JPH05202379A - Persistent fragrance and flavor imparter and modifier - Google Patents

Abstract

PURPOSE:To obtain the subject modifier, containing (+ or -)-ambrox having a spe cific structure as an active ingredient and having better fragrance than that of natural (-)-ambrox and excellent persistence. CONSTITUTION:The objective modifier contains (+ or -)-3a,6,6,9a-tetramethyldecahydronaphto-[2,1-b]furan [(+ or -)-ambrox] expressed by the formula as an active ingredient.

Description

Detailed Description of the Invention

The present invention provides the following formula (A)

[0002]

[Chemical 2]

[±] -3, which is not described in the conventional literature, represented by
a, 6,6,9a-tetramethyldodecahydronaphtho (2,
1, b) Furan (hereinafter, referred to as (±) -unblocks) as an active ingredient. The present invention relates to a persistent aroma and flavor imparting or modulating agent.

The above formula (A) (±) -Ambrox is
A novel manufacturing method developed by the inventors of the present invention, which has not been described in the prior art, that is, the following formula (1)

[0005]

[Chemical 3]

In the formula, R represents a hydrogen atom, a methyl group or an ethyl group, and (±) -trans-β-monocyclohomofarnesic acid or its ester is represented by trifluoroacetic acid (CF ₃ COOH). Following reaction (2)

[0007]

[Chemical 4]

(±) -3a, 6,6,9a-
Tetramethyldodecahydronaphtho- [2,1, b] -furan-2-one (hereinafter referred to as (±) -norambrenolide) is formed, and the compound of formula (2) is hydrogenated bis- (2
-Methoxy-ethoxy) -aluminum sodium to reduce the formula (3)

[0009]

[Chemical 5]

After (±) -2,5,5,8a-tetramethyl-1- (2-hydroxyethyl) -2-hydroxydecalin represented by the formula (3), the compound of the formula (3) was added in the presence of a base. By cyclizing the above with P-toluenesulfonic acid chloride, it can be industrially advantageously synthesized from an inexpensive compound by a simple operation. The compound of the formula (A) can be added as an active ingredient to, for example, various synthetic flavors, natural flavors, prepared flavor compositions and the like, and can be used as an excellent and persistent aroma and flavor imparting or modulating agent.

Ambergris is a dried foreign substance which is considered to be a pathological stone generated in the intestine of Mackerel whale, and is an extremely important and expensive animal flavoring substance. Usually, Ambergris is dissolved in alcohol. It is used as a tincture as a raw material for various flavors. However,
Recently, Ambergris has become difficult to obtain due to restrictions such as the capture of whales.

It is known that various fragrance components are present in the tincture of Ambergris, and a key substance of the fragrance component is, for example, the following formula (B).

[0013]

[Chemical 6]

It is known to be (-)-unblocks represented by The above formula (B) (-)-unblocks has 4 asymmetric carbon atoms and may have 8 types of stereoisomerism, but it is a naturally occurring, highly diffusive and very strong typical compound. It is known that the compound having a strong Ambergris odor has a moiety in which each condensed ring forms a trans configuration as shown in the above formula (B) and has optical activity (-). -It is known that it only shows the body.

In recent years, with the difficulty of obtaining Ambergris, the above-mentioned compound of formula (B) by the synthetic method has been used as a raw material for the prepared perfume. Conventionally, as a method for synthesizing (−)-unblocks of the above formula (B), for example, starting material is (−)-sclareol which is an optically active substance present in the essential oil of natural Salvia sclarea,
This is oxidized with chromic acid to synthesize (+)-noramblenolide [Helv. Chim. Acta., 14,
570 (1931)], followed by reduction of (+)-norambrenolide, followed by cyclization [D.
ragocoReport, 11/12, 276-28
3 (1979)].

[0016]

[Chemical 7]

However, in the above production method, the starting raw material sclareol is, for example, Salvia sclare.
It is an expensive raw material that is present in the essential oil of a in only a few percent,
In addition, since sclareol depends on natural products, it lacks stability in the supply of raw materials, and because chromic acid, which is harmful as a reaction reagent, is used, there is a problem in terms of environmental hygiene. There are many drawbacks and disadvantages such as the use of lithium aluminum and the fact that the produced (-)-unblocks is extremely expensive, which is a big limitation when it is used as a raw material of a prepared perfume composition. .

As another proposal, as a method for synthesizing the above formula (2) (±) -norambrenolide, which is the synthetic intermediate of the above formula (A) of the present invention, for example, (±) -trans-β - in dichloromethane mono cycloalkyl homo off Arne sills acid, four methods for synthesizing the presence of tin tetrachloride and than tin chloride of a Lewis acid _{(SnBr 4, TiCl 4, BF} 3:
Et ₂ O) and a protonic acid (sulfuric acid, trichloroacetic acid) have been proposed for their reactivity [Ch.
emissary Letters, pp.757-760
(1981); pp.729-732 (1983)].

[0019]

[Chemical 8]

However, this proposal requires a very low temperature of −78 ° C. which is not industrially suitable, and the above formula (2)
Other isomers are produced and the yield is 57%, which is not always satisfactory. It is also mentioned that the above catalysts other than tin tetrachloride have no significant stereoselective effect.

In view of the fact that (-)-unblocks of the optically active substance of the above formula (B) is extremely expensive as described above and cannot be widely used as a raw material for various prepared perfume compositions, the present inventors consider it. Is optically inactive by total synthesis irrespective of natural raw materials, and as shown in the formula (A), each of the fused ring-forming parts has a trans configuration (natural type).
A method for synthesizing (±) -unblocks, which has never been synthesized in the past, and the fragrance characteristics of the formula (A) have been studied.

As a result, (±) -ambroxes, which are optically inactive from synthetic or easily available and inexpensive raw materials, and each of which forms each condensed ring has a trans configuration as shown in the formula (A). It has been discovered that can be industrially produced at low cost. In particular, a trans-formula of the following formula (1) which can be easily synthesized or obtained easily from inexpensive dihydro-β-ionone

[0023]

[Chemical 9]

In the formula, R represents a hydrogen atom, a methyl group or an ethyl group, and is represented by (±) -trans-β-monocyclohomofarnesic acid [Patent application by the same applicant 58-188536 specification (Japanese Patent Publication No.
-9903)] or the following formula (3) which can be easily synthesized from the ester thereof in two steps.

[0025]

[Chemical 10]

Cyclization of (±) -2,5,5,8a-tetramethyl-1- (2-hydroxyethyl) -2-hydroxydecalin represented by ## STR3 ## in the presence of a base and P-toluenesulfonic acid chloride. By doing so, it was discovered that (±) -unblocks, which is an optically inactive substance represented by the formula (A), can be industrially easily and inexpensively totally synthesized.

Further, surprisingly, the compound of formula (A), which is an optically inactive substance, has a fragrance of (-)-ambrox of the formula (B), which is an optically active substance synthesized from the above-mentioned sclareol. It has been found to have a comparable excellent amber-like odor and exhibit excellent persistence. Thus, according to the studies by the present inventors, the compound of the formula (A) is industrially advantageous at a significantly lower cost than the (−)-unblocks of the formula (B) of the optically active substance. It has been found that the compound is a useful compound that can be synthesized at low cost and can be widely used, for example, as a raw material for various prepared perfume compositions.

The above-mentioned compound of the formula (A) of the present invention is in good harmony with various kinds of natural flavors and synthetic flavors, and, for example, flavors such as wood, flower, green, fruit, musk and citrus. It has been discovered that it is a useful compound that can be incorporated into a composition and used as a soft, rounded, long-lasting aroma and flavor imparting or modulating agent.

Therefore, an object of the present invention is to provide a persistent aroma and flavor imparting or modulating agent which comprises the above-mentioned compound of the formula (A) which has not been described in the prior art as an active ingredient.

The (±) -ambrox which is the optically inactive substance of the formula (A) of the present invention can be synthesized industrially advantageously and inexpensively, for example, as shown in the following reaction formula.

[0031]

[Chemical 11]

In the above reaction formula, the above-mentioned formula (1) (±) -trans-β-monocyclohomofarnesic acid, which is the starting material, can be easily synthesized from dihydro-β-ionone and is obtained. It can be easily obtained by converting a mixture of the cis-form and the trans-form into an ethyl ester and subjecting it to precision distillation.

The above formula (2) (±) -norambrenolide is obtained by, for example, (±) -trans-β-monocyclohomofarnesic acid, which can be obtained as described above, in an organic solvent, if necessary. , For example, can be easily synthesized by reacting with trifluoroacetic acid.

The above reaction is carried out, for example, at about -20 ° to about 50 °.
It can be easily carried out by subjecting the reaction to a reaction temperature of about 10 ° C. for about 10 minutes to about 5 hours. Trifluoroacetic acid used in the reaction is easily available on the market, and the amount of trifluoroacetic acid used is, for example, in the range of about 0.5 to about 10 times the weight of the compound of the formula (1). Preferred examples of the organic solvent include solvents such as dichloromethane, carbon tetrachloride, benzene, hexane and toluene. The amount of the organic solvent used is not particularly limited, but a range of about 0.5 to about 10 times by weight the amount of the compound of the formula (1) can be preferably exemplified. After the reaction is completed, water is added according to a conventional method,
The organic layer is washed successively with an aqueous NaHCO ₃ solution and the organic layer is dried, and then the solvent is distilled off to obtain a crude oil. This oil can be purified, if necessary, by a purification means such as silica gel chromatography (ether 4: pentane 1: benzene 2).

To synthesize the above formula (3) (±) -2,5,5,8a-tetramethyl-1- (2-hydroxyethyl) -2-hydroxydecalin, for example, the formula obtained above is used. (2) the compound, in an organic solvent if necessary, hydrogenating bis - (2-methoxy - ethoxy) - be easily synthesized by reduction with sodium aluminum _{[NaAlH 2 (OCH 2 CH 2} OCH 3) 2] You can The above reaction can be carried out, for example, at a temperature in the range of about 20 ° to about 80 ° C for about 1 to about 10 hours. The amount of bis- (2-methoxy-ethoxy) -aluminum hydride sodium used is, for example, about 0.5 to about 2 times by weight the amount of the compound of the formula (2). You can As the organic solvent, for example, organic solvents such as toluene, benzene, hexane, ether and the like can be exemplified, and as the usage amount of these organic solvents,
For example, a range of about 1 to about 20 times by weight of the compound of formula (2) can be mentioned. After completion of the reaction, the reaction solution is subjected to a conventional method by using an aqueous solution of NaOH, water, an aqueous solution of acetic acid and Na.
The compound is washed successively with an aqueous solution of HCO ₃ and dried, and then the organic solvent is distilled off to obtain a white crystalline compound of formula (3).

In order to synthesize the formula (A) (±) -unblocks of the present invention, for example, the compound of the formula (3) obtained as described above is subjected to, for example, p-toluenesulfonic acid chloride in the presence of a base. It can be easily synthesized by contacting with. Examples of the base used in the reaction include bases such as pyridine, quinoline, triethylamine and the like. The amount of these bases used may be, for example, in the range of about 1 to about 20 times by weight the amount of the compound of the formula (3). The amount of p-toluenesulfonic acid chloride to be used can be preferably exemplified in the range of about 1 to about 10 mols based on the compound of the formula (3). The reaction is, for example, about -20 to about 50.
It can be performed at a temperature in the range of about C for about 1 to about 12 hours. After completion of the reaction, the reaction solution is poured into water and extracted with toluene, for example, and a hydrochloric acid aqueous solution is prepared according to a conventional method.
The compound (A) can be obtained as white crystals by washing with water and an aqueous solution of NaHCO ₃ and then distilling off the organic solvent.

The above-mentioned formula (A) (±) -ambrox of the present invention is an optically active substance of a natural type in spite of being an optically inactive substance, it is an amber-like aroma comparable to the aroma of (-)-ambrox. It has been found that it has a remarkable persistence especially when mixed with other flavors, and is useful as a persistent aroma and flavor imparting or modulating agent. The compound of the formula (A) has an excellent persistence and a soft and rounded aroma and flavor as an aroma or flavor imparting or modulating component especially for various cosmetics, foods and drinks, health care, hygiene, pharmaceuticals and the like.

More specifically, by adding (±) -unblocks of the formula (A) to, for example, one or more synthetic single-use flavors, various novel persistent flavor and aroma imparting or modulating agents can be obtained. It can be prepared. In addition, for example, by blending with a synthetic essential oil such as bergamot oil, lemon oil, geranium oil, mandarin oil, lavender oil, etc., to prepare a novel and persistent long-lasting aroma and flavor imparting or modulating agent which naturally essential oil naturally has. You can Further, for example, natural oils such as orange oil, lime oil, lemon oil, grapefruit oil, oak moss oil, citronella oil, vetiver oil, cinnamon oil, patchouli oil, thyme oil, clove oil, bergamot oil, and rose oil. It is possible to prepare a novel long-lasting aroma and flavor imparting or modulating agent that is well harmonized and emphasizes the characteristics of the oil production.

Furthermore, among the natural flavors and the synthetic single flavors, two or more blended flavors such as rose, jasmine, lira, mokusei, carnation, and muguet single floral (single floral flavor) or a combination thereof are used. Fragrance compositions such as floral bouquets and modern floral or oriental bouquets with green, spicy or aldehyde notes added to them, as well as flavor compositions such as strawberry, lemon, orange, grapefruit, apple and pineapple. It is possible to obtain a novel aroma and flavor imparting or modulating agent which has a mild and rich naturalness and is emphasized in terms of durability.

The amount of (±) -unblocks of the formula (A) to be compounded varies depending on the purpose and the aroma and flavor imparting or modulating agent to be compounded, but for example, about 0.001 of the total.
A range of about 50 wt% can be exemplified.

Thus, according to the present invention, it is possible to provide a persistent aroma and flavor imparting agent or an improved reinforcing agent comprising (±) -unblocks of the formula (A) as an active ingredient, and by using the agent, the formula (A) ) (±) -unblocks as an aroma and flavor ingredient, foods and drinks characterized by containing (±) -unblocks of the formula (A) as an aroma ingredient, It is possible to provide health care, hygiene, pharmaceuticals and the like characterized by containing (±) -ambrox of the formula (A) as an aroma and flavor component.

For example, drinks such as fruit juice drinks, fruit liquors, milk drinks, carbonated drinks; frozen desserts such as ice creams, sorbets, popsicles; Japanese and Western confectioneries, siamese, chewing gums, bread Nourishment, coffee, cocoa, tea, tea, etc .; Japanese soups, western soups; soups; flavor seasonings, instant drinks and foods, snack foods, etc. It is possible to provide foods and drinks containing an appropriate amount. Also, for example, shampoos,
Hair creams, pomades and other cosmetic bases for hair; cosmetics in which an appropriate amount capable of imparting its unique fragrance is added to oscilloscope, lipstick, other cosmetic bases and cosmetic detergent bases, etc. Can be provided. Furthermore, laundry detergents, disinfecting detergents, deodorant detergents and various other health and hygiene detergents; various health and hygiene materials such as toothpaste, tissue, toilet paper, etc .; to facilitate taking medicines. It is possible to provide health, hygiene and pharmaceutical products in which an appropriate amount capable of imparting a unique flavor is mixed with or applied to health, hygiene and pharmaceutical products such as corrigents and flavoring agents.

Several modes of production examples and utilization examples of (±) -unblocks of the formula (A) of the present invention will be described in more detail below with reference to Reference Examples and Examples.

[0044]

EXAMPLES Reference Example 1 Decahydro-3a, 6,6,9a-tetramethyl- (3a
α, 5aβ, 9aα, 9bβ)-(±) -naphtho [2,1-
b] Synthesis of furan-2 (1H) -one ((±) -norambrenolide) (2).

A mixed solution of 2.2 g of (±) -trans-β-monocyclohomofarnesic acid and 2 ml of dichloromethane was added to 16 ml of trifluoroacetic acid at 0 ° C., and the mixture was stirred at the same temperature for 2 hours. The reaction solution is poured into ice water, washed with an aqueous solution of sodium bicarbonate, the organic layer is dried over magnesium sulfate, and then the solvent is distilled off. The resulting crude oil was subjected to silica gel column chromatography with a developing solution of ether 4: pentane 1: benzene 2 to obtain (±) -norambrenolide (1.4 g). Yield 64%.

Mp: 119-121 ° C. (hexane) IR: 1770 cm^{-1 1} H-NMR (CDCl₃) Δ = 0.84 (3H, s),
0.89 (3H, s), 0.91 (3H, s), 1.34
(3H, s), 2.2-2.5 (2H, m)Reference example 2 (±) -2,5,5,8a-tetramethyl-2- (2-hi
Droxyethyl) -3-hydroxydecalin (3)
Success.

1.2 g of (±) -norambrenolide
(5 mmol), 70% in a solution of 12 g dry toluene
A mixed solution of 20 ml (8 mmol) of a bis- (2-methoxy-ethoxy) aluminum hydride toluene solution and 2.4 ml of dry toluene was added at 50 ° C for 1 hour, and the mixture was stirred at the same temperature for 2 hours. After cooling, 10% NaOH aqueous solution 50
poured into ml and the organic layer was further washed with 10% NaOH aqueous solution,
After sequentially washing with water, an aqueous 3% acetic acid solution and an aqueous sodium hydrogen carbonate solution, the organic solvent was distilled off to obtain 1.2 g of the target compound of formula (3) diol as white crystals. Yield 99%.

Reference Example 3 (±) -3a, 6,6,9a-Tetramethyldodecahydronaphtho (2,1, b) furan [(±) -Ambrox]
Synthesis of (A).

1.2 g (5 mmol) of the diol of the formula (3) and 3 g (16 mmol) of P-toluenesulfonic acid chloride were added to 30 ml of dry pyridine at 0 ° C., and at the same temperature for 2 hours at room temperature (10 ° -15 ° C.). After stirring at ℃) for 2 hours,
I left it overnight.

The reaction solution was poured into water to obtain 200 m of toluene.
The mixture was extracted with 1 and washed with 5% aqueous hydrochloric acid solution, water and sodium bicarbonate aqueous solution in that order, and then the solvent was distilled off to obtain 0.72 g of the compound of formula (A) as white crystals. Yield 63%.

[0051] ^{IR (KBr): 1000cm -1 1} H NMR (CDCl 3) δ = 0.84 (6H, s),
0.88 (3H, s), 1.09 (3H, s), 3.85
(2H, m).

Example 1 The following components (parts by weight) were mixed as a gardenia-type compounded fragrance composition.

Benzyl Acetate 100 Hydroxy Citronellal 150 Coumarin 10 Jasmine Absolute 30 Orange Flower Absolute 20 Phenylmethyl Calvinyl Acetate 30 Heliotropin 100 Bergamot Oil 100 Linalool 100 Amylcinnamic Aldehyde 40 Ylang Ylang Oil 70 Galaxolide 30 α-Ionone 100 Tolu-resinoid 20 Phenylacetaldehyde 15 Isoeugenyl acetate 35 Civet 10% Alcohol 10 Octylaldehyde 10% Alcohol 5 Decylaldehyde 10% Alcohol 5 Cyclohexylbutyrate 30 By adding (±) -Ambrox 60 g to the above composition 940 g A new gardenia tone that is natural and has excellent durability Fragrance composition was obtained. Further, 60 g of (-)-unblocks instead of (±) -unblocks was added to 940 g of the above composition to prepare a compounded fragrance composition, and the prepared fragrance composition containing the product of the present invention was prepared by 10 professional panelists. Compared. As a result, specialized panelists 1
All 9 out of 0 people said that the prepared perfume composition to which the product of the present invention was added was superior to the above-mentioned prepared perfume composition of the comparative product in terms of durability.

Example 2 The following components (parts by weight) were mixed as a bouquet type fragrance composition.

Phenylethyl Alcohol 180 Linalyl Acetate 30 Bergamot Oil 40 Geranium Oil 50 Benzyl Acetate 60 Heliotropin 80 Geraniol 110 Laventer Oil 20 β-Ionone 100 Amyl Salicylate 45 Tarpinyl Acetate 135 Cedar Oil 100 Citronellol 50 ──────── 1000 By adding 20 g of (±) -unblocks to 980 g of the above composition, a novel bouquet-prepared fragrance composition having natural and excellent durability was obtained.

A fragrance composition was prepared by adding 20 g of (-)-unblocks instead of (±) -unblocks to 980 g of the above composition, and 10 specialist panelists added the product of the present invention. Compared to perfume composition. As a result, 6 out of 10 professional panelists said that the prepared perfume composition to which the product of the present invention was added was excellent in aroma and persistence.

Example 3 The following components (parts by weight) were mixed as an orchid-type prepared fragrance composition.

Cyclopentadecanolide 50 Coumarin 10 Heliotropin 30 Ylang Ylang Oil 80 Methylionone 100 Neroli Oil 30 Hydroxy Citronellal 50 Linalool 70 Isobutyl Salicylate 110 5-Cyclohexadecenone 20 Amyl Salicylate 140 Oakmos Absolute 7 Phenylacetyl Aldehyde Phenylethyl Alcohol 200 Benzyl Acetate 60 ───── 1000 A new formulation with excellent persistence with emphasis on fresh and more natural lantern type by adding (±) -Ambrox 90 g to 910 g of the above composition. A perfume composition was obtained.

Further, 90 g of (-)-unblocks was added to 910 g of the above composition in place of (±) -unblocks to prepare a mixed fragrance composition, and 10 expert panelists added the product of the present invention. Compared to perfume composition. As a result, 8 out of 10 professional panelists determined that the prepared perfume composition to which the product of the present invention was added was excellent in terms of durability and novel naturalness.

Claims (1)

[Claims] 1. The following formula (A): (±) -3a, 6,6,9a-tetramethyldodecahydronaphtho (2,1, b) furan represented by the formula (2) as an active ingredient.