JP2005336144A - LARGE CYCLIC LACTONE HAVING SUBSTITUENT AT (omega-3) POSITION - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain large cyclic lactones having not only musk fragrance strong and excellent in durability but nitromusk-like fragrance characteristics, powdery feeling and animal like fragrance, through fragrance characterization. <P>SOLUTION: The new compounds are expressed by the general formula (wherein n expresses 7-13). The method for producing the same is provided. Especially, the new compounds which have not been reported in former techniques are n=9: 11-methylidene-14-tetradecanolide and 11-methyl-14-tetradecanolide, and n=8: 10-methylidene-13-tridecanolide and 10-methyl-13-tridecanolide. The fragrance composition and the fragrance article contain at least one species of the new compounds. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to a macrocyclic lactone musk having musk-like aroma characteristics and having a methyl or methylidene group at the (ω-3) position as a perfume compound. Moreover, it is related with the fragrance | flavor composition which uses at least 1 sort (s) among these.

  As is widely known, musk-based fragrances have long been prized as expensive fragrances, and not only their elegant and fascinating fragrances but also have a high retention effect that suppresses the diffusion of other volatile fragrance compounds. Therefore, it has been widely used as a fragrance fragrance. With the progress of chemical technology in the modern era, natural musk components have been isolated, structurally determined and chemically synthesized. On the other hand, many compounds with musk-like aroma such as nitromusk and polycyclic musk that do not exist in nature have been discovered and have come to be widely used as substitutes for animals and plants. In recent years, attention has been focused on diversifying consumer needs and the safety of chemical substances, and expectations for highly biodegradable macrocyclic musks are increasing. It is being developed one after another.

With regard to macrocyclic musks, it has been known for a long time that C ₁₄ -C ₁₆ lactones have a musk-like aroma. However, these are considerably different in terms of fragrance and strength, and there are practically available as fragrances, and there are only 3 to 4 compounds that are currently on the market. Examples of the most widely used include 15-pentadecanolide and 11 (or12) -pentadecene-15-olide. Further, according to Non-Patent Document 1, 7-hexadecene-16-oride (Paper 105) and 16-hexadecanolide (Paper 923) are cited as useful musk aroma substances.

Patent Document 1 describes various methods for producing C _{14 to} C ₁₇ lactones. These lactones may be substituted with a methyl group at the 1 or 2 position counted from the ring oxygen atom, and have a double bond at the 2 or 3 position counted from the ring oxygen atom. And 15-methyl- and 14-methyl-pentadecanolide and the like are also included. These compounds were synthesized in accordance with the above-described method for producing 11 (or12) -pentadecene-15-olide, but only described as having an interesting fragrance. Is not shown at all.

  Patent Document 2 describes macrocyclic musk lactones for many saturated and unsaturated, unsubstituted and methyl substituted 14-17 lactones. However, they relate to the use of these useful precursors, ω-halogenated fatty acids, without any mention of the aroma of each lactone.

  In Patent Document 3, 14-methyl-11-hexadecene-16-orido, 14-methyl-12-hexadecene-16-orido, and 14-methyl-hexadecanolide are valuable and aromatic substances having a strong and pleasant musk aroma. It is described that. However, this patent only refers to these three compounds and does not describe homologues with different carbon numbers. According to Non-Patent Document 2, it is shown that the musk-like aroma of macrocyclic lactones has a strong musk-like aroma in the vicinity of 14 to 16 carbon atoms, and the macrocyclic lactone having 17 carbon atoms has a musk-like aroma. For example, a stronger musk scent than the compound described in Patent Document 3 is expected for homologues with a small number of carbon atoms because of its weakness. In addition, those manufacturing methods use cyclododecanone as a starting material according to the method of 11 (or12) -pentadecene-15-oride.

  Patent Document 4 also describes odorant compositions containing various 15- to 17-membered lactones. These lactones may be substituted with a methyl group between the 3rd position and the 4th position from the carbonyl group as counted from the ring oxygen atom as a general formula, and from the 3rd position and the carbonyl group as counted from the ring oxygen atom. It describes that a double bond may be present between the 3-positions. These compounds are described as having a musk odor and often having an interesting powdery, fruity, or scented side note. In this patent, dozens of kinds of compounds having the structure shown above are actually obtained and their aroma characteristics are described. According to it, each compound has a common incense-like fragrance, but has other characteristic side notes. In other words, in the fragrance material, the change in fragrance characteristics due to a slight difference in structure is large, and as a result, it can be said that the value as the fragrance material is found only by actually preparing a compound and smelling it.

