JPH04330032A - Production of e,z-2,13-octadecadiene compound - Google Patents

Abstract

PURPOSE:To provide a method for stereosecifically and readily producing E, Z-2,13-octadecadiene compounds useful as an insectan pheromone ingredient. CONSTITUTION:The subject method is to produce E,Z-2,13-octadiene compounds as follows. A compound expressed by the formula CH3(CH2)3HC=CH(CH2)9 CidenticalCMgX (X represents halogen) is allowed to react with an orthoformic acid ester to provide Z-13-octadecen-2-ynal diethyl acetal or a compound expressed by the formula CH3(CH2)3CidenticalC(CH2)9CidenticalCMgX (X is same as described above) is allowed to react with the orthoformic acid ester to afford 2,13-octadecadiynal diethyl acetal. The respective compounds are then respectively hydrogenated and subsequently hydrolyzed to provide E,Z-2,13-octadienal. Furthermore, the obtained compound is reduced with a metallic hydride and then acetylated to afford E,Z-2,13-octadecadienyl acetate.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a useful method for producing an E,Z-2,13-octadecadiene compound, which is important as one of the insect pheromones of the order Lepidoptera.

0002

BACKGROUND OF THE INVENTION In recent years, the application of sex pheromones as a method of pest control has attracted attention, and methods such as monitoring, mass attraction, and control of communication disruption are being widely studied. In particular, when sex pheromones are used in communication disruption methods, it is industrially essential to supply pheromone raw materials with high purity and at low cost. Among lepidopteran insect pheromones, those having an E,Z-2,13-octadecadiene structure include the following. Insect name (scientific name)
Sex pheromone Synanth
edon tipuliformis :E, Z-2
,13-octadecadienyl acetate Z
enzera pyrina
: 〃 Tineo
la bisselliea (Hummel): E, Z
-2,13-octadecadienal

(Ko
iganal II) For the synthesis of E,Z-2,13-octadecadienyl acetate, Ramiand
By coupling the Z-isomer at position 13 with an organozinc reagent following carbocupration of acetylene under a Pd catalyst, the E-isomer at position 2 was converted into propargyl-type alcohol sodium (2-methoxy e
The E,Z-2,13-octadecadiene skeleton is constructed by reduction of aluminum hydride. (Synthetic community
cation, 19(15), 2703-271
2 (1989)) and Sorochinskaya
et al. used the Wittig reaction of the Z-form at position 13 and the E-form at position 2 with propargyl alcohol and pentadec-Z-10-
It is synthesized by reducing the propargyl alcohol obtained after alkylation with enyl bromide with lithium aluminum hydride. (Khi
m Prir Soedin, 2, 264 ~26
6 (1989)) Furthermore, regarding E,Z-2,13-octadecadienal (Koiganal II), Yamaoka et al. and synthesizes aldehydes. (Mass spectrometry.33(3)189.(1
985))

0003

[Problems to be Solved by the Invention] All of the three synthetic methods described above stereoselectively reduce the triple bond of propargyl type alcohol with metal aluminum hydride to obtain the E form at the 2-position. This takes advantage of the stereoisomerism of , which allows double bonds to form. However, the aluminum metal hydride used is very expensive and difficult to handle due to the risk of ignition in the air, making it unsuitable for use on an industrial scale. Also, aldehyde E, Z-
Regarding 2,13-octadecadienal, the post-treatment method of chromic acid when oxidizing the corresponding alcohol is complicated and has many problems. Therefore, there has been a need for an industrial method for producing E,Z-2,13-octadecadiene compounds suitable for large-scale synthesis.

0004

[Means for Solving the Problems] As a result of intensive studies to solve these problems, the present inventors found that the general formula CH3 (
CH2)3HC=CH(CH2)9C≡C-MgX (
A Grignard reagent represented by the formula (1-1) (wherein X represents a halogen atom) and an orthoformic acid alkyl ester represented by the general formula CH(OR)3 (wherein R represents a methyl group or an ethyl group). By reacting, the general formula
CH3(CH2)3HC=CH(CH2)9C≡CCH
(OR)2...Z-13-octadecene-2-innal diethyl acetal shown by (2-1) or the general formula CH3(CH2)3C≡C(CH2)9C≡C
MgX (wherein X represents a halogen atom)...The Grignard reagent represented by (1-2) and the same orthoformic acid ester as described above are reacted to obtain the general formula CH3(CH2
)3C ≡C(CH2)9C≡CCH(OR)2...(2
2,13-octadecadiinal diethyl acetal represented by -2), and then hydrogenated and hydrolyzed to produce CH3(CH2)3HC.
=CH(CH2)9HC=CHCHO...If we use E,Z-2,13-octadecadienal shown in (3), the double bond at position 2 is conjugated with the formyl group of the functional group, so it is automatically Therefore, it has become clear that the E-body is guaranteed. Furthermore, when this is reduced with metal hydride, CH3 (
CH2)3HC=CH(CH2)9HC=HCCH2O
H...(4) becomes E,Z-2,13-octadecadien-1-ol, and when this is acetylated, CH3(CH2)3HC=CH(CH2)9CH=HC
CH2OCOCH3...E, Z-2,1 shown by (5)
We have found that 3-octadecadienyl acetate can be synthesized stereoselectively. By using this process, E, Z-2, 1, which is important as one of the insect pheromones of Lepidoptera, can be produced.
3-Octadecadienal and E,Z-2,13-octadecadienyl acetate can be produced with high purity and at low cost.

The Grignard reagent (1-1 or 1-2), which is the starting material of the present invention, is prepared by reacting methylmagnesium chloride, ethylmagnesium bromide, etc. with Z-12-heptadecen-1-yne or 1,12-heptadecadiyne. It can be easily obtained by CH3MgCl (or CH3CH2MgBr
) + CH3(CH2)3HC=CH(CH2)9C
≡CH → CH3(CH2)3HC=
CH(CH2)9C≡C-MgX (X=halogen atom)...(1-1) CH3MgCl( or CH3
CH2MgBr) + CH3(CH2)3C≡C(
CH2)9C≡CH → CH3(C
H2) 3C≡C(CH2)9C≡C-MgX (same as before)
...(1-2) The solvents used in this reaction are tetrahydrofuran, ethyl ether, n-
Ethers such as butyl ether and hydrocarbons such as toluene, benzene, and xylene are used alone or in combination.

The Grignard reagent and the orthoformic acid alkyl ester are used in at least equimolar amounts, or the orthoformic acid alkyl ester is used in 1 to 1.5 times the molar amount, and the reaction is carried out at a reaction temperature of 60 to 140°C, preferably 80 to 100°C. The reaction is completed in 4 to 10 hours. Examples of the orthoformic acid alkyl esters used here include ethyl orthoformate and methyl orthoformate.

The acetal (2-1 or 2-2) obtained here is then subjected to a hydrogenation reaction, and the catalysts used here include P-2 nickel, Raney nickel, Lindlar catalyst, Pd-C, and Pd-C. -BaSO4, Pd-Al2O
3. Pd-diatomaceous earth, Pd-BaCO3, Pd-Ca
Examples include CO3, Rh-C, Ru-C, and the like. Among these, P-2 nickel is superior. The amount of catalyst used is 0.001 to 0.2 equivalent relative to the reaction substrate, and the hydrogen pressure is in the range of normal pressure to 10 kg/cm2G, preferably 1 to 5 kg/cm2G. The reaction temperature is 0~
Although the temperature is 80℃, it greatly affects the reaction rate, so the temperature is 20~5℃.
0℃ is better. After the reaction, the catalyst is removed by conventional separation operations. In the hydrolysis reaction, the compound after hydrogenation is easily converted into an aldehyde group by dissolving it in an organic solvent and stirring it with aqueous hydrochloric acid, acetic acid, etc. Examples of organic solvents include hydrocarbons such as toluene, benzene, and hexane, as well as tetrahydrofuran, ethyl ether, and methylene chloride. It is desirable that the amounts of the reaction product, 20% hydrochloric acid water, and organic solvent are approximately equal in volume. The reaction time is preferably 5 to 120 minutes, particularly 5 to 60 minutes. The reaction temperature is 0 to 60°C, but it is preferably 0 to 40°C since polymerization or trimer formation may occur at high temperatures. After the reaction is complete, simply wash the organic layer to remove the solvent so that it becomes neutral, and the highly pure 2-position E isomer (3
) is generated. This product can be purified by ordinary isolation operations, such as distillation and column chromatography, and if the acetate (5) is to be obtained, it can be carried out to the next step by concentration.

The reduction reaction of the aldehyde (3) can generally be carried out using metal hydrides, specifically lithium aluminum hydride, sodium borohydride, lithium borohydride, sodium hydride, diisobutyl aluminum hydride ( DIBAL-H) etc. may be reacted in various solvents, but from the viewpoint of cost and ease of use, it is preferable to use a NaOH aqueous solution of sodium borohydride, 0.5 to 2.0 times the mole of the aldehyde, and tetrahydrofuran. , ethanol or methanol per mole of aldehyde
Using 00 to 600 g, reduce at -30 to 40°C. In particular, when the reaction temperature is high, 1,4-reduction occurs and causes the formation of impurities, so a temperature of -30 to 10°C is desirable.

Acetylation of alcohol (4) is carried out without a solvent or in an inert solvent using acetic anhydride, acetyl bromide, acetyl chloride, etc. as an acetylating agent, usually in an equimolar to 3-fold molar amount relative to the alcohol. 0~13
The reaction is carried out in the range of 0°C. Examples of the solvent include hexane, petroleum ether, benzene, toluene, and acetic acid, but the reaction may be carried out in the presence of a basic compound such as pyridine and triethylamine as a deoxidizing agent. After the reaction, conventional isolation methods such as distillation, column chromatography,
Easily isolated and purified by solvent extraction etc.

0010

[Example] Examples are shown below. Reference example 1. Production of Z-12-heptadecen-1-yne:
Add 250 g of xylene and 23 g of metallic sodium dispersed to a particle size of 100 μm or less into a reactor.
When the mixture was heated to 110° C. and acetylene gas was blown therein at a flow rate of 1 L/min for 1 hour, sodium acetylide was obtained almost quantitatively. Next, this xylene dispersion solution of sodium acetylide was charged into an autoclave with an internal volume of 2 L, and after adding 600 g of liquid ammonia, the temperature was maintained at -10 to -5°C and the pressure was maintained at 3.5 to 4 kg/cm2G, and 1-bromo- Z-10-pentadecene
289 g was added dropwise over 1 hour, and after the completion of the addition, the xylene in the organic layer was removed, and this concentrate was distilled under reduced pressure, and the boiling point was 1.
182.5 g (yield 78%) of Z-12-heptadecen-1-yne was obtained at 48-151°C/2 mmHg.

Reference Example 2. Production of 1,12-heptadecadiine: The reactor was cooled to -40°C and liquid ammonia 6
00 ml, and 88 g of 1,12-tridecadiine was added from -40°C. Next, small pieces of metallic sodium were added little by little at -40°C, totaling 12 g. After stirring at -34°C for 1 hour, a solution of 100 g of n-butyl iodide dissolved in 150 ml of ethyl ether was added dropwise at -34°C, and the mixture was stirred at -34 to -32°C for 12 hours. After the reaction, 30 g of ammonium chloride was added at -40°C to recover ammonia. Pure water to the residue
300g was added, extracted with ethyl ether, concentrated and distilled to obtain 61g of 1,12-heptadecadiine (boiling point 150-153°C/2mmHg) yield 52
．． 6%.

Example 1-1. Z-13-octadecene-
Production of 2-innal diethyl acetal (2): A reactor was charged with a tetrahydrofuran solution (tetrahydrofuran 300 g) of ethylmagnesium bromide equivalent to 1 mole, and 234 g of Z-12-heptadecen-1-yne was added dropwise at 50 to 60°C. did. Next, after stirring at 60°C for 1 hour, 150 g of ethyl orthoformate was added dropwise over 30 minutes, followed by stirring at 90°C for 7 hours. After the reaction, 70 g of NH4Cl and 400 g of pure water were added to separate the layers, and the organic layer was distilled after removing tetrahydrofuran under reduced pressure. Z-13-octadecene-2
269 g of -innal diethyl acetal was obtained (yield 80%, boiling point 165-170°C/0.1 mm)
Hg).

Example 1-2. Production of E,Z-2,13-octadecadienal (3): In an autoclave reactor, Z-13-octadecene-2-innal diethyl acetal (336 g) and 200 g of ethanol were added.
15g of nickel acetate to 2.8g of sodium borohydride
P-2 nickel obtained by reduction with 5 kg/cm2G was added, 4 g of ethylenediamine was added, and hydrogen was introduced at a hydrogen pressure of 5 kg/cm2G. The reaction was stopped when hydrogen no longer decreased, 300 g of n-hexane and 300 g of pure water were added to separate the layers, the organic layer was taken, and the n-hexane was removed under reduced pressure. Next, add the concentrate, 300 ml of tetrahydrofuran, and 300 ml of 10% HCl water to the reactor.
Stirred at 20-25°C for 1 hour. 10% NaOH after reaction
After adjusting the pH to 7 with water, the organic layer was separated, concentrated, and distilled to obtain 215 g of E,Z-2,13-octadecadienal. Purity 93%, boiling point 170
~174°C/1mmHg, yield 82%.

Example 2-1. Production of 2-13-octadecadiinal diethyl acetal (2-2): A solution of ethylmagnesium bromide in tetrahydrofuran (78 g of tetrahydrofuran) equivalent to 0.27 mol was charged in a reactor, 60 g of 1,12-heptadecadiine was added dropwise at 60°C. Next, after stirring at 60°C for 1 hour, 40g of ethyl orthoformate was added dropwise over 30 minutes, and the mixture was heated to 90°C for 7 hours.
Stir for hours. After reaction, NH4Cl20g, pure water 10
0 g was added and the liquid was separated, and the tetrahydrofuran in the organic layer was removed under reduced pressure and then distilled to obtain 70 g of 2,13-octadecadiinal diethyl acetal (yield 81%, boiling point 178-186 °C/0.4mm
Hg).

Example 2-2. Production of E,Z-2,13-octadecadienal (3): 2,13-octadecadienal diethyl acetal (
70g) and 3 nickel acetate in 50g of ethanol.
．． Add P-2 nickel obtained by reducing 9g with 0.8g of sodium borohydride, and add 1g of ethylenediamine.
was added, and hydrogen was introduced at a hydrogen pressure of 5 kg/cm2G. The reaction was stopped when hydrogen no longer decreased, 100 g of n-hexane and 100 g of pure water were added to separate the layers, the organic layer was taken, and the n-hexane was removed under reduced pressure. Next, the above concentrate and tetrahydrofuran were added to the reactor.
ml, add 100g of 10% HCl water, 20-25
Stirred at ℃ for 1 hour. After reaction, adjust the pH to 7 with 10% NaOH water.
When the organic layer was taken, concentrated and distilled, 53g of E,Z-2,13-octadecadienal was obtained.
was gotten. Purity 93%, boiling point 175-179℃/
1.2 mmHg, yield 80%.

Example 3. Production of E,Z-2,13-octadecadienyl acetate (5): E,Z-2 in the reactor
, 262 g of 13-octadecadienal and 100 g of tetrahydrofuran were cooled to 0°C, and 18 g of sodium borohydride was added to 150 g of 1% NaOH solution.
A solution dissolved in g was added dropwise so that the temperature did not exceed 5°C. After the dropwise addition, the mixture was stirred at 5°C for 1 hour. Next, 60 g of 50% aqueous acetic acid was slowly added dropwise to consume unreacted sodium borohydride. The organic layer was separated and concentrated under reduced pressure to obtain alcohol (4). Next, the concentrated alcohol (4), 500 ml of n-hexane, and 110 g of triethylamine were charged, and 78.5 g of acetyl chloride was added dropwise without exceeding 40°C. After dropping, stir at 40°C for 3 hours, add 400g of pure water to separate the liquids, and add 5% Na.
After washing with 400 g of HCO3 water, n-hexane was concentrated and distilled to obtain 234 g of E,Z-2,13-octadecadienyl acetate. (Yield 76%) Boiling point 179-183℃/1mmHg, Purity E, Z: 9
2.5%, E,E: 3.3%, Z,E: 1.2%
, Z, Z: 1.8%.

[0017]

As described above, according to the present invention, insect pheromone components such as E,Z-2,13-octadecadienal and E,Z-2,13-octadecadienyl acetate, E,Z-2,13-octadecadiene compounds can be easily produced stereospecifically.

Claims (3)

[Claims] [Claim 1] CH3(CH2)3HC=CH(CH2
)9C≡CMgX (in the formula, X represents a halogen) and CH(
OR)3 (in the formula, R represents a methyl group or an ethyl group)
Z-13 is obtained by reacting with the orthoformic acid ester shown by
-octadecene-2-innal diethyl acetal, hydrogenated and then hydrolyzed to form E,Z-2,13-
E, Z- characterized by being octadecadienal
A method for producing a 2,13-octadecadiene compound. [Claim 2] CH3(CH2)3C≡C(CH2)9C
≡CMgX (in the formula, X represents halogen) and CH(OR)
3 (wherein R represents a methyl group or an ethyl group) is reacted with orthoformic acid ester to form 2,13-octadecadiinal diethyl acetal, which is hydrogenated and then hydrolyzed to form E,Z- A method for producing an E,Z-2,13-octadecadiene compound, characterized in that it is 2,13-octadecadienal. 3. E,Z-2,13-octadecadienal obtained by the method according to claim 1 or 2 is reduced with a metal hydride and then acetylated to obtain E,Z-2,13- E, characterized in that it is octadecadienyl acetate,
A method for producing Z-2,13-octadecadiene compound.