JPS6048516B2 - Cyclohexenyl-β-ketols, their preparation and use - Google Patents

Description

[Detailed description of the invention] ・o The present invention relates to the following formula (■) H3CCH,0OH 2,1,1 1<~CH" formula (formerly provided that in the formula, R represents a hydrogen atom or a methyl group, and Z'
This invention relates to cyclohexenyl-β-ketols represented by 4,4 ethylene dioxide, and their production and utilization.

4-Hydroxy-β-damascone and β-damascenone represented by the following formulas are known aroma components that are isolated and collected from natural tobacco leaves and naturally sourced Bulgarian rose oil, respectively. The present inventors have conducted research on the synthesis of the above-mentioned natural aroma components and their analogous compounds. As a result, it was discovered that the cyclohexenyl-β-ketol represented by the above formula (■), which has not been described in any literature, can be easily synthesized from inexpensive and easily available raw materials.

Furthermore, the compound represented by the formula (■) is 4-hydroxy-β
- In addition to being useful as intermediates for the synthesis of damascone, β-damascenone, and their analogues (desmethyl derivatives), these three compounds themselves have a unique floral aroma with a green and dull feel. It was also discovered that it is a long-lasting fragrance ingredient. Thus,
The compound of formula (■) above has remarkable usefulness as an excellent long-lasting aroma imparting or modulating agent. It was found that it is useful as a long-lasting aroma imparting or modulating agent in a wide range of applications such as luxury goods, cosmetics, and health and hygiene pharmaceuticals.

Therefore, an object of the present invention is to provide a compound of the formula (■) which has not been described in any literature, and its production method and utilization. The above objects and many other objects and advantages of the present invention will become more apparent from the following description. The above formula of the present invention (
■) The compound can also be represented by the following formula (■). The compound of formula (■) of the present invention is obtained by subjecting an acetylcyclohexenone ketal represented by the following formula (1), where R and Z' have the same meanings as above, to an aldol condensation reaction with acetaldehyde in the presence of an alkali. It can be easily obtained by

This can be shown in a process diagram as follows.
The above formula (1) compound formula (1)' and formula (1)'' compound are also compounds that have not been described in many literatures, such as the following process diagram) ~,
It can be manufactured according to No. 1.

The details of producing the raw material formula (1)' or formula (1)'' compound of the present invention according to the above process diagram are disclosed in Japanese Patent Application No. 2-52-114306 filed on the same date by the same applicant. Name: Acetyl cyclohexenone ketals and uses)
It is described in detail in the specification. Briefly, a heated reaction product of 2-trimethylsilyloxy-4-alkoxy-1,3-butadiene of the above formula (2) and menthyl oxide of the above formula (3) is heated to ethylene in the presence of an acid catalyst. By reacting with glycol, the above formula (1)
1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene can be produced. Furthermore, the compound of formula (1)' is treated with a methylating agent and then treated with a halogen such as chlorine, bromine, iodine, etc.
Next, a compound of formula (1)'' can be produced by dehydrohalogenation reaction in the presence of a base.

According to the present invention, acetylcyclohexenone ketals represented by the above formula (1), namely 1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene represented by the above formula (1) or the formula ( 1) 1-acetyl-2,6,6-trimethyl-4,
By subjecting 4-ethylenedioxy-1-cyclohexene to an aldol condensation reaction with acetaldehyde in the presence of an alkali, the following formula (■), where R represents a hydrogen atom or a methyl group, and Z' represents 4,4-ethylenedioxy It is possible to produce cyclohexenyl-β-ketols represented by the following, which represent an oxy group.

The above reaction can be carried out, for example, by contacting the acetylcyclohexanone ketal of formula (1) with an alkali such as lithium amide or magnesium bromide amide in an inert organic solvent, and further contacting with acetaldehyde. , the compound of formula (■) can be selectively produced in good yield.

