JP2010095447A - 13-oxabicyclo[10.3.0]pentadeca-1(12)-ene compounds, 12-methyl-13-oxabicyclo[10.3.0]pentadecane compounds, and perfume composition containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide compounds having a sandalwood-like incense, and to provide a perfume composition containing the same. <P>SOLUTION: The compounds having the sandalwood-like incense are a 13-oxabicyclo[10.3.0]pentadeca-1(12)-ene compound represented by formula (1) (wherein, R<SP>1</SP>is methyl or H) and a 12-methyl-13-oxabicyclo[10.3.0]pentadecane compound represented by formula (2) (wherein, R<SP>2</SP>, R<SP>3</SP>are each methyl or H), and are new compounds. The perfume composition includes one or more of these compounds. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to 13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes, 12-methyl-13-oxabicyclo [10.3.0] pentadecanes, and a perfume composition containing the same. About. More specifically, a novel 14-substituted-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene having a pleasant aroma with a high-class feel of a wood-like aroma reminiscent of natural sandalwood The present invention relates to 12-methyl-13-oxabicyclo [10.3.0] pentadecanes substituted or unsubstituted at the 14-position, and perfume compositions using these.

  As compounds that are bicyclic and have an ether bond in one ring, 13-oxabicyclo [10.3.0] pentadecane (formula (20)) [trade name; Cyclamber, Henkel Co., Ltd.] or 3-oxabicyclo [ 10.3.0] pentadeca-6-ene (formula (21)) [trade name; Muskogen, Drago Co.] is known [for example, see Patent Document 1]. However, these compounds are each considered to be a compound having a soft Ryusen fragrance, or a compound having a slightly diffusible woody and musk fragrance, and the odor quality is clearly different from the sandalwood-like fragrance. In addition, 14-methyl-13-oxabicyclo [10.3.0] pentadecane (formula (22)) [see Patent Document 2], 15,15-dimethyl-13-oxabicyclo [10.3.0] pentadecane ( Formula (23)) [see Non-Patent Document 1] is known, but there is no detailed explanation about the fragrance to the extent that the compound of formula (22) is said to have a tree-like fragrance.

  As the aroma of sandalwood oil (sandalwood oil), sandalwood such as the Indian Mysore region is considered the highest grade, but it has become extremely difficult to obtain due to the recent ban on logging. When the aromas of the compounds of formula (20) to formula (23) are compared with the aroma of sandalwood oil, the aroma is clearly different and the aroma is weak.

JP2003-213295A (paragraph number 0015) European Patent Application No. 75866 42nd Symposium on Fragrance, Terpene, and Essential Oils Abstracts 368-364, 1998, Gifu Pharmaceutical University

  With recent changes in the needs for various fragrances and fragrances used in fragrances, it is desired to develop a fragrance material that is more superior in quality and has a new fragrance. In particular, compounds having sandalwood-like scents are considered the scents that are of most interest to naturally oriented consumers. Accordingly, an object of the present invention is to provide a compound having sandalwood-like fragrance that satisfies the above-mentioned demand, and to provide a fragrance composition containing the same.

  In view of the above circumstances, as a result of intensive studies on the 13-oxabicyclo [10.3.0] pentadecane derivative that is considered to be an easily available and stable compound, the inventors of the present invention are adjacent to oxygen in a small cyclic ether compound. A compound having no hydrogen on the bridgehead carbon is easily and inexpensively obtained from cyclododecanone, and a compound having no hydrogen on the bridgehead carbon adjacent to the oxygen of the small-ring cyclic ether compound is It was found that it was very useful as an active ingredient of a fragrance composition, and the present invention was completed based on this finding.

That is, the present invention relates to 13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes represented by the formula (1) (wherein R ¹ represents a methyl group or hydrogen), and 12-methyl-13-oxabicyclo [10.3.0] pentadecane represented by the formula (2) (wherein R ² and R ^{3 each} represent a methyl group or hydrogen), and one or more thereof A fragrance composition containing

  The 13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes and 12-methyl-13-oxabicyclo [10.3.0] pentadecane obtained by the present invention are both novel compounds. It is a compound with a strong wooden-like fragrance that is clear and clear, and is expected to be used as a fragrance.

  13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes [formula (1)] and 12-methyl-13-oxabicyclo [10.3.0] pentadecanes in the present invention, 13 -Oxabicyclo [10.3.0] pentadecanes [Formula (2)] are all novel compounds. Although the synthesis method of the present invention is not limited, as one synthesis method, cyclododecanone [Formula (10)] can be synthesized as a starting material. A synthesis example will be described below. A reaction system diagram including an intermediate compound of this synthesis example is shown below.

Cyclododecanone [Formula (10)] as a starting material is a known general compound including a synthesis method, and is also sold as a reagent and can be easily obtained.
Cyclododecanone [Formula (10)] is converted to 3-chloro-1-propene or 3-chloro in an ether solvent such as diethyl ether, t-butyl methyl ether, tetrahydrofuran, dioxane or the like in the presence of alkali. By reacting with 2-methyl-1-propene, 2- (2-methyl-2-propenyl) cyclododec-1-one [formula (11)] or 2- (2-propenyl) cyclododec-1-one [ After being converted to the formula (12)], this is cyclized with sulfuric acid, and 14,14-dimethyl- belonging to 13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes [formula (1)] 13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes [formula (3)] or 14-methyl-13-oxabicyclo [10.3.0] penta Mosquito -1 (12) - ene [formula (4)] are synthesized.

