JPH072680B2 - Of producing sex pheromones - Google Patents

Description

The present invention relates to a method for producing an insect sex pheromone. More specifically, using a 1,3-butadienyl metal compound,
Pest of the red cotton worm (red bollworm m)
oth, Diparopsis castanea Hmps) for the production of sex pheromone acetic acid (9,11-dodecadienyl).

This sex pheromone is useful for controlling pests in cotton cultivation.

[Prior art]

Many methods for synthesizing 9,11-dodecadienyl acetate are already known. The following can be mentioned as the example.

1) A method in which an acetylene compound is obtained by a coupling reaction of a haloalkyl ether and acetone, an yne compound is obtained by performing a coupling reaction of the acetylene compound and a vinyl halide, and then a diene compound obtained by reducing a triple bond is passed ( R. Rossi, Synthesis, 1981, 359.R. Rossi, A Carpita, M.
G.Quirici, MLGaudenzi, Tetrahedron, 38 , 631 (198
2)) 2) Method utilizing coupling reaction of alkenylborane and vinyl halide (R. Rossi, A. Carpita, MGQuirici, Tetrahedron, 37 , 261)
7 (1981)) 3) Method using coupling reaction of alkenyl halide and vinyl magnesium bromide (D. Michelot, Synthesis, 130 (1983)) 4) Method using Wittig reaction (S. Ranganthan, R. Kumar , V.Maniktala, Synthetic Conmu
micatums, 12 , 921 (1982)) 5) Method utilizing the coupling reaction of aryl dithiocarbamates with halides (T. Hayashi, M. Yanagida, Y. Matsuda, T. Oishi, Tetrahedr)
on Lett, 24 , 2665 (1974)) 6) Method using triethylaluminum ate complex of arylphenyl zelenium anion (Y.Yamamoto, Y.Saito, K.maruyama, Tetrahodron Lett. 2
3 , 4597 (1982) 7) Method using Pummerer rearrangement (H. Ishibashi, H. Komatsu, K. Maruyama, M. Ikeda, Tetrahe
dron, Lett., 26, 5791 (1985)) 8) 1- methods using benzenesulfonyl-4-trimethylsilyl-2-butene (C-N Hsiao, H.Shechter, Tetrahedron Lett., 25, 1219
(1984)) Each of these methods has a drawback that the introduction of the diene bond is carried out stepwise, and therefore the reaction process becomes long.

[Problems to be solved by the invention]

An object of the present invention is to provide a method for efficiently producing acetic acid (9,11-dodecadienyl) by introducing a diene bond, which has been conventionally performed stepwise, in one step.

[Means for solving problems]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is an efficient method for producing 9,11-dodecadienyl acetate by introducing a diene bond in a single step using a 1,3-butadienyl metal compound, the details of which will be described below.

[Action]

The present invention is 1,3-butadienyl represented by the general formula (1) CH ₂ ═CH—CH═CHM (1) (M is selected from MgX or Li, and X is selected from chlorine, bromine or iodine). Metal compound and general formula (2) X CH ₂ (CH ₂ ) ₆ CH ₂ OR (2) (X is selected from chlorine, bromine and iodine, and R is selected from 1-ethoxyethyl or 2-tetrahydropyranyl. ) From a haloalcohol protected with an alcohol group (hereinafter abbreviated as haloalkyl ether), a compound represented by the general formula (3) CH ₂ ═CHCH═CHCH ₂ (CH ₂ ) ₆ CH ₂ OR (3) And a diene ether represented by the following) in the presence of a copper catalyst,
After deprotection, acetylation is carried out to produce 9,11-dodecadienyl acetate.

Examples of the 1,3-butadienyl metal compound include Grignard reagents such as 1,3-butadienyl magnesium chloride, 1,3-butadienyl magnesium bromide and 1,3-butadienyl magnesium iodide, or 1,3 -Butadienyl lithium can be mentioned. The Grignard reagent is a method developed by the present inventors (Chemical Society of Japan No. 50).
It can be prepared by the Annual Reenactment Proceedings 1V06 (1985)).

Lithium compounds include n-butyllithium, s and organotin compounds such as 1-tributylstannyl-1,3-butadiene developed by the present inventors (Proceedings of the 49th Annual Meeting of the Chemical Society of Japan 2Z07 (1984)). It can be prepared by reacting an alkyllithium such as -butyllithium or methyllithium with an ether solvent such as ether or THF at a low temperature of -50 to -80 ° C in an inert gas atmosphere.

Examples of the haloalcohol include 8-chloro-1-octanol, 8-bromide-1-octanol, and 8-iodo-1-octanol, and preferably 8-bromide-1-
Octanol and 8-iodo-1-octanol. Examples of the alcohol protecting group include 1-ethoxyethyl, 2-tetrahydropyranyl and the like.

The copper catalyst may be any monovalent copper compound, such as cuprous iodide and cuprous bromide. Further, a dissolution aid such as dimethyl sulfide may be added to increase the solubility of the copper compound.

The reaction between the 1,3-butadienyl metal compound and the haloalkyl ether is performed in an inert atmosphere such as nitrogen or argon.

As the reaction solvent, a solvent such as diethyl ether, THF, monoglyme, diglyme or the like is used.

When a Grignard reagent is used as the 1,3-butadienyl metal compound, the amount of the copper catalyst is 5 to 50 mol%, preferably 10 to 30 mol% based on 1 mol of the haloalkyl ether.

The amount of Grignard reagent is preferably 1.0 mol or more per 1 mol of haloalkyl ether.

This reaction can be carried out by adding a Grignard reagent to an ether solution containing a copper catalyst and a haloalkyl ether. Reaction temperature during addition is -50 to -20 ° C
However, it is not necessary to perform any cooling after the addition is completed, and the reaction can be carried out at 0 to 25 ° C.

A reaction time of 30 minutes or more is sufficient. When a lithium compound is used as the 1,3-butadienyl metal compound, the reaction proceeds without the copper catalyst, but the presence of the copper catalyst is preferable because the yield is improved.

The amount of copper catalyst is 0.2 to 1 mol of haloalkyl ether.
2.0 mol It is preferably 0.5 to 1.5 mol.

The lithium compound is preferably used in an amount of 1.0 mol or more based on the haloalkyl ether.

This reaction can be carried out by sequentially adding a lithium compound and a haloalkyl ether to an ether solution containing a copper catalyst. The solution temperature at the time of adding the lithium compound is −
90 to -50 ° C, preferably -80 to -60 ° C.

The solution temperature at the time of adding the haloalkyl ether is -50 to -20.
C., preferably -40 to -20.degree.

After completion of the addition, the reaction is completed at 0 to 20 ° C for 3 to 5 hours, but after the addition of the haloalkyl ether, the reaction temperature is 15 minutes to
It is preferable to carry out the reaction at 0 to 20 ° C. after the reaction for 1 hour. The thus-produced diene ether can be treated with 10% water-containing methanol in the presence of a paratoluenesulfonic acid catalyst to remove the protecting group to produce 9,11-dodecadienol.

The sex pheromone acetic acid 9,11-dodecadienyl can be easily produced by acetylating the thus produced 9,11-dodecadienol with, for example, acetic anhydride in pyridine.

Hereinafter, the present invention will be described in more detail with reference to examples.

〔Example〕

Example 1 300 m equipped with reflux condenser, dropping funnel and septum
Into a three-necked flask (1), 1.50 g of scrap metal magnesium and 0.5 g of zinc chloride were put, and after sufficiently heating under reduced pressure and drying, the atmosphere was replaced with nitrogen. A 0.5 ml THF solution of 0.5 ml of 1,2-dibromoethane was added, 35 ml of THF was further added, and the mixture was vigorously stirred. After dropping 2.82 g of 1-chloro-1,3-butadiene, ultrasonic treatment was performed for 1.5 hours, and heating under reflux was performed for 1.5 hours. 1,10−
When titration was performed with s-butyl alcohol using phenanthroline as an indicator, the concentration of the present Grignard reagent was 0.545 mol /.

In a 50 ml three-necked flask equipped with a septum, 102 mg of cuprous iodide, 776 mg of 8-iodo-1- (2-tetrahydropyranyloxy) octane and 3 ml of THF were placed, and 5 ml of the Grignard reagent was added at -30 ° C under a nitrogen stream. Dropped. After completion of dropping, the mixture was stirred at -30 to 0 ° C for 30 minutes. After adding 10 ml of saturated aqueous ammonia chloride, the reaction solution was extracted with ether (2 x 30
ml). The extract was dried over anhydrous sodium sulfate and then the solvent was distilled off to obtain 687 mg of 12- (2-tetrahydropyranyloxy) -1,3-dodecadiene.

