JP2000053675A - Macrocyclic lactone compound, its production and perfume composition containing the compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a macrocyclic lactone excellent in quality of perfume, having powdery touch and having the musk-like perfume, and further to provide a production method thereof and a perfume composition containing the compound. SOLUTION: This macrocyclic lactone [(R)-isomer or racemic isomer] is represented by the formula [a double broken line represents a single bond or a double bond; (m') is an integer of 1-9, and (n') is an integer of 0-7 with the proviso that the total of (m') and (n') is an integer of 8-10; with the proviso that when the double broken line is a single bond and the compound is the racemic isomer, the total of (m') and (n') is not 9]. The compound of the formula is synthesized by cyclizing an ester compound composed of a carboxylic acid having an unsaturated bond at the terminal and an alcohol having the double bond at the terminal by a metathesis reaction to provide a macrocyclic compound having the double bond, and optionally hydrogenating the obtained macrocyclic compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel macrocyclic lactone compound, a method for producing a macrocyclic lactone compound containing the novel macrocyclic lactone compound, and a fragrance composition containing the macrocyclic lactone compound. More specifically, the present invention relates to the compound having a musk-like odor, a method for producing the compound, and a fragrance composition containing the macrocyclic lactone compound.

[0002]

2. Description of the Related Art At present, research has been conducted on macrocyclic compounds having a large number of musk fragrances in order to make it difficult to obtain natural musk fragrances from the viewpoint of animal protection and to meet the changing tastes of fragrances. The results have been reported (for example, IB Bersuker et al., New J. Med.
Chem. 1991, Vol. 15, p. 307; Shozo Abe, Fragrance No. 96, September 1970, p. 19). Of these macrocyclic compounds, muscone (3-methylcyclopentadecanone) is the largest synthetic target and a structural model for the development of similar compounds. As a macrocyclic lactone compound similar to mucon, a mixture of regioisomers obtained by Bayer-Villiger oxidation of dl-muscon is known (British Patent No. 306,352). No quality was reported and there was no report that each isomer was synthesized individually,
Furthermore, the optically active substance has not been scrutinized at all.

[0003] Incidentally, macrocyclic musk compounds are difficult to synthesize and are expensive, so that nitromusks represented by musk ketone and musk xylol, which can be synthesized stably and inexpensively, galaxolide (registered trademark) and tonalide ( Polycyclic musks represented by TM) occupy most of the market, and macrocyclic musk compounds represented by exaltone, exaltolide, and ethylene brassate account for less than 10% of the musk market. However, from the viewpoint of increasing natural consciousness and environmental considerations in recent years, these macrocyclic compounds having almost no problem not only in direct safety of the compounds but also in accumulating property and degradability have been attracting attention again. However, the aroma of macrocyclic musk compounds generally lacks the powdery feeling that is one of the characteristics of nitro musks and polycyclic musks, and the macrocyclic synthetic musk compounds developed so far are still satisfactory. I couldn't do it. Therefore, it is desired to develop a novel macrocyclic musk compound having an excellent flavor and a powdery feeling that satisfies the effect as a fragrance material at the time of actual preparation, the problem on the environment after use, and the problem of synthesis. It is rare.

[0004]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a novel macrocyclic compound which satisfies such demands, has excellent fragrance, has a powdery feeling, and has a musk-like odor. Aim. Another object of the present invention is to provide a method for easily producing a macrocyclic compound having the above properties. Further, another object of the present invention is to provide
An object of the present invention is to provide a fragrance imparting agent comprising a macrocyclic compound having the above-mentioned characteristics and a fragrance composition containing the same.

[0005]

Means for Solving the Problems The present inventors have synthesized various macrocyclic compounds by various synthetic methods in order to achieve the above object, and have conducted intensive studies on their fragrances, their potential as compounded materials, and the like. As a result, the present invention has been accomplished by finding that a specific lactone compound having a methyl group at the 3-position has excellent flavor and powdery feeling, and that the lactone compound can be easily produced by a specific production method.

That is, the first aspect of the present invention relates to the general formula (1)

Embedded image (In the formula, m is an integer of 1 to 9, n is an integer of 0 to 7, and the sum of m and n is an integer of 8 to 10.)
(R) or racemic ester compound represented by
Represented by the general formula (2), wherein the ring is closed by a metathesis reaction.

Embedded image (Wherein m and n have the same meanings as described above). A method for producing a macrocyclic lactone compound having a double bond ((R) form or racemic form) represented by the formula:

The second invention is characterized in that a macrocyclic lactone compound having a double bond ((R) form or racemic form) represented by the general formula (2) is hydrogenated.
General formula (3)

Embedded image (Wherein m and n have the same meanings as described above). A process for producing a macrocyclic lactone compound ((R) form or racemic form) represented by the formula:

The third invention provides the macrocyclic lactone compound ((R) form or racemic form) described in the first invention.
Wherein the ester compound ((R) form or racemic form) represented by the general formula (1) is converted to a compound represented by the general formula (4)

Embedded image Β-butyrolactone ((R) form or racemic form) represented by the general formula (5)

Embedded image (Wherein, X is a halogen atom, and n is an integer of 0 to 7).
General formula (6)

Embedded image In the presence of a copper compound represented by CuX ¹ (6) (wherein X ¹ is a halogen atom), a ring-opening reaction is carried out to obtain a compound of the general formula (7)

Embedded image Wherein n is as defined above, and the terminal unsaturated carboxylic acids ((R) form or racemic form) represented by the formula (8)

Embedded image (Wherein m is an integer of 1 to 9), wherein the macrocyclic lactone compound ((R) form) is obtained by esterification with a terminal unsaturated alcohol represented by the formula: Or a racemic form).

The fourth aspect of the present invention relates to the general formula (9)

Embedded image (Wherein the double dashed line indicates a single bond or a double bond, and m ′
Is an integer from 1 to 9; n 'is an integer from 0 to 7; the sum of m' and n 'is an integer from 8 to 10; provided that the double dashed line is a single bond and the compound is racemic In the case of a body, the sum of m 'and n' excludes 9. The present invention provides a macrocyclic lactone compound ((R) form or racemic form) represented by the formula (1):

The fifth aspect of the present invention provides a macrocyclic lactone compound having a double bond ((R) form or racemic form) represented by the above general formula (2).

The sixth invention provides a fragrance imparting agent comprising a macrocyclic lactone compound represented by the above general formula (9). The seventh invention provides a fragrance composition containing the macrocyclic lactone compound represented by the general formula (9).

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a method for producing a macrocyclic lactone compound of the present invention, a novel macrocyclic lactone compound, a fragrance imparting agent comprising the novel macrocyclic lactone compound, and a fragrance composition containing the novel macrocyclic lactone compound This will be described in more detail. First, a method for synthesizing the macrocyclic lactone compound represented by the general formula (2) or (3) is performed by, for example, the following method.

[0013]

Embedded image (In the formula, X, X ¹ , m and n have the same meanings as described above, and the double bond is a trans form, a cis form, or a mixture of a trans form and a cis form.)

