JPH09110740A - Unsaturated halogen compound and production of sexual pheromone using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound useful as a starting raw material for readily producing (R, Z)-7,15-hexadecadiene-4-olide extremely high in sexual attracting action on Heptophylla picea Motshulsky as a plant insect pest. SOLUTION: This compound is shown by formula I (X is Br, Cr or I) such as 1-chloro-(Z)-3,11-docadiene. The compound is reacted with metal magnesium in an organic solvent to give a Grignard reagent, which is reacted with β- carbomethoxypropionyl chloride to give a keto-ester of formula II. Then the keto-ester is reduced to prepare a hydroxy-ester of formula III, which is further lactonized to give (R,Z)-7,15-hexadecadiene-4-olide of formula IV.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing (Z) -7,15-hexadecadiene-4-olide, which has an extremely high sex-inducing effect on the scarab beetle belonging to the family Coleoptera, Scarabaeidae and a method for producing the same. It relates to unsaturated halogen compounds used in.

[0002]

[Prior Art] Japanese beetle (Heptophylla picea Mot
shulsky) is an insect of the order Coleoptera and is a pest that causes great damage to trees, crops, and flowers. It is said that the number of tea gardens is increasing year by year in recent years. On the other hand, with regard to the use of insecticides, its persistence has developed into a social problem. Under these circumstances, in order to effectively control the Japanese chafer, it is necessary to predict the developmental ecology and use sex pheromones to trap and remove a large amount of male adults or to disrupt communication. Interest is increasing. Therefore, it is extremely important to find a convenient method for synthesizing the sex pheromone of Pleurotus cornucopiae.

The sex pheromone of Pleurotus cornucopia is represented by the following formula (R, Z) -7,15-hexadecadiene-4.
-It has been made clear that it is Oride.

Embedded image It has also been found that even the racemic body shows male attraction activity, and that the symmetrical body does not inhibit attraction. However, there is no report that the synthesis of this compound was studied in detail.

[0004]

SUMMARY OF THE INVENTION The object of the present invention is to
An object of the present invention is to provide a simple method for producing (Z) -7,15-hexadecadiene-4-olide. Since the side chain of the compound contains two double bonds, it is extremely important to find a simple method for introducing this portion.

[0005]

Means for Solving the Problems As a result of intensive studies for solving the above-mentioned problems, the present inventors have found that by using a novel halogen compound, it is a Nagachacogane sex pheromone (R, Z) -7. The present invention has been completed by finding that 15-hexadecadiene-4-olide or its racemate can be produced more easily.

That is, the unsaturated halogen compound according to claim 1 has the general formula

Embedded image (In the formula, X represents a bromine atom, a chlorine atom, or an iodine atom.).

The following equation according to claim 2

Embedded image The method for producing the oxacyclopentane compound represented by
A step of reacting the unsaturated halogen compound according to claim 1 with metallic magnesium in an organic solvent to prepare a Grignard reagent, and reacting the Grignard reagent with β-carbomethoxypropionyl chloride to give the following formula:

Embedded image And a step of preparing the keto ester represented by the formula:

Embedded image And a step of lactonizing the hydroxy ester.

The unsaturated halogen compound is, for example, 3-
Using bromo-1-propanol and 8-nonenal,
It can be easily manufactured. That is, 3-bromo-
After protecting the hydroxyl group of 1-propanol with a protective group, for example, a trimethylsilyl group, it is converted into a triphenylphosphonium salt in a solvent such as acetonitrile or DMF.

Next, the Wittig reaction is carried out using 8-nonenal. At that time, the solvent was diethyl ether, tetrahydrofuran, or 1 mol of the phosphonium salt.
Toluene, n-hexane, 1,4-dioxane, etc. may be used alone or in a mixture of 500 to 1500 ml. As the base, n-butyllithium, NaH, tert-butoxypotassium, sodium bis (trimethylsilyl) amide, etc. are added in an amount of 0.98 to 1 mol with respect to 1 mol of the phosphonium salt.
The reaction is carried out at -20 ° C to 20 ° C using a 1.1-fold molar amount. Next, 8-nonenal is added dropwise at -78 ° C to 20 ° C to complete the reaction.

After the reaction, the by-produced triphenylphosphine oxide is removed, the trimethylsilyl group is removed under acidic conditions using hydrochloric acid or the like, and an isolation operation such as distillation is carried out to obtain (Z) -3,11- Dodecadiene-1-ol is easily obtained. Next, unsaturated halogen compounds are obtained by various halogenation reactions. Examples of the halogenating agent used here include thionyl chloride, thionyl bromide,
Phosphorus tribromide, CCl ₄ -triphenylphosphine, CB
r ₄ -triphenylphosphine and the like can be mentioned. The outline of these reactions is shown in the following formula.

[0011]

Embedded image

Another method is to use 9-decen-1-yne. After reacting 9-decene-1-yne with methylmagnesium chloride, ethylene oxide was added in an amount of 1.3 to 1.6 with respect to 1 mol of 9-decene-1-yne.
The reaction is completed by adding mol dropwise. Next, when partial hydrogenation is carried out in the presence of various hydrogenation catalysts, (Z) -3,11
-Dodecadien-1-ol is easily obtained. Examples of the catalyst used here include a Lindlar catalyst, a P-2Ni catalyst, and palladium-carbon.
Finally, the same halogenation reaction as above gives the unsaturated halogen compound in good yield. These reactions are shown in the following equations.

[0013]

Embedded image

It will be shown below that the oxacyclopentane compound can be easily synthesized by using the halogen compound thus obtained. The unsaturated halogen compound is diethyl ether or tetrahydrofuran alone, or in a mixed solvent with toluene, xylene or the like,
Reacts with magnesium metal to lead to the corresponding Grignard reagent. At this time, 200 to 800 g of the solvent and 1.0 to 1.2 mol of magnesium are used with respect to 1 mol of the unsaturated halogen compound, and the preparation is usually performed in an inert gas atmosphere under the conditions not exceeding 90 ° C. Then, from succinic anhydride, a known method (Org.Syn.Vol.3, p.169-1) was used.
71 (1955)) and β-carbomethoxypropionyl chloride and -78 ° C to 0 ° C, preferably -6.
The keto ester can be obtained by reacting at about 0 to -30 ° C.

Next, by reducing the ketoester using various reducing agents such as sodium borohydride,
A hydroxy ester is obtained. The reducing agent used here should be one that does not reduce the ester group. Further, an optically active hydroxyester can be obtained by using a chiral reducing agent and a reducing method. For example, a method of reducing in the presence of an optically active amino alcohol called "chirald" manufactured by Aldrich as a reducing agent, and asymmetric hydrolysis using lipase PS can be used.

However, in the present invention, it is sufficient to obtain a racemate. Therefore, the carbonyl group may be reduced with sodium borohydride in ethanol or tetrahydrofuran solvent. Sodium borohydride is 1.0 to 1 mol to the above ketoester.
Using 3.0 mol, preferably 1.2 to 1.5 mol,
It is desirable to carry out the reduction at 10 to 10 ° C.

Finally, the above hydroxy ester in benzene or toluene with a catalytic amount of p-toluenesulfonic acid at 50 to 100 ° C., preferably 60 to 80 ° C.,
When methanol is removed and lactonization is carried out, the target racemic compound (Z) -7,15-hexadecadiene-4-olide is obtained. (Z) -7,15-hexadecadiene-4
-Olides can be isolated by conventional purification procedures such as column chromatography, preparative thin layer chromatography, flash chromatography. The above process is shown by the following equation.

[0018]

Embedded image

[0019]

EXAMPLES Example 1 (Z) -3,11-dodecadien-1-ol (intermediate
(Part 1) 3-bromo-1-propanol (138 g, 1.0 mol), n-hexane 500 m
1, triethylamine 111 g (1.1 mol) was added,
Trimethylchlorosilane (125 g, 1.15 mol) was added dropwise at 30 ° C or lower, and then the mixture was stirred for 1 hour. Next, 700 ml of pure water was added thereto for liquid separation, the organic layer was taken, and n-hexane was removed under reduced pressure to obtain 210 g of a concentrate.

