JPH0210141B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the following formula (1) However, in the formula, R represents a lower alkyl group, and relates to a novel method for producing alkyl 12-hydroxy-cis-9-dodecenate represented by the following formula. More specifically, the following formula (2), which has not been described in any known literature, However, in the formula, R represents a lower alkyl group, and the above formula (1)12 is characterized in that an alkyl 12-(2-tetrahydropyranyloxy)-cis-9-dodecenate represented by the following is brought into contact with an acid catalyst. Regarding the method for producing alkyl -hydroxy-cis-9-dodecenate, the novel compound of the formula (2) can be, for example, the compound of the following formula (3). However, in the formula, R represents a lower alkyl group, and it can be easily produced from an alkyl 8-formyloctanoate represented by the following formula. The above formula can be industrially advantageously produced by the method of the present invention
(1) Alkyl 12-hydroxy-9-dodecenate is
It is useful as an important synthetic intermediate for 9-dodecene-12-olide, which has a mint-like sweet fruit aroma and is known as an aroma component in yuzu. Conventionally, regarding the synthesis of ethyl 12-hydroxy-cis-dodecenate, JP-A-56-90076 has 12
It is described that ethyl 12-hydroxy-cis-9-dodecenoate was obtained by partially hydrogenating ethyl -hydroxy-9-dodecenoate using a Lindlar catalyst. However, the synthesis route for the raw material ethyl 12-hydroxy-9-dodecinate is not described, and its synthesis is thought to require multiple steps. The present inventors have conducted research to develop an industrially advantageous method for producing the 12-hydroxy-cis-9-dodecenic acid lower alkyl ester of formula (1). As a result, 12-(2-tetrahydropyranyloxy)-cis-9-dodecenoic acid represented by the above formula (2), which has not been described in any known literature, can be easily synthesized from commercially available alkyl oleate. It has been discovered that it can be easily produced from alkyl 8-formyloctanoate of the formula (3). Furthermore, the formula
(2) It has been discovered that the new compound can be easily converted into alkylalkyl 12-hydroxy-cis-9-dodecenate of formula (1) simply by contacting with an acid catalyst and with a high yield. Furthermore, formula (1) of the above formula (2) new compound by acid catalyst
In addition to the advantages of easy operation and high yield of more than about 80%, the conversion to the compound of formula (1) has excellent stereospecificity of, for example, a cis ratio of more than 93%. It was found that there is an advantage in selectively acquiring Therefore, the object of the present invention is to provide a new synthetic method that can advantageously produce a compound of formula (1) from a novel compound of formula (2) with excellent yield and stereospecificity using industrially easy operations and equipment. It is on offer. The above objects and many other objects and advantages of the present invention will become more apparent from the following description. The novel compound of formula (2) used in the method of the present invention can be obtained, for example, from alkyl 8-formyloctanoate of formula (3), which can be easily obtained by ozone oxidation of alkyl oleate. It can be easily synthesized by contacting with 3-tetrahydropyranyloxypropylenetriphenylphosphorane in the presence of an organic solvent. According to the method of the present invention, an excellent The compound of formula (1) can be industrially advantageously produced with good yield and stereospecificity in a short process which is advantageous in terms of operation and equipment. In addition to the production example of the compound of formula (2) above, it can be shown diagrammatically as follows. In the formula, R is, for example, methyl, ethyl, propyl,
Indicates a lower alkyl group such as butyl, pentyl, etc. Further, Ph represents a phenyl group, and THP represents a tetrahydropyranyl group. use

[Formula] is halogenated 3-tetrahydropyranyloxy-n-propyltriphenylphosphonium salt

It can be obtained by reacting [Formula] (wherein X represents a halogen atom) with a base. The above formula