That is, β-butyrolactone of the formula (4) is reacted with an organomagnesium compound of the formula (5) in the presence of a copper halide catalyst of the formula (6) (T. Sato et al. Tetrahedron Le
tt. , 21, 3377-3380, 1980
Year), to obtain a terminal unsaturated carboxylic acid (7), and then esterify the terminal unsaturated alcohol (8) to obtain a compound of the formula (1)
Metathesis reaction (Mich
ael J. M. Et al., Angew. Chem. Int.
Ed. Engl. 1997, 36, 1101-1
103 years) to obtain a novel macrocyclic lactone compound (2) having a double bond. Further, by hydrogenating the double bond of the macrocyclic compound having a double bond, a saturated product (3) is formed.

The β-butyrolactone represented by the formula (4) is commercially available as a racemate or a known method (for example, a method for asymmetric hydrogenation of diketene; Japanese Patent Application Laid-Open No. 6-128245).
And Japanese Patent Application Laid-Open No. 7-206885) and those produced by a method equivalent thereto can be used. The terminally unsaturated carboxylic acid represented by the formula (7) is obtained by converting the β-butyrolactone represented by the formula (4) into the formula (5) in the presence of a copper halide catalyst represented by the formula (6). Obtained by reacting with an organomagnesium compound. In the organomagnesium compound represented by the formula (5), X
Is a halogen atom (here, examples of the halogen atom are fluorine, chlorine, bromine, iodine, etc.), and n is 0
To 7 are integers.

Preferred organomagnesium compounds include allyl magnesium chloride, 3-butenyl magnesium chloride, 4-pentenyl magnesium chloride, 5-hexenyl magnesium chloride, 6-
Heptenyl magnesium chloride, 7-octenyl magnesium chloride, 8-nonenyl magnesium chloride, 9-decenyl magnesium chloride, allyl magnesium bromide, 3-butenyl magnesium bromide, 4-pentenyl magnesium bromide, 5
-Hexenyl magnesium bromide, 6-heptenyl magnesium bromide, 7-octenyl magnesium bromide, 8-nonenyl magnesium bromide, 9
-Decenyl magnesium bromide, allyl magnesium iodide, 3-butenyl magnesium iodide,
4-pentenyl magnesium iodide, 5-hexenyl magnesium iodide, 6-heptenyl magnesium iodide, 7-octenyl magnesium iodide, 8-nonenyl magnesium iodide, 9-decenyl magnesium iodide and the like. .

More preferred organomagnesium compounds include 3-butenyl magnesium bromide, 4-pentenyl magnesium bromide, 5-hexenyl magnesium bromide, 6-heptenyl magnesium bromide, 7-octenyl magnesium bromide, and 8-nonenyl magnesium bromide. , 9-decenylmagnesium bromide and the like.

In the copper compound represented by the formula (5), X
¹ is a halogen atom (here, as an example of a halogen atom,
Fluorine, chloro, bromo, iodine and the like. ).
Preferred specific examples of copper compounds include cuprous chloride, cuprous iodide, cuprous bromide and the like.

The solvent used in this reaction is
Any solvent may be used as long as it is an inert solvent that does not participate in the reaction.For example, benzene, toluene, aromatic solvents such as xylene, diethyl ether, diisopropyl ether, methyl tert butyl ether, 1,2-dimethoxyethane, tetrahydrofuran, 1,4-dioxane,
Organic solvents such as ether solvents such as 1,3-dioxolane, and mixtures thereof are preferred. Among them, ether solvents such as diethyl ether, diisopropyl ether, methyl tertbutyl ale, 1,2-dimethoxyethane, tetrahydrofuran, 1,4-dioxane, and 1,3-dioxolan are preferable, and tetrahydrofuran is particularly preferable. The amount of the solvent to be used is generally 5-200 volumes, preferably 10-100 volumes, particularly preferably 30-70 volumes, per 1 part by weight of β-butyrolactone (4).

In this reaction, the amount of the organomagnesium compound represented by the formula (5) is usually 1.0 to 3.0 mol, preferably 1. mol, per 1 mol of the β-butyrolactone represented by the formula (4). It is used in an amount of from 01 to 1.5 mol. Also,
The copper compound represented by the formula (6) is a β compound represented by the formula (4)
-It is generally used in an amount of about 0.1 to 20 mol%, preferably about 2.0 to 10 mol%, per 1 mol of butyrolactone. Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. The reaction is usually carried out at a temperature of about -80 to 30C, preferably at a temperature of about -30 to 50C, usually for 10 minutes to 8 hours.
The reaction is performed for about an hour, preferably about 30 minutes to about 2 hours, and the reaction is completed. These conditions can be appropriately changed depending on the amounts of the reactants, copper compounds, and the like used. After completion of the reaction, the desired product can be isolated by performing ordinary post-treatments and, if necessary, using a method such as distillation or column chromatography.

In this reaction, β- represented by the formula (4)
The configuration on the asymmetric carbon atom in butyrolactone is
It is known that the organic magnesium compound represented by the formula (5) is almost completely inverted by nucleophilic attack (T.
Sato et al., Tetrahedron Lett. , 2
1, 3377-3380, 1980), (R)-
(R) -terminal unsaturated carboxylic acid is obtained from β-butyrolactone, while (S) is obtained from (S) -β-butyrolactone.
A terminally unsaturated carboxylic acid is obtained while maintaining optical purity. By the above reaction, terminal unsaturated carboxylic acids represented by the formula (7), for example, 3-methyl-5-hexenoic acid,
Methyl-6-heptenoic acid, 3-methyl-7-octenoic acid, 3-methyl-8-nonenoic acid, 3-methyl-9-decenoic acid, 3-methyl-10-undecenoic acid, 3-methyl-
11-dodesenic acid, 3-methyl-12-tridecenoic acid and the like are obtained.

The ester compound represented by the formula (1) is obtained by esterifying a terminal unsaturated carboxylic acid represented by the formula (7) with a terminal unsaturated alcohol (8) in the presence of an acid catalyst. It can be obtained by: In the terminal alcohols represented by the formula (8), m is an integer of 1 to 9. Preferred specific examples of the terminal alcohols represented by the formula (8) include, for example, allyl alcohol and 3-butene-1.
-Ol, 4-penten-1-ol, 5-hexene-
1-ol, 6-hepten-1-ol, 7-octen-1-ol, 8-nonen-1-ol, 9-decene-
Examples thereof include 1-ol and 10-undecene-1-ol.

In this reaction, the terminal unsaturated alcohol represented by the formula (8) is usually used in an amount of 1.0 to 3.0 mol per mol of the terminal unsaturated carboxylic acid represented by the formula (7).
Preferably it is used in an amount of 1.05 to 2.5 mol. Examples of the acid catalyst used in the esterification reaction include hydrochloric acid,
A mineral acid such as sulfuric acid, an organic acid such as p-toluenesulfonic acid, or a mixture thereof can be suitably used. The amount of the acid catalyst to be used is generally 0.1 to 20 mol%, preferably 0.5 to 10 mol, per 1 mol of the terminal unsaturated carboxylic acid (6).
Mol%.

The solvent used in the reaction is as follows:
For example, aromatic solvents such as benzene, toluene, and xylene are exemplified. The amount of the solvent used is usually 1 to 50 times the volume with respect to 1 part by weight of the terminal unsaturated carboxylic acid (6),
Preferably, the capacity is 2 to 25 times. This reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. In addition, the reaction is carried out by stirring and dehydrating under heating and reflux conditions, usually for about 30 minutes to 24 hours, preferably for 30 minutes.
The reaction is performed for about 10 minutes to about 10 hours, and the process is completed. These conditions can be appropriately changed depending on the amounts of the reactants and the acid catalyst used. After completion of the reaction, the desired product can be isolated by performing ordinary post-treatments and, if necessary, using a method such as column chromatography.

