JPS5919535B2 - Method for producing r-ionone and its derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides the following formula (1) useful as an iris flavoring substance:
However, in the formula, R1 represents hydrogen or a methyl group, and is a known compound represented by 4-(2,2-dimethyl-6-methylene-cyclohexyl)-3-buten-2-one [γ-ionone] or 4-( 2,2-dimethyl-3-methyl-6-methylene-cyclohexino(ha)-3-butene-
The present invention relates to a method for producing 2-one [gamma-ylon] industrially and with much higher purity and yield than conventional methods.

Conventionally, many proposals have been made regarding the production of γ-ionone, but it has not been possible to selectively obtain γ-ionone with high purity and high yield.

For example, Helv. Chim. Acta. , 4l volume, 1
According to page 359 (1958), according to the following formula,
γ-Citral is synthesized from the raw material 2-carbalkoxy-3,3-dimethyl-cyclohexan-1-one through multiple steps, and γ-ionone is obtained from it.

This method has many reaction steps and complicated reaction operations,
In addition to the disadvantage that the overall yield of the mixed product of γ-ionone and α-ionone from the raw materials is low, only on the order of a few percent, only about 1% of the mixed product is obtained.
There is a defect that about 0 to 15% is γ-ionone and the remainder is α-ionone, and γ-ionone cannot be obtained selectively. Also, d-ionone is converted into γ-
As a method for converting to ionone, Liebig. A
nn. , Vol. 652, p. 115 (1962) describes a method for producing γ-ionone according to the following formula.

The reaction product obtained by this method in multiple steps and in low yield is also a mixture of γ-ionone and d-ionone,
Only a mixed composition of γ-:α-=58:42 is obtained. In addition, a production method from transpsoid ionone was also proposed (Angew.Chem., vol. 74, 944
Page, 1962), but it is complicated and yields only a mixture of α-ionone and γ-ionone. In addition, in the above formula (1), γ-ylon in which R1 is a methyl group is an aromatic substance contained in iris oil, and no proposal is known regarding the synthetic method that can be used for this substance. do not have.

The present inventors selectively produce γ-ionone or γ-ionone, which is particularly useful as a fragrance substance, in high yield and high purity.
Research was conducted to develop a manufacturing method.

As a result, e.g. γ-cyclocitral or γ-
From methylcyclocitral, the following formula (2), where 0R represents a group that can be eliminated by an acid catalyst, and R
1 represents hydrogen or methyl group, 4-(
2,2-dimethyl- or 2,2-dimethyl-3-methyl-6-methylene-cyclohexyl)-4-monosubstituted butan-2-one is obtained, and by contacting the 2Y arsenide with an acid catalyst, It has been discovered that γ-ionone or γ-ione represented by the following formula (1) can be selectively obtained in high yield and purity by performing the ROH removal reaction.

Therefore, an object of the present invention is to provide an industrially advantageous method for selectively producing γ-ionone or γ-ionone with high purity and high yield.

The above objects and many other objects and advantages of the present invention will become more apparent from the following description. The above raw material formula (2) used in the method of the present invention is, for example, a known compound γ-cyclocitral or γ-methylcyclo citral and the following formula (4), where 0R represents a group that can be eliminated by acid catalyst, preferably R is alkyl, acyl, acylphosphoryl, phosphoryl, trialkylsilyl, dialkylpolyl, alkyl, lucogycyporyl, di It can be easily produced by condensation reaction with an isopropenyl derivative represented by alkoxypolyl, a group selected from the group consisting of lithium atoms and sodium atoms.

The reaction of γ-cyclocitral or γ-methylcyclocitral of formula (3) above with the isopropenyl derivative of formula (4) can be carried out, for example, in the presence of a tertiary amine, preferably in an ether organic solvent, to -80°C to about -40°C, preferably at a low temperature of about -80°C to about -60°C, about 2 to
This can be carried out by bringing a compound of formula (3Y) into contact with a compound of formula (4Y) for about 7 hours.

This reaction can also be carried out in the presence of Lewis acids such as titanium tetrachloride, aluminum chloride, tin tetrachloride, zinc chloride and the like. The amount of the formula (4) compound to be used for the formula (3) compound is preferably the formula (4) for 1 mole of the formula (3)-f compound.
The f-hyde compound is about 1 mol to about 2 mol, and about 1 to about 1.
About 5 mol is more preferable. The amount of tertiary amine used for the compound of formula (3) may be almost the same as in the case of the compound of formula (4>11(.). Examples of the ether organic solvent include diethyl ether, dipropyl ether,
diisopropyl ether, dibutyl ether, mono- or di-ethylene glycol dimethyl ether, mono- or di-ethylene glycol diethyl ether,
Examples include tetrahydrofuran, dioxane, and mixtures thereof. Furthermore, examples of the above-mentioned tertiary amine include triethylamine, trimethylamine, tributylamine, and pyridine. Examples of compounds of the above formula (4) include lower alkyl groups in the formula R/) SC, ~C; C2-C5 acyl groups such as arotyl, propionyl, and butynyl; acylphosphoryl in C2-C; C1 A trialkylsilin group having a lower alkyl group of ~C2: a dialkylporyl group having a lower alkyl group of C, ~C4: a lower alkyl group of C1 to C4 and a C, ~
Preferred examples include isopropenyl derivatives selected from the group consisting of an alkylalkoxyporyl group having a C4 lower alkoxy group; a dialkoxyporyl group having a C1 to C4 lower alkoxy group; Li; and Na.

When the group R in these formula (4Y arsenic compounds) is a polyyl group-containing group as described above, polyyl hydroxides are produced as a by-product during the reaction, so a mild oxidizing agent such as hydrogen peroxide is used. According to the method of the present invention, for example, the 4-(2,2-dimethyl-dimethyl-
Alternatively, by contacting 2,2-dimethyl-3-methyl-6-methylene-cyclohexyl)-4-monosubstituted butan-2-one with an acid catalyst, the r-ionone of formula (1) can be easily removed by ROH reaction. Alternatively, it can be converted to γ-iron.

This reaction is carried out in the same ethereal organic solvent as described above.
Preferably, alumina, silica, alumina-silica, celite, activated clay, solid acids, dilute mineral acids, organic sulfonic acids, etc. may be brought into contact with compounds of formula (2). In particular, alumina, especially neutral The use of alumina gives good results. Since the reaction proceeds at room temperature, there is no need for particular cooling or heating, although such temperature conditions can be employed if desired. Usually from about 0°C to about A temperature in the range of about 60°C is most often used.The amount of acid catalyst used is preferably as small as possible, for example in the range of about 0.01 to about 40% by weight based on the starting compound of formula (2). The amount can be selected as appropriate.The amount of these acid catalysts used can also be changed appropriately depending on the reaction temperature.Additionally, the amount of the solvent to be used is in excess, for example, about 30 times to about 80 times the volume of the compound of formula (2). After the solvent is distilled off and recovered, the reaction product is subjected to vacuum distillation, column chromatography (
For example, silica gel column lyhexane-ether (9
:l volume ratio) eluent).

Next, several examples of implementing the method of the present invention will be explained in more detail by way of examples.

For reference, production examples of the compound of formula (2) are also described. Example 1 Synthesis of 4-(2,2-dimethyl-6-methylene-cyclohexyl)-4-hydroxy-butan-2-one: 0.355 mol (97.3 f1) of dibutylpolyl-trifluoromethanesulfonate was added to -78°C. to coagulate it, and add triethylamine 0
．． A solution of 355 mol (35.99) in 300 mt of ether is added.

Return the temperature to room temperature and make a homogeneous system. Then -78℃ again
The mixture was cooled to 250 wL of ether and a solution of 0.355 mol (20.69) acetone in 1 liter of ether was added dropwise. After 20 minutes, 0.355 moles of γ-cyclocitral (54
A solution of 1) in 250 ml of ether is added dropwise.

After dropping, the mixture was stirred at a reaction temperature of -78°C to -60°C for about 4 hours and 30 minutes.

After the reaction is completed, a solution of 1,000 ml of phosphorus buffer with a pH of 7 and 2,000 ml of methanol is added to the reaction product at the same temperature, and the cooling bath is removed. When the temperature rises to 0℃, 28
Add 600 ml of % hydrogen peroxide solution and stir at room temperature for 1 hour. Add 3,000 ml of water and recover methanol by distilling it off at normal pressure. The aqueous layer is extracted with dichloromethane, and the dichloromethane layer is dried over anhydrous sodium sulfate. Dichloromethane is distilled and recovered at normal pressure, and the residual liquid is subjected to vacuum distillation to obtain a boiling point of 120° to 12.
The oily substance 4-(
2,2-dimethyl-6-methylene-cyclohexyl)
5.2.61 of -4-hydroxy-butan-2-one (yield 71%) was obtained. Synthesis of γ-ionone; 4-(
2,2-dimethyl-6-methylene-cyclohexyl)
- Neutral alumina 5θ is added to a solution of 0.074 mol (15.59) of 4-hydroxy-butan-2-one in 1000 ml of ether and stirred overnight at room temperature.

After removing the alumina by filtration and recovering the ether by distilling it off under normal pressure, the remaining liquid was distilled under reduced pressure to obtain a boiling point of 91° to 92°C/1.
α-ionone 9.21 (yield 65
%) was obtained.

The obtained γ-ionone had an excellent iris-like aroma. Example 2 Synthesis of 4-(2,2-dimethyl-3-methyl-6-methylene-cyclohexyl)-4-hydroxy-butan-2-one; dibutylpolyl trifluoromethanesulfonate 0.355 mol (97.39) was coagulated at -78°C, and 0.355 mol of triethylamine (35
．． Add 9 g) of 300 ml of ether solvent.

Return the temperature to room temperature and make a homogeneous system.

Thereafter, the mixture was cooled to −78° C. again, and a solution of 0.355 mol (20.69 mol) of acetone in ether 250 was added dropwise.
After 20 minutes, 0.0% of γ-methylcyclotral was added to the reaction system.
A solution of 355 mol (58 g) of ether 250 is added dropwise. After dropping, the mixture is stirred and reacted at a reaction temperature of -78°C to -60°C for 5 hours. After the reaction is complete, add 1,000 ml of phosphorus buffer with a pH of 7 and 2,000 ml of methanol to the reaction product at the same temperature.
Add mi solution and remove cooling bath. When the temperature rises to 0° C., 600 ml of 28% hydrogen peroxide solution is added and stirred at room temperature for 1 hour and 30 minutes in order to oxidize by-product dibutyl polyl hydroxide to boric acid. 3000m1 of water!
and methanol is distilled off and recovered at normal pressure.

The oil content is extracted from the aqueous layer with dichloromethane, and the dichloromethane layer is dried with anhydrous sodium sulfate. Dichloromethane is distilled and recovered at normal pressure, and the residual liquid is subjected to vacuum distillation to reduce the boiling point to 130° to 13.
The oil 4-(
2,2-Dimethyl-3-methyl-6-methylene-cyclohexyl)-4-hydroxy-butan-2-one60.
A yield of 2g (74.6%) was obtained. Synthesis of γ-iron;
4-(2,2-dimethyl-3-methyl-6-
methylene-cyclohexyl)-4-hydroxy-butan-2-one 0.074 mol (16.9 g) of ether 1
Add alumina-silica (1:l) 39 to the 000 solution and stir at 10°C to 15°C overnight.

Claims (1)

[Claims] 1 The following formula (2), ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) However, in the formula, O
4-(2,2-dimethyl- or 2,2-dimethyl-3-methyl-6-
There are the following formulas (1), ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (1), which are characterized by bringing methylene-cyclohexyl)-4-substituted butan-2-one into contact with an acid catalyst to cause a de-ROH reaction. In the formula, R^1 has the same meaning as above, and a method for producing a γ-ion and its derivatives represented by: 2 R of the leaving group OR is selected from the group consisting of alkyl, acyl, acylphosphoryl, phosphoryl, trialkylsilyl, dialkylboryl, alkylalkoxyboryl, dialkoxyboryl, lithium atom, sodium atom, and hydrogen atom The manufacturing method according to claim 1, which is a group comprising: 3 The compound of formula (2) is γ-cyclocitral represented by the following formula (3), ▲ has a mathematical formula, chemical formula, table, etc. ▼ (3) where R^1 represents hydrogen or a methyl group. Or γ-methylcyclocitral and the following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (4) However, in the formula, R is alkyl, acyl, acylphosphoryl, phosphoryl, trialkylsilyl, dialkylboryl, alkylalkoxyboryl, dialkoxy The method according to claim 1, which is obtained by condensation reaction with an isopropenyl derivative represented by: boryl, a group selected from the group consisting of lithium atoms and sodium atoms.