  It is oxidized from 2- (2-propenyl) cyclododec-1-one [Formula (12)], which is the above intermediate, to 2- (2-oxopropyl) cyclododecan-1-one [Formula (13)], The monoalkenyl-ketone body is reacted with methylmagnesium halide to synthesize a diol body and then dehydrated and condensed to form a cyclized 12, 14, 14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [ Equation (5)] is synthesized.

  On the other hand, 2- (2-propenyl) cyclododec-1-one [formula (12)] was reacted with methylmagnesium halide to give 1-methyl- (2-propenyl) cyclododec-1-ol [formula (15). And partially oxidized to 1-methyl- (2-oxopropenyl) cyclododec-1-ol [formula (16)] and further hydrogenated to 1-methyl- (2-hydroxypropyl) cyclododec-1-ol [formula (17)], and by intramolecular ring closure by dehydration condensation, 12,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (6)] is synthesized.

  In addition, the above 1-methyl- (2-propenyl) cyclododec-1-ol [Formula (15)] is partially oxidized to 1-methyl- (2-oxoethenyl) cyclododec-1-ol [Formula (18)]. This is hydrogenated to 1-methyl-2- (2-hydroxyethyl) cyclododec-1-ol [formula (19)], and is subjected to intramolecular cyclization by dehydration condensation to give 12-methyl-13-oxabicyclo [10 3.0] pentadecane [Formula (7)] is synthesized.

  14,14-dimethyl-13-oxabicyclo [10.3.0] belonging to 13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes [formula (1)] synthesized above. Pentadeca-1 (12) -ene [formula (3)], 14-methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [formula (4)], and 13-oxabicyclo [10.3.0] pentadecenes [12,14,14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (5)], 12,14-dimethyl- belonging to [formula (2)] 13-oxabicyclo [10.3.0] pentadecane [formula (6)] and 12-methyl-13-oxabicyclo [10.3.0] pentadecane [formula (7)] are both novel compounds, Clear and clear It has a strong wood-like flavor that can be used as an active ingredient of the perfume.

  The perfume composition according to the present invention contains at least one of the above compounds, and includes various cosmetics including perfume, eau de cologne, eau de toilette, fragrances, detergents including soap, shampoo, detergent, aerosol products, etc. Can be used in a wide range of fields.

EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited to these.
In the following examples, the measurement of gas chromatography (GC) was carried out using a gas chromatography apparatus [manufactured by Shimadzu Corporation, “GC-2010” (model number)], a column [manufactured by GL Sciences Inc., “TC”. -WAX "(model number) 60 m x 0.32 mm, I.V. D. 0.25 μm], the column temperature was raised from 80 ° C. to 210 ° C. at a rate of 3 ° C. per minute, and the infrared absorption spectrum (IR) was measured by an infrared absorption spectrum measuring apparatus [manufactured by Hitachi, Ltd. "270-30" (model number)], gas chromatography / mass spectrometry (GC-MS) is a gas chromatography / mass spectrometer [manufactured by Agilent Technologies, "6890" / "5973" (model number)] Used.

Hereafter, the synthesis example of this invention compound and the intermediate synthesis example are described.
a) 14,14-Dimethyl-13-oxabicyclo [10.3.0] pentadecenca-1 (12) -ene [Formula (3)]:

[Intermediate Synthesis Example 1]
Synthesis of 2- (2-methyl-2-propenyl) cyclododec-1-one [Formula (11)] (Method 1);
[Synthesis of 2- (2-methyl-2-propenyl) cyclododec-1-one [formula (11)] from cyclododecanone [formula (10)]
To a 1 L four-necked flask equipped with a stirrer, thermometer and reflux condenser, cyclododecanone (91 g, 0.5 mol), toluene (90 ml), 47% aqueous sodium hydroxide (200 g), 50% aqueous tetrabutylammonium iodide ( 3.2 g), warmed to 90 ° C., and dropwise added 3-chloro-2-methyl-1-propene (67.5 g, 0.5 mol × 1.5) over 1 hour with stirring. After completion, stirring was continued for 7 hours at the same temperature. The organic layer of this reaction mixture was separated and acidified (pH 2) with 5% dilute sulfuric acid aqueous solution, and then the organic layer was washed with saturated brine (250 ml × 3) and further dried over magnesium sulfate. The organic phase was concentrated under reduced pressure to give a yellow oil (yield; 128.8 g). This yellow oily substance was distilled under reduced pressure to remove the first crystalline raw material flowing out (under 1 mmHg, 134 ° C. to 160 ° C.), and a fraction (yield; 85 g, GC area percentage shows 80%. Was purified using a glass distillation column packed with three Sruzer packs to obtain a transparent oil (yield: 56 g, boiling point: 135 ° C.-138 ° C./2 mmHg, GC Retention time; 28.2 minutes, GC purity; 95.7%).