By the above reaction, an ester compound represented by the formula (1), for example, 9'-decenyl 3-methyl-5-hexenoate, 10'-undecenyl 3-methyl-5-
Hexenoate; 8'-nonenyl 3-methyl-6-heptenoate, 9'-decenyl 3-methyl-6-heptenoate, 10'-undecenyl 3-methyl-6-heptenoate; 7'-octenyl 3-methyl-7-octenoate 8'-nonenyl 3-methyl-7-octenoate, 9'-decenyl 3-methyl-7-octenoate; 6'-heptenyl 3-methyl-8-nonenoate,
7'-octenyl 3-methyl-8-nonenoate, 8 '
-Nonenyl 3-methyl-8-nonenoate; 5'-hexenyl 3-methyl-9-decenoate, 6'-heptenyl 3-methyl-9-decenoate, 7'-octenyl 3
-Methyl-9-decenoate; 4'-pentenyl 3-methyl-10-undecenoate, 5'-hexenyl 3-
Methyl-10-undecenoate, 6'-heptenyl 3
-Methyl-10-undecenoate; 3'-butenyl 3
-Methyl-11-dodecenoate, 4'-pentenyl3
-Methyl-11-dodecenoate, 5'-hexenyl 3
-Methyl-11-dodecenoate; allyl 3-methyl-
12-tridecenoate, 3'-butenyl 3-methyl-
12-tridecenoate, 4'-pentenyl 3-methyl-12-tridecenoate, and the like are obtained. Equation (2)
The macrocyclic lactone compound having a double bond represented by
It is obtained by subjecting the ester compound represented by the formula (8) to an intramolecular metathesis reaction.

The metathesis reaction of the ester compound (1) can be carried out, for example, by using a known rhenium catalyst (Maarten F. et al.).
C. P. Et al., Synlett, 1991, 507-5.
08), osmium catalyst (Bruce MN et al.,
J. Am. Chem. Soc. , 1988, 110
Volume, 960-961), a tungsten catalyst (Didi)
er V. , Tetrahedron Letter
s. , 1980, 21, 1715-1718; U.S. Patent No. 4,490,544; U.S. Patent No. 4,51.
U.S. Pat. No. 4,525,364; U.S. Pat. No. 4,536,299), molybdenum catalyst (Ho
uri A. F. J. et al. Am. Chem. Soc. ,
1995, 117, 2943-2944) or a ruthenium catalyst (Michael JM et al., Ang.
ew. Chem. Int. Ed. Engl. , 1997
Year, 36, 1101-1103, Peter Sc
hwab et al. Am. Chem. Soc. , 1996
Year, Vol. 118, pp. 100-110, Dias E. et al. L.
J. et al. Am. Chem. Soc. , 1997, 11
9, 3887-3897), particularly preferably using a ruthenium catalyst. The amount of the metathesis catalyst to be used is generally 1 / 1,000 to 1/5 mol, preferably 100 mol, per 1 mol of the ester compound (8).
It is 1/10 to 1/10 mole.

As the solvent used in the present metathesis reaction, any solvent can be used as long as it is an inert solvent which does not participate in the reaction. For example, chlorinated solvents such as methylene chloride, chloroform and the like can be used. Benzene, chlorobenzene, toluene, xylene and the like, aromatic solvents, diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, 1,3-dioxolan, dioxane and the like organic solvents and the like, or a mixed solvent thereof is preferably used. Methylene chloride is particularly preferred. The amount of the solvent to be used is generally 10-1000 volumes, preferably 100-500 volumes, per 1 part by weight of the ester compound (1). This metathesis reaction is usually performed in an inert gas atmosphere such as nitrogen gas or argon gas. Further, the reaction is usually performed at 5 to 50 ° C.
About 30 minutes to 20 hours, preferably about 2 hours to 10 hours. The reaction is completed under the conditions such as a reactant used, a metathesis catalyst, etc. Can be appropriately changed depending on the amount of After completion of the reaction, the desired product can be isolated by performing ordinary post-treatments and, if necessary, using a method such as column chromatography.

In the above metathesis reaction, carbon-carbon double bonds are coupled with each other to form a new carbon-carbon double bond. A general example of the metathesis reaction is shown below. A catalyst is bonded to one of the double bonds in the molecule, an ethylene molecule is cut out, and a conjugate of a catalyst substrate is formed. This couples with the other double bond in the molecule, the catalyst ([M] = CH ₂ ) is cleaved, and a new cyclic carbon-carbon double bond is formed. However, the metathesis reaction is not limited to this. In the following formulas, the wavy line indicates a double bond, a trans form, a cis form, or a mixture of a trans form and a cis form.

[0029]

Embedded image ([M] = CH ₂ represents the above-mentioned rhenium, osmium, tungsten, molybdenum or ruthenium catalyst, etc.)

By the above metathesis reaction, a macrocyclic lactone compound having a double bond represented by the formula (2), for example, 3-methyl-8-cyclotetradecene-14-olide,
3-methyl-6-cyclopentadecene-15-olide,
3-methyl-8-cyclopentadecene-15-olide,
3-Methyl-10-cyclohexadecene-16-olide and the like are obtained. The macrocyclic lactone compound having a double bond thus obtained is a 9: 1 to 3: 2 mixture of a trans-form and a cis-form according to ¹ H-NMR spectrum analysis. These trans-isomer and cis-isomer can be easily separated by using reversed-phase HPLC (high performance liquid chromatography). In the macrocyclic compound (2) having a double bond as described above, the double bond may be any of a trans form, a cis form, or a mixture of a trans form and a cis form.

On the other hand, the saturated macrocyclic lactone compound represented by the above formula (3) is formed by hydrogenating the double bond of the macrocyclic lactone compound having a double bond represented by the formula (2). You. In the present hydrogenation reaction, for example, a hydrogenation catalyst such as a nickel catalyst such as Raney nickel, a palladium catalyst such as palladium-carbon, a rhodium catalyst such as rhodium-silica, or a ruthenium catalyst such as ruthenium-alumina is generally used. Particularly preferred as the hydrogenation catalyst is a palladium catalyst. The amount of the hydrogenation catalyst to be used is generally 0.1 to 100% by weight, preferably 1 to 100% by weight based on 1 part by weight of the macrocyclic lactone compound (2) having a double bond.
-20% by weight.

The solvent used in the present hydrogenation reaction may be any solvent as long as it is an inert solvent which does not participate in the reaction. For example, alcohol solvents such as methanol, ethanol and isopropanol, and diethyl ether And organic solvents such as ether solvents such as diisopropyl ether, tetrahydrofuran, dimethoxyethane, 1,3-dioxolan, and dioxane; hydrocarbon solvents such as hexane, heptane and octane; and mixed solvents thereof. The amount of the solvent to be used is generally 0.5 to 100 with respect to 1 part by weight of the macrocyclic lactone compound having a double bond (2).
Double volume, preferably 1 to 30 times volume. Further, the reaction is usually carried out at a temperature of about 0 to 250 ° C., preferably 20 ° C.
The reaction is usually performed at a temperature of about
The reaction is completed for about 30 minutes to about 30 hours, preferably for about 30 minutes to about 20 hours, at a hydrogen pressure of normal pressure to about 20 atm. These conditions are based on the amount of the reactants and hydrogenation catalyst used. Can be changed as appropriate.
After completion of the reaction, the desired product can be isolated by performing ordinary post-treatments and, if necessary, using a method such as column chromatography.

By the above reaction, a saturated macrocyclic lactone compound represented by the formula (3), for example, 3-methyl-14-cyclotetradecanolide, 3-methyl-16-cyclohexadecanolide and the like are obtained.

The reaction in the present invention can be carried out in a batch system or a continuous system.
The macrocyclic compounds represented by the above general formulas (2) and (3) obtained after column chromatography purification have a musk-like odor.

On the other hand, the novel macrocyclic lactone compound of the present invention is a compound represented by the following general formula (9) among the compounds represented by the above general formula (2) or (3).

[0036]

Embedded image (In the formula, the double dashed lines, m ′ and n ′ have the same meanings as described above.)

Specific examples of the novel macrocyclic compound represented by the general formula (9) are as shown in the following table. In addition, in the following tables, a wavy line shows a trans form, a cis form, or a mixture of a trans form and a cis form of a double bond.

[0038]

[Table 1]

As shown in the following examples, all of these compounds have a musk-like aroma, and those having a (R) -configuration at the 3-position are particularly preferable, and (R) -3-methyl- 8-cyclotetradecene-14-olide, (R) -3
-Methyl-14-cyclotetradecanolide, (R) -3
-Methyl-6-cyclopentadecene-15-olide and (R) -3-methyl-15-cyclopentadecanolide are excellent musk aromas having a high-grade powdery feeling;
Has odor intensity.

These novel macrocyclic lactone compounds have high palatability, excellent fragrance imparting effects, strong masking power for base odors such as soap, bleaching odor or ozone odor, and are very useful fragrance materials. It is. By blending one or more of these compounds, including trans and cis isomers, with the object, the compound has a strong diffusibility and retention property, and imparts a fresh and highly palatable fragrance to the compound. Alternatively, the fragrance of the compounding object can be improved, and a fragrance composition such as an excellent fragrance imparting composition or a fragrance improving reinforcing composition can be provided.

The amount of the novel macrocyclic lactone compound to be added to the fragrance composition of the present invention is not particularly limited.
It is preferably from 0.01 to 50% by weight, particularly preferably from 0.1 to 20% by weight. The flavor composition of the present invention may be blended with a conventionally used compounded flavor such as a compounded flavor. Here, the fragrance component usually used, a wide range of fragrance is used,
For example, Arctander S.A. , "Perfume
and Flavor Chemicals ", pub
flushed by the author, Mont
clair, N.M. J. (U.S.A.), 1969, can be used.
Typical examples are α-pinene, limonene, cis-
3-hexenol, phenylethyl alcohol, styryl acetate, eugenol, rose oxide, linalool, vanzaldehyde, muscone and the like.

According to the fragrance composition thus obtained,
It is possible to provide a musk-like aroma imparting freshness and high palatability. The compound represented by the general formula (9) or the fragrance composition containing the compound according to the present invention includes cosmetics, health and hygiene materials,
Can be used as a fragrance component of miscellaneous goods, pharmaceuticals, etc.
Cosmetics, health and hygiene materials, miscellaneous goods, pharmaceuticals and the like containing these compounds or compositions as fragrance components can be provided. Shampoos, rinses, perfumes,
Colons, hair tonics, hair creams, poma
And other hair cosmetic base materials, soaps, dishwashing detergents, laundry detergents, softeners, disinfecting detergents, deodorant detergents, indoor air fresheners, furniture care, disinfectants, insecticides, bleaching agents, etc. Unique fragrance can be imparted to various types of health and hygiene detergents, toothpastes, mouthwashes, toilet paper, and fragrances for facilitating ingestion of pharmaceuticals.
The commercial value can be increased by blending in the amount usually blended in this industry.

[0043]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these, and may be changed without departing from the scope of the present invention. The following equipment was used in the measurement of physical properties and the like below. Nuclear magnetic resonance spectrum: AMX-400 (400 MH
z) (manufactured by Bruker) Internal standard substance: tetramethylsilane (in deuterated chloroform) Gas chromatography: HP5890A (HEWL)
Infrared absorption spectrum (IR): IR-800 (manufactured by JASCO Corporation) Polarimeter: DIP-360 (manufactured by JASCO Corporation) Mass spectrometry spectrum: M-80B (manufactured by Hitachi, Ltd.) The measurement of the optical purity of musclactone was performed by the following method. Measuring instruments and measurement conditions High performance liquid chromatography Pump: L-6200 (manufactured by Hitachi, Ltd.) Detector: L-4000 (manufactured by Hitachi, Ltd.)

Example 1 Preparation of (R) -3-methyl-6-cyclopentadecene-15-olide (m = 8, n = 1) (1) (R) -3-methyl-6-heptene Preparation of Acid In a 1 L round bottom flask, 0.61 g (6.1) cuprous chloride was used.
To a solution of 6 mol) of tetrahydrofuran (128 ml) was added dropwise a solution of 3-butenylmagnesium bromide in 128 ml of tetrahydrofuran (1.16 mol / L; 148.48 mmol) at 0 ° C. over 15 minutes under nitrogen stream stirring. After completion of the dropwise addition, (R) -β-butyrolactone (optical purity 9)
5.6% e. e. ) 120 ml of a solution of 10.6 g (123.46 mmol) in tetrahydrofuran was added dropwise over 70 minutes, and after completion of the addition, the mixture was stirred at 0 ° C for 60 minutes. After 100 ml of 2N hydrochloric acid was added to make an acidic solution, 100 ml of water was added, the tetrahydrofuran layer was separated, and the aqueous layer was extracted with 200 ml of diethyl ether. The combined organic layer was washed with 100 ml of water and 100 ml of saturated saline, the solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain a colorless oil (R)- 3-methyl-6-heptenoic acid (13.44 g,
Yield 75.0%, chemical purity 98.0%).

Physical data of (R) -3-methyl-6-heptenoic acid [α] _D ²³ + 4.46 ° (C = 1,01, MeOH) IR (neat): 3600-2400 (OH), 17
^{00 (C = O) cm -1} 1 H-NMR (400MHz, CDCl 3): δ 1
3.0-8.0 (1Hb), 5.78 (1H dd)
t), 4.98 (2H m), 2.37 (1H q),
2.17 (1Hq), 2.10-1.92 (3H
m), 1.45 (1Hm), 1.32 (1Hm),
0.98 (3Hd) gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 50 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 8.39 min

(2) Preparation of (R) -9'-decenyl 3-methyl-6-heptenoate 10.0 g of (R) -3-methyl-6-heptenoic acid (7
0.3 mmol), 9-decene-1-ol 22.0 g
(140.6 mmol; Takasago International Corporation Trepanol), and 0.67 g of p-toluenesulfonic acid monohydrate
(3.52 mmol) was dissolved in 30 ml of dehydrated toluene, and the mixture was heated under reflux for 3 hours while performing azeotropic dehydration. After cooling to room temperature, the organic layer was treated with 50 ml of water, 50 ml of a saturated aqueous solution of sodium hydrogencarbonate and 50 ml of a saturated saline solution, and after the solvent was distilled off, purified by silica gel column chromatography (hexane: ethyl acetate = 40: 1). (R) -9'-decenyl 3-methyl-6-heptenoate (16.2 g, yield 76.7%, chemical purity 9) as a colorless oil.
1.5%).

(R) -9'-decenyl 3-methyl-6
Physical data of heptenoart [α] _D ²³ + 1.38 ° (C = 1.02, MeOH) IR (neat): 1740 (C = O) cm ⁻¹ MS (EI) m / z: 280 (M ⁺ ), 265,25
1,238,220,196,183,165,14
3,125,110,97,82,69,55,41,
27, 14 ¹ H-NMR (400 MHz, CDCl ₃ ): δ5.
80 (2H m), 4.96 (4H m), 4.05
(2Ht), 2.31 (1Hq), 2.18-1.
91 (6H m), 1.63 (2H m), 1.49-
1.30 (12Hm), 0.95 (3Hd) Gas chromatography analysis: Column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 13.92 min

(3) Production of (R) -3-methyl-6-cyclopentadecene-15-olide 2 L of dichloromethane was degassed under reduced pressure in a 5 L round-bottom reaction flask, and then replaced with nitrogen.

2.0 g (2.41 mmol) of the metathesis catalyst of the formula was added and (R) -9'-decenyl 3-methyl-6
A dichloromethane solution (2 L) of 13.5 g (48.1 mmol) of heptenoate is added dropwise at 25 ° C. over about 5 hours and stirred for 1 hour. After the completion of the reaction, the mixture was washed with 1 L of a 10% aqueous sodium hydroxide solution.
Wash once with 1 L of saturated saline. After evaporating the solvent, silica gel column chromatography (hexane:
The product was purified with ethyl acetate (30: 1) to give a colorless oil (R) -3-methyl-6-cyclopentadecene-15-
Oride (5.7 g, yield 51.6%, chemical purity 99.3)
%, Trans-form: cis-form = 7: 3).

[0049]

Embedded image

Physical data of (R) -3-methyl-6-cyclopentadecene-15-olide [α] _D ²⁴ −6.06 ° (C = 1.04, MeOH) IR (neat): 1735 (C = O), 970 (tr
ans), 710 (cis) cm ^-1 MS (EI) m / z: 252 (M ⁺ ), 234, 21
0,192,177,163,150,137,12
4,109,95,81,67,54,41,28,1
4. ¹ H-NMR (400 MHz, CDCl ₃ ): δ
32 (2H m), 4.19 (1H m), 4.04
(1H m), 2.31 (1H m), 2.16-1.
94 (6Hm), 1.65 (2Hm), 1.49-
1.17 (12Hm), 0.90 (3Hd) Gas chromatography analysis: Column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 13.73 min (transformer), 13.86 ( Cis form)

Example 2 (R) -3-methyl-15-
Preparation of cyclopentadecanolide (m = 8, n = 1) (R) -3-methyl-6-cyclopentadecene-15
A mixture of 1.8 g (7.13 mmol) of oride, 0.2 g of 5% palladium-carbon and 4 ml of hexane was added to 30
The mixture is stirred and hydrogenated at 25 ° C. and normal pressure hydrogen for 19 hours in a ml eggplant flask. After separating the catalyst and removing the solvent, a colorless oily (R) -3-methyl-15-cyclopentadecanolide (1.86 g, yield 98.7%, chemical purity 94.3) was obtained.
%, Optical purity 94.8%).

Physical data of (R) -3-methyl-15-cyclopentadecanolide [α] _D ²⁴ + 4.51 ° (C = 1.02, MeOH) IR (neat): 1740 (C = O) cm ^-1 MS (EI) m / z: 254 (M ⁺ ), 236, 21
1,194,179,166,152,138,12
4,110,96,82,69,55,41,27,1
3. ¹ H-NMR (400 MHz, CDCl ₃ ): δ
20 (1H m), 4.05 (1H m), 2.23
(2Hd), 2.01 (1Hm), 1.61 (2H
m), 1.47-1.14 (20H m), 0.96
(3Hd) Gas chromatography analysis: Column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 13.78 High performance liquid chromatography analysis: column: CHIR
ALCEL OD-H (4.6 mm x 250 mm; manufactured by Daicel Chemical) x 2, solvent: hexane, flow rate: 0.5 m
1 / min, retention time R-body (26.9m
in), S-body (29.0 min)

Reference Example 1 Preparation of (S) -3-methyl-6-cyclopentadecene-15-olide (m = 8, n = 1) (1) (S) -3-methyl-6-heptene Production of acid (S) -β-butyrolactone (optical purity 95.1% e.
e. ) 25 ml of a 2.00 g (23.23 mmol) solution of tetrahydrofuran, 30 ml of a solution of 3-butenylmagnesium bromide in tetrahydrofuran (1.01
Mol / L, 30.20 mmol), cuprous chloride 0.12
g (1.16 mmol) in tetrahydrofuran mixture 7
The same operation as in Example 1 was carried out using 5 ml, and the mixture was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to give (S) -methyl-colorless oil.
6-Heptenoic acid (2.38 g, yield 72.0%, chemical purity 96.6%) was obtained.

(2) Production of (S) -9'-decenyl 3-methyl-6-heptenoate 1.60 g of (S) -3-methyl-6-heptenoic acid (1
1.25 mmol), 9-decene-1-ol 3.52
g (22.50 mmol, Takasago International Corporation Trepanol), and p-toluenesulfonic acid monohydrate 0.11
g (0.56 mmol) and 30 ml of dehydrated toluene, the same operation as in Example 1 was performed, and silica gel column chromatography (hexane: ethyl acetate = 40: 1).
~ 35: 1) and purified as a colorless oil (S) -9'-decenyl 3-methyl-6-heptenoate (2.96 g,
The yield was 88.8% and the chemical purity was 94.7%).

(3) Preparation of (S) -3-methyl-6-cyclopentadecene-15-olide 600 ml of a dichloromethane solution of 0.24 g (0.29 mmol) of the metathesis catalyst, (S) -9'-decenyl 3
The same operation as in Example 1 was carried out using 200 ml of a dichloromethane solution of 2.70 g (9.63 mmol) of -methyl-6-heptenoate and purified by silica gel column chromatography (hexane: ethyl acetate = 40: 1). (S) -3-methyl-6-cyclopentadecene-15-olide as a colorless oil (1.53 g, yield 60.6).
%, Chemical purity 92.6%, trans form: cis form = 8:
2) was obtained. (S) -3-methyl-6-cyclopentadecene-15
Physical data of oride [α] _D ²⁴ + 4.80 ° (C = 1.00, MeOH)

Reference Example 2 (S) -3-methyl-15-
Preparation of cyclopentadecanolide (m = 8, n = 1) (S) -3-methyl-6-cyclopentadecene-15-
Using 0.60 g (2.38 mmol) of oride, 0.06 g of 5% palladium-carbon and 5 ml of hexane,
The same operation as in Example 2 was carried out, and the mixture was purified by silica gel column chromatography (hexane: ethyl acetate = 30: 1) to obtain a colorless oil (S) -3-methyl-15-cyclopentadecanolide (0.1%). 46 g, yield 75.1%, chemical purity 91.3%, optical purity 94.9%). Physical data of (S) -3-methyl-15-cyclopentadecanolide [α] _D ²³ -1.22 ° (C = 0.98, MeOH) High performance liquid chromatography analysis: column: CHIR
ALCEL OD-H (4.6 mm x 250 mm; manufactured by Daicel Chemical) x 2, solvent: hexane, flow rate: 0.5 m
1 / min, retention time R-body (26.9m
in), S-body (29.0 min)

Example 3 (R) -3-methyl-10-
Cyclohexadecene-16-olide (m = 5, n = 5)
(1) Production of (R) -3-methyl-10-undecenoic acid (R) -β-butyrolactone (optical purity 95.6% e.
e. ) 60 ml of a solution of 3.46 g (40.25 mmol) in tetrahydrofuran, 60 ml of a solution of 7-octenylmagnesium bromide in tetrahydrofuran (1.02
Mol / L, 61.33 mmol), cuprous chloride 0.19
The same operation as in Example 1 was performed using 120 g of a 9 g (2.01 mmol) tetrahydrofuran mixture,
Purification by silica gel column chromatography (hexane: ethyl acetate = 5: 1) gave a colorless oil (R) -3-
Methyl-10-undecenoic acid (5.65 g, yield 69.
6%, chemical purity 98.2%).

Physical data of (R) -3-methyl-10-undecenoic acid [α] _D ²³ + 6.37 ° (C = 1.02, MeOH) IR (neat): 3400-2400 (OH), 17
^{10 (C = O) cm -1} MS (EI) m / z: 180 (MH 2 O), 162,151,138,
127, 118, 110, 102, 96, 87, 81,
69, 55, 41, 28, 18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ 1
3.0-9.0 (1Hb), 5.89-5.76 (1H
m), 5.05-4.89 (2H m), 2.39
(1Hbs), 2.18 (1Hbs), 2.09-
1.88 (3Hm), 1.55-1.12 (10H
m), 0.97 (3Hd) Gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 50 ° C.-250 ° C. (heating at 10 ° C./min), retention time = 9.16 min

(2) Preparation of (R) -6'-heptenyl 3-methyl-10-undecenoate 2.5 g of (R) -3-methyl-10-undecenoic acid
2.38 mmol), 6-hepten-1-ol
98 g (17.33 mmol) and 0.19 g (0.62 mmol) of p-toluenesulfonic acid monohydrate;
The same operation as in Example 1 was performed using 30 ml of dehydrated toluene, and the mixture was purified by silica gel column chromatography (hexane: ethyl acetate = 50: 1) to obtain (R) -6′-heptenyl 3-methyl colorless oil. -10-undecenoate (3.32 g, yield 89.9%, chemical purity 9)
8.8%).

(R) -6'-heptenyl 3-methyl-1
Physical data of 0-undecenoate [α] _D ²³ + 3.28 ° (C = 1.01, MeO
H) IR (neat): 1735 (C = O) cm ^-1 MS (EI) m / z: 294 (M ⁺ ), 276, 26
6,252,237,223,209,199,19
1,181,171,163,151,138,12
3,110,96,81,67,55,41,29,1
8. ¹ H-NMR (400 MHz, CDCl ₃ ): δ
87-5.75 (2Hm), 5.04-4.91 (4
Hm), 4.06 (2Ht), 2.32-2.26.
(1Hq), 2.13-2.08 (1Hq),
2.08-2.01 (4Hm), 2.00-1.89
(1Hm), 1.69-1.59 (2Hm), 1.48
-1.22 (14Hm), 0.94 (3Hd) Gas chromatography analysis: Column: NB-1 (3
0 m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc., measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 14.94 min

(3) Preparation of (R) -3-methyl-10-cyclohexadecene-16-olide 450 ml of a dichloromethane solution of 0.28 g (0.34 mmol) of the metathesis catalyst, (R) -6'-heptenyl 3-ol 2.0 g of methyl-10-undecenoate (6.7 g)
9 mmol) of dichloromethane solution (150 ml), the same operation as in Example 1 was carried out, and silica gel column chromatography (hexane: toluene = 4: 1 to 1).
1: 2), and purified as a colorless oil (R) -3-methyl-
10-cyclohexadecene-16-olide (0.77
g, yield 42.7%, chemical purity 99.2%, trans-form: cis-form = 8: 2).

Physical data of (R) -3-methyl-10-cyclohexadecene-16-olide [α] _D ²⁴ + 3.50 ° (C = 1.00, MeOH) IR (neat): 1730 (C = O ), 965 (tr
ans), 715 (cis) cm ^-1 MS (EI) m / z: 266 (M ⁺ ), 248, 23
8,224,206,191,178,163,14
9,138,123,109,95,82,67,5
5,41,29,18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ
37-5.24 (2Hm), 4.20-4.09 (1
Hm), 4.07-3.95 (1Hm), 2.30.
-2.22 (1H m), 2.20-2.11 (1H
m), 2.10-1.99 (4H m), 1.95 (1
Hm), 1.68-1.59 (2Hm), 1.47-
1.04 (14Hm), 0.96 (3Hd) Gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 14.99 min (transformer), 15.08 min (cis body)

Example 4 (R) -3-methyl-16-
Preparation of cyclohexadecanolide (m = 5, n = 5) (R) -3-methyl-10-cyclohexadecene-16
-Olide 0.22 g (0.97 mmol), 5% palladium-carbon 0.006 g, and hexane 3 ml were operated in the same manner as in Example 2 and silica gel column chromatography (hexane: ethyl acetate = 30:
Purified in 1) to give a colorless oil (R) -3-methyl-16
-Cyclohexadecanolide (0.23 g, yield 100
%, Chemical purity 99.2%).

Physical data of (R) -3-methyl-16-cyclohexadecanolide [α] _D ²⁴ + 1.71 ° (C = 1.00, MeOH) IR (neat): 1735 (C = O) cm ^-1 MS (EI) m / z: 266 (M ^<+> ), 250, 23
5,225,217,208,193,180,16
6,152,138,124,110,96,82,6
9, 55, 41, 29, 18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ 4.
21-4.13 (1Hm), 4.09-4.02 (1
Hm), 2.23 (1Hd), 2.19 (1H
m), 2.04-1.93 (1H m), 1.68-
1.59 (2Hm), 1.45-1.13 (22H
m), 0.95 (3Hd) Gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measuring temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 14.91 min High performance liquid chromatography analysis: column: CHIR
ALCEL OD-H (4.6 mm x 250 mm; manufactured by Daicel Chemical) x 2, solvent: hexane, flow rate: 0.5 m
1 / min, retention time R-body (25.6m
in), S-body (28.2 min)

Example 5 Preparation of (R) -3-methyl-8-cyclotetradecene-14-olide (m = 5, n = 3) (1) (R) -3-methyl-8-nonene Production of acid (R) -β-butyrolactone (optical purity 95.6% e.
e. 25 ml of a solution of 2.03 g (23.59 mmol) in tetrahydrofuran and 30 ml of a solution of 5-hexenylmagnesium bromide in tetrahydrofuran (1.02 g).
Mol / L, 30.61 mmol), cuprous chloride 0.1
The same operation as in Example 1 was performed using 65 ml of a mixture of 17 g (1.18 mmol) of tetrahydrofuran,
Purification by silica gel column chromatography (hexane: ethyl acetate = 6: 1) gave a colorless oil (R) -3-
Methyl-8-nonenoic acid (2.92 g, 60.6% yield,
(Chemical purity 83.3%).

Physical data of (R) -3-methyl-8-nonenoic acid [α] _D ²⁴ + 7.73 ° (C = 1.04, MeOH) IR (neat): 3600-2400 (OH), 17
^{10 (C = O) cm -1} MS (EI) m / z: 152 (M-H 2 O), 141,
137, 128, 123, 119, 115, 110, 1
05, 100, 95, 87, 82, 69, 60, 55,
41, 29, 18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ 1
2.6-8.3 (1Hb), 5.85-5.74 (1Hb)
m), 5.03-4.90 (2H m), 2.38-
2.34 (1H m), 2.18-2.12 (1H
m), 2.07-2.01 (2H m), 2.00-
1.91 (1H m), 1.44-1.20 (6H
m), 0.97 (3Hd) Gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 50 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 6.67 min

(2) Preparation of (R) -6'-heptenyl 3-methyl-8-nonenoate 2.30 g of (R) -3-methyl-8-nonenoic acid
3.51 mmol), 6-hepten-1-ol
The same operation as in Example 1 was carried out using 85 g (16.21 mmol), 0.077 g (0.41 mmol) of p-toluenesulfonic acid monohydrate and 20 ml of dehydrated toluene, and silica gel column chromatography ( Hexane: toluene = 1: 1 to 1: 3), and purified as a colorless oil (R) -6′-heptenyl 3-methyl-8-nonenoate (3.45 g, yield 95.5%, chemical purity 82). .6
%).

(R) -6′-heptenyl 3-methyl-8
-Physical data of nonenoart IR (neat): 1740 (C = O) cm ^-1 MS (EI) m / z: 266 (M ⁺ ), 248, 23
8,224,209,197,183,171,16
3,152,143,135,123,110,96,
81, 69, 55, 41, 29, 18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ5.
87-5.75 (2Hm), 5.04-4.91 (4
Hm), 4.06 (2Ht), 2.32-2.26.
(1Hq), 2.13 to 2.08 (1Hq), 2.
08-2.01 (4Hm), 2.00-1.89 (1
Hm), 1.69-1.59 (2Hm), 1.48-
1.22 (14Hm), 0.94 (3Hd) Gas chromatography analysis: Column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 12.81 min

(3) Preparation of (R) -3-methyl-8-cyclotetradecene-14-olide A solution of 0.41 g (0.50 mmol) of a metathesis catalyst in 500 ml of dichloromethane, and (R) -6′-heptenyl 3 Using a dichloromethane solution (300 ml) of 3.20 g (9.91 mmol) of -methyl-8-nonenoate, the same operation as in Example 1 was performed and silica gel column chromatography (hexane: toluene = 2: 1 to 1).
1: 1) and purified as a colorless oil (R) -3-methyl-8-cyclotetradecene-14-olide (1.11).
g, yield: 46.2%, chemical purity: 98.2%, trans-form: cis-form = 9: 1).

Physical data of (R) -3-methyl-8-cyclotetradecene-14-olide [α] _D ²⁴ -18.8 ° (C = 1.01, MeOH) IR (neat): 1740 (C = O), 970 (tr
ans), 715 (cis) cm ^-1 MS (EI) m / z: 238 (M ⁺ , 220, 210,
195,187,178,163,149,136,1
22, 109, 95, 82, 67, 55, 41, 29,
18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ
44 (2Hm), 4.18-4.06 (2Hm),
2.33-2.25 (1 Hm), 2.14-2.07
(1H m), 2.06-1.93 (5H m), 1.
58 (2Hm), 1.47-1.15 (10Hm),
0.96 (3Hd) gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measurement temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 12.636 min (transformer), 12.870 min (cis body)

Example 6 (R) -3-methyl-14
(M = 5, n = 3) Preparation of Cyclotetradecanolide (R) -3-Methyl-8-cyclotetradecene-14
The same operation as in Example 2 was carried out using 0.45 (1.89 mmol) of oride, 0.013 g of 5% palladium-carbon and 3.0 ml of hexane to obtain (R) -3-methyl-colorless oily substance. 14-cyclotetradecanolide (0.45 g, yield 99.1%, chemical purity 98.2%)
I got

Physical data of (R) -3-methyl-14-cyclotetradecanolide [α] _D ²⁴ + 1.49 ° (C = 1.01, MeOH) IR (neat): 1740 (C = O) cm ^-1 MS (EI) m / z: 240 (M ^<+> ), 222, 20
7,197,189,180,165,152,13
8, 124, 110, 96, 82, 69, 55, 41,
29,18 ¹ H-NMR (400 MHz, CDCl ₃ ): δ 4.
19 (1H m), 4.05 (1H m), 2.28
(1H m), 2.17 (1H m), 2.01 (1H
m), 1.72-1.57 (2H m), 1.49-
1.18 (18Hm), 0.98 (3Hd) Gas chromatography analysis: column: NB-1 (30
m × 0.25 mm × 0.4 μm; manufactured by GL Sciences Inc.), measuring temperature: 100 ° C. to 250 ° C. (heating at 10 ° C./min), retention time = 12.895 min High performance liquid chromatography analysis: column: CHIR
ALCEL OD-H (4.6 mm x 250 mm; manufactured by Daicel Chemical) x 2, solvent: hexane, flow rate: 0.5 m
1 / min, retention time R-body (27.6m
in), S-body (31.6 min)

Reference Example 3 Preparation of (S) -3-methyl-8-cyclotetradecene-14-olide (m = 5, n = 3) (1) (S) -3-methyl-8-nonene Production of acid (S) -β-butyrolactone (optical purity 95.1% e.
e. 2.00 g (23.23 mmol) in tetrahydrofuran solution 15 ml, 5-hexenylmagnesium bromide solution in tetrahydrofuran 30 ml (1.00
Mol / L, 30.20 mmol), cuprous chloride 0.1
The same operation as in Example 1 was performed using 65 g of a mixed solution of 15 g (1.16 mmol) of tetrahydrofuran, and silica gel column chromatography (hexane:
Ethyl acetate = 3: 1) to give a colorless oil (S)-
3-methyl-8-nonenoic acid (2.42 g, yield 50.0
%, Chemical purity 81.7%). Physical data of (S) -3-methyl-8-nonenoic acid [α] _D ²⁴ -1.60 ° (C = 1.00, MeOH)

(2) Production of (S) -6'-heptenyl 3-methyl-8-nonenoate 2.19 g of (S) -3-methyl-8-nonenoic acid (10.
52 mmol), 1.50 g of 6-hepten-1-ol
(13.18 mmol), 0.063 g (0.33 mmol) of p-toluenesulfonic acid monohydrate, and 20 ml of dehydrated toluene, the same operation as in Example 1 was performed, and silica gel column chromatography (hexane :
Purification with toluene = 1: 1) yielded a colorless oil (S)-
6'-heptenyl 3-methyl-8-nonenoate (2.
36 g, yield 75.3%, chemical purity 89.4%). Physical data of (S) -6′-heptenyl 3-methyl-8-nonenoate [α] _D ²⁴ −6.11 ° (C = 1.02, MeOH)

(3) Preparation of (S) -3-methyl-8-cyclotetradecene-14-olide 400 ml of a dichloromethane solution of 0.28 g (0.34 mmol) of the metathesis catalyst, (S) -6′-heptenyl 3 The same operation as in Example 1 was performed using a dichloromethane solution (200 ml) of 2.00 g (6.71 mmol) of -methyl-8-nonenoate, and silica gel column chromatography (hexane: toluene = 2: 1 to 1).
2: 3) and purified as a colorless oil (S) -3-methyl-
8-cyclotetradecene-14-olide (0.83 g,
Yield 50.4%, purity 97.1%, trans-form: cis-form = 9: 1) were obtained. (S) -3-methyl-8-cyclotetradecene-14
Physical data of oride [α] _D ²⁴ + 17.7 ° (C = 1.00, MeOH)

Reference Example 4 (S) -3-methyl-14
Preparation of cyclotetradecanolide (m = 5, n = 3) (S) -3-methyl-8-cyclotetradecene-14
The same operation as in Example 2 was performed using 0.30 g (1.26 mmol) of oride, 0.009 g of 5% palladium-carbon, and 3.0 ml of hexane to obtain a colorless oil (S) -3-methyl- 14-Cyclotetradecanolide (0.31 g, yield 100%, chemical purity 96.5%) was obtained. Physical data of (S) -3-methyl-14-cyclotetradecanolide [α] _D ²⁵ -3.56 ° (C = 1.01, MeOH) High performance liquid chromatography analysis: column: CHIR
ALCEL OD-H (4.6 mm x 250 mm; manufactured by Daicel Chemical) x 2, solvent: hexane, flow rate: 0.5 m
1 / min, retention time R-body (27.6m
in), S-body (31.6 min)

Example 7 Evaluation of Aroma Quality of the macrocyclic lactone compound having a double bond and the saturated macrocyclic lactone compound synthesized in Examples 1 to 6 and Reference Examples 1 to 4 was evaluated by seven people. Performed by a specialized panel. The results are shown in Tables 2-1 to 2-2 and 2-3. As can be seen from the table, all compounds have a musk-like odor, especially (R) -3-methyl-8-cyclotetradecene-14.
Oride, (R) -3-methyl-14-cyclotetradecanolide, (R) -3-methyl-6-cyclopentadecene-15-olide and (R) -3-methyl-15-cyclopentadecanolide Had excellent musk aroma and odor intensity with a luxurious powdery feeling. on the other hand,
All (S) -forms had weak odor intensity, and had weak characteristics as musk fragrance. However, the racemic form, which is a 1: 1 mixture of the (R) -form and the (S) -form, is inferior in both flavor and strength as compared with the (R) -form, but is sufficiently used as a musk fragrance material. It was in the range that I could do.

[0078]

[Table 2-1]

[0079]

[Table 2-2]

[0080]

[Table 2-3]

Example 12 Production of Fragrance Composition Using the six types of macrocyclic lactone compounds produced in Examples 1 to 6, six kinds of floral-type fragrance compositions of the following formula were prepared, and The evaluation was carried out by a panel of experts. As a result, a powdery musk-like fragrance having high palatability could be imparted to all fragrance compositions containing the compound of the present invention, and a fragrance having unity and gentle fragrance was obtained.

(Fragrance composition) 3-Methyl macrocyclic lactone compound 40 Nonylaldehyde 3 Basil essential oil 8 Bergamot essential oil 60 1-citronellal 10 1-citronellol 20 Clarisage essential oil 5 Methyl dihydrojasmonate 30 Helioboke (registered trademark) ¹⁾ 3 Kovanol (registered trademark) ²⁾ 100 Citral 35 Lemon essential oil 110 Linaxol (registered trademark) ³⁾ 130 Linalyl acetate 70 Orange essential oil 240 Orbitone (registered trademark) ⁴⁾ 60 Patchouli essential oil 7 Santalex T (registered trademark) ⁵⁾ 57 stiraryl Acetate 12 Total 1000

1) 2-methyl-3- (3,4-methylenedioxy-phenyl) -propanol: origin
e: Takasago International Corporation 2) 4 (3)-(4-hydroxy-4-methylpentyl) -3-cyclohexene-1-carboxaldehyde: origin: Takasago International Corporation 3) 2,6-dimethyl Mixture of -2-octanol and 3,7-dimethyl-3-octanol: origin:
Takasago International Corporation 4) 7-Acetyl-1,2,3,4,5,6,7,8-
Octahydro-1,1,6,7-tetramethyl-naphthalene: original: Takasago International Corporation 5) 3- (5,5,6-trimethylbicyclo [2.2.
1] Hept-2-yl) cyclohexanol: orig
ine: Takasago International Corporation

[0083]

Industrial Applicability The novel macrocyclic lactone compound having a 3-methyl structure according to the present invention is a musk fragrance having a powdery feeling lacking in conventional macrocyclic musk compounds, and a fragrance composition containing these as an active ingredient. It is a fragrance material that can impart high palatability and unity to objects. That is, the novel macrocyclic lactone compound of the present invention has excellent properties as a fragrance and can be used as a substitute for a natural musk fragrance, and a fragrance composition containing these as an active ingredient can be used in various cosmetics, health and hygiene materials, pharmaceuticals, and the like. Used in a wide range of fields.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Yamazaki Tetsuro 1-4-11 Nishi-Hachiman, Hiratsuka-shi, Kanagawa Prefecture F-term in Takasago International Co., Ltd. 4C062 JJ70 4H059 BA36 BB19 BB22 BB46 BC10 CA99 DA09 EA35

Claims (7)

[Claims] 1. A compound of the general formula (1) (In the formula, m is an integer of 1 to 9, n is an integer of 0 to 7, and the sum of m and n is an integer of 8 to 10.)
(R) or racemic ester compound represented by
Wherein the ring is closed by a metathesis reaction. (Wherein m and n have the same meanings as described above). A process for producing a macrocyclic lactone compound having a double bond ((R) form or racemic form) represented by the formula: 2. A compound of the general formula (2) (Wherein, m is an integer of 1 to 9, n is an integer of 0 to 7, and the sum of m and n is 8 to 10). ((R) -form or racemic-form) hydrogenated, characterized by the general formula (3) (Wherein, m and n have the same meanings as described above). (R) or a racemic form. 3. The ester compound represented by the general formula (1) is a compound represented by the general formula (4): Β-butyrolactone ((R) form or racemic form) represented by the following general formula (5): (Wherein, X is a halogen atom, and n is an integer of 0 to 7).
A ring-opening reaction is carried out in the presence of a copper compound represented by the general formula (6): CuX ¹ (6) (wherein X ¹ is a halogen atom). 8] (Wherein, n has the same meaning as described above), and a terminal unsaturated carboxylic acid ((R) form or racemic form) represented by the general formula (8) is obtained. The macrocyclic lactone compound according to claim 1, wherein the compound is obtained by esterification with a terminal unsaturated alcohol represented by the formula (wherein, m is an integer of 1 to 9). (R) or racemic). 4. A compound of the general formula (9) (Wherein the double dashed line indicates a single bond or a double bond, and m ′
Is an integer from 1 to 9; n 'is an integer from 0 to 7; the sum of m' and n 'is an integer from 8 to 10; provided that the double dashed line is a single bond and the compound is In the case of the racemic form, 9 is excluded from the sum of m ′ and n ′. A) a macrocyclic lactone compound ((R) form or racemic form). 5. A compound of the general formula (2) (Wherein n is an integer of 0 to 7, m is an integer of 1 to 9, and the sum of m and n is an integer of 8 to 10). Compound ((R) form or racemic form). 6. A fragrance imparting agent comprising the macrocyclic lactone compound represented by the general formula (9) according to claim 4. 7. A fragrance composition comprising the macrocyclic lactone compound represented by the general formula (9) according to claim 4.