The reaction is preferably carried out at as low a temperature as possible, below room temperature, for example, at a reaction temperature of about -100°C to about +30°C. A temperature of about -80°C to about +10°C can be more preferably employed. The reaction time can be appropriately selected depending on the reaction temperature, for example, about 3 minutes to 4011 hours. Reaction times such as Specific examples of the above-mentioned alkali include, for example:
Lithium amides such as lithium diisopropylamide, lithium di-n-butylamide, lithium diisobutylamide, lithium diethylamide, lithium dicyclohexylamide, lithium-N-methylamide, lithium-N-ethylanilide, lithium diphenylamide, etc.; magnesium bromide-N-methylanilide , magnesium bromide amides such as magnesium bromide-N-ethylanilide and the like.
The amount of these amides used as an alkali can be appropriately selected, and for example, about 1 to about 10 mol can be used per 1 mol of the acetylcyclohexenone ketal of formula (1). . A usage amount of about 1.2 to about 5 moles can be more preferably employed. Further, there is no particular restriction on the amount of acetaldehyde used, and for example, the amount used is about 1 to about 50 mol, more preferably about 2 to about 10 mol, per 1 mol of the compound of formula (1). be able to. Examples of inert organic solvents used in the reaction include diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, dimethoxyethane, benzene,
Examples of 3t include ethers such as toluene and n-hexane, aliphatic and aromatic hydrocarbons, and combinations of multiple types thereof. The amount of these solvents to be used can be selected as appropriate, and based on the weight of the acetylcyclohexenone ketal of formula (1), for example, about 2 to about 100 times the weight,
More preferably, the amount used is about 10 to about 5 times the amount. 3L of the obtained compound of formula (■) can be obtained by injecting the reaction product into water, for example, and adding a suitable solvent, for example n-
The solvent phase can be isolated by extraction with solvents such as hexane, benzene, toluene, ether, ethyl acetate, chloroform, methylene chloride, carbon tetrachloride, etc., and the solvent phase is, for example, neutralized, washed with water for 40 minutes, dried, and concentrated. If desired, it can be further purified by vacuum distillation, column chromatography, or other known purification means.

For example, cyclohexenyl-β-ketols of the formula (■) obtained as described above, for example, 1-(3'-hydroxybutyroinolet)-6 in which R is a hydrogen atom
,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene, 1-(3'-hydroxybutyroinolate)-2,6,6-trimethyl4,4-ethylenedioxy, in which R is a methyl group. Oxy-1-cyclohexene is an oily compound that has not been described in any literature, and the former has a temperature of 124° to 126°.
°C/0.01 wrmH da, the latter exhibiting a boiling point of 123° to 127'°C/0.01 wgnHy. The results of infrared and nuclear magnetic resonance spectra of these compounds not described in literature are shown in Examples below. Furthermore, it has been found that these compounds of formula (■) have a unique green and dull floral fragrance and are long-lasting fragrance components. According to the present invention, a compound represented by the above formula (Π), which can be produced, for example, as described above, in which R has the same meaning as above, and Z' represents a 4,4-ethylenedioxy group It is possible to provide a persistent fragrance imparting or modulating agent characterized by containing at least one of the above as an active ingredient.

These compounds of formula (■) exhibit unique properties as persistent fragrance imparting or modulating agents capable of imparting a persistent floral fragrance in a wide range of fields such as luxury goods, cosmetics, and health/hygiene/pharmaceuticals. Thus, for example, fragrances, tobacco, various cosmetic creams, toques, lotions, hair and hair care products, long-lasting soaps, toiletries, dust paper, antiperspirants, dandruff agents, etc. It is useful as a unique long-lasting aroma imparting liquid modulator in a wide range of fields such as health, hygiene, and pharmaceuticals. The numerical aspect k of implementing the present invention will be explained in more detail below using reference examples and examples.

Evening example 1 Production of 2-trimethylsilyloxy-4-methoxy-1,3-butadiene 250 da of triethylamine and 2 d of zinc chloride
．． A solution of 225 y of trimethylsilyl chloride and 100 y of 4-methoxy-3-buten-2-one in 600 ml of benzene was added dropwise to the 5 ml suspension at room temperature over 1 hour.