Then, the above concentrate, triphenylphosphine (262.3 g, 1.0 mol) and 400 g of acetonitrile were added to another flask, and the mixture was stirred at 90 ° C. for 20 hours. After the reaction, acetonitrile was removed under reduced pressure, 800 g of tetrahydrofuran was added, and the mixture was cooled to 10 ° C. Then, 112.2 g of potassium tert-butoxide
(1.0 mol) was added, and the mixture was stirred for 1 hour and then at -78 ° C.
After cooling to 8-nonenal 84.5 g (0.6 mol)
Was dripped. After the reaction, the temperature was returned to room temperature, 20 ml of pure water was added to stop the reaction, tetrahydrofuran was removed under reduced pressure, and triphenylphosphine was filtered. To the obtained organic layer, 500 ml of 10% hydrochloric acid water was added and stirred vigorously,
When the organic layer was neutralized with diluted NaOH water and distilled under reduced pressure, (Z) -3,11-dodecadien-1-ol 6 was obtained.
7.3g (62% yield, bp129-134 ° C / 3mm
Hg) was obtained.

(Z) -3,11-dodecadien-1-o
(2) Synthesis of alcohol (intermediate) In a 2 liter flask, 24.3 g of magnesium and 300 ml of tetrahydrofuran were added, and methyl chloride was wiped in under N ₂ atmosphere to prepare methyl magnesium chloride according to a conventional method. Next, at 30 ° C., 135 g of 9-decen-1-yne was added dropwise. After stirring for 2 hours as it was, 56 g of ethylene oxide was added dropwise at a temperature not exceeding 20 ° C. After the dropping, 300 g of 20% hydrochloric acid water was added for hydrolysis, the organic layer was taken, and tetrahydrofuran was removed under reduced pressure. The obtained residue was charged into an autoclave and n-
200 ml of hexane and 1.5 g of Lindlar's catalyst were added and hydrogen was introduced at a hydrogen pressure of 5 kgf / cm ² to complete the reaction. After the reaction, the catalyst was filtered off, and n-hexane was collected under reduced pressure and distilled to obtain 119.5 g (yield 66%) of (Z) -3,11-dodecadien-1-ol.

1-chloro- (Z) -3,11-dodecadi
Synthesis of ene (Z) -3,11-dodecadien-1-ol 90.5
g (0.5 mol) and triethylamine 53 g (0.52
Mol) and 300 ml of dichloromethane were placed in a 2-liter flask, and 65.5 g (0.55 mol) of thionyl chloride was added dropwise at a temperature not exceeding 40 ° C. Then 4
After stirring at 0 ° C. for 2 hours, 400 ml of pure water was added for liquid separation, and the organic layer was washed twice with 400 g of 5% NaOH water. After liquid separation, dichloromethane in the organic layer was removed under reduced pressure and distilled, and 86.8 g of 1-chloro (Z) -3,11-dodecadiene (yield 87%, bp 117 to 124) was obtained.
C./3 mmHg) was obtained. The obtained compound is 1-chloro- (Z) -3,11-dodecadiene,
Mass spectrum (FIG. 1), NMR spectrum (FIG. 2),
Confirmed by IR spectrum (FIG. 3).

1-bromo- (Z) -3,11-dodecadi
Synthesis of ene (Z) -3,11-dodecadien-1-ol 18.1
g (0.1 mol) and 30 ml of tetrahydrofuran were placed in a reactor, and CBr ₄ (40 g, 0.122 mol) dissolved in 20 ml of tetrahydrofuran was added dropwise.
Next, triphenylphosphine (34 g, 0.13 mol) dissolved in 30 ml of tetrahydrofuran was added dropwise under temperature conditions not exceeding 40 ° C, and the mixture was further stirred for 1 hour. Next, after adding 5 ml of methanol, the tetrahydrofuran was removed under reduced pressure, the mixture was extracted with n-hexane, and triphenylphosphine oxide was filtered off and distilled.
Bromo- (Z) -3,11-dodecadiene 22.5 g
(Yield 93%, bp 129 to 136 ° C./3 mmHg) were obtained. The obtained compound was 1-bromo- (Z) -3,
It was confirmed to be 11-dodecadiene by mass spectrum (FIG. 4), NMR spectrum (FIG. 5), and IR spectrum (FIG. 6).