687 mg of 12- (2-tetrahydropyranyloxy) -1,3-dodecadiene was dissolved in 10 ml of 10% water-containing methanol.

After adding 50 mg of p-toluenesulfonic acid to this solution and heating and stirring at 50 ° C. for 2 hours, the solvent was distilled off under reduced pressure. The residue was extracted with ether (2 × 30 ml), and the extract was washed with aqueous sodium hydrogen carbonate solution (2 × 30 ml), saturated saline (2 × 30 ml) and water (2 × 30 ml).

After drying the organic phase over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 556 mg of a crude alcohol. The crude alcohol was purified by silica gel column chromatography (developing solution hexane: ethyl acetate = 9: 1) to obtain 9,11-dodecadienol 389.
to obtain mg.

The alcohol compound was dissolved in a solution consisting of 2 ml of acetic anhydride and 10 ml of pyridine and stirred at 0 ° C. for 18 hours and at room temperature for 18 hours. The reaction solution was poured into 30 g of ice and extracted with n-pentane (2 x 3
0 ml). The extract was washed with 1% hydrochloric acid (3 × 30 ml), saturated ammonium chloride (2 × 30 ml) and water (2 × 30 ml), and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was subjected to silica gel column chromatography (developing solution: hexane:
Purification with ethyl acetate = 9: 1) yielded 328 mg of 9,11-dodecadienyl acetate. The yield was 61% based on iodide. The spectral data of the diene ester form was in agreement with the literature values. ^{When the} isomer ratio was determined by ¹ H-NMR, E / Z =
It was 70/30.

Example 2 A septum, a nitrogen introducing tube and a calcium chloride tube were attached.
1-tributylstannyl-1,3-
3.15 g of butadiene and 20 ml of THF were added. The reaction solution is -78
After cooling to ℃, 5.4 ml (7,12 mmol) of a hexane solution of n-butyllithium was added dropwise under a nitrogen stream. After stirring for 30 minutes, this solution was placed in a 100 ml three-necked flask and the first iodinated solution was added.
Copper (740 mg) and THF (40 ml) were added, the system was replaced with nitrogen, and the solution was added dropwise to a solution cooled to -78 ° C. Raise the temperature of the reaction solution to -30 ° C,
A solution of 867 mg of 8-bromo-1- (1-ethoxyethyloxy) octane in 5 ml of THF was added dropwise. 3 at -30 ° C after completion of dropping
The mixture was stirred for 0 minutes, then the dry ice / acetone bath was removed, and the mixture was stirred for 3 hours. Saturated ammonia chloride water 30
The reaction was stopped by adding ml, and ether extraction (2 × 30 ml) was performed. The extract was a saturated aqueous solution of ammonium chloride (2 x
30 ml), saturated sodium hydrogen carbonate solution (2 × 30 ml), and dried over anhydrous sodium sulfate. After distilling off the solvent,
The residue is purified by silica gel column chromatography 1,
2- (1-ethoxyethyloxy) -1,3-dodecadiene
413 mg was obtained. The yield was 53%.

Thereafter, the same procedure as in Example 1 is carried out to obtain 9,11-dodecadienyl acetate 35
3 mg was obtained. The isomer ratio was E / Z = 68/32.

[Effects of the Invention] As is clear from the above description, the present invention enables the introduction of a diene bond, which was conventionally performed in multiple steps, in one step, and an agriculturally useful sex pheromone can be efficiently produced. .

Claims (1)

[Claims] 1. A 1,3-butadienyl represented by the general formula (1) CH ₂ ═CHCH═CHM (1) (M is selected from MgX or Li, and X is selected from chlorine, bromine or iodine). Metal compound and general formula (2) X CH ₂ (CH ₂ ) ₈ CH ₂ OR (X is selected from chlorine, bromine or iodine, and R is 1-
It is selected from ethoxyethyl or 2-tetrahydropyranyl. ) From a haloalcohol having a protected alcohol group, a diene represented by the general formula (3) CH ₂ ═CHCH═CHCH ₂ (CH ₂ ) ₆ CH ₂ OR (3) (R is the same as the following (2)) A process for producing 9,11-dodecadienyl acetate, which comprises producing ether, deprotecting the diene ether thus produced, and acetylating the produced diene alcohol.