  Non-Patent Document 3 describes a method for synthesizing 12-methyl-15-pentadecanolide and 12-methylidene-15-pentadecanolide. These compounds are described as having a mild musk-like fragrance, but there are two synthesis methods starting from 1- (3′-hydroxypropyl) -2-oxocyclododecane-1-carbonitrile. 12-methylidene-15-pentadecanolide is obtained by going through the ring expansion reaction, and 12-methyl-15-pentadecanolide is obtained by hydrogenating this. However, in this reaction, many steps are required for obtaining 1- (3′-hydroxypropyl) -2-oxocyclododecane-1-carbonitrile as a starting material, and further 3 to 5 steps are required. It is not industrially suitable, such as using chemicals that are difficult to use industrially, such as sodium hydride. In addition, there is no mention of a method for obtaining an object having a different carbon number.

Although various macrocyclic musks have been studied, only the 3 to 4 compounds shown in the beginning are actually used in the perfume industry to meet the diversifying consumer needs. Development of new macrocyclic musks having excellent aroma characteristics is also desired.
Japanese Patent Publication No. 54-8679 Canadian Patent No. 1221105 JP-A-10-204078 Japanese Patent Laid-Open No. 11-193395 S. Arctander Perfume and Flavor Chemicals Abe, Fragrance, 96, 19-27 (1970) helv. Chim. Acta 70, 760-765 (11987)

  In view of the above situation, the present invention meets the demands of the fragrance industry and consumers for the development of new macrocyclic lactone musks with excellent aroma characteristics. It is desirable that the manufacturing method is easy.

  We have general formula 1

（式中、ｎは７〜１３を表す）の新規な製造法を見出し、特にｎ＝９の１１−メチリデン−１４−テトラデカノリドおよびｎ＝８の１０−メチリデン−１３−トリデカノリドが先行技術中に報告されていない新規化合物で、香気特性評価を行った結果、強く且つ持続性に優れたムスク香を有するだけでなく、ニトロムスク的な香気的特徴を持ち、パウダリー感および動物的な優れた香気を有する大環状ラクトンムスクであることを見出した。

(Wherein n represents 7 to 13) has been found, in particular 11-methylidene-14-tetradecanolide with n = 9 and 10-methylidene-13-tridecanolide with n = 8 reported in the prior art As a result of odor characteristics evaluation with a new compound that has not been made, it has not only a strong and durable musk fragrance, but also has a nitromusk-like fragrance characteristic, a powdery feeling and an animal-like fragrance It was found to be a macrocyclic lactone musk.

  Further, the compound represented by the general formula 2 obtained by hydrogenating the compound represented by the general formula 1 by a method known per se.

（式中、ｎは７〜１３を表す）で示される化合物のうち、特にｎ＝９の１１−メチル−１４−テトラデカノリドおよびｎ＝８の１０−メチル−１３−トリデカノリドが先行技術中に報告されていない新規化合物で、香気特性評価を行った結果、強く且つ持続性に優れたムスク香を有するだけでなく、ニトロムスク的な香気的特徴を持ち、パウダリー感および動物的な優れた香気を有する大環状ラクトンムスクであることを見出した。また、本発明においては、これら新規化合物の中の少なくとも１種を含む香料組成物及び芳香品の提供する。

(Wherein n represents 7 to 13), n = 9 11-methyl-14-tetradecanolide and n = 8 10-methyl-13-tridecanolide have been reported in the prior art. As a result of odor characteristics evaluation with a new compound that has not been strong, not only has a strong and durable musk aroma, but also has a nitromusk-like aroma characteristic, a powdery feeling and an animal-like aroma It was found to be a cyclic lactone musk. Moreover, in this invention, the fragrance | flavor composition and fragrance | flavor containing at least 1 sort (s) in these novel compounds are provided.

  The macrocyclic lactones of the present invention are novel compounds having a strong and durable musk aroma. Furthermore, according to the method for producing macrocyclic lactones of the present invention, these novel macrocyclic lactones can be produced safely and efficiently.

The present inventors obtain a condensation reaction with γ-butyrolactone and a dicarboxylic acid ester represented by the general formula (3) ROOC (CH ₂ ) nCOOR (where n = 7 to 13, R represents an alkyl group or an alkenyl group). The following general formula 4

（但しｎ、Ｒは上記と同じ意味を表、Ｍはアルカリ金属を示す）で示される２−（ω−アルコキシカルボニルアルカノイル）−４−ブタノリッドのアルカリ金属塩を加水分解、脱炭酸させて得られた、一般式５

It is obtained by hydrolyzing and decarboxylating an alkali metal salt of 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide represented by the formula (where n and R represent the same meaning as described above, and M represents an alkali metal). General formula 5

（但しｎ、Ｍは上記と同じ意味を表す）で示されるω−ヒドロキシ−（ω−３）−ケトアルカン酸アルカリ金属塩をそのままＷｉｔｔｉｇ反応などによりカルボニル基をメチリデン化して、一般式６

(Wherein n and M represent the same meaning as described above) ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt is methylidene converted to methylidene by the Wittig reaction, etc.

（但しｎは上記と同じ意味を表す）のω−ヒドロキシ−（ω−３）−メチリデンアルカン酸を得、これを分子内環化することにより、一般式１

(Wherein n represents the same meaning as described above) ω-hydroxy- (ω-3) -methylidenealkanoic acid is obtained, and this is intramolecularly cyclized to give a general formula 1

（式中、ｎは７〜１３を表す）で示される（ω−３）−メチリデンアルカノリドが得られることを見出した。

It was found that (ω-3) -methylidenealkanolide represented by (wherein n represents 7 to 13) is obtained.

Further, the general formula 5

（但しｎ、Ｍは上記と同じ意味を表す）のω−ヒドロキシ−（ω−３）−ケトアルカン酸アルカリ金属塩を四級アンモニウム塩の存在下にベンジルクロリドなどのハロゲン化物と反応させ、一般式７

Ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt of (wherein n and M represent the same meaning as described above) is reacted with a halide such as benzyl chloride in the presence of a quaternary ammonium salt. 7

（但し、ｎは上記と同じ意味を表し、Ｒ’はカルボン酸アルカリ金属塩とハロゲン化物の反応において許容されうる任意の基を表す）で示されるエステルを得た後に、これを分子エステル交換することにより一般式８

(Wherein n represents the same meaning as described above, and R ′ represents an arbitrary group acceptable in the reaction of an alkali metal carboxylate with a halide), and this is subjected to molecular transesterification. General formula 8

（式中、ｎは７〜１３を表す）で示される（ω−３）−ケトアルカノリドを得、これにＷｉｔｔｉｇ反応などによりカルボニル基をメチリデン化して、一般式１

(Wherein n represents 7 to 13) (ω-3) -ketoalkanolide is obtained, and the carbonyl group is methylidene converted to the general formula 1 by Wittig reaction or the like.

（式中、ｎは７〜１３を表す）で示される（ω−３）−メチリデンアルカノリドが得られることを見出した。

It was found that (ω-3) -methylidenealkanolide represented by (wherein n represents 7 to 13) is obtained.

  Further, the (ω-3) -methylidenealkanolide thus obtained is hydrogenated by a method known per se to convert the methyl group to give a compound represented by the general formula 2

（式中、ｎは７〜１３を表す）で示される（ω−３）−メチルアルカノリドが得られる。

(Wherein n represents 7 to 13) (ω-3) -methylalkanolide is obtained.

  Of the (ω-3) -methylidenealkanolide represented by the general formula (1) and the (ω-3) -methylalkanolide represented by (2), particularly 11-methylidene-14 having n = 9 Tetradecanolide and 11-methyl-14-tetradecanolide, n = 8 10-methylidene-13-tridecanolide and 10-methyl-13-tridecanolide are novel compounds not reported in the prior art. The structural formulas of these compounds are shown in FIG.

  It has been found that these novel macrocyclic lactones are macrocyclic lactone musks that not only have a strong and durable musk aroma, but also have a nitromusk-like aroma characteristic. These are useful compounds in the perfume industry.

  Moreover, in this invention, the fragrance | flavor composition and fragrance | flavor containing at least 1 sort (s) in these novel compounds are provided.