Halogenated 3-tetrahydropyranyloxy represented by [Formula]
The reaction between the n-propyltriphenylphosphonium salt and the base can be carried out in the presence of an inert organic solvent. Examples of such solvents include, for example:
In addition to N,N-dimethylformamide, dimethylsulfoxide, tetrahydrofuran, ether, dioxane, 1,2-dimethoxyethane, etc.
Examples include aromatic and aliphatic hydrocarbons such as benzene, toluene, xylene, and ligroin. These organic solvents can be used alone or in combination. There is no particular restriction on the amount used, but for example, it is preferably about 2 to
For example, the amount used is about 50 times by weight, more preferably about 2 to about 5 times by weight. Preferred examples of the halogen in the halogenated 3-tetrahydropyranyloxy-n-propyltriphenylphosphonium salt include chlorine, bromine and iodine. Furthermore, examples of the base include butyllithium, phenyllithium, lithium diethylamide, sodium methoxide, sodium hydride, sodium amide, potassium hydride, sodium-tert-butoxide, and the like. The amount of these bases to be used can be changed and selected as appropriate, but it is preferable to use them in an amount of around equimolar to a slight excess. So, about 1~
An example of the amount used is about twice the molar amount. The above 3-tetrahydropyranyloxypropylenetriphenylphosphorane forming reaction is, for example,
The temperature can be suitably selected from a wide range of about -78°C to about 100°C. The reaction is e.g.
It can be completed in about 20 hours. Further, it is preferable that the reaction system is substantially anhydrous, and further,
For example, it is preferable to carry out under an atmosphere of an inert gas such as nitrogen or argon. The compound of formula (2) used in the method of the present invention can be obtained by reacting a halogenated 3-tetrahydropyranyloxy-n-propyltriphenylphosphonium salt with a base in the presence of an organic solvent, for example, as described above. 3-tetrahydropyranyloxypropylenetriphenylphosphorane and the above formula
(3) It can be produced by reacting with alkyl 8-formyloctanoate. The reaction can be carried out in the presence of the same organic solvent as exemplified for the phosphorane formation reaction. The reaction proceeds at room temperature, and can be carried out, for example, at a temperature of about 40° C. or lower, but since it is an exothermic reaction, it is convenient to carry out, for example, under water-cooling conditions or other suitable cooling conditions. The reaction is likewise preferably carried out under substantially anhydrous conditions and under an inert gas atmosphere. During the reaction, it is not necessary to separate and use 3-tetrahydropyranyloxypropylenetriphenylphosphorane, and the reaction can be carried out by adding the alkyl 8-formyloctanoate formula (3) to the reaction product liquid that forms the phosphorane. Can be done. The reaction is preferably carried out so that the amount of the 3-tetrahydropyranyloxy-n-propylenetriphenylphosphorane is about 1 to about 2 times the mole of the compound of formula (3), and about 1 to about 2 times the amount by mole. About 1.2 times the molar amount is more preferable. There is no particular restriction on the reaction time, and for example, a range of about 0.5 to about 20 hours, more preferably about 0.5 to about 5 hours can be exemplified. After the reaction is complete, the solvent is distilled off, the oil is extracted from the residue with, for example, n-hexane, the oil layer is washed with saturated saline, the n-hexane is distilled off, and the mixture is separated by vacuum distillation or silica gel column chromatography. By doing so, the desired expression (2)
Alkyl 12-(2-tetrahydropyranyloxy)-cis-9-dodecenate can be obtained with high purity and high yield. In the above reaction, the cis-type compound is selectively produced, and the amount of the trans-type compound is usually about 7% or less, and in many cases substantially zero. Specific examples of the compound of formula (2) above and their boiling points are illustrated below.