Thereafter, the reaction is carried out at 60°C for 2Vf. After the reaction is complete, the reaction product is poured into ether 61 and filtered through Celite. By concentrating the oral fluid and distilling the resulting residue under reduced pressure, pure 2-trimethylsilyloxy-4-methoxy 1
, 3-butadiene (76%). boiling point:
43-44℃/3-Hy nuclear magnetic resonance spectrum (CCI,): δ0.20 (9H
, 10s), 3.54 (3H, s), 3.97 (2H,
br0ads), 5.22 (IH, d, J=12Hz)
, 6.74 (IH, d, J = 12 Hz) Reference Example 2 Production of 1-acetyl-6,6-dimethyl-4,4-15 ethylenedioxy-1-cyclohexene In an A8OOml autoclave, 2-trimethylsilyloxy-4-methoxy 100 y of 1,3-butadiene and 20 y of mesityl oxide were charged and reacted at 180°C for 2 hours.

After cooling, the reaction mixture was diluted with ethylene 2 (glycol 18.0yNp
-Toluenesulfonic acid 1.0g and benzene 500wL
1 and reacted at 80°C for 3 minutes by azeotropic method. After the reaction is completed, the reaction product is washed with sodium carbonate water. Wash the benzene layer with water, MySO. The residue 2 obtained after drying and concentration is distilled under reduced pressure to obtain 28.0y (67%) of pure 1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene. Boiling point: 80
~81℃/0.05-Hy Rf (SlO2): 0.27 (n-hexane/ethyl acetate 3/1) Infrared absorption spectrum (liquid film): 1665, 1620, 1090 cm-1 Nuclear magnetic resonance spectrum (CDCl3 ): δ1.26 (6H, s), 1.68 (2H, s), 2.
27 (3H, s), 2.50 (2H, d, J=4Hz)
, 3.95 (4H, s), 6.67 (IH, t, J=4
Hz) Mass Svector Ni m/E2lO (M゛), 19
5,167,109,107,87,86,81,43
,42,41B2-trimethylsilyloxy4-methoxy1,3-butadiene 30q) Mesityl oxide 10
A solution consisting of f and 100ml of xylene was heated at 150°C.
React for 1 hour.

After the reaction is completed, the reaction product is concentrated, and to the resulting residue are added 8 das of ethylene glycol, 0.5 das of p-toluenesulfonic acid, and 100 mL of benzene, and the mixture is reacted for 1 hour under refluxing benzene. After cooling, the reaction product is washed with sodium carbonate water and the benzene layer is separated. Wash the benzene layer with water and use MdaSO. After drying, it is concentrated, and the resulting residue is distilled under reduced pressure to obtain 11.0 Da (52%) of pure 1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene. ; Example 3 Production of 1-acetyl-1-bromo-2,6,6-trimethyl-4,4-ethylenedioxycyclohexane ~ Under a nitrogen atmosphere, in a suspension of 15.0 y of cuprous iodide in 200 ml of diethyl ether, While cooling at 0°C, 150 mι of an ether solution of methyllithium (1.0 mmol/mL) was added, and the mixture was reacted at the same temperature for 30 minutes.

Next, a solution of 10.5 y of 1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene in 40 ml of ether is added to the above solution at 0° C., and the mixture is reacted at the same temperature for 4 hours. Furthermore, a solution of 24 g of bromine in 40 ml of benzene was added to the above solution while cooling at -60°C, and a three-powder reaction was carried out at 0°C. After the reaction is completed, the reactant is poured into sodium hydrogen aqueous solution, washed, and the ether layer is separated. Wash the ether layer with hypo water, heavy soap water, water, MySO. After drying, concentrate. By distilling the obtained residue under reduced pressure, pure 1-acetyl-1-bromo-2,6,6-trimethyl-4,4-
13.4g of ethylenedioxycyclohexane (88%
)obtain. Boiling point: 92-93°C/0.03Tfr1rL
Hydrogen Rf (SiO2): 0.41 (n-hexane/ethyl acetate 3/1) Infrared absorption spectrum (liquid film): 16
90,1090 cm nuclear magnetic resonance spectrum (CDCl3
): δ1.06 (3H, s), 1.22 (3H, d, J
=7Hz), 1.47(3H,s), 1.3~2.7(
5H), 2.71 (biliary, s), 3.85 (4H, S)B
Methylmagnesium iodide is prepared by dropping a solution of 2.5y of methyl iodide in 40ml of ether at room temperature into a mixture of 0.36y of metallic magnesium in 10ml of ether under a nitrogen atmosphere, and then carrying out a three-powder reaction.

1.0 y of cuprous iodide was added to this Grignard reagent solution, and then, under cooling at 0°C, a solution of 2.1 y of 1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-cyclohexene in 50 ml of ether. Drop in for 1 hour.
Furthermore, after reacting at the same temperature for 4 hours, the reaction solution was cooled to -40°C, a solution of 4.0 g of bromine in 10 mt of benzene was added, and
React at 30°C for 30 minutes. After the reaction is completed, the reactant is poured into sodium hydroxide solution, washed, and the ether layer is separated. Wash the ether layer with hypo water, heavy soap water, water, and MfISO.
After drying, concentrate. The resulting residue was purified by silica gel chromatography (100y) [n-hexane/ethyl acetate 6/1] to obtain pure 1-acetyl-1-bromo-2,6,6-trimethyl-4,4-ethylenedioxy. 2.911 (82%) of cyclohexane are obtained.

Reference Example 4 Production of 1-acetyl-2,6,6-trimethyl-4,4-ethylenedioxy-1-cyclohexene A11-acetyl-1-bromo-2,6,6-trimethyl-4,4-
Ethylenedioxycyclohexane 12.2y) Lithium chloride 4.2y) Lithium carbonate 7.4y and DMFlOO
ml of the mixture was subjected to a 2011 Terama reaction at 100°C.

After cooling, it is added to the reactants. - Add 200 ml of gel and sip. Add water to the oral fluid and separate the ether layer. Wash the ether layer with water, MqSO. After drying, concentrate. By distilling the obtained residue under reduced pressure, pure 1-acetyl-1
-bromo-2,6,6-trimethyl-4,4-ethylenedioxy-1-cyclohexene at 7.0 Da (78%
)obtain. Boiling point: 82-83℃/0.057WLHyRf
(SlO2): 0.28 (n-hexane/ethyl acetate 3/1) 3 Infrared absorption spectrum (liquid film): 1690
, 1090c77z nuclear magnetic resonance spectrum (CDCI.

): δ1.16 (6H, s), 1.63 (3H, s),
1.67 (kawa, s), 2.26 (2H, s), 2.32
(3H, s), 44.96 (4H, S) mass vector m /E224 (M”), 209,181,136,
128,95,87,86,43,42,41B1-acetyl-1-bromo2,6,6-trimethyl-4,4
- 3.0 g of ethylenedioxycyclohexane, DBU (
A solution consisting of 7.5 Da (1,8-diazabicyclo[5,3,0]-7-undensen) and 20 ml of toluene is reacted at 100°C for 2 hours.

After the reaction is completed, the reaction mass is washed with cold INHCI water and the toluene layer is separated. Wash the toluene layer with heavy soap and water, Mf
After drying with lSO4, concentrate. The resulting residue was purified by silica gel column chromatography (100 Da) [n-hexane/ethyl acetate 6/1] to obtain pure 1-acetyl-2,6,6-trimethyl-4,4-ethylenedioxy- 1.59 (68%) of 1-cyclohexene is obtained.
Example 1; 1-(3'-hydroxybutyroinolate)-6,
Production of 6-dimethyl-4,4-ethylenedioxy-1-cyclohexene Under nitrogen atmosphere, diisopropylamine 4
．． 09 in THF2Oml solution under cooling at -78°C,
26.0 ml of n-hexane solution (1.5 mmol/mL) of n-butyorlithium was added, and then 1-acetyl-6,6-dimethyl-4,4-ethylenedioxy-1-
Add cyclohexene 4.2y(7)THFlOmι solution and react at the same temperature for 1.5 hours.