  In the present invention, the synthesis of ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt can be carried out using the method disclosed in Japanese Patent Application Laid-Open No. 11-228480, which is our prior patent. That is, 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide can be obtained by reacting γ-butyrolactone with a dicarboxylic acid ester in the presence of a condensing agent comprising a base.

  As the condensing agent mentioned here, condensing agents generally used for Claisen condensation or Dakeman condensation of esters are used, and specific examples include alkali metals such as lithium, sodium, potassium, lithium hydride, sodium hydride, potassium hydride. Alkali metal hydrides such as, alkali metal salts of ammonia such as lithium amide, sodium amide, potassium amide, alkali metal amides of amines such as lithium diisopropylamide, sodium diisopropylamide, lithium N-methylanilide, sodium N-methylanilide, Sodium methoxide, sodium ethoxide, sodium n-propoxide, sodium isopropoxide, sodium n-butoxide, potassium t-butoxide Id alkali metal alcoholate alcohol, sodium naphthalene, organic alkali metal compounds such as triphenyl methyl sodium, etc., such as.

  In the present invention, the condensing agent is preferably an alkali metal alcoholate represented by a general formula ROM (R is an alkyl group having 1 to 4 carbon atoms, and M represents an alkali metal). In the present invention, the amount of the condensing agent to be used is not particularly limited, but is preferably 0.1 to 5 equivalents, more preferably 0.5 to 3 equivalents with respect to 1 mol of γ-butyrolactone. Moreover, in this invention, it is preferable that the usage-amount of dicarboxylic acid ester is excess mole with respect to (gamma) -butyrolactone, and 2 times mole or more is especially preferable. This is because the selectivity is particularly improved when the amount is 2 times or more.

  It is preferable for efficient reaction that unreacted dicarboxylic acid ester is recovered from the reaction mixture and recycled in the condensation reaction, and recovery of unreacted dicarboxylic acid ester from the reaction mixture can be easily performed by simple distillation. I can do it. Combined use of an excess molar amount of the dicarboxylic acid ester and recycling reuse realizes a more efficient reaction.

R of the dicarboxylic acid ester represented by the general formula (3) ROOC (CH ₂ ) nCOOR used in the present invention is an alkyl group or an alkenyl group. The group is particularly preferred for use. Specific examples of R include methyl, ethyl, propyl, butyl, isobutyl, pentyl, hexyl, 2-ethylhexyl, octyl, allyl, 2-butenyl, 5-hexenyl group and the like. In particular, a methyl group is preferable.

  Next, when 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide is hydrolyzed in an alkaline basic aqueous solvent, it immediately undergoes hydrolysis and decarboxylation, and ω-hydroxy- (ω-3) -ketoalkanoic acid alkali A metal salt is formed. The alkaline base used for the hydrolysis is not particularly limited as long as it can hydrolyze esters and lactones. However, alkali hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, sodium carbonate, carbonate Alkali metal carbonates such as potassium can be used.

  The alkali metal salt of ω-hydroxy- (ω-3) -ketoalkanoic acid is selectively crystallized from the aqueous reaction mixture thus obtained and separated into solid and liquid to separate the alkali metal salt of ω-hydroxy- (ω-3) -ketoalkanoic acid. A cake containing is obtained. By removing water by a general method such as solvent replacement or vacuum concentration, a highly pure ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt can be obtained.

  Next, conversion to (ω-3) -methylidenealkanolide will be described. As a method for obtaining (ω-3) -methylidenealkanolide from ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt, ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt is methylidene. And then acidifying and intramolecular esterification, and adding a halide to ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt for esterification, followed by intramolecular transesterification, (ω- 3) A method of obtaining a ketoalkanolide and methylating it.

  First, of the above methods, a case where an ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt is converted into methylidene as it is will be described. The reaction route is as shown in the following reaction formula 1.

（式中、ｎ、Ｍは上記と同じ意味を表す。）

(In the formula, n and M have the same meaning as described above.)

For the methylidation of the alkali metal salt of ω-hydroxy- (ω-3) -ketoalkanoic acid, a generally used alkylidene reaction of a ketone group can be used. Examples of the reaction method include Wittig reaction, Peterson olefination reaction, Johnson olefination, and Tube reaction, but Wittig reaction is preferred because of the ease of reaction. The reaction is carried out by suspending in an organic solvent generally used for Wittig reaction. Examples of the solvent include toluene, THF, benzene, chloroform, ether, and the like, and THF and toluene are preferable because of easy handling. The amount used is not particularly limited, but it is sufficient that the slurry can be suspended and stirred. X of the phosphonium salt represented by Ph ₃ PCH ₃ X includes Br, Cl, I and the like, and the amount used is 1 to 10 equivalents, preferably 1 to 5 equivalents. Examples of bases used for ylidation include potassium t-butoxide, potassium n-butoxide, sodium methoxide, sodium ethoxide, sodium hydride, n-butyllithium, lithium ethoxide and the like. t-Butoxide and the like are preferable. The amount used is 0.5 to 5 equivalents, preferably 0.5 to 2 equivalents, relative to the phosphonium salt. The reaction temperature is -20 to 150 ° C, preferably 0 to 90 ° C. After the reaction is complete, there is no problem using an acidified reaction mixture without purification. However, since the product is crystalline and water-soluble, it is once separated into solid and liquid and suspended in water by adding water to the cake. It is possible to easily remove organic substances such as triphenylphosphine oxide by washing with toluene after preparing the solution. Then, highly purified omega-hydroxy- (omega-3) -methylidene alkanoic acid is obtained by acidifying a water layer part. (Ω-3) -methylidenealkanolide can be easily obtained by cyclizing this in the molecule by high dilution method, polymerization-depolymerization method, etc., and lactonization.

  Next, the case of passing through ketolactone from an ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt will be described. The reaction route is shown in the following reaction formula 2.

（式中、ｎ、Ｍ、Ｒ’は上記と同じ意味を表し、Ｘはハロゲン原子を表す。）

(In the formula, n, M and R ′ represent the same meaning as described above, and X represents a halogen atom.)

  The alkali metal salt of ω-hydroxy- (ω-3) -ketoalkanoic acid can be esterified by a known method. For example, Synthetic organic chemistry, R.A. B. WAGNER, H.M. D. As described in ZOOK, 1953 (Third Print. 1961), Chapter 14-290, 484P, an alkyl ester is easily obtained by reacting a halide in the presence of a quaternary ammonium salt.

  Examples of the halide in the production method of the present invention include benzyl chloride, 2-ethenyl chloride, 2-bromoacetylthiophene, 2-chloromethylthianaphthene, and benzyl chloride is used because of its ease of use and availability. Preferably used. The amount of benzyl chloride used is 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the alkali metal salt of ω-hydroxy- (ω-3) -ketoalkanoic acid. In the reaction, benzyl chloride serves as a solvent and may or may not be used, but toluene or the like may be used. Examples of the quaternary ammonium salt include tetrabutylammonium hydrogen sulfate, triethylbenzylammonium chloride, triethylbenzylammonium bromide, trioctylmethylammonium chloride, and tetrabutylammonium hydrogensulfate is particularly preferable. It is 0.01-0.1 equivalent with respect to-(omega-3) -ketoalkanoic acid alkali metal salt, Preferably it is 0.01-0.05 equivalent. The reaction temperature is 0 to 150 ° C, preferably 50 to 100 ° C. After the reaction, after diluting with an organic solvent such as toluene, the benzyl ester is selectively crystallized, and solid-liquid separation is performed by centrifugal filtration or the like, whereby a high-purity benzyl ester is easily obtained. Excess benzyl chloride can be easily recovered from the filtrate side.

  The obtained benzyl ester is mixed with glycols such as tetraethylene glycol and then cyclized by transesterification and polymerization-depolymerization to obtain (ω-3) -ketoalkanolide.

  Furthermore, (ω-3) -methylidene alkanolide can be easily obtained by methylidation in the same manner as described above.

  The (ω-3) -methylidenealkanolide thus obtained is easily converted into a methyl group by a hydrogenation reaction in the presence of a catalyst as shown in Reaction Scheme 3 by a method known per se (ω -3) -methylalkanolide is obtained. Although there is no limitation in particular as a catalyst, Pd-C, Raney nickel, etc. are mentioned. Although a solvent may or may not be used, when used, ethyl acetate, hexane, cyclohexane, methanol and the like can be mentioned, and the amount used is 1 to 10 times by weight. The reaction temperature may be 0 to 100 ° C., and the pressure may be normal pressure or pressurization.

（式中、ｎは上記と同じ意味を表す。）

(In the formula, n represents the same meaning as described above.)

  Next, the method of the present invention will be described in detail by examples. However, the following examples are given for illustration only and should not be construed as limiting in any way.

(Example 1) Synthesis of 11-methylidene-14-tetradecanolide 1,11-Undecanedioic acid dimethyl ester (1057 g, 4.33 mmol) was charged into a reactor, and heated and stirred at 105 ° C. in a reduced pressure state of 80 kPa. A mixture of γ-butyrolactone (92.6 g, 1.08 mol) and 28 wt% sodium methoxide-methanol solution (207.64 g, 1.08 mol) at room temperature is heated to 1,11-undecane Methanol was distilled off while dropping dropwise into the acid dimethyl ester over 30 minutes. After reacting for 30 minutes as it was, the pressure was reduced to 26.7 kPa, and the reaction was further continued for 240 minutes.

  Next, after returning this to normal pressure, n-hexane (1060 g) was added, followed by extraction with a 3% aqueous sodium hydroxide solution (1440 g, 1.08 mol). After removing the aqueous layer, the hexane layer was washed with water (200.0 g: 2 times). n-Hexane was distilled off under reduced pressure. 807 g of remaining oil was obtained. GC analysis of the oil revealed that it contained 98% 1,11-undecanedioic acid dimethyl ester.

  On the other hand, the aqueous layer was heated to reflux for 2 hours, and then organic substances were extracted and removed with toluene (1500 g, 5 times). Further, the aqueous layer was crystallized at 20 ° C., and solid-liquid separation was performed by centrifugal filtration. The obtained cake was freed of water under reduced pressure to obtain 230 g of a dry powder. When this was acidified and analyzed by GC, it contained 99% ω-hydroxy- (ω-3) -ketotetradecanoic acid. Charge dry powder (200 g), methyltriphenylphosphine bromide (765 g, 2.14 mol), toluene (3500 g), THF (1900 g), cool to 0 ° C. with stirring, and potassium t-butoxide (183 g, 1.63 mol) Was added. After refluxing for 6 hours, the mixture was cooled, and the crystal was separated into solid and liquid by suction filtration. 6000 g of water was added to the cake to make it suspended. After washing with 2000 g of toluene three times, the aqueous layer was acidified, extracted with ethyl acetate, washed, and the solvent was recovered to obtain 130 g of a crystalline residue containing 14-hydroxy-11-methylidene-tetradecanoic acid (n = 9) as the main product. Obtained. Tetraethylene glycol (100 g) is added thereto, the pressure is reduced to 6.7 kPa, and the mixture is heated to 100 ° C. to remove the distilled water. Further, after reducing the pressure to 4 kPa, the internal temperature is raised to 250 ° C. and an intramolecular esterification reaction is performed to obtain a distillate. This was extracted with n-hexane, washed with water (three times), and concentrated in a solvent to obtain 78.5 g of a cyclized product. This contained 99.2% by weight of 11-methylidene-14-tetradecanolide. The yield was 30 mol% / butyrolactone.

1H-NMR (CDCl3, 400 MHz) 4.74 (2H) d J = 22.7 Hz; 4.17 (2H) t J = 5.3 Hz; 2.35 (2H) t J = 6.2 Hz;
2.13-2.05 (4H) m; 1.85-1.19 (2H) m;
1.70-1.62 (2H) m; 1.48-1.23 (12H) m
13C-NMR (CDCl3) 174.11; 149.07; 109.49;
63.70; 35.98; 34.34; 31.32; 28.01;
26.86; 26.79; 26.70; 26.47;
26.10; 24.82;
IR (film) 2925; 2860; 1735; 1445; 1240;
1170; 885
MS 238 (8); 123 (8); 109 (12); 95 (64);
82 (100); 67 (85); 55 (47); 41 (52);

  Odor: It has a musk-like odor with an animal character. Slightly nitromusk-like elements.