1-iodo- (Z) -3,11-dodecazi
Synthesis of ene (Z) -3,11-dodecadien-1-ol 18.1
g (0.1 mol) and 200 ml of n-hexane were put in a reactor, cooled to 0 ° C., and 10.1 g (0.1% of triethylamine).
1 mol), and added thereto methanesulfonyl chloride 1
2.6 g (0.11 mol) was added dropwise so as not to exceed 40 ° C. After dropping, the mixture was stirred at room temperature for 1 hr, 400 g of pure water was added, and the layers were separated. The organic layer was taken out and n-hexane was removed to obtain a concentrated liquid. Next, in another reactor, 600 g of acetone, 195 g of NaI (1.3 mol) were placed, and 60 ° C.
The above concentrated liquid was added dropwise at, and the mixture was stirred under reflux for 3 hours. After the reaction, the mixture was hydrated, the organic layer was taken out, acetone was removed under reduced pressure, and the residue was distilled.
/ 3 mmHg) was obtained. The obtained compound is 1-iodo- (Z) -3,11-dodecadiene, mass spectrum (FIG. 7), NMR spectrum (FIG. 8), I.
Confirmed by R spectrum (FIG. 9).

Example 2 4-keto- (Z) -7,15-hexadecadienoic acid methyl ester
Le Synthesis of (Intermediate) 1-chloro - (Z)-3,11-dodecadiene (20
(g, 0.1 mol), magnesium (2.5 g) and tetrahydrofuran (50 ml) were used to prepare a Grignard reagent by a conventional method. Next, another reactor was charged with β-carbomethoxypropionyl chloride (15 g, 0.1 mol) and 150 g of tetrahydrofuran, cooled to −60 ° C., and Cu was added.
0.15 g of Cl was added and the Grignard reagent was added dropwise. Next, after stirring for 2 hours, the temperature was returned to room temperature, 250 ml of saturated aqueous ammonium chloride was added, the organic layer was separated and the tetrahydrofuran was removed under reduced pressure to obtain 29 g of a concentrate. This was directly used for the next step. The retention time in GLC analysis (DB-WAX, φ0.25 mm × 30 m, column temperature 150 to 230 ° C. (5 ° C./min temperature increase)) was 21.5 minutes.

(Z) -7,15-hexadecadiene-4
-Synthesis of Olide 29 g of the above concentrate was charged into a reactor together with 100 ml of tetrahydrofuran, cooled to 0 ° C., and sodium borohydride (5.0 g, 0.132 mol) was added to 1% NaOH water 8
What was dissolved in 0 ml was added dropwise under temperature conditions not exceeding 10 ° C. After completion of dropping, the mixture was returned to room temperature and stirred for about 2 hours. After the reaction, the organic layer was taken and tetrahydrofuran was removed under reduced pressure. 100 ml of toluene was added to the residue,
p-Toluenesulfonic acid was added, and the mixture was stirred at 80 ° C for 1 hr. After the reaction, 200 ml of pure water, then 5% NaHCO
₃ Toluene was removed under reduced pressure by sequentially washing with 200 ml of water. GLC analysis of the residue revealed a retention time of 2
There is a peak at 7.7 minutes, which is (Z) by GC-MS analysis.
It was confirmed to be -7,15-hexadecadiene-4-olide, which was consistent with a natural product (extract from Naga Chakogane). Part of this residue was purified by silica gel column chromatography to obtain 1.2 g of (Z) -7,15-hexadecadiene-4-olide. The yield is 1-
61.3% with chloro- (Z) -3,11-dodecadiene
Met.

[0027]

INDUSTRIAL APPLICABILITY According to the present invention, an oxacyclopentane compound having an extremely high sex-inducing effect on the Japanese long-spotted chafer can be easily produced.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hiroyuki Suzuki 1 at 28, Nishi-Fukushima, Chugaku-mura, Nakakubiki-gun, Niigata Prefecture Shin-Etsu Chemical Co., Ltd.

Claims (2)

[Claims] 1. A compound of the general formula (In formula, X represents a bromine atom, a chlorine atom, or an iodine atom.) The unsaturated halogen compound represented by these. 2. A step of reacting the unsaturated halogen compound according to claim 1 with metallic magnesium in an organic solvent to prepare a Grignard reagent;
By reacting with -carbomethoxypropionyl chloride: And a step of preparing a ketoester represented by the formula: The following formula including the step of preparing a hydroxy ester represented by: and the step of further lactonizing the hydroxy ester Is represented by (Z) -7,15-hexadecadiene-4-
Manufacturing method of orido.