JP5014732B2 - Method for producing anteisoaliphatic aldehyde and perfume composition containing the same - Google Patents

Description

  The present invention relates to a method for producing an antiisoaliphatic aldehyde useful as a perfume and use thereof.

  Anteisoaliphatic aldehydes (compounds in which a methyl group is bonded to the third carbon from the methyl terminus of a straight chain aldehyde) have been found in yuzu peel oil and have an important contribution to the aroma of yuzu (Patent Document 1, Non-Patent Document 1). However, regarding these synthesis methods, only synthesis methods that are difficult to implement industrially have been known. For example, the method of synthesizing from 2-methylbutanal and ω-bromoalkanoic acid ester uses lithium aluminum hydride, which is easy to ignite, and uses highly toxic PCC. Since 2-methylbutanal is easily racemized under basic conditions during the reaction, it is difficult to synthesize optically active substances by this method (Patent Document 1). In addition, when synthesizing optically active 6-methyloctanal from 4-methylpentyl alcohol, sec-butyllithium, which easily ignites, is used, which also has a problem in industrial production (non-patent document). 2). Moreover, in the case of the synthesis | combination by hydroformylation of 5-methyl 1-heptene, the problem that 5-methyl- 1-heptene was not easy to obtain was obstructing industrial manufacture (nonpatent literature 3).

  On the other hand, optically active anteisoaliphatic aldehydes are known compounds that are synthesized as synthetic intermediates and related substances of insect pheromones (Non-patent Documents 2 and 4). However, including these studies, there was no report on the aroma of optically active antisoaliphatic aldehydes.

Patent No. 2604630 J. et al. Agric. Food Chem. 38, 1544 (1990) Tetrahedron 45, 2649 (1989) Chimica e l'Industria 55, 262 (1973) Agric. Biol. Chem. 47, 869 (1983

  Anteisoaliphatic aldehydes known for their usefulness as fragrances have been difficult to industrially produce by conventional synthetic methods. Therefore, development of a method for synthesizing an anteisoaliphatic aldehyde that can be applied to industrial production and development of a method for synthesizing an optically active anteisoaliphatic aldehyde have been a problem.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have reacted 1-halogeno-2-methylbutane with magnesium to form a Grignard reagent, and this is a ω-halogenoalkanenitrile in the presence of a copper salt catalyst. It is found that an anteisoaliphatic nitrile can be easily synthesized by reducing it to an anteisoaliphatic nitrile and that it can be easily reduced, and without using racemization by using optically active 1-halogeno-2-methylbutane. It was also found that an optically active anteisoaliphatic aldehyde can be easily synthesized. In addition, the optically active anteisoaliphatic aldehyde thus obtained has excellent aroma characteristics and can be used as a fragrance composition, thereby completing the present invention.

  Thus, the present invention provides the following formula (5)

[Wherein X represents a halogen atom]
1-halogeno-2-methylbutane represented by the following formula (4)

[Wherein X represents a halogen atom]
In the presence of a copper salt catalyst, the Grignard reagent represented by the following formula (3) is obtained:

[Wherein X represents a halogen atom, and n represents an integer in the range of 1 to 7]
Is reacted with ω-halogenoalkanenitrile represented by the following formula (2):

[Wherein n represents an integer in the range of 1 to 7]
An anteisoaliphatic nitrile represented by the following formula (1):

[Wherein n represents an integer in the range of 1 to 7]
The manufacturing method of the anteiso aliphatic aldehyde represented by these is provided.

  The present invention also provides the following formula (5 '):

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and X indicates a halogen atom.]
An optically active 1-halogeno-2-methylbutane represented by the following formula (4 ′)

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and X indicates a halogen atom.]
In the presence of a copper salt catalyst, the Grignard reagent represented by the following formula (3)

[Wherein X represents a halogen atom, and n represents an integer in the range of 1 to 7]
Is reacted with ω-halogenoalkanenitrile represented by the following formula (2 ′)

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and n indicates an integer in the range of 1 to 7.]
An optically active anteisoaliphatic nitrile represented by the following formula (1 ′):

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and n indicates an integer in the range of 1 to 7.]
The manufacturing method of the optically active anteiso aliphatic aldehyde represented by these is provided.

  The present invention also provides the method for producing the above optically active anteisoaliphatic aldehyde, wherein the optically active anteisoaliphatic aldehyde represented by the formula (1 ′) is optically active 6-methyloctanal or optically active 8-methyldecanal. Is to provide.

  The present invention also provides a fragrance composition comprising optically active 6-methyloctanal and / or optically active 8-methyldecanal as an active ingredient.

  The present invention also provides the above-described fragrance composition, wherein the enantiomeric excess of optically active 6-methyloctanal and optically active 8-methyldecanal is 60% ee or more.

  By the production method provided by the present invention, it is possible to obtain an antiisoaliphatic aldehyde in a short process using low-cost raw materials, low toxicity and low production, and mass production by using as an industrial production method. Is possible. Further, by using optically active 1-bromo-2-methylbutane as a raw material, an optically active anteisoaliphatic aldehyde can be obtained in good yield without causing racemization. Further, the obtained optically active anteisoaliphatic aldehyde has excellent aroma characteristics and can be widely used as a fragrance composition.

  Hereinafter, the present invention will be described in more detail.

  A synthesis process of an anteisoaliphatic aldehyde according to the present invention is shown in the following reaction formula A.

[X represents a halogen atom, n represents an integer in the range of 1 to 7, THF represents tetrahydrofuran, NMP represents N-methylpyrrolidone, and DIBAL represents diisobutylaluminum hydride]
(First step)
The Grignard reagent of formula (4) can be easily synthesized according to reaction formula A by reacting 1-halogeno-2-methylbutane of formula (5) with magnesium. The starting material 1-halogeno-2-methylbutane of the formula (5) can be easily obtained as a commercial product. It can also be easily synthesized by a known method of halogenating 2-methyl-1-butanol. Specific examples of 1-halogeno-2-methylbutane of the formula (5) include 1-bromo-2-methylbutane and 1-chloro-2-methylbutane.

  The amount of magnesium used in the preparation of the Grignard reagent is usually within a range of 1 to 3 mol, preferably 1.1 to 1.3 mol, relative to 1 mol of 1-halogeno-2-methylbutane of the formula (5). Can be. The reaction can be carried out in an ether solvent, and examples of the ether solvent used include diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, cyclopentyl methyl ether and the like. The amount used can usually be 3 to 30 times the amount of 1-halogeno-2-methylbutane of formula (5). At this time, the reaction temperature is in the range of 0 ° C. to 60 ° C., preferably in the range of 20 ° C. to 40 ° C., and stirring is performed for about 60 minutes to 180 minutes.

(Second step)
The step of obtaining the anteisoaliphatic nitrile of formula (2) by reacting the Grignard reagent of formula (4) obtained in the first step with the halogenated nitrile of formula (3) is the second step. The reaction is carried out by dissolving the halogenated nitrile of formula (3) in a solvent and cooling, and dropwise adding the solution of the Grignard reagent of formula (4) obtained in the first step.

  Examples of the copper salt to be used include copper (I) chloride, copper (I) bromide, copper (I) iodide, copper chloride (II) -lithium chloride double salt, and the like. The amount used is usually 0.01 to 0.1 mol, preferably 0.03 to 0.05 mol, per 1 mol of the halogenated nitrile of formula (3).

  The halogenated nitrile of formula (3) used is 2-bromoethanenitrile, 3-bromopropanenitrile, 4-bromobutanenitrile, 5-bromopentanenitrile, 6-bromohexanenitrile, 7-bromoheptanenitrile, Although it is 8-bromooctanenitrile, it can be purchased as a commercial product.

  Examples of the solvent to be used include ether solvents such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, cyclopentylmethyl ether, and more preferably N, N-dimethylformamide, N-methyl. Examples include -2-pyrrolidone added as an auxiliary solvent. The amount used can be usually 30 to 50 times the amount of the halogenated nitrile of formula (3).

  The reaction temperature can be in the range of −50 ° C. to 20 ° C., but it is preferably in the range of −30 ° C. to 0 ° C.

  By performing the above reaction, 4-methylhexanenitrile, 5-methylheptanenitrile, 6-methyloctanenitrile, 7-methylnonanenitrile, 8-methyldecanenitrile, 9-methylundecanenitrile, 10-methyldodecanenitrile, etc. An antiisoaliphatic nitrile of formula (2) can be obtained. The obtained antiisoaliphatic nitrile of the formula (2) can be used as it is in the next step as a crude product, but is separated from the reaction mixture by a method known per se, for example, vacuum distillation, silica gel column chromatography, etc. Can be purified.

(Third process)
Next, the step of reducing the anteisoaliphatic nitrile of formula (2) obtained in the second step to obtain the anteisoaliphatic aldehyde of formula (1) is the third step. The reduction can be performed, for example, using diisobutylaluminum hydride as a reducing agent. The reaction can be carried out by dissolving the anteisoaliphatic nitrile of the formula (2) obtained in the second step in a hydrocarbon solvent, and dropping a solution obtained by dissolving diisobutylaluminum hydride in a hydrocarbon solvent. it can.

  Examples of the hydrocarbon solvent include hexane and toluene. The amount used can usually be 3 to 30 times the amount of the antiisoaliphatic nitrile of formula (2). The amount of diisobutylaluminum hydride used is usually in the range of 1 to 2 mol, preferably 1.1 to 1.3 mol, and usually 5 to 5 mol based on the anteisoaliphatic nitrile of formula (2). It is used by dissolving in 10 times the amount of hydrocarbon solvent.

  Although the reaction temperature can be carried out in the range of -80 ° C to 0 ° C, it is preferably carried out in the range of -30 ° C to -10 ° C. Next, the obtained reaction solution is hydrolyzed by adding a known method, for example, dilute hydrochloric acid, dilute sulfuric acid, citric acid aqueous solution, tartaric acid aqueous solution, acetic acid aqueous solution, etc. Antiisoaliphatic aldehydes such as -methyloctanal, 7-methylnonanal, 8-methyldecanal, 9-methylundecanal and 10-methyldodecanal can be obtained.

  The obtained anteisoaliphatic aldehyde of the formula (1) can be separated from the reaction mixture and purified by a method known per se, for example, distillation under reduced pressure, silica gel column chromatography and the like.

  Next, the synthesis process of the optically active anteisoaliphatic aldehyde according to the present invention is shown in the following reaction formula B.

[X represents a halogen atom, n represents an integer in the range of 1 to 7, THF represents tetrahydrofuran, NMP represents N-methylpyrrolidone, and DIBAL represents diisobutylaluminum hydride]
(First step)
The Grignard reagent of the formula (4 ′) can be easily synthesized according to the reaction formula B by reacting the optically active 1-halogeno-2-methylbutane of the formula (5 ′) with magnesium. The optically active 1-halogeno-2-methylbutane of the formula (5 ′) as a starting material can be easily obtained as a commercial product. It can also be easily synthesized by a known method for halogenating optically active 2-methyl-1-butanol. Specific examples of the optically active 1-halogeno-2-methylbutane of the formula (5) include, for example, (S) -1-bromo-2-methylbutane, (R) -1-bromo-2-methylbutane, (S) — Examples thereof include 1-chloro-2-methylbutane and (R) -1-chloro-2-methylbutane.

  The amount of magnesium used in the preparation of the Grignard reagent is usually 1 to 3 mol, preferably 1.1 to 1.3 mol, relative to 1 mol of the optically active 1-halogeno-2-methylbutane of the formula (5 ′). Can be within the range of The reaction can be carried out in an ether solvent, and examples of the ether solvent used include diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, cyclopentyl methyl ether and the like. The amount thereof used is usually 3 to 30 times the amount of the optically active 1-halogeno-2-methylbutane of the formula (5 '). At this time, the reaction temperature is in the range of 0 ° C. to 60 ° C., preferably in the range of 20 ° C. to 40 ° C., and stirring is performed for about 60 minutes to 180 minutes.

(Second step)
The step of reacting the optically active Grignard reagent of the formula (4 ′) obtained in the first step with the halogenated nitrile of the formula (3) to obtain the optically active anteisoaliphatic nitrile of the formula (2 ′) is the second step. First, the copper salt and the halogenated nitrile of the formula (3) are dissolved in a solvent and cooled, and the solution of the Grignard reagent of the formula (4 ′) obtained in the first step is dropped therein.

  Examples of the copper salt to be used include copper (I) chloride, copper (I) bromide, copper (I) iodide, copper chloride (II) -lithium chloride double salt, and the like. The amount used is usually 0.01 to 0.1 mol, preferably 0.03 to 0.05 mol, per 1 mol of the halogenated nitrile of formula (3).

  The halogenated nitriles of formula (3) used are 2-bromoethanenitrile, 3-bromopropanenitrile, 4-bromobutanenitrile, 5-bromopentanenitrile, 6-bromohexanenitrile, 7-bromoheptanenitrile and Although each optically active substance of 8-bromooctanenitrile, it can be purchased as a commercial product.

  Examples of the solvent to be used include ether solvents such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, cyclopentylmethyl ether, and more preferably N, N-dimethylformamide, N-methyl. Examples include -2-pyrrolidone added as an auxiliary solvent.

  The amount used can usually be 5 to 30 times the amount of the halogenated nitrile of formula (3). The reaction temperature can be in the range of −50 ° C. to 20 ° C., but it is preferably in the range of −30 ° C. to 0 ° C.

  By performing the above reaction, (S) -4-methylhexanenitrile, (R) -4-methylhexanenitrile, (S) -5-methylheptanenitrile, (R) -5-methylheptanenitrile, (S) -6-methyloctanenitrile, (R) -6-methyloctanenitrile, (S) -7-methylnonanenitrile, (R) -7-methylnonanenitrile, (S) -8-methyldecanenitrile, (R) Formula (2) of -8-methyldecanenitrile, (S) -9-methylundecanenitrile, (R) -9-methylundecanenitrile, (S) -10-methyldodecanenitrile, (R) -10-methyldodecanenitrile ) Of optically active anteisoaliphatic nitriles. The obtained optically active anteisoaliphatic nitrile of the formula (2) can be separated from the reaction mixture and purified by a method known per se, for example, distillation under reduced pressure, silica gel column chromatography and the like.

(Third process)
Next, the step of reducing the optically active anteisoaliphatic nitrile of formula (2 ′) obtained in the second step to obtain the optically active anteisoaliphatic aldehyde of formula (1 ′) is the third step. The reduction can be performed, for example, using diisobutylaluminum hydride as a reducing agent. The reaction is carried out by dissolving the anteisoaliphatic nitrile of the formula (2 ′) obtained in the second step in a hydrocarbon solvent, and adding dropwise thereto a solution obtained by dissolving diisobutylaluminum hydride in a hydrocarbon solvent. Can do. Examples of the hydrocarbon solvent include hexane and toluene. The amount used thereof can be usually 3 to 30 times the amount of the optically active anteisoaliphatic nitrile of the formula (2 ′). The amount of diisobutylaluminum hydride used is usually in the range of 1 to 2 mol, preferably 1.1 to 1.3 mol, based on the optically active anteisoaliphatic nitrile of formula (2 ′). It is used by dissolving in 5 to 10 times the amount of hydrocarbon solvent.

  Although the reaction temperature can be carried out in the range of -80 ° C to 0 ° C, it is preferably carried out in the range of -30 ° C to -10 ° C.

  Next, the obtained reaction solution is hydrolyzed by adding a known method, for example, dilute hydrochloric acid, dilute sulfuric acid, citric acid aqueous solution, tartaric acid aqueous solution, acetic acid aqueous solution, etc. (S) -4-methylhexanal, (R) -4-methylhexanal, (S) -5-methylheptanal, (R) -5-methylheptanal, (S) -6-methyloctanal, (R) -6-methyloctanal, (S)- 7-methylnonanal, (R) -7-methylnonanal, (S) -8-methyldecanal, (R) -8-methyldecanal, (S) -9-methylundecanal, (R)- 9-methylundecanal, (S) -10-methyldodecanal, (R) -10-methyldodecanal optically active anteisoaliphatic aldehyde can be obtained. The obtained optically active anteisoaliphatic aldehyde of the formula (1) can be separated from the reaction mixture and purified by a method known per se, for example, distillation under reduced pressure, silica gel column chromatography and the like.

  Of the optically active anteisoaliphatic aldehydes thus obtained, optically active 6-methyloctanal and optically active 8-methyldecanal have unique aroma characteristics that have not existed so far. It is as shown in Table 1 below.

  As shown in Table 1, (S) -6-methyloctanal of the present invention has a fresh and sweet green, citrus characteristic odor, and (R) -6-methyloctanal has a fat-like characteristic odor. Have Further, (S) -8-methyldecanal has a characteristic aroma of fresh bitter citrus, and (R) -8-methyldecanal has a green, fresh oily characteristic aroma. Therefore, the optically active substance can be used as a fragrance material that imparts strength and variation to the fragrance of the fragrance composition due to the characteristic fragrance characteristics of each.

  On the other hand, the known racemic 6-methyloctanal has both oily and citrus and green fragrances, but there are no significant features such as (S) and (R), and the entire fragrance is blurred. It is inferior as a fragrance material. Although racemic 8-methyldecanal also has both a fat-like and sweet citrus fragrance, there are no significant features such as (S) and (R) isomers, and the entire fragrance is blurred. Is inferior.

  The optically active 6-methyloctanal and optically active 8-methyldecanal represented by the formula (1 ′) of the present invention have a characteristic aroma as described above and can be used as a fragrance material. However, by adding to the fragrance composition which is another fragrance component, the effect of improving and enhancing the fragrance is obtained while maintaining harmony with the fragrance composition. Therefore, according to the present invention, there is also provided a fragrance composition comprising the optically active 6-methyloctanal and / or optically active 8-methyldecanal of the present invention as an active ingredient.

  The enantiomeric excess of the optically active 6-methyloctanal and optically active 8-methyldecanal used in the fragrance composition of the present invention is 60% ee or more, preferably 80% ee or more, more preferably 90 from the viewpoint of fragrance. % Ee or higher is preferable.

  For example, 98% ee (S) -6-methyloctanal has a remarkably fresh and sweet green, citrus aroma, and 80% ee (S) -6-methyloctanal is also significantly fresh and sweet. Green, citrus scent, 60% ee (S) -6-methyloctanal has a slightly fresh and sweet green, citrus scent, but 40% ee (S) -6-methyl octanal is There are no salient features of the oily and citrus, green fragrance, but the entire fragrance is blurred.

  In addition, 98% ee (R) -6-methyloctanal has an extremely fat-like aroma, and 80% ee (R) -6-methyloctanal has a fat-like aroma. 60% ee (R) -6-methyloctanal has a slightly oily scent, while 40% ee (R) -6-methyloctanal has both oily and citrus, green scents. There is no remarkable feature of the thing, and the whole fragrance is blurred.

  On the other hand, 98% ee (S) -8-methyldecanal has a citrus aroma with a very pronounced fresh bitter taste, and 80% ee (S) -8-methyldecanal has a significantly fresh bitter taste. 60% ee (S) -8-methyldecanal has a slightly fresh bitter citrus fragrance, but 40% ee (S) -8-methyldecanal There are no noticeable features of both oily and sweet citrus fragrances, and the entire fragrance is blurred.

  In addition, 98% ee (R) -8-methyldecanal has a very distinctive green, fresh oil-like characteristic aroma, and 80% ee (R) -8-methyldecanal is significantly green. 60% ee (R) -8-methyldecanal is slightly green and has a fresh oil-like characteristic aroma, but 40% ee (R)- 8-Methyldecanal has both an oily and sweet citrus fragrance, but no significant features and the entire fragrance is blurred.

  Other perfume materials that can be used when preparing a perfume composition using the optically active 6-methyloctanal and optically active 8-methyldecanal used in the perfume composition of the present invention include Perfume Chemistry Review 1, Examples include synthetic fragrances and natural fragrances described in 2, 3 (Okuda Osamu, Yodogawa Shoten Publishing), synthetic fragrances (Into Motoichi, Kagaku Kogyo Nippo Publishing).

  Further, the fragrance composition of the present invention prepared as described above is added to foods, feeds, cosmetics, toiletries, industrial products, etc., thereby imparting a characteristic fragrance to the product and diversifying it. Unique products that satisfy consumer needs can be provided.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

Example 1
A synthetic thermometer of (±) -6-methyloctanenitrile , a dropping funnel, and a 200 mL four-necked flask equipped with a Dimroth condenser were charged with scraped magnesium (2.9 g, 0.12 mol), and the inside of the system was replaced with argon. did. A small amount of iodine and dry THF (20 g) were added thereto and stirred. A portion of a solution of (±) -1-bromo-2-methylbutane (15.1 g, 0.10 mol) in dry THF (70 g) was added through a dropping funnel and heated to 40 ° C. to start production of a Grignard reagent. I let you. When the generation start of the Grignard reagent was confirmed, the reaction solution was ice-cooled and cooled to 20 ° C., and the remaining (S) -1-bromo-2-methylbutane solution was added dropwise at a speed that kept the internal temperature at about 20 ° C. After completion of dropping, the mixture was stirred for 1 hour.

  Copper bromide (I) (0.72 g, 5.0 mmol) was charged into a 200 mL four-necked flask equipped with another thermometer and a dropping funnel, and the system was purged with argon. Dry N-methylpyrrolidone (33.7 g, 0.34 mol), dry THF (60 g) and 4-bromobutyronitrile (12.6 g, 85 mmol) were charged there, and cooled to −20 ° C. in a dry ice / methanol bath. did. The THF solution of the Grignard reagent prepared earlier was charged into the dropping funnel while filtering so that magnesium waste did not enter with glass wool. The Grignard reagent was added dropwise from the dropping funnel at a speed not exceeding the internal temperature of -5 ° C. After completion of dropping, the mixture was stirred for 2 hours while maintaining the temperature as it was. Thereafter, the reaction solution was poured into a 20% aqueous ammonium chloride solution (200 g), and the temperature was raised to room temperature. After separating the organic phase, the aqueous phase was extracted with hexane (50 g). The combined organic phases were washed twice with saturated brine (100 g), dried over anhydrous magnesium sulfate, and then the solvent was distilled off with an evaporator. This was purified by distillation under reduced pressure (boiling point 81 ° C./1.1 kPa) to obtain (±) -6-methyloctanenitrile (10.5 g, yield 88%, GLC purity 91%).

1H-NMR (400 MHz, CDCl3): δ 0.85 (t, 3H, J = 7.3 Hz), 0.85 (d, 3H, J = 6.4 Hz), 1.13 (m, 2H), 1 .26-1.52 (m, 5H), 1.64 (m, 2H), 2.33 (t, 2H, J = 7.1 Hz)
13 C-NMR (100 MHz, CDCl 3): δ 11.39, 17.21, 19.13, 25.75, 26.27, 29.39, 34.21, 35.70, 119.91
MS: 138 (2), 124 (32), 110 (94), 96 (29), 83 (48), 69 (43), 57 (49), 54 (100), 41 (75), 29 (23 )

Example 2
Synthesis of (±) -6-methyloctanal In a 200 mL four-necked flask equipped with a dropping funnel with a septum rubber and an argon balloon, (±) -6-methyloctanenitrile (4.2 g, 30 mmol) and toluene (30 g) were added. The mixture was cooled to −20 ° C. with a dry ice / methanol bath. A 0.97M hexane solution of DIBAL (34 mL, 33 mmol) was transferred to the dropping funnel with a syringe and slowly dropped from there. After completion of the dropwise addition, the mixture was stirred as it was for 2 hours, and then added with dry ice and cooled to -60 ° C. Methanol (10 g) was charged into the dropping funnel and slowly dropped from there. Thereafter, the reaction solution was poured into a 20% aqueous citric acid solution (200 g), and vigorously stirred until the gel-like precipitate was dissolved. After separating the organic phase, the aqueous phase was extracted with hexane (20 g), and the combined organic phase was washed with 5% aqueous sodium hydrogen carbonate solution (30 g) and saturated brine (30 g). After drying over anhydrous magnesium sulfate, the solvent was distilled off with an evaporator. This was purified by silica gel column chromatography to obtain (±) -6-methyloctanal (1.3 g, yield 31%, GLC purity 95%).

1H-NMR (400 MHz, CDCl3): δ 0.83 (d, 3H, J = 6.3 Hz), 0.84 (t, 3H, J = 7.4 Hz), 1.11 (m, 2H), 1 .22-1.37 (m, 5H), 1.60 (m, 2H), 2.41 (dt, 2H, J = 1.8, 7.3 Hz), 9.75 (t, 1H, J = 1.8Hz)
13C-NMR (100 MHz, CDCl 3): δ 11.42, 19.18, 22.47, 26.72, 29.47, 34.27, 36.34, 44.02, 203.02
MS: 124 (2), 113 (7), 109 (7), 95 (61), 83 (11), 69 (37), 57 (100), 43 (30), 41 (65), 29 (29 )

Example 3
A synthetic thermometer of (S) -6-methyloctanenitrile , a dropping funnel, a 200 mL four-necked flask equipped with a Dimroth condenser was charged with shavings magnesium (2.9 g, 0.12 mol), and the inside of the system was replaced with argon. did. A small amount of iodine and dry THF (20 g) were added thereto and stirred. A part of a dry THF (70 g) solution of (S) -1-bromo-2-methylbutane (15.1 g, 0.10 mol) was added from the dropping funnel and heated to 40 ° C. to start production of a Grignard reagent. I let you. When the generation start of the Grignard reagent was confirmed, the reaction solution was ice-cooled and cooled to 20 ° C., and the remaining (S) -1-bromo-2-methylbutane solution was added dropwise at a speed that kept the internal temperature at about 20 ° C. After completion of dropping, the mixture was stirred for 1 hour.

  Copper bromide (I) (0.72 g, 5.0 mmol) was charged into a 200 mL four-necked flask equipped with another thermometer and a dropping funnel, and the system was purged with argon. Dry N-methylpyrrolidone (33.7 g, 0.34 mol), dry THF (60 g) and 4-bromobutyronitrile (12.6 g, 85 mmol) were charged there, and cooled to −20 ° C. in a dry ice / methanol bath. did. The THF solution of the Grignard reagent prepared earlier was charged into the dropping funnel while filtering so that magnesium waste did not enter with glass wool. The Grignard reagent was added dropwise from the dropping funnel at a speed not exceeding the internal temperature of -5 ° C. After completion of dropping, the mixture was stirred for 2 hours while maintaining the temperature as it was. Thereafter, the reaction solution was poured into a 20% aqueous ammonium chloride solution (200 g), and the temperature was raised to room temperature. After separating the organic phase, the aqueous phase was extracted with hexane (50 g). The combined organic phases were washed twice with saturated brine (100 g), dried over anhydrous magnesium sulfate, and then the solvent was distilled off with an evaporator. This was purified by distillation under reduced pressure (boiling point 98 ° C./2.0 kPa) to obtain (S) -6-methyloctanenitrile (9.0 g, yield 76%, GLC purity 97%).

1H-NMR, 13C-NMR and MS were consistent with (±) -6-methyloctanenitrile.
[Α] (20 ° C., D line, c = 1.20, chloroform): + 9.46 °

Example 4
Synthesis of (S) -6-methyloctanal (S) -6-methyloctanenitrile (7.0 g, 50 mmol) and hexane (25 g) were added to a 200 mL four-necked flask equipped with a dropping funnel with a septum rubber and an argon balloon. The mixture was cooled to −30 ° C. with a dry ice / methanol bath. A 0.97M hexane solution of DIBAL (57 mL, 55 mmol) was transferred to the dropping funnel with a syringe and slowly dropped from there. After completion of the dropwise addition, the mixture was stirred as it was for 2 hours, and then added with dry ice and cooled to -60 ° C. Methanol (10 g) was charged into the dropping funnel and slowly dropped from there. Thereafter, the reaction solution was poured into a 20% aqueous solution of sodium potassium tartrate (200 g) and vigorously stirred until the gel-like precipitate was dissolved. After separating the organic phase, the aqueous phase was extracted with hexane (20 g), and the combined organic phase was washed with 20% aqueous tartaric acid solution (30 g), 5% aqueous sodium hydrogen carbonate solution (30 g), and saturated brine (30 g). . After drying over anhydrous magnesium sulfate, the solvent was distilled off with an evaporator. This was purified by distillation under reduced pressure (boiling point 76 ° C./2.0 kPa) to obtain (S) -6-methyloctanal (2.9 g, yield 40%, GLC purity 95%).

1H-NMR, 13C-NMR and MS were consistent with (±) -6-methyloctanal.
[Α] (20 ° C., D line, c = 1.32, chloroform): + 9.36 °

Example 5
A synthetic thermometer of (±) -8-methyldecanenitrile , dropping funnel, 200 mL four-necked flask equipped with a Dimroth condenser was charged with shavings magnesium (2.9 g, 0.12 mol), and the system was purged with argon did. A small amount of iodine and dry THF (20 g) were added thereto and stirred. A portion of a solution of (±) -1-bromo-2-methylbutane (15.1 g, 0.10 mol) in dry THF (70 g) was added through a dropping funnel and heated to 40 ° C. to start production of a Grignard reagent. I let you. When the generation start of the Grignard reagent was confirmed, the reaction solution was ice-cooled and cooled to 20 ° C., and the remaining (S) -1-bromo-2-methylbutane solution was added dropwise at a speed that kept the internal temperature at about 20 ° C. After completion of dropping, the mixture was stirred for 1 hour.

  Copper bromide (I) (0.72 g, 5.0 mmol) was charged into a 200 mL four-necked flask equipped with another thermometer and a dropping funnel, and the system was purged with argon. Thereto were charged dry N-methylpyrrolidone (33.7 g, 0.34 mol), dry THF (60 g), 6-bromohexanenitrile (15.0 g, 85 mmol) and cooled to −20 ° C. in a dry ice / methanol bath. . The THF solution of the Grignard reagent prepared earlier was charged into the dropping funnel while filtering so that magnesium waste did not enter with glass wool. The Grignard reagent was added dropwise from the dropping funnel at a speed not exceeding the internal temperature of -5 ° C. After completion of dropping, the mixture was stirred for 2 hours while maintaining the temperature as it was. Thereafter, the reaction solution was poured into a 20% aqueous ammonium chloride solution (200 g), and the temperature was raised to room temperature. After separating the organic phase, the aqueous phase was extracted with hexane (50 g). The combined organic phases were washed twice with saturated brine (100 g), dried over anhydrous magnesium sulfate, and then the solvent was distilled off with an evaporator. This was purified by distillation under reduced pressure (boiling point 69 ° C./0.3 kPa) to obtain (±) -8-methyldecanenitrile (12.8 g, yield 90%, GLC purity 87%).

1H-NMR (400 MHz, CDCl3): δ 0.83 (d, 3H, J = 6.4 Hz), 0.85 (t, 3H, J = 7.3 Hz), 1.10 (m, 2H), 1 .21-1.36 (m, 7H), 1.44 (m, 2H), 1.65 (quant, 2H, J = 7.4 Hz), 2.33 (t, 2H, J = 7.1 Hz)
13C-NMR (100 MHz, CDCl 3): δ 11.46, 17.20, 19.23, 25.44, 26.81, 28.76, 29.17, 29.51, 34.39, 36.49, 119.94
MS: 166 (1), 152 (15), 138 (87), 124 (14), 110 (54), 96 (72), 82 (69), 69 (31), 57 (72), 55 (72 ), 43 (39), 41 (100), 29 (34)

Example 6
Synthesis of (±) -8-methyldecanal A 200 mL four-necked flask equipped with a dropping funnel with a septum rubber and an argon balloon was charged with (±) -6-methyloctanenitrile (1.7 g, 30 mmol) and toluene (20 g). The mixture was cooled to −78 ° C. with a dry ice / methanol bath. A 0.94M hexane solution of DIBAL (10.6 mL, 30 mmol) was transferred to the dropping funnel with a syringe and slowly dropped from there. After completion of the dropping, the mixture was stirred as it was for 2 hours, and then methanol (6 g) was charged into the dropping funnel and slowly dropped from there. Thereafter, the reaction solution was poured into a 20% aqueous sodium potassium tartrate solution (100 g) and stirred vigorously until the gel-like precipitate dissolved. After separating the organic phase, the aqueous phase was extracted with hexane (20 g), 10% aqueous acetic acid (50 g) was added to the combined organic phase, and the mixture was stirred for 2 hours. The organic phase was separated and washed with 5% aqueous sodium hydrogen carbonate solution (30 g) and saturated brine (30 g). After drying over anhydrous magnesium sulfate, the solvent was distilled off with an evaporator. This was purified by silica gel column chromatography to obtain (±) -8-methyldecanal (1.5 g, yield 88%, GLC purity 94%).

1H-NMR (400 MHz, CDCl3): δ 0.83 (d, 3H, J = 6.4 Hz) 0.84 (t, 3H, J = 7.3 Hz), 1.09 (m, 2H), 1. 20-1.36 (m, 9H), 1.62 (quint, 2H, J = 7.2 Hz), 2.41 (dt, 2H, J = 1.9, 7.3 Hz), 9.75 (t , 1H, J = 1.9Hz)
13C-NMR (100 MHz, CDCl 3): δ 11.46, 19.25, 22.17, 26.93, 29.27, 29.53, 29.76, 34.42, 36.58, 43.99, 203.06
MS: 141 (3), 123 (34), 109 (5), 95 (31), 81 (56), 70 (49), 67 (34), 57 (100), 55 (92), 43 (50 ), 41 (84), 29 (37)

Example 7
(S) -8-Methyldecanenitrile synthesis thermometer, dropping funnel, 200 mL four-necked flask equipped with a Dimroth condenser was charged with shavings magnesium (2.9 g, 0.12 mol), and the system was purged with argon did. A small amount of iodine and dry THF (20 g) were added thereto and stirred. A part of a dry THF (70 g) solution of (S) -1-bromo-2-methylbutane (15.1 g, 0.10 mol) was added from the dropping funnel and heated to 40 ° C. to start production of a Grignard reagent. I let you. When the generation start of the Grignard reagent was confirmed, the reaction solution was ice-cooled and cooled to 20 ° C., and the remaining (S) -1-bromo-2-methylbutane solution was added dropwise at a speed that kept the internal temperature at about 20 ° C. After completion of dropping, the mixture was stirred for 1 hour.

  Copper bromide (I) (0.72 g, 5.0 mmol) was charged into a 200 mL four-necked flask equipped with another thermometer and a dropping funnel, and the system was purged with argon. Thereto were charged dry N-methylpyrrolidone (33.7 g, 0.34 mol), dry THF (60 g), 6-bromohexanenitrile (15.0 g, 85 mmol) and cooled to −20 ° C. in a dry ice / methanol bath. . The THF solution of the Grignard reagent prepared earlier was charged into the dropping funnel while filtering so that magnesium waste did not enter with glass wool. The Grignard reagent was added dropwise from the dropping funnel at a speed not exceeding the internal temperature of -5 ° C. After completion of dropping, the mixture was stirred for 2 hours while maintaining the temperature as it was. Thereafter, the reaction solution was poured into a 20% aqueous ammonium chloride solution (200 g), and the temperature was raised to room temperature. After separating the organic phase, the aqueous phase was extracted with hexane (50 g). The combined organic phases were washed twice with saturated brine (100 g), dried over anhydrous magnesium sulfate, and then the solvent was distilled off with an evaporator. This was purified by distillation under reduced pressure (boiling point 74 ° C./0.3 kPa) to obtain (S) -8-methyldecanenitrile (10.5 g, yield 74%, GLC purity 96%).

1H-NMR, 13C-NMR and MS were consistent with (±) -8-methyldecanenitrile.
[Α] (20 ° C., D line, c = 1.51, chloroform): + 8.38 °

Example 8
Synthesis of (S) -8- methyldecanal A dropping funnel with a septum rubber and a 200 mL four-necked flask equipped with an argon balloon were charged with (S) -6-methyloctanenitrile (5.0 g, 30 mmol) and hexane (15 g). The mixture was cooled to −30 ° C. with a dry ice / methanol bath. A 0.97M hexane solution of DIBAL (34 mL, 33 mmol) was transferred to the dropping funnel with a syringe and slowly dropped from there. After completion of the dropwise addition, the mixture was stirred as it was for 2 hours, and then added with dry ice and cooled to -60 ° C. Methanol (6 g) was charged into the dropping funnel and slowly dropped from there. Thereafter, the reaction solution was poured into a 20% aqueous sodium potassium tartrate solution (100 g) and stirred vigorously until the gel-like precipitate dissolved. After separating the organic phase, the aqueous phase was extracted with hexane (20 g), 10% aqueous acetic acid (50 g) was added to the combined organic phase, and the mixture was stirred for 2 hours. The organic phase was separated and washed with 5% aqueous sodium hydrogen carbonate solution (30 g) and saturated brine (30 g). After drying over anhydrous magnesium sulfate, the solvent was distilled off with an evaporator. This was purified by distillation under reduced pressure (boiling point 61 ° C./0.3 kPa) to obtain (S) -8-methyldecanal (3.4 g, yield 67%, GLC purity 96%).

1H-NMR, 13C-NMR, and MS were consistent with (±) -8-methyldecanal.
[Α] (20 ° C., D line, c = 1.39, chloroform): + 8.09 °

Example 9
Each component (part by weight) shown in Table 2 was mixed as an orange flavor basic preparation composition.

  To this basic preparation composition, 6-methyloctanal and 8-methyldecanal synthesized in the ratio of Table 3 were added, and perfume compositions A to F were prepared.

Each of these fragrance compositions was added in an amount of 5 parts by weight to 995 parts by weight of a 60% aqueous ethanol solution, and a specialized panelist performed sensory evaluation on the flavor. The results are shown in Table 4.

Claims (2)

Following formula (5 ')

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and X indicates a halogen atom.]
An optically active 1-halogeno-2-methylbutane represented by the following formula (4 ′)

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and X indicates a halogen atom.]
In the presence of a copper salt catalyst, the Grignard reagent represented by the following formula (3) is obtained:

[Wherein X represents a halogen atom, and n represents an integer in the range of 1 to 7]
Is reacted with ω-halogenoalkanenitrile represented by the following formula (2 ′)

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and n indicates an integer in the range of 1 to 7.]
An optically active anteisoaliphatic nitrile represented by the following formula (1 ′):

[In the formula, * indicates that the configuration of carbon marked with * is R or S, and n indicates an integer in the range of 1 to 7.]
The manufacturing method of the optically active anteiso aliphatic aldehyde represented by these. The method for producing an optically active anteisoaliphatic aldehyde according to claim 1 , wherein the optically active anteisoaliphatic aldehyde represented by the formula (1 ') is optically active 6-methyloctanal or optically active 8-methyldecanal.