Example 2 Synthesis of 11-methyl-14-tetradecanolide
Ethyl acetate (540 g) and 5% -Pd-C (1.70 g) were added to 11-methylidene-14-tetradecanolide (6.0 g, 0.025 mol), and the mixture was stirred under a hydrogen atmosphere at normal pressure and room temperature for 2 hours. did. After removing the catalyst by filtration, the filtrate was washed with water (three times) and the solvent was recovered to obtain 5.9 g of a concentrated residue. GC analysis showed 98.9%. The yield was 97 mol%.

1H-NMR (CDCl3, 400 MHz) 4.10-3.99 (2H) m;
2.38-2.19 (2H) m; 1.71-0.93 (21H) m;
0.79 (3H) d J = 6.9 Hz
13C-NMR (CDCl3) 174.23; 64.05; 35.69;
34.02; 30.97; 29.98; 27.80; 26.72;
26.69; 26.46; 25.81; 24.79; 20.29;
IR (film) 2930; 2860; 1720; 1460; 1235;
1180; 1150; 1115; 1070; 895
MS 240 (3); 212 (17); 194 (12); 179 (15);
139 (19); 123 (11); 111 (21); 97 (51);
84 (78); 69 (83); 55 (100); 41 (80);

  Odor: Has a musk-like odor with a somewhat nitromusk-like element.

(Example 3) Synthesis of 12-methyl- 15-pentadecanolide Dry powder of sodium 15-hydroxy-12 -ketopentadecanoate obtained according to Example 1 using 1,12-dodecanedioic acid dimethyl ester as a raw material (100 g) Benzyl chloride (130 g, 1.03 mol) and tetrabutylammonium hydrogen sulfate (3.5 g, 0.01 mol) were added to the mixture. After heating to 80 ° C. and reacting for 4 hours, toluene (230 g) was added. After washing with water (50 g, 3 times), the solvent was concentrated to obtain 208 g of a concentrated residue. Toluene (300 g) was added thereto to dissolve the residue, and then cooled to 5 ° C. to precipitate crystals. The cake obtained by solid-liquid separation by suction filtration was dried under reduced pressure to obtain 61 g of dry powder. Tetraethylene glycol (326 g, 1.68 mol) and tetrabutoxytitanium (0.10 g) were added, and the mixture was heated and stirred at normal pressure and 150 ° C. for 4 hours. To this was added polyethylene glycol dimethyl ether (20 g) as a solvent, and the pressure was gradually reduced and the temperature was raised while removing the light boiling portion. When tetraethylene glycol was gradually added dropwise at a liquid temperature of 260 ° C./1.3 kPa, the distillate separated into two layers. When the upper layer was extracted with n-hexane, washed with water, and concentrated with a solvent, 29 g of a concentrated residue was obtained. As a result of GC analysis of this product, 74% of 12-ketopentadecanolide was contained. This was purified by silica gel column to obtain 18 g (0.070 mol) of 99% purified product by GC.

  This was charged with methyltriphenylphosphine bromide (30.3 g, 0.085 mol), toluene (92 g), THF (21 g), cooled to 0 ° C. with stirring, and potassium t-butoxide (8.8 g, 0.078 mol). Was added. After reacting for 3 hours, water (25 g) was added dropwise. The organic layer was washed with water (3 times), and then the concentrated residue obtained by solvent recovery was suspended in n-hexane (153 g), and the crystal was removed by filtration under reduced pressure. The filtrate was concentrated under reduced pressure to obtain 19 g of concentrate. This was purified using a silica gel column to obtain 13.4 g of 12-methylidene-15-pentadecanolide having a GC of 99%. The yield was 15 mol% / 15-hydroxy-12-ketopentadecanoic acid sodium salt.

1H-NMR (CDCl3, 400 MHz) 4.73 (2H) d J = 17 Hz; 4.16 (2H) t J = 5.5 Hz; 2.33 (2H) t J = 6.6 Hz; 2.14-2 .04 (4H) m; 1.82-1.75 (2H) m;
1.68-1.64 (2H) m; 1.46-1.31 (14H) m;
13C-NMR (CDCl3) 173.94; 148.96; 109.59;
63.82; 36.11; 34.42; 31.53; 27.53;
27.18; 27.14; 26.69; 26.56; 26.21;
26.05; 25.89; 24.82
IR (film) 2925; 2860; 1750; 1460; 1440; 1250; 1165; 890
MS 252 (11); 123 (9); 109 (14); 95 (63);
82 (100); 67 (74); 55 (37); 41 (35);

  Odor: A musk incense with a somewhat cyclopentadecanolic animatic character.