Further, an acetaldehyde 4.4y(7)THFIOmι solution was added to the above solution while cooling at -78°C, and the mixture was reacted at the same temperature for 1.5 hours. After the reaction is completed, the reaction product is poured into cold ammonium chloride water and extracted with ether. Wash the ether layer with water and add MySO. After drying with
4.5 Da (88%) of 4-ethylenedioxy-1-cyclohexene is obtained. Boiling point: 124-126°C/0.01
-HyRf(SiO2): 0.10(n-hexane/
Ethyl acetate 3/1) Infrared absorption spectrum (liquid film): 3
450, 1660, 1620, 1090, 950cm-
1 nuclear magnetic resonance spectrum (CDCl3): δ1.19 (3H, d, J = 6Hz), 1.28 (6H
, s), 1.68 (2H, s), 2.48 (2H, d,
J=4Hz), 2.6-2.8 (2H), 3.32 (out, BrOads), 3.94 (4H, s), 4.18 (
IH, 7n), 6.62 (IH, t, J = 4Hz) Example 2 1-(3'-Hydroxybutyroinolate)-2,
6,6-trimethyl-4,4-ethylenedioxy-1-
Preparation of cyclohexene Under a nitrogen atmosphere, -78
While cooling at °C, a solution of n-butyllithium in n-hexane (
1.5 mmol/mι) was added, then 1
-acetyl-2,6,6-trimethyl-4,4-ethylenedioky-1-cyclohexene 4.5y(7)THFl
Add Oml solution. Eh, react at the same temperature for one and a half hours.

Furthermore, a solution of 4.4 Da of acetaldehyde in THFlOmι was added to the above solution while cooling at -78 DEG C., and the mixture was reacted at the same temperature for 1.5 hours.

After the reaction is completed, the reaction product is poured into cold ammonium chloride water and extracted with ether. Wash the ether layer with water, MySO. After drying, concentrate. The obtained residue was distilled under reduced pressure to obtain 5.2y of pure 1-(3'-hydroxybutyroinolate)-2,6,6-trimethyl-4,4-ethylenedioxy-1-cyclohexene (97% ).
B. P. :123~127°C/0.01TnmHgR
f(SlO2): 0.13 (n-hexane/ethyl acetate 3/1) IR (liquid film): 3450, 1685, 10
90cm-1NMR (CDCI.

): δ1.18 (6H, s) 1.19 (3H, d, J=
6Hz), 1.62 (3H, s), 1.67 (2H, s
), 2.25 (kawa, s), 2.6-2.8 (2H), 3
．． 36 (IH, BrOads), 3.95 (4H, s)
, 4.30 (IH, m) Example 3 Usage example. Mitomoe J', rιlow + 4ιv↑H gain"゛bpyro. 1-(3'-
Hydroxybutyroinolate)-6,6-dimethyl-4
,4-ethylenedioxy-1-cyclohexene 10fI
The resulting composition is long-lasting, has an accentuated floral note with a hint of green, modified from the original composition, and has a sweetness throughout the fragrance composition.
There was harmony.

Also, 1-(3'-hydroxybutyroyl-6)-6,
When 1-(3'-hydroxybutyroinolet)-2,6,6-trimethyl-4,4-ethylenedioxy-1-cyclohexene is used instead of 6-dimethynoole-4,4-ethylenedioxy-1-cyclohexene had the same effect as above, but the feeling of drowsiness was somewhat emphasized. According to the above formulation example, the mixed composition 10f1,
Cigarettes are prepared using the flavored tobacco sprayed onto the tobacco mixture 100y.

Claims (1)

[Claims] 1 The following formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼Formula (II) However, in the formula,
R represents a hydrogen atom or a methyl group, and Z' is 4,4-
Cyclohexenyl-β-ketols representing an ethylenedioxy group. 2 The following formula (I), ▲Mathematical formulas, chemical formulas, tables, etc. are available▼Formula (I), where R and Z' have the same meanings as above, and acetylcyclohexenones represented by acetaldehyde in the presence of an alkali. The following formula (II) is characterized by an aldol condensation reaction with
However, in the formula, R and Z' have the same meanings as above. 3 Formula (II) below ▲There are mathematical formulas, chemical formulas, tables, etc.▼Formula (II) However, in the formula,
A fragrance composition containing as an active ingredient at least one type of cyclohexenyl-β-ketol represented by R and Z' having the same meanings as above.