From the infrared absorption spectrum (IR) and mass spectrometry (MS), it was confirmed that this product was 2- (2-methyl-2-propenyl) cyclododec-1-one [Formula (11)].
IR: 2944, 1716, 1474, 958.
MS (m / z): 236 (M ⁺ , 84%), 221 (15), 193 (11), 181 (11), 165 (10), 152 (10), 137 (21), 125 (62) , 112 (47), 95 (100), 82 (83), 67 (69), 55 (98), 41 (63).

[Intermediate Synthesis Example 2]
Synthesis of 2- (2-methyl-2-propenyl) cyclododec-1-one [Formula (11)] (Method 2);
[Synthesis of 2- (2-methyl-2-propenyl) cyclododec-1-one [formula (11)] from cyclododecanone [formula (10)]
Into a 2 L four-necked flask equipped with a stirrer, thermometer, and reflux condenser with a calcium chloride tube, 750 ml (1.35 mol) of lithium diisopropylamide tetrahydrofuran (Aldrich, 1.8M concentration) was added, While stirring, the mixture was cooled to 5 ° C. or lower, and while maintaining this temperature, cyclododecanone (246 g, 1.35 mol) dissolved in 300 ml of tetrahydrofuran was added thereto over 2 hours, and stirring was further continued for 30 minutes. At the same temperature or lower, 3-chloro-2-methyl-1-propene (163.3 g, 1.35 mol) was added dropwise over 30 minutes, and after completion of the dropwise addition, the temperature was gradually raised and stirring was continued at room temperature all day and night. The organic layer of this reaction mixture was separated and treated in the same manner as in Method 1 to obtain a transparent oil (yield; 156 g, boiling point: 136 ° C. to 138 ° C./2 mmHg, GC purity: 96.1%).

[Synthesis Example 1 of the Compound of the Present Invention]
Synthesis of 14,14-dimethyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [formula (3)];
[2- (2-Methyl-2-propenyl) cyclododec-1-one [formula (11)] to 14,14-dimethyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [ Synthesis of Formula (3)]
In a 100 mL four-necked flask equipped with a stirrer, thermometer, and condenser, 98% sulfuric acid [5 g, 0.0225 mol × 2.4] was placed, stirred vigorously while cooling with ice water, and 2- (2-methyl- 2-Propenyl) cyclododec-1-one (5.3 g, 0.0225 mol) was added dropwise over 20 minutes, and after completion of the addition, the temperature was returned to room temperature and stirring was continued for 4 to 5 hours. Isopropyl ether (60 ml) was added to the reaction mixture, and then poured into ice water (100 ml) to separate the aqueous layer and the oil layer. The organic phase was adjusted to pH 7 with saturated aqueous sodium hydrogen carbonate (approximately 50 ml), washed with saturated brine (50 ml × 2), and dried over magnesium sulfate. After removing the desiccant by filtration, the organic phase was concentrated under reduced pressure to give a yellow oil (yield; 4.81 g, yield; 90.6%). This compound is purified by silica gel column chromatography using normal hexane-isopropyl ether (volume ratio; 9: 1) as a developing solvent, and then further distilled in a glass tube oven to produce a substantially single peak on GC. (Yield; 3.9 g) was obtained (boiling point: 141-143 ° C./6 mmHg, GC retention time: 25.8 minutes, GC purity: 99.6%).

From the fact that no vinyl proton is observed in proton NMR, and from the infrared absorption spectrum (IR) and mass spectrometry (MS), this product was converted into 14,14-dimethyl-13-oxabicyclo [10.3.0] pentadeca-1. (12) -ene [Formula (3)] was confirmed.
IR: [FIG. 1] 2932, 2864, 1714, 1472, 1368.
MS (m / z): 236 (M ⁺ , 53%), 193 (13), 179 (20), 165 (19), 151 (10), 137 (68), 125 (100), 112 (83) 95 (21), 81 (23), 67 (21), 55 (30), 41 (28).

b) 14-Methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [formula (4)]:

[Intermediate Synthesis Example 3]
Synthesis of 2- (2-propenyl) cyclododec-1-one [Formula (12)];
[Synthesis of 2- (2-propenyl) cyclododec-1-one [formula (12)] from cyclododecanone [formula (10)]
To a 1 L four-necked flask equipped with a stirrer, thermometer and reflux condenser, cyclododecanone (91 g, 0.5 mol), toluene (90 ml), 47% sodium hydroxide aqueous solution (200 g), 50% tetrabutylammonium bromide aqueous solution ( 9.1 g) and stirring at room temperature, 3-chloro-1-propene (76.5 g, 0.5 mol × 2) was added dropwise over 2 hours. After completion of the dropwise addition, the mixture was further stirred at room temperature for 7 hours. Continued. The organic layer of this reaction mixture was separated and acidified (pH 2) with 5% dilute sulfuric acid aqueous solution, and then the organic layer was washed with saturated brine (250 ml × 3) and further dried over magnesium sulfate. The organic phase was concentrated under reduced pressure to give a yellow oil (yield; 123 g, boiling point; 142 ° C. to 149 ° C./5 mmHg). GC purity; 70%). Further rectification gave a clear oil (yield: 70.5 g, boiling point: 131 ° C. to 136 ° C./3 mmHg, GC purity: 97.1%).

From the infrared absorption spectrum (IR) and mass spectrometry (MS), it was confirmed that this product was 2- (2-propenyl) cyclododec-1-one [Formula (12)].
IR: 2932, 1710, 1644, 1474, 914.
MS (m / z): 222 (M ⁺ , 47%), 193 (8), 179 (15), 165 (23), 149 (17), 137 (17), 123 (16), 111 (56) 98 (90), 81 (76), 67 (77), 55 (100), 41 (71).

[Synthesis Example 2 of the Compound of the Present Invention]
Synthesis of 14-methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [Formula (4)];
From [2- (2-propenyl) cyclododec-1-one [formula (12)] to 14-methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [formula (4)] Composition]
To a 100 mL four-necked flask equipped with a stirrer, a thermometer, and a condenser, 98% sulfuric acid (5 g, 0.0225 mol × 2.4) was placed, and 2- (2-propenyl) was stirred vigorously while cooling with ice water. ) Cyclododec-1-one (5 g, 0.0225 mol) was added dropwise over 20 minutes. After completion of the addition, stirring was further continued at room temperature for 5 hours. Isopropyl ether (60 ml) was added to the reaction mixture, and then poured into ice water (100 ml) to separate the aqueous layer and the oil layer. The organic phase was separated with a separatory funnel, and the organic phase was neutralized with saturated aqueous sodium hydrogen carbonate (approximately 50 ml), washed with saturated brine (50 ml × 2), and dried over magnesium sulfate. After removing the desiccant by filtration, the organic phase was concentrated under reduced pressure to give a yellow oil (yield; 4.53 g, yield; 85%, GC purity; 94%).
Further distillation yielded a clear oil (3.4 g). This was purified by column chromatography, and further distilled by a glass tube oven (boiling point: 130 to 133 ° C./8 mmHg) to obtain a compound having a substantially single peak on GC (GC retention time; 28. 1 minute, GC purity; 99.4%).

14-Methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene was found from the absence of vinyl protons in proton NMR and infrared absorption spectrum (IR) and mass spectrometry (MS). [Formula (4)] was confirmed.
IR: [FIG. 2] 2932, 2860, 1694, 1470, 1448, 1232, 1210.
MS (m / z): 222 (M +, 57%), 193 (5), 179 (18), 165 (28), 137 (10), 124 (73), 111 (100), 98 (74), 81 (11), 68 (16), 55 (21), 41 (15).

c) 12, 14, 14-Trimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (5)]:

[Intermediate Synthesis Example 4]
Synthesis of 2- (2-oxopropyl) cyclododecan-1-one [Formula (13)];
[Synthesis of 2- (2-oxopropyl) cyclododecan-1-one [Formula (13)] from 2- (2-propenyl) cyclododec-1-one [Formula (12)]
A 300 mL four-necked flask equipped with a stirrer, a thermometer, a gas inlet tube, and a condenser with a gas discharge tube was charged with dimethylformamide-water (80 ml, volume ratio; 70:10), palladium chloride (1.77 g, 0.1 mol). × 1.1) and cuprous chloride (9.8 g, 0.1 mol) were added, and oxygen was introduced from an oxygen cylinder at room temperature for 60 minutes. Subsequently, stirring was continued while introducing oxygen, and 2- (2-propenyl) cyclododec-1-one (27.5 g, 0.11 mol) dissolved in dimethylformamide (30 ml) was added dropwise. However, the introduction of oxygen was continued for 26 hours at room temperature. The reaction mixture was poured into well-cooled 3N hydrochloric acid (330 ml), toluene (twice with 160 ml), and the toluene layers were combined, saturated brine (20 ml), saturated aqueous sodium bicarbonate (20 ml), saturated brine (20 ml). ). After drying over anhydrous magnesium sulfate, the desiccant was removed and the solvent was concentrated under reduced pressure to give an oil (yield; 27.0 g, GC purity; 74.7%). This oil was used in the next reaction as it was.
In order to confirm this product, a part was taken and purified by column chromatography and then recrystallized from methanol to obtain white crystals (GC retention time; 50.4 minutes, GC purity ; 96.2%, melting point). ; 56~57 ℃).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), it was confirmed that the product was 2- (2-oxopropyl) cyclododecan-1-one [formula (13)]. confirmed.
IR: 1718, 1474, 1242, 1172, 724.
GC-MS (m / z): 238 (M ⁺ , 33%), 195 (38), 181 (20), 167 (5), 140 (6), 127 (8), 114 (46), 98 ( 37), 83 (25), 71 (30), 55 (50), 43 (100).

[Intermediate Synthesis Example 5]
Synthesis of 2- (2-hydroxy-2-methylpropyl) -1-methylcyclododecan-1-ol [formula (14)];
[2- (2-oxopropyl) cyclododecan-1-one [formula (13)] to 2- (2-hydroxy-2-methylpropyl) -1-methylcyclododecan-1-ol [formula (14)] Synthesis]
In a 300 mL four-necked flask equipped with a stirrer, dropping funnel, thermometer and reflux condenser, a tetrahydrofuran solution (80 g, 0.08 mol × 2.4) of methylmagnesium chloride with a concentration of 3.0 mol in an inert gas atmosphere. A solution of 2- (2-oxopropyl) cyclododecan-1-one (17.8 g, 0.08 mol) in tetrahydrofuran (70 ml) was added dropwise from a dropping funnel at room temperature. Although the temperature rose to around 50 ° C., after stirring, the stirring was continued for 3 hours, and after confirming the disappearance of the starting material 2- (2-oxopropyl) cyclododecan-1-one by gas chromatography, The reaction solution was added to a saturated aqueous ammonium chloride solution (320 ml). Toluene (320 ml) was added thereto and stirred for several minutes. The organic layer was washed with saturated brine (320 ml), dried over anhydrous magnesium sulfate, the desiccant was filtered off, and used for the next reaction as it was. It was.

[Synthesis Example 3 of the Compound of the Present Invention]
Synthesis of 12, 14, 14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (5)] [2- (2-hydroxy-2-methylpropyl) -1-methylcyclododecane-1- Synthesis of 12, 14, 14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (5)] from all [Formula (14)]
The above crude 2- (2-hydroxy-2-methylpropyl) -1-methylcyclododecane was added to a 50 mL four-necked flask equipped with a stirrer, a dropping funnel, a thermometer, and a water separator with a reflux condenser (Dean Stark). -1-ol [Formula (14)] (1.68 g, 6 mmol) was dissolved in toluene (25 ml), and paratoluenesulfonic acid (0.16) was added thereto, followed by azeotropic dehydration under reflux conditions for 2 hours and a half. Reaction was performed. After cooling to room temperature, each was washed with saturated brine (50 ml), saturated aqueous sodium hydrogen carbonate (50 ml) and saturated brine (50 ml), dried over magnesium sulfate, the desiccant was removed, and the organic phase was removed under reduced pressure. Concentration gave an oil (yield; 1.26 g). This was purified by silica gel chromatography [silica gel manufactured by Kanto Chemical Co., Ltd., filler: 40 g of silica gel, developing solution: hexane / IPE mixed solvent solution (volume ratio: 97/3)], and further distilled under reduced pressure (190-195). C./2 mmHg) to obtain a transparent oil (yield; 0.63 g). In the GC measurement, two peaks were observed due to the presence of geometric isomers (first peak; 42.4% at 29.4 minutes, second peak; 30.1% at 29.8 minutes; total of two peaks) Area percentage; 98.8%).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), this product was converted into 12, 14, 14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (5 )].
IR: [FIG. 3] 2929, 2860, 1694, 1470, 1448, 1366, 1278, 1276.
GC-MS (m / z):
First peak: 238 (M +, 37%), 223 (100), 180 (5), 135 (5), 125 (15), 111 (97), 98 (18), 81 (9), 69 (15 ), 55 (20), 43 (26).
Second peak: 238 (M +, 35%), 223 (38), 125 (7), 111 (100), 98 (21), 81 (8), 69 (9), 55 (14), 43 (22 ).

d) 12,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (6)]:

[Intermediate Synthesis Example 6]
Synthesis of 1-methyl- (2-propenyl) cyclododec-1-ol [Formula (15)] From [2- (2-propenyl) cyclododec-1-one [Formula (12)] to 1-methyl- (2-propenyl) ) Cyclododec-1-ol [Synthesis of Formula (15)]
In a 100 mL four-necked flask equipped with a stirrer, dropping funnel, thermometer, and reflux condenser, tetrahydrofuran solution (40 g, 0.08 mol × 1.2) of methyl magnesium chloride with a concentration of 3.0 mol under an inert gas atmosphere. Then, a tetrahydrofuran (70 ml) solution of 2- (2-propenyl) cyclododec-1-one (17.8 g, 0.08 mol) was dropped from the dropping funnel at about room temperature. Although the temperature rose to around 45 ° C., the mixture was stirred as it was for 2 hours, and after gas chromatography confirmed that the unreacted raw material 2- (2-propenyl) cyclododecan-1-one had disappeared. The reaction solution was poured into an aqueous ammonium chloride solution. Toluene (280 ml) was added thereto and stirred for several minutes. The organic layer was washed with saturated brine (280 ml), the toluene layer was dried over anhydrous magnesium sulfate, and the desiccant was filtered off. It was. The product was confirmed by partially purifying by silica gel chromatography (silica gel manufactured by Kanto Chemical Co., Inc., filler; silica gel 20 g, developing solution; hexane / IPE mixed solvent solution (volume ratio; 5/1)). The oil (yield; 0.97 g) was separated by gas chromatography (GC) and subjected to infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS). Two peaks were seen due to the presence of the body (first peak; 22.7% at 41.0 minutes, second peak; 74.4% at 42.6 minutes; total area percentage of 2 peaks; 97.1%).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), it was confirmed that the product was 1-methyl- (2-propenyl) cyclododec-1-ol [Formula (15)]. confirmed.
IR: 3464, 2936, 2864, 1474, 1450, 1376.
GC-MS (m / z):
First peak: 238 (M ⁺ , 7%), 223 (18), 180 (9), 149 (8), 135 (12), 125 (28), 111 (74), 97 (43), 81 ( 40), 71 (99), 55 (58), 43 (100).
Second peak: 238 (M ⁺ , 11%), 223 (24), 183 (13), 149 (8), 135 (12), 125 (28), 111 (100), 98 (46), 81 ( 32), 71 (84), 55 (47), 43 (77).

[Intermediate Synthesis Example 7]
1-methyl- (2-oxopropenyl) cyclododec-1-ol [formula (16)]
[Synthesis of 1-methyl- (2-oxopropenyl) cyclododec-1-ol [Formula (16)] from 1-methyl- (2-propenyl) cyclododec-1-ol [Formula (15)]
To a 200 mL four-necked flask equipped with a stirrer, a thermometer, a gas inlet tube, and a condenser with a gas discharge tube, dimethylformamide-water (80 ml, volume ratio; 70:10) palladium chloride (1.77 g, 0.1 mol ×) 1.1), cuprous chloride (9.8 g, 0.1 mol) was added, and 2- (2-propenyl) cyclododec-1-one (27. 5 g, 0.11 mol) of dimethylformamide (30 ml) solution was added dropwise. After completion of the dropwise addition, oxygen was further introduced for 28 hours at room temperature while stirring. The reaction mixture was poured into well-cooled 3N hydrochloric acid (330 ml), extracted with toluene (twice with 160 ml), the toluene layers were combined, saturated brine (200 ml), saturated aqueous sodium bicarbonate (200 ml), saturated brine (200 ml). ). After drying over anhydrous magnesium sulfate, the desiccant was removed and the organic phase was concentrated under reduced pressure to give an oil (yield; 2.38 g).

[Intermediate Synthesis Example 8]
Synthesis of 1-methyl- (2-hydroxypropyl) cyclododec-1-ol [Formula (17)] From [1-methyl- (2-oxopropenyl) cyclododec-1-ol [Formula (16)] to 1-methyl- (2-Hydroxypropyl) cyclododec-1-ol [Synthesis of Formula (17)]
To a 30 mL four-necked flask equipped with a stirrer, dropping funnel, thermometer, reflux condenser, 1-methyl- (2-oxopropenyl) cyclododec-1-ol (2.38 g, 9 mmol), 1,4-dioxane- A mixed solution of water (16 ml, volume ratio; 1: 1) was added, and powdered sodium borohydride (0.35 g, 9 mmol) was added little by little while stirring at room temperature. Although the reaction solution turned black, stirring was continued at 50 ° C. for 11 hours, and after confirming that the raw material had disappeared by gas chromatography, the reaction solution was poured into 5% dilute hydrochloric acid little by little. Toluene (80 ml) was added thereto, and the mixture was stirred for several minutes. The toluene layer was separated, the water tank was extracted again with toluene (80 ml), the toluene layers were combined and washed with saturated brine (100 ml), and the organic layer was washed with anhydrous sulfuric acid. Dry with magnesium, and remove the desiccant. This was used as such for the next reaction.
In order to confirm the product, a part of the toluene solution obtained above was concentrated, and the crystals obtained by leaving in a refrigerator were separated, washed with methanol, dried and then subjected to gas chromatography ( GC) (GC retention time; single peak broad at 68.5 minutes, GC purity; 95.3%, melting point; 117-118 ° C.).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), this product is 1-methyl- (2-hydroxypropyl) cyclododec-1-ol [formula (17)]. It was confirmed.
IR: 3300, 2936, 1478, 1374, 1142, 1074.
GC-MS (m / z): 256 (M ⁺ , 1%), 238 (14), 223 (20), 194 (13), 180 (7), 149 (5), 138 (8), 125 ( 25), 112 (100), 96 (28), 81 (26), 71 (55), 55 (39), 43 (77).

[Synthesis Example 4 of the Compound of the Present Invention]
Synthesis of 12,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (6)] [2- (2-hydroxypropyl) -1-methylcyclododecan-1-ol [formula (17) ], 14,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [Synthesis of Formula (6)]
A 50 mL four-necked flask equipped with a stirrer, a dropping funnel, a thermometer, and a water separator equipped with a reflux condenser (Dean Stark) was charged with crude 2- (2-hydroxypropyl) -1-methylcyclododecane-1- All (1.62 g, 6 mmol) was dissolved in toluene (25 ml), paratoluenesulfonic acid (0.16 g) was added thereto, and an azeotropic dehydration reaction was performed while stirring under reflux conditions. Since the generation of water was not seen at all in 2.5 hours, it was cooled to room temperature, washed with saturated brine (50 ml), saturated aqueous sodium hydrogen carbonate (50 ml) and saturated brine (50 ml), dried over magnesium sulfate, After removing the desiccant, the organic phase was concentrated under reduced pressure (200-210 ° C./2 mmHg) to give an oil (yield; 1.3 g). This was purified by silica gel chromatography (silica gel manufactured by Kanto Chemical Co., Inc., filler: 30 g of silica gel, developing solution: hexane / IPE mixed solvent solution (volume ratio: 97/3), and further distilled (200-210 ° C. under reduced pressure). / 2 mmHg) to give a clear oil (yield; 0.97 g) GC measurement showed four peaks due to the presence of geometric isomers (first peak; 42.4 at 29.4 minutes). %, Second peak; 30.1% at 29.8 minutes, third peak; 10.9% at 31.2 minutes, fourth peak; 15.4% at 32.2 minutes, total area of four peaks Percentage; 98.8%).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), this product was converted into 12,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (6)]. It was confirmed that.
IR: [FIG. 4] 2936, 2864, 1472, 1448, 1378, 1086.
GC-MS (m / z):
First peak: 238 (M +, 37%), 223 (100), 180 (5), 135 (5), 125 (15), 111 (97), 98 (18), 81 (9), 69 (15 ), 55 (20), 43 (26).
Second peak: 238 (M +, 35%), 223 (38), 125 (7), 111 (100), 98 (21), 81 (8), 69 (9), 55 (14), 43 (22 ).
Third peak: 238 (M +, 24%), 223 (52), 125 (7), 111 (100), 98 (15), 81 (8), 69 (9), 55 (13), 43 (19 ).
Fourth peak: 238 (M +, 24%), 223 (74), 125 (7), 111 (100), 98 (19), 81 (8), 69 (10), 55 (14), 43 (19 ).

e) 12-methyl-13-oxabicyclo [10.3.0] pentadecane [Formula (7)]

[Intermediate Synthesis Example 9]
Synthesis of 1-methyl- (2-oxoethenyl) cyclododec-1-ol [formula (18)] [1-methyl- (2-propenyl) cyclododec-1-ol [formula (15)] to 1-methyl- (2 -Oxoethenyl) cyclododec-1-ol [Synthesis of Formula (18)]
To a 1 L four-necked flask equipped with a stirrer, dropping funnel, thermometer, reflux condenser, sodium periodate (42.8 g, 0.05 mol × 4), carbon tetrachloride (90 ml), acetonitrile (90 ml), water (130 ml) was added and stirred at room temperature, to this was added 1-methyl- (2-propenyl) cyclododec-1-ol (11.9 g, 0.05 mol), and further ruthenium chloride (0.3 g 0.05 mol × 0.03) was added and stirred. Heat was gradually generated and the temperature rose to about 40 ° C. After stirring at the same temperature for 5 hours and confirming by GC that the raw materials are consumed, water (300 ml) is added to separate the organic phase, and the aqueous phase is extracted with methylene chloride (60 ml × 2). These were washed with saturated brine (100 ml × 2), and the organic phase was concentrated under reduced pressure. Since the remaining oil contained solids, it was extracted with diethyl ether (100 ml), filtered through Celite, and the ether layer was concentrated to give an oil (yield; 11.8 g). This was used immediately in the next reaction.

[Intermediate Synthesis Example 10]
Synthesis of 1-methyl-2- (2-hydroxyethyl) cyclododec-1-ol [Formula (19)] From [1-methyl- (2-oxoethenyl) cyclododec-1-ol [Formula (18)] to 1-methyl -2- (2-Hydroxyethyl) cyclododec-1-ol [Synthesis of Formula (19)]
Crude 1-methyl- (2-oxoethenyl) cyclododec-1-ol (11.8 g, 0.049 mol) and 1,4-dioxane were added to a 500 mL four-necked flask equipped with a stirrer, dropping funnel, thermometer and reflux condenser. -Water (110 ml of mixed solution, volume ratio; 1: 1) was added and stirred at room temperature. To this, sodium borohydride (2.7 g, 0.049 mol × 1.5) was added little by little and reacted at 40-50 ° C. for 4 hours. 200 ml of water was poured into the reaction solution, extracted with isopropyl ether (100 ml × 2), and the organic layer was washed with saturated brine (100 ml) and concentrated under reduced pressure to obtain an oily substance (yield; 8. 65 g). This was purified by silica gel chromatography (silica gel manufactured by Kanto Chemical Co., Inc .; 345 g, developing solution; hexane / IPE mixed solvent solution (volume ratio; 5/1)) to obtain a transparent oil (yield; 7.3 g). Two peaks were observed due to geometric isomers by GC measurement (first peak; 6.3% at 37.8 minutes, second peak; 90.4% at 44.3 minutes; total area percentage of two peaks; 96.7%).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), this product was obtained as 1-methyl-2- (2-hydroxyethyl) cyclododec-1-ol [formula (19)]. I confirmed that there was.
IR: 3508, 3012, 1368, 1224.
GC-MS (m / z):
First peak: 242 (M ⁺ , 2%), 227 (5), 209 (26), 180 (5), 166 (8), 149 (5), 135 (8), 125 (21), 115 ( 37), 97 (100), 82 (31), 71 (76), 55 (54), 43 (93).
Second peak: 242 (M ⁺ , 2%), 227 (5), 209 (23), 166 (7), 149 (5), 135 (8), 125 (19), 115 (38), 97 ( 100), 81 (26), 71 (74), 58 (50), 43 (98).

[Synthesis Example 5 of the Compound of the Present Invention]
Synthesis of 12-methyl-13-oxabicyclo [10.3.0] pentadecane [formula (7)] [12 from [1-methyl-2- (2-hydroxyethyl) cyclododec-1-ol [formula (19)] -Methyl-13-oxabicyclo [10.3.0] pentadecane [Synthesis of Formula (7)]
In a 200 mL four-necked flask equipped with a water separator (Dean Stark) equipped with a stirrer, dropping funnel, thermometer and reflux condenser, the above crude 1-methyl-2- (2-hydroxyethyl) cyclododeca-1 was added. -Allol was dissolved in toluene (125 ml), paratoluenesulfonic acid (0.8 g) was added thereto, and an azeotropic dehydration reaction was carried out with stirring under reflux conditions. Since the generation of water disappeared in 3 hours, the mixture was cooled to room temperature, and washed successively with saturated brine (250 ml), saturated aqueous sodium hydrogen carbonate (100 ml) and saturated brine (250 ml). After drying over magnesium sulfate and removing the desiccant, the organic phase was concentrated under reduced pressure (100-120 ° C./2 mmHg) to give an oil (yield; 8.16 g). This was purified by silica gel chromatography (silica gel manufactured by Kanto Chemical Co., Inc .; 145 g, developing solution; hexane / IPE mixed solvent solution (volume ratio: 5/1), and further distilled (200 ° C./3 mmHg) under reduced pressure to be transparent. An oily product (yield; 3.3 g) was obtained, and two peaks were observed due to geometric isomers by GC measurement (first peak; 62.0% at 31.8 minutes, second peak; 33.7). 37.7% per minute, 2 peak total area percentage; 99.7%).

From the infrared absorption spectrum (IR) and gas chromatography / mass spectrometry (GC-MS), the product is 12-methyl-13-oxabicyclo [10.3.0] pentadecane [Formula (7)]. It was confirmed.
IR: [FIG. 5] 2936, 2868, 1472, 1450, 1374, 1046, 1032.
GC-MS (m / z):
First peak: 224 (M +, 16%), 209 (31), 97 (100), 84 (19), 71 (8), 55 (15), 41 (20).
Second peak: 224 (M +, 8%), 209 (59), 97 (100), 84 (19), 71 (11), 55 (19), 41 (24).

  14,14-dimethyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [formula (3)], 14-methyl-13-oxabicyclo [10] obtained as described above. 10.3.0] pentadeca-1 (12) -ene [formula (4)], 12, 14, 14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (5)], 12, Aroma evaluation was performed on 14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (6)] and 12-methyl-13-oxabicyclo [10.3.0] pentadecane [formula (7)], respectively. went. 14,14-Dimethyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [Formula (3)] is a fragrance having a natural sandal-like spread and strength alone. 14-methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [Formula (4)] was also a fragrance reminiscent of natural sandals with sweetness. In addition, 12,14,14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (5)] has a santalol-like scent and has a 12,14-dimethyl-13-oxa Bicyclo [10.3.0] pentadecane [Formula (6)] also has a scent similar to that of 12, 14, 14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (5)]. It had a roll-like high-class sweetness. Furthermore, 12-methyl-13-oxabicyclo [10.3.0] pentadecane [Formula (7)] had a strong aroma reminiscent of natural sandals.

  Moreover, the fragrance | flavor composition containing these compounds was prepared, and the usability to a compound fragrance | flavor was evaluated. Evaluation was carried out with respect to five types of perfume compositions as a composition containing any one of the above five compounds ([A-1] to [A-5]) as an example, and the compound of the present invention as a comparative example. And a composition containing 14-methyl-13-oxabicyclo [10.3.0] pentadecane [formula (22)], which is a known similar compound ([B-2], [B-5], [B-8], [B-11]), a known compound similar to 14,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [formula (24)] ([ B-3], [B-6], [B-9], [B-112]) and a composition ([B-1], [B-4], [B-] 7] and [B-10]), and the determination was made by three incense experts.

a) Rose type fragrance composition Table 1 shows the composition of the rose type fragrance composition, and Table 2 shows the evaluation results.

b) Muget type fragrance composition The composition of the muget type fragrance composition is shown in Table 3, and the evaluation results are shown in Table 4.

c) Musk type fragrance composition Table 5 shows the composition of the musk type fragrance composition, and Table 6 shows the evaluation results.

d) Heliotrope type fragrance composition Table 7 shows the composition of the heliotrope type fragrance composition, and Table 8 shows the evaluation results.

e) Jasmine type fragrance composition Table 9 shows the composition of the jasmine type fragrance composition, and Table 10 shows the evaluation results.

  From the above evaluation results, it was confirmed that the compound of the present invention has a comfortable sandalwood-like aroma with a high-class feeling.

  The novel compound of the present invention can be easily synthesized from general-purpose chemical compounds and has a pleasant tree-like fragrance with a high-class feeling, is useful as a new fragrance composition, and is widely used in cosmetics, fragrances and the like. Can be used for

14 is an infrared absorption spectrum (IR) of 14,14-dimethyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [Formula (3)]. It is an infrared absorption spectrum (IR) of 14-methyl-13-oxabicyclo [10.3.0] pentadeca-1 (12) -ene [Formula (4)]. It is an infrared absorption spectrum (IR) of 12,14,14-trimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (5)]. It is an infrared absorption spectrum (IR) of 12,14-dimethyl-13-oxabicyclo [10.3.0] pentadecane [Formula (6)]. It is an infrared absorption spectrum (IR) of 12-methyl-13-oxabicyclo [10.3.0] pentadecane [Formula (7)].

Claims (3)

13-oxabicyclo [10.3.0] pentadeca-1 (12) -enes represented by the formula (1) (wherein R ¹ represents a methyl group or hydrogen).

12-methyl-13-oxabicyclo [10.3.0] pentadecane represented by the formula (2) (wherein R ² and R ^{3 each} represent a methyl group or hydrogen).

  A fragrance composition comprising one or more compounds of the formula (1) according to claim 1 and the compound of formula (2) according to claim 2.

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