Example 4 Synthesis of 12 -methyl-15-pentadecanolide Ethyl acetate (190 g) and 5% -Pd-C (0.61 g) were added to 12-methylidene-15-pentadecanolide (2.12 g, 8.4 mmol). The mixture was stirred for 1 hour at normal pressure and room temperature in a hydrogen atmosphere. After removing the catalyst by filtration, the filtrate was washed with water (three times) and the solvent was recovered to obtain 2.08 g of a concentrated residue. GC analysis showed 94.5%. The yield was 92 mol%.

1H-NMR (CDCl3, 400 MHz) 4.20-4.04 (2H) m;
2.35-2.30 (2H) m; 1.71-1.09 (23H) m;
0.87 (1H) d J = 6.9 Hz
13C-NMR (CDCl3) 174.05; 64.09; 35.35;
34.49; 31.50; 30.78; 27.55; 27.13;
26.55; 26.44; 26.42; 25.86; 25.83;
24.87; 24.13; 20.09
IR (film) 2925; 2860; 1745; 1460; 1250; 1170; 1110
MS 254 (3); 226 (16); 153 (11); 123 (12);
111 (22); 97 (47); 84 (72); 69 (78);
55 (100); 41 (83)

  Odor: Has an elegant musk scent like cyclopentadecanolide and has nitromusk characteristics.

(Example 5) Synthesis of 10-methylidene- 13-tridecanolide Dry powder of sodium 13-hydroxy-10-ketotridecanoate obtained according to Example 1 using 1,10-decanedioic acid dimethyl ester as a raw material (67 g, 0 .25 mol), methyltriphenylphosphine bromide (179 g, 0.50 mol), toluene (500 g), THF (130 g) were charged into a reaction vessel, cooled to 0 ° C. with stirring, and potassium t-butoxide (55 g, 0.49 mol). ) Was added. The mixture was cooled after refluxing for 4 hours, and the crystal was separated into solid and liquid by suction filtration. 500 g of water was added to the cake to obtain a suspended state. After washing with 500 g of toluene three times, the aqueous layer was acidified, extracted with ethyl acetate, washed, and the solvent was recovered to obtain 47 g of a crystalline residue containing 13-hydroxy-10-methylidene-tridecanoic acid (n = 8) as the main product. Obtained. This was cyclized by intramolecular transesterification to obtain 33 g of a cyclized product. This contained 99.0% by weight of 10-methylidene-13-tridecanolide. The yield was 62 mol% / sodium 13-hydroxy-10-ketotridecanoate.

  Odor: It has a musk-like odor with animatic and slightly nitromusk characteristics. Has a strong scent.

Example 6 Synthesis of 10-methyl-13-tridecanolide
Ethyl acetate (100 g) and 5% -Pd-C (1.50 g) are added to 10-methylidene-13-tridecanolide (10.6 g, 0.050 mol), and the mixture is stirred for 2 hours at room temperature under a hydrogen atmosphere. did. After removing the catalyst by filtration, the filtrate was washed with water (three times) and the solvent was recovered to obtain 10.2 g of a concentrated residue. GC analysis showed 99.2%. The yield was 95 mol%.

  Odor: Cyclopentadecanolic musk aroma and nitromusk character. Has a strong scent.

  The present invention relates to macrocyclic lactones that are important in the perfume industry. According to the present invention, it is possible to easily produce macrocyclic lactones having a substituent at the (ω-3) position having a different carbon number from inexpensive and readily available raw materials, and novel macrocyclic lactones having excellent aroma characteristics Can be obtained.

Claims (6)

11-methylidene-14-tetradecanolide. 10-methylidene-13-tridecanolide. 11-methyl-14-tetradecanolide. 10-methyl-13-tridecanolide. ω-Hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt is methylidene and then acidified for intramolecular esterification, or ω-hydroxy- (ω-3) -ketoalkanoic acid alkali metal salt is halide Is added to the esterification, followed by intramolecular transesterification to obtain (ω-3) -ketoalkanolide and methylidene,

(In the formula, n represents 7 to 13) A process for producing (ω-3) -methylidenealkanolide. A fragrance composition comprising at least one selected from the compounds according to claim 1.