[Table] Ethyl senate
According to the method of the present invention, the alkyl 12-hydroxy-9-dodecenate of formula (1) can be obtained by contacting a compound of formula (2), which can be obtained as described above, with an acid catalyst, preferably in an alcoholic solvent. It can be easily obtained by detetrahydro-pyranylation. Detetrahydropyranylation is
For example, about 5° to about 80°C, more preferably about
At a temperature of about 10° to about 50°C, for example, about 0.5 to about 24
It can be easily carried out under reaction conditions of about 1 hour.
Preferred examples of acid catalysts used in the reaction include inorganic and organic acids such as phosphoric acid, hydrochloric acid, sulfuric acid, and p-toluenesulfonic acid. The amount of these catalysts to be used can be selected as appropriate, and the above formula
(2) For example, the amount may range from about 0.01 to about 10% by weight based on the compound. Further, as the organic solvent, alcohols such as methanol, ethanol, etc. can be preferably used. The amount of the organic solvent to be used can be appropriately selected, and may be, for example, about 1 to about 5 times the weight of the compound of formula (2) above. After the reaction is completed, the compound of formula (1) can be easily obtained by, for example, neutralizing with a suitable alkali, washing with water, and distilling off the solvent. Hereinafter, several embodiments of carrying out the method of the present invention will be explained in more detail with reference to Examples. Reference Example 1 Synthesis of methyl 8-formyl-octanoate Methyl oleate (59 g) was dissolved in methylene chloride (310 g), and ozone (11 g) was introduced at -78°C. After completion, the solution is poured into a suspension of zinc powder (25g) and acetic acid (75g) to perform a reductive decomposition reaction. After completion of the filtering process, the mother liquor is washed with water, washed with heavy sodium chloride, neutralized, and dried to recover methylene chloride. The resulting residual liquid is purified by distillation under reduced pressure to a boiling point of 115-120℃ (3
methyl 8-formyl-octanoate (mmHg)
Obtain 38 g (83% yield). Reference example 2 Reference example 2 62g of ethyl oleate instead of methyl oleate
By carrying out the reaction in the same manner as in Reference Example 1, 43 g of ethyl 8-formyloctanoate having a boiling point of 120 to 122°C (3 mmHg) is obtained. (Yield 89%) Reference Example 3 Synthesis of methyl 12-(2'-tetrahydropyranyloxy)-cis9-dodecenate 69 g of 3-tetrahydropyranyloxypropyltriphenylphosphonium bromide was added to 500 ml of dry THF under an argon atmosphere. Make it hard. −
Cool to 30°C, and add 80ml of 1.5N-n-butyllithium hexane solution dropwise into the solution to form a red phosphorane solution. Next, a solution of 22 g of methyl 8-formyloctanoate in 50 ml of dry THF was added dropwise to react at the same temperature. After the dropwise addition is complete, remove the cooling bath and allow the mixture to return to room temperature. After the reaction is completed, THF is recovered under reduced pressure and the residue is extracted with n-Hexane. After washing the extracted layer with water and drying, n-Hexane is recovered and the residual liquid is distilled to obtain 12-(2′-tetrahydropyranyloxy)-cis-9-dodecene, which has a boiling point of 135-140°C (0.01 mmHg). 27 g of methyl acid are obtained. Yield 83
%, and the cis ratio was determined by the GLC Peak ratio (cis/trans = 93/7). (Using PEG20MZm) Reference Example 4 Synthesis of ethyl 12-(2'-tetrahydropyranyloxy)-cis-9-dodecenate In Example 1, dimethoxyethane (DME) was used instead of THF, and n-butyllithium was synthesized. Using 1-butoxypotassium instead, and further adding 8-
By performing the same procedure using 24 g of ethyl formyl octanoate, the boiling point was 139-142°C (0.01 mm
29 g (yield: 87%) of ethyl 12-(2'-tetrahydropyranyloxy)-cis-9-dodecenate having Hg) was obtained. (cis ratio increased by 98.3%) Example 1 Methyl 12-hydroxy-cis-9-dodecenate Methyl 12-(2'-tetrahydropyranyloxy)-cis-9-dodecenate obtained in Reference Example 3 20
1% para-toluenesulfonic acid (PTSA)-methanol (200 g) and left overnight at room temperature. Add 10g of soda ash powder to recover methanol, extract the residue with ether, wash with brine, recover the ether after drying, and distill the remaining liquid under reduced pressure (boiling point
12g of methyl 12-hydroxy-cis,9-dodecenate (108-110℃/0.5mmHg) (yield 85%)
get. Example 2 Ethyl 12-hydroxy-cis-9-dodecenate 25 g of ethyl 12-(2'tetrahydropyranyloxy)-cis-9-dodecenate obtained according to Reference Example 4
The reaction was carried out in the same manner as in Example 1 using a 1% sulfuric acid-ethanol system instead of 1% PTSA-methanol, and 15 g of ethyl 12-hydroxy-cis-9-dodecenate ( yield
84%).

Claims (1)

[Claims] 1. The following formula (2) However, in the formula, R represents a lower alkyl group, and the following formula (1) is characterized in that an alkyl 12-(2-tetrahydropyranyloxy)-cis-9-dodecenate represented by the following is brought into contact with an acid catalyst. However, in the formula, R has the same meaning as above, and the method for producing alkyl 12-hydroxy-cis-9-dodecenate represented by: