLUTION: The objective compound of formula II (R1 is a lower alkyl) [e.g. ethyl (E)-4-methyl-8-methylene-4,9-decadienoate] is produced by reacting (A) an allyl alcohol compound of formula I (e.g. 2-methyl-6-methylene-1,7- octadien-3-ol) with (B) a trialkyl orthoacetate of formula CH3 C(OR)3 (R is a lower alkyl) (preferably triethyl orthoacetate, etc.), in the presence of (C) an acid (preferably propionic acid, etc.), preferably at 120-180 deg.C using preferably 3-10 times mol of the component B and 0.01-0.1 equivalent of the component C based on the component A.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing an unsaturated carboxylic acid ester useful as an intermediate for various chemical raw materials such as fragrances and pharmaceuticals, and a useful fragrance using the unsaturated carboxylic acid ester as an intermediate. The present invention relates to a method for producing β-sinensal.

[0002]

2. Description of the Related Art The following general formula (VIII)

[0003]

Embedded image Β-Sinensal [(E, E) -2,6-dimethyl-10-
Methylene-2,6,11-dodecatrienal] is an important flavor and flavor component of Chinese orange oil (Citrus sinensus L.)
It is a compound with a unique citrus flavor and flavor.

Heretofore, as a method for producing β-sinensal, for example, a method represented by the following reaction formula (Bull.
Chem. Soc. Jpn, 57, 1935 (1984)) is known.

[0005]

Embedded image However, the proposed method has difficulty in obtaining carbenoids used during the process, uses a harmful substance called PCC (pyridinium chlorochromate), has a long reaction process, and has a low production efficiency. There are many problems.

As a method for producing β-sinensal, a method represented by the following reaction formula (Tetrahedron Let
t., 25, 30, 3213 (1984)).

[0007]

Embedded image However, in this method, the starting materials γ-methyl-γ-vinyl-γ-butyrolactone and 2-trimethylsilylmethyl-1,3-butadiene are not commercially available, and the former is prepared from vinyl Grignard and ethyl levulinate. The latter is chloromethyltrimethylsilane and 2-chloro-1,
There are problems such as the need to adjust from 3-butadiene, the use of a toxic substance called benzene, and the long reaction time of the first step.

[0008]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a method for producing β-sinensal simply, efficiently and in a short time using easily available raw materials.

Another object of the present invention is to provide a method for easily and efficiently producing an unsaturated carboxylic acid ester which is an intermediate of β-sinensal using starting materials such as β-myrcene which are inexpensive and easily available. As an issue.

[0010]

Means for Solving the Problems In order to achieve the above object, a method for producing an unsaturated carboxylic acid ester and β-sinensal according to the present invention has the following constitution.

(1) General formula (I)

[0012]

Embedded image And a trialkyl orthoacetate represented by the general formula (II) CH ₃ C (OR) ₃ (II) (wherein R represents a lower alkyl group such as a methyl group or an ethyl group). Characterized by reacting in the presence of an acid, general formula (III)

[0013]

Embedded image (Wherein, R ₁ represents a lower alkyl group such as a methyl group and an ethyl group).

(2) The method for producing an unsaturated carboxylic acid ester according to the above (1), wherein the trialkyl orthoacetate is trimethyl orthoacetate or triethyl orthoacetate.

(3) The above (1), wherein the acid is propionic acid.
Or a method for producing an unsaturated carboxylic acid ester according to (2).

(4) The allyl alcohol compound has the general formula (I)
V)

[0017]

Embedded image Is regioselectively oxidized with m-chloroperbenzoic acid to give the general formula (V)

[0018]

Embedded image The method for producing an unsaturated carboxylic acid ester according to any one of the above (1) to (3), wherein the epoxide is represented by the formula (1), and then an allyl alcohol is obtained by reacting lithium diisopropylamide. .

(5) The general formula (III) according to any one of the above (1) to (4)

[0020]

Embedded image (Wherein R ₁ represents a lower alkyl group such as a methyl group or an ethyl group) by selectively reducing an unsaturated carboxylic acid ester represented by the following formula (VI)

[0021]

Embedded image To form an aldehyde compound represented by the general formula (VII)

[0022]

Embedded image (Wherein R ₂ is an alkyl group), wherein propylidenealkylimine represented by the general formula (V) is condensed in the presence of lithium diisopropylamide and then hydrolyzed with an acid.
III)

[0023]

Embedded image A method for producing β-sinensal represented by the formula:

(6) The propylidenealkylimine is
The process for producing β-sinensal according to the above (5), which is propylidene-tert-butylimine or propylidenecyclohexylimine.

[0025]

BEST MODE FOR CARRYING OUT THE INVENTION A preferred method for producing β-sinensal of the present invention is shown in the following reaction formula.

[0026]

Embedded image First, the general formula (I)

[0027]

Embedded image Can be produced by a known method represented by the above-mentioned reaction formula. That is,
Starting from readily available β-myrcene as a starting material, tri-substituted olefin is oxidized regioselectively with m-chloroperbenzoic acid (MCPBA), and the resulting epoxide is reacted with lithium diisopropylamide (LDA). And the desired allyl alcohol compound can be obtained.

Next, as shown in the above reaction formula C, the obtained allyl alcohol form is converted into an unsaturated carboxylic acid ester form by reaction with trialkyl orthoacetate in the presence of an acid. The acid here is an organic acid or an inorganic acid, and specific examples thereof include acetic acid, trifluoroacetic acid, propionic acid, paratoluenesulfonic acid, potassium hydrogen sulfate, and Amberlyst 15E (manufactured by Rohm and Haas Company).
And the like, and an acidic ion exchange resin, and the like, and propionic acid is particularly preferably used.

In the present invention, the amount of the acid to be used is preferably 0.001 to 0.3 equivalent, more preferably 0.005 to 0.2 equivalent, and still more preferably 0.1 to 0.3 equivalent to the allyl alcohol compound. It is 01 to 0.1 equivalent.

Further, specific examples of the trialkyl orthoacetate used in the present invention include, but are not limited to, methyl orthoacetate and ethyl orthoacetate. The amount of the trialkyl orthoacetate used is preferably 1 to 3 with respect to the allyl alcohol compound.
The molar amount is 0 times, preferably 2 to 20 times, and more preferably 3 to 10 times.

The solvent used in the reaction of the present invention can also serve as an excess of trialkyl orthoacetate. However, a solvent having a boiling point higher than the reaction temperature, sufficient solubility, and inert to each raw material should be selected. Can be.

Further, the reaction temperature is preferably 50 to 25.
A range of 0 ° C. can be selected, but more preferably 10 ° C.
The temperature is in the range of 0 to 200 ° C, more preferably 120 to 180 ° C.

In the reaction of the present invention, a low-boiling alcohol is produced, and the low-boiling alcohol is preferably distilled off from the reaction system under normal pressure or reduced pressure.

The unsaturated carboxylic acid ester obtained by the above reaction can be purified to high purity only by distillation and fractionation of the reaction solution, depending on the kind of the acid or the trialkyl orthoacetate used. Further, after ordinary reaction treatment, purification can be performed by silica gel column chromatography, distillation, or the like. Here, the normal reaction treatment is
After completion of the reaction, the reaction mixture is cooled to room temperature, saturated aqueous sodium hydrogen carbonate is added, and the mixture is extracted with ether.The extract is washed with saturated saline, dried over anhydrous sodium sulfate, and the low-boiling substances are recovered under reduced pressure to obtain a crude product. It is.

The unsaturated carboxylic acid ester is subsequently converted to He
lv. Chim. Acta 50 (8), 2440-2445 (1967) can be used to induce β-sinensal by a known method. That is, the unsaturated carboxylic acid ester is selectively reduced to aldehyde with diisobutylaluminum hydride (DIBAH) or the like, and the obtained aldehyde compound is condensed with propylidenealkylimine by LDA.
Subsequent hydrolysis with an acidic aqueous solution gives β
-You get Sinnensal.

Specific examples of the propylidenealkylimine used herein include propylidene-tert-butylimine and propylidenecyclohexylimine, but the present invention is not limited thereto. Examples of the acidic aqueous solution include, but are not limited to, aqueous hydrochloric acid and aqueous sulfuric acid.

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

[0038]

[Example 1] [Example 1] From β-myrcene to 2-methyl-6-methylene-1,7-octadie
Production of m- 3 -chlorobenzoic acid 230.7 g (purity 80% or more,
(1.07 mol or more), 2250 ml of chloroform was added thereto, and the mixture was heated to 30 ° C. to completely dissolve the mixture, then cooled to −40 ° C., and 150.0 g of β-myrcene (GC purity 86
%, 0.95 mol) was slowly added dropwise. The mixture was reacted at 0 to 5 ° C. for 5 hours, the precipitate was filtered, and low-boiling substances were removed from the filtrate under reduced pressure. Ethyl acetate (750 ml) was added to the residue, and the mixture was washed twice with saturated aqueous sodium hydrogen carbonate and further with saturated saline.
The organic phase was freed from low-boiling substances under reduced pressure. The obtained crude product was distilled to obtain 133 g of an epoxide compound (GC purity 87).
%). The yield is 80 mol based on β-myrcene
%Met.

Next, 56.8 g of diisopropylamine
(0.56 mol) and 570 ml of ether,
After cooling to 20 ° C., 375 ml of a normal butyl lithium hexane solution (1.50 mol / l) was added dropwise at −10 ° C. or lower. The reaction was carried out at 0 to -5 ° C for 30 minutes, and again at -10
And cooled to 57.0 g (0.33 g)
mol) and 266 ml of ether were added dropwise at 0 ° C or lower. The reaction was carried out at 0 ° C. for 15 hours, 300 ml of water was slowly added, the aqueous phase was separated and removed, and the organic phase was washed twice with a saturated aqueous ammonium chloride solution and further with a saturated saline solution. Was removed. 57 g of the obtained crude product was distilled to obtain an allyl alcohol compound (2-methyl-6-methylene-1,7-
45 g (GC purity 86%) of octadien-3-ol) were obtained. The yield was 78 mol% based on the epoxide.

Ethyl (E) -4-methyl-8-methylene-4,9-deca
Production of dienoate To 50 g (0.28 mol) of the above allyl alcohol compound (2-methyl-6-methylene-1,7-octadien-3-ol),
373 g (2.30 mol) of triethyl orthoacetate and 1.5 g (0.02 mol) of propionic acid were added, and the internal temperature was 1%.
At 10 ° C, the internal temperature was reduced to 14 over 1 hour while distilling off low-boiling substances.
After the temperature was raised to 0 to 150 ° C, the reaction was carried out at the same temperature for 1 hour. After cooling, low-boiling substances were distilled off under reduced pressure, followed by distillation under reduced pressure to obtain an unsaturated carboxylic acid ester (ethyl
(E) -4-methyl-8-methylene-4,9-decadienoate) 5
1.5 g (GC purity 89%) were obtained. The yield was 73 mol% based on the allyl alcohol compound.

Synthesis of β-Sinensal The unsaturated carboxylic acid ester obtained above (ethyl
(E) -4-Methyl-8-methylene-4,9-decadienoate) 1
Hexane (250 ml) was added to 2.5 g (0.05 mol), and the mixture was cooled to -70 ° C. To this, 50 m of a diisobutylaluminum hydride hexane solution (1.0 mol / l) was added.
1 was slowly added dropwise, followed by 4 ° C at -60 to -65 ° C.
Allowed to react for hours. 130 ml of 5% hydrochloric acid aqueous solution at -10 to 0 ° C
Was added dropwise, and the aqueous phase was separated and removed. The organic phase was washed with a saturated aqueous solution of sodium bicarbonate and a saturated saline solution, and low-boiling substances were distilled off under reduced pressure to obtain a crude product. This was distilled to obtain 9.0 g (GC purity: 72%) of an aldehyde ((E) -4-methyl-8-methylene-4,9-decadienal). The yield was 73 mol% based on the unsaturated carboxylic acid ester.

Then, 20.6 g of diisopropylamine
(0.20 mol) was added with 290 ml of ether, and -1
After cooling to 0 ° C., 119.3 ml of a normal-butyllithium hexane solution (1.57 mol / l) was slowly added dropwise. After reacting at 0 to -5 ° C for 30 minutes, 24.9 g of propylidene-cyclohexylimine (0.18m
ol) in 100 ml of ether was added dropwise, and 3
The reaction was performed for 0 minutes. Next, the reaction solution was cooled to −60 ° C., and a solution of 29.0 g (0.12 mol) of the above aldehyde compound in 100 ml of ether was added dropwise, followed by a reaction at −60 to −65 ° C. for 30 minutes and then at room temperature for 1 hour. Was. Reaction solution
After cooling to ℃, 10% sulfuric acid aqueous solution 725 g was added dropwise, and reacted at 30 ℃ for 30 minutes. The aqueous phase was separated and removed, and the organic phase was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, and then the low-boiling substances were distilled off under reduced pressure to obtain a crude product. This was purified by silica gel column chromatography to obtain β-sinensal 18.1
g (GC purity 89%) was obtained. The yield was 63 mol% based on the aldehyde compound.

[0043]

According to the method of the present invention for producing β- sinensal, easily available raw materials can be used, and the production process can be shortened, and β- sinensal can be produced simply and efficiently. Further, unsaturated carboxylic acid esters useful as intermediates for various chemical raw materials such as fragrances and medicines can be easily and efficiently produced.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI C07C 67/42 C07C 67/42 69/587 69/587 (72) Inventor Akio Hasebe 1573-4 Funagata Noda-shi, Chiba Pref. Company Noda branch office

Claims (6)

[Claims] 1. A compound of the general formula (I) And a trialkyl orthoacetate represented by the general formula (II) CH ₃ C (OR) ₃ (II) (wherein R represents a lower alkyl group) in the presence of an acid Having the general formula (III): (Wherein R ₁ represents a lower alkyl group). 2. The process for producing an unsaturated carboxylic acid ester according to claim 1, wherein the trialkyl orthoacetate is trimethyl orthoacetate or triethyl orthoacetate. 3. The method for producing an unsaturated carboxylic acid ester according to claim 1, wherein said acid is propionic acid. 4. The allyl alcohol compound has the general formula (IV): Is regioselectively oxidized with m-chloroperbenzoic acid to give the general formula (V): The method for producing an unsaturated carboxylic acid ester according to any one of claims 1 to 3, which is an allyl alcohol compound obtained by reacting with an epoxide compound represented by the formula (1) and then reacting with lithium diisopropylamide. 5. The general formula according to claim 1, wherein
(III) Wherein R ₁ represents a lower alkyl group, and selectively reducing the unsaturated carboxylic acid ester with diisobutylaluminum hydride to give a compound of the general formula (VI) To form an aldehyde compound represented by the general formula (VII): (Wherein R ₂ is an alkyl group) wherein propylidenealkylimine is condensed in the presence of lithium diisopropylamide and then hydrolyzed with an acid. A method for producing β-sinensal represented by the formula: 6. The method according to claim 5, wherein said propylidenealkylimine is propylidene-tert-butylimine or propylidenecyclohexylimine.