JPS58118536A - Preparation of jasmones - Google Patents

Abstract

PURPOSE:To prepare the titled compound useful as a high-quality perfume for cosmetics, soaps, etc., easily and in high yield, without using harmful metallic catalyst, etc., by using a gamma-keto-carboxylic acid ester as a raw material, and subjecting the material successively to the cyclization reaction and the alkylation reaction. CONSTITUTION:The gamma-ketocarboxylic acid ester of formulaI(R1 is substituted or unsubstituted alkyl or aryl; R2 is alkyl, alkenyl or alkynyl) is cyclized in a solvent preferably benzene, etc., in the presence of a basic catalyst (e.g. potassium tert-butoxide) at 50-200 deg.C, and the resultant 2-substituted-1,3-dioxocyclopentane of formula II is made to react with an alkylation agent selected from alkyl alkali, aryl alkali and the compound of formula III (R3 is alkyl or CH2COOR4; R4 is alkyl; X is Cl, Br or I) to obtain the objective compound of formula IV.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for converting 2- from γ-ketocarboxylic acid ester.
The present invention relates to a method for producing jasmones via 1,3-dioxocyclopentane.

In recent years, jasmones have come to occupy an increasingly important position as jasmine flavoring agents in cosmetics, soaps, and other high-grade fragrances.

Conventionally, as an industrial method for producing jasmones, (1) an oxyacid ester obtained by condensation of a levulinate ester and an alkyl halide with a Grignard reagent is dehydrated, and the resulting lactone is treated with a phosphoric acid catalyst or medium. , How to obtain jasmones (p-1! 4-bo W, peg:
H, J, , 0JLitnc, ), cJa Ordinary 14
74 (1937); 1. G, pa4&yLIy
J: F, P, 785.540; B, P, 4
53゜5j 8; Engineering, V1Mar, LLn-bJke
zya-eJ,, J: Madertr, ZJQ
4, P-convex (12), 29 (1961); O,'
A. Tomoyo 456 (1964)).

(2) Acetylene ketal obtained by condensing a cyclic ketal derived from methyl vinyl ketone with acetylene or a metal salt of an acetylene derivative is converted into a 1,4-diketone using methanol, sulfuric acid, and mercury sulfate, and this is converted into an alkaline aqueous solution. method (0゜3i6J, R, Bt4GL
: J, AWL, QJzl, SσG,, 吃麊, 935
936 (1964)).

However, method (1) has the drawbacks of low selectivity and yield, and method (2) requires a large number of steps and uses a harmful metal as a catalyst.

As a result of intensive study on a method for producing jasmone that would improve these drawbacks, the present inventors found that jasmone, which can be easily obtained from furan or furfural, was found by the method previously proposed by the present inventors (Japanese Patent Application No. 56-62342). The present invention was completed based on the discovery that jasmones can be obtained with good selectivity and in an industrially advantageous manner by using r-ketocarboxylic acid ester as a raw material and subjecting it to a cyclization reaction and then an alkylation reaction.

That is, the method of the present invention involves subjecting a γ-ketocarboxylic acid ester to a cyclization reaction in the presence of a base catalyst to form a 2-at-1
, 5-dioquinocyclopentane, and then reacting this compound with an alkylating agent such as an alkyl alkali, an aryl alkali, or an alkyl magnesium halide to produce jasmones.

The γ-ketocarboxylic acid ester used in the method of the present invention has the general formula (1) (wherein 31 represents a substituted or unsubstituted alkyl group or aryl group, and R2 represents an alkyl group, an alkenyl group, or an alkynyl group). This is a compound represented by

In the compound represented by general formula (1), R may be any alkyl group or aryl group, but is preferably a lower alkyl group such as methyl, ethyl, propyl or butyl group, or a phenyl group. . Also, R
2 is preferably an alkyl group having 4 to 14 carbon atoms. Such compounds include methyl-4-one n-decanoate,
Methyl-4-one-7-ene loop phosphate, Methyl-4-one-7-ene n-decanoate, Ethyl-4-one n-nonanoate, Propyl-4-one n-nonanoate, Methyl-4-one 9-dodecanoate -7-yne, 9-dodecanoic acid-
Examples include 9-butyl-4-one.

These γ-ketocarboxylic acid esters are subjected to a cyclization reaction in the presence of a base catalyst to form the general formula (II), (wherein R2
has the same meaning as in general formula (1)).

The basic catalyst used in this cyclization reaction is an alkali metal or alkaline earth metal alcoholade, preferably a sodium or potassium tertiary alcoholade. For example, potassium tert-butoxide, sodium tert-butoxide, potassium 2-methyl-2
-butoxide, medium-2-methyl-2-butoxide, and the like.

These base catalysts are 1 of γ-ketocarboxylic acid esters.
In the range of 0.1 to 10 moles, preferably 0.1 to 10 moles.
It is used in a range of 2 to 4 moles.

A solvent is usually used in the cyclization reaction. As a solvent,
Although hydrocarbon solvents can be used, aromatic solvents such as benzene, toluene, xylene, and 0-dichlorobenzene are generally used.

The temperature of the cyclization reaction is in the range of 50 to 200°C, preferably in the range of 90 to 160°C from the viewpoint of reaction rate.

After removing the catalyst, solvent, moisture, and alcohol from the reaction mixture containing 2-substituted-1,3-dioxocyclopentane obtained by the reaction under the above reaction conditions, the next alkyl Carry out the reaction. Alternatively, 2-substituted-1,6-dioxocyclopentano may be separated and purified using operations such as distillation and extraction and used in the next reaction.

The 2-substituted-1,3-dioxocyclopentane obtained by the above reaction is reacted with an alkylating agent to produce jasmones.

The alkylating agent used in the method of the present invention can be an alkyl alkali, an aryl alkali or a compound of the general formula (% formula % ([) (where IIL3 is an alkyl or
In this case, R4 is an alkyl group), and X is a chlorine, bromine or iodine atom. Specifically, as the alkyl alkali, for example, methyllithium, ethyllithium, propyllithium, looptillithium, χ-butyllithium, etc. are often used, and as the aryl alkali, phenyllithium is often used. Furthermore, as the alkylating agent represented by the general formula (button), for example,
Methylmagnesium iodide, methylmagnesium chloride,
Methylmagnesium bromide, (methyl 2-ethanoate)magnesium iodide, (methyl 2-ethanoate)magnesium bromide, (methyl 2-ethanoate)-magnesium chloride, (ethy 2-ethanoate)magnesium bromide etc. are used.

These alkylating agents are used in an amount of 0.8 to 1.5 mol per mol of 2-substituted-1,6-dioxocyclopentano.

This alkylation reaction is usually carried out in a solvent.

As the solvent, ethers or a mixture of an organic solvent inert to the reaction and ethers can be used.

As the ethers, for example, dialkyl ether, diaryl ether, alkylaryl ether, and polyalkyl ether are used. Particularly preferred are diethyl ether, tetrahydrofuran, and the like.

Such a solvent is mixed with 2-substituted-1,3-dioquino-7 clopentane obtained by cyclizing the γ-ketocarboxylic acid ester and removing the catalyst, solvent, water, alcohol, etc., and added to this mixture. Preferably, the alkylation reaction is carried out by gradually adding the alkylating agent while cooling.

In addition, when using a miscible solvent as a reaction solvent in the first half of the cyclization reaction and the second half of the alkylation reaction, after the cyclization reaction, the 2-substituted-
The alkylation reaction may be continued by adding an alkylating agent to the reaction mixture containing 1,3-dioxocyclopentano.

Of course, 2-substituted-1,3-dioxo-7 clopentane may be isolated and subjected to the alkylation reaction.

The alkylation reaction is carried out in a temperature range of -80 to 60°C under a deoxygenated and dehydrated atmosphere. The obtained reaction mixture is hydrolyzed with an acid or an acidic salt, and the organic layer from which the solvent is removed is distilled to obtain jasmones.

By the reaction described above, jasmones having the general formula shown in the following formula can be obtained from the γ-ketocarboxylic acid ester.

(1) ROM 01) (V) (In general formula (g), R2 and R have the same meanings as in general formulas (I) and (1)).

Among jasmones, dihydrojasmone, jasmo/, methyl dihydrojasmonate, and methyl jasmonate are particularly preferred because of their unique aromatic properties.

As described above, according to the method of the present invention, jasmones can be derived in a two-step reaction using γ-ketocarboxylic acid ester, which is an advantageous raw material for processing. In this method, if the reaction is carried out without isolating the intermediate product during the process, the target product can be obtained with high selectivity through a simple process.

The present invention will be explained below with reference to Examples.

Example 1 N-methyl-4-one decanoate 20.9 (100 mmol) was added little by little to 500 rIL1 of a dry xylene solution containing buttonram tertiary butoxide 2 sfj (200 mmol) and heated to 1'40'O. Continue stirring for the next 4 hours. After cooling, the reaction solution was concentrated, and when the total amount reached 500 d, 2[) Oml of xylene was further added. 5a for this
otrtl water is added to extract the soluble matter from the organic layer, and the aqueous layer is separated. Hydrochloric acid was added to the resulting aqueous layer to adjust the pH to 2.0.
The solvent was concentrated to dryness under reduced pressure, and the remaining oil layer was
Add 00+++l of ether, separate the insoluble matter, and dry the ether layer.

The above ether layer is dehydrated and stirred under a deoxidized atmosphere while keeping the temperature below 0°C. Add to this a 100 W ether solution containing 6.6 g (55 mmol) of OH3M and Br obtained by a conventional method.
Add Ll little by little and return to room temperature.

Add an aqueous solution containing excess ammonium chloride to the reaction solution,
After hydrolysis and neutralization, the organic layer is separated and dried, and the solvent is distilled off. When the remaining oil layer was distilled under reduced pressure F, 11
8-122°O (12mmHg) fraction 8. Of! (
48 mmol) was also obtained. The nuclear magnetic resonance spectrum, infrared absorption spectrum, and gas chromatography of this were measured and compared with commercially available dihydrojasmone standard products.
Spectra and retention times matched. The yield was 48% based on the raw material γ-keto acid methyl ester.

Example 2 Buttonram 6th-butoxide 26! ! Dry xylene dissolved gsoomeVCn-methydecanoate/L/-4-one-7-yne 2017 (100 mmol) containing (200 mmol) is added little by little, and stirring is continued for 4 hours after heating to 14o0C. After cooling, the reaction solution was concentrated to a total volume of 3o arn.
1 of xylene. 50 more
Add 0 ml of water and extract the solubles into the aqueous layer. Separate the aqueous layer and add hydrochloric acid to adjust the pH to 2.0. The solvent is concentrated to dryness under reduced pressure, the remaining oil layer is extracted with 2001 ether, insoluble matter is separated, and the ether layer is dried.

The above ether layer is dehydrated and stirred under a deoxidized atmosphere while keeping the temperature below 0°C. 2 To this, 6.6g (55g) obtained by a conventional method was added.
An ether solution containing 10 mmol) of OH3M pBr
Add 0 mA' little by little and then return to room temperature.

Add an aqueous solution containing excess ammonium chloride to the reaction solution,
After hydrolysis and neutralization, the organic layer is separated, dried, and the solvent is distilled off.

The remaining oil layer was dissolved in 100+nl of methanol, and 5'% Pj-C4003-% prepared by a conventional method was added to this.
A catalyst (LkNth catalyst) α5y is added and reduced under normal pressure hydrogen. After absorbing 1400 d of hydrogen gas, the catalyst was separated by f, and methanol was distilled off from the reaction solution. Furthermore, the remaining oil layer was distilled under reduced pressure to obtain a fraction 6.7 (41 mmol) having a boiling point of 107 to 1100015 and an aromatic aroma. As a result of measuring nuclear magnetic resonance spectrum, infrared absorption spectrum, and gas chromatography of this product, the spectrum and retention time matched those of the standard reagent of cis-jasmone.

The yield was 41% based on the raw material γ-keto acid methyl ester.

Example 3 Obtained using the same amount of raw materials as in Example 1 and using the same method.
．． 200 ml of 3-dioquino-2-pentylcyclopenta/ether solution is stirred under a dehydrated and oxygen-free atmosphere while keeping the temperature below Kn°C. To this, BrMf prepared by a conventional method
Add 100 ml of an ether solution containing 39.8 g (55 mmol) of OH2000ON little by little, and then return to room temperature.

Add an aqueous solution containing excess ammonium chloride to the reaction solution,
Hydrolysis and neutralization are performed, the organic layer is separated and dried, and the solvent is distilled off. To the remaining oil layer, 100 +++ l of methanol is added, 05 g of 5% PI-O catalyst is added thereto, and hydrogenation reduction is carried out under hydrogen by a conventional method. When the absorption of hydrogen gas was completed, the catalyst was separated, the solvent was distilled off, and the remaining oil layer was distilled under reduced pressure.
100 g of a fraction of °O/0.2 mmH was obtained.

When the nuclear magnetic resonance spectrum, infrared absorption spectrum, and gas chromatography of this aromatic fraction were measured, the spectrum and retention time matched those of a standard product of methyl dihydrojasmonate.

The yield was 45% based on the raw material γ-keto acid methyl ester.

Example 4 Obtained in the same manner as in Example 1 using the same amount of raw materials.
, 200 WL of 6-thioxo 2-pentyl cyclopentane ether solution was dehydrated and heated at -30°C under a deoxygenated atmosphere.
Keep stirring below.

To this, a cooled ether solution containing 0H3L=1-29 prepared by a conventional method is added little by little, and the mixture is returned to room temperature. Thereafter, the reaction solution was treated and the reactant was purified and identified in the same manner as in Example 1, and as a result, 8.5 g (50 mmol) of dihydrojasmone was obtained.

The yield was 50% based on the raw material γ-keto acid methyl ester.

Claims (1)

[Claims] 1) General formula (1) % formula % (1) (wherein R1 represents a substituted or unsubstituted alkyl group or aryl group, and R2 represents an alkyl group, alkenyl group or alkynyl group) ) in the presence of a basic catalyst to the general formula (n) (wherein, R2 has the same meaning as in the general formula (1))
2-substituted-1,3-dioxocyclobear 4 represented by
/Km, and then this compound is alkyl alkali, aryl alkali or general formula (1) % formula % () (wherein R3 is alkyl or -0H2000R4 (wherein, R4 is an alkyl group), X is chlorine, bromine or iodine) (in which R2 and R3 have the same meanings as in general formulas (1) and (1)) ) A method for producing jasmones.