JPH03223222A - 1-halo-(e,z)-7,9-alkadiene compound and its production - Google Patents

Abstract

NEW MATERIAL:Compounds of formula I (R<5> is H or CH3; X<2> is Br or Cl). USE:A raw material for synthesis of a synthetic insect sex pheromone or synthetic perfumes and an intermediate for synthesis of conjugate dienes. PREPARATION:A phosphonium salt of formula II (R<3> is H or 1-15C alkyl; R<4> is phenyl or 1-10C alkyl; X<1> is Br, I or Cl) is made to react with a base and subsequently subjected to Wittig reaction with a 9-halo-(E)-2-nonen-1-al of formula III to obtain the objective compound of formula IV. The above-mentioned reaction is carried out in a solvent such as benzene or THF in an inert gas current at -78-80 deg.C for 30min-1hr.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention is a novel, undocumented product that is extremely useful as an intermediate for the synthesis of conjugated diene compounds and as a raw material for the production of synthetic insect pheromones and synthetic fragrances. 1-halo-(E,Z)-
This invention relates to a 7,9-alkadiene compound and a method for producing the same.

(Prior Art and Problems) It is well known that the Witzteig reaction is a very effective means for synthesizing conjugated diene-based unsaturated compounds. However, when synthesizing compounds such as acetates, alcohols, and aldehydes that have conjugated diene bonds, such as those found in insect pheromones, even after the Witzteig reaction, active groups such as hydroxyl groups and halogen atoms are added to the terminals of the intermediate products. factors must remain. For this purpose, either the oxo group side or the phosphoranylidene group side must be difunctional to carry out the Wittich reaction.

At present, it is common to carry out the Witzteig reaction with either the oxo group or the phosphoranylidene group held in the form of a hydroxyl group or its ether bond. This method has drawbacks such as an increased number of steps for protection and deprotection of hydroxyl groups, and the need to use extremely special and expensive reagents, so it cannot be said to be industrially viable. For example, Floelof et al. synthesized aldehydes by oxidizing methyl-7-bromoheptanoate and then carrying out the Witzteig reaction using the anion of diethyl-2-(cyclohexylimino)-ethylphosphonate (U.S. Patent No. 3845108).

Toluene 2) (COOH)2 2) to 0H 2) (C)13cO) 20 Dolysine and Henrik et al. have carried out a similar route synthesis in which the hydroxyl group is protected in the form of tetrahydropyranyl ether ( Tetrahedron.

33° NaHCO8 NaH.

In the absence of MF nO2 salts, however, both synthetic routes lack versatility in raw materials, are expensive, and are considered impractical for large-scale reactions.

On the other hand, in order to synthesize E,Z conjugated diene compounds, there are attempts to first synthesize the en-yn form and then cis-hydrogenate the triple bond, but this also requires the use of hydrogenated borane compounds. The problem is that many of them are very expensive.

European grape vine
At present, there is a growing trend to use sex pheromone agents such as E,Z-7,9-dodecagenyl acetate, which is a pheromone of moth), to control pests. A synthetic method is desired.

(Means for solving the problem) As a result of the inventors' various studies in view of this point,
General formula R3CH2PR'3.X' (R3 in the formula is a hydrogen atom or an alkyl group having 1 to 15 carbon atoms, After converting the phosphonium salt represented by (which is an alkyl group) into phosphoranylidene using various bases, the general formula 0HCCH=CH(CH2)6
When the Witzteig reaction is performed with 9-halo-(E)-2-nonenal represented by l (in the formula x2 is a bromine or chlorine atom), a novel 1-halo-(E)-
7,9-decadiene and 1-hero E, Z-7.9-
The alkadiene compound can be synthesized efficiently, the new compound obtained has high geometric purity, and from this (^)゛ Grape is a sex pheromone (E, Z)
-7,9-dodecagenyl acetate, (B) "Kaikoga" sex pheromone E, Z-10°12-hexadecadien-1-ol, (C) Filbert worm sex pheromone, E, Z Synthetic insect pheromone such as -8,10-dodecagenyl acetate and E-7,9-dodecagenyl acetate (which is the sex pheromone component of DJ Kanshanoshin Ihamaki) can be easily obtained. It has been found that it is extremely useful as a raw material for producing synthetic fragrances.

2) 20tNaOH (CH3CO) 20 (Z) (E) CH3CH-CH(:H-CH(CH2) 70COC
)13(E) CH2=CHCH-CH(CH2) 60COCH3 The present invention was achieved based on such knowledge, and the first invention is the general formula % formula % ) (R5 in the formula is a hydrogen atom or a methyl group. , x2 are bromine and chlorine atoms).

Z) -7,9-alkadiene compound, and the second invention relates to a compound of the general formula R3CH2PR'3.Xl (in the formula, R3 is a hydrogen atom or an alkyl group having 1 to 15 carbon atoms, and R4 is phenyl group or alkyl group having 1 to 1 o carbon atoms, xl is bromine,
After treating the phosphonium salt represented by the general formula 0HCCH=CH(CH2)11 X' (where X
2 is the same as above) A method for producing a 1-halo-(E,Z)-7,9-alkadiene compound by carrying out a Witzteich reaction with 9-halo-(E)-2-nonen-1-al represented by It provides:

First, the method for producing a 1-hero(E,Z)-7°9-alkadiene compound according to the present invention will be described in detail.
The phosphonium salt compound represented by R'3. Trialkylphosphines such as triarylphosphines having a benzene ring (the benzene ring may be substituted with an alkyl group such as methyl or ethyl, a hydroxyl group, an alkoxy group, a halogen, etc.) and tri-t-butylphosphine Can be mentioned.

This reaction is carried out in various solvents while heating and mixing the two.

The solvents used for this are nitriles such as acetonitrile, aromatic hydrocarbons such as benzene, toluene, and xylene, and tetrahydrofuran.
Reaction at 20-200°C under anhydrous conditions is preferred.

This phosphonium salt is treated with a base to form a phosphoranylidene, and the bases used for this process include those that generate carbanions such as n-butyllithium;
There are bases that generate alkoxy anions, such as potassium t-butoxide, and the optimal base can be selected depending on the type of phosphonium salt. The solvents used are benzene, toluene, hexane, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide,
These include ethyl ether and glyme (methyl ether of ethylene glycol), and both are preferably anhydrous.

On the other hand, the above general formula % -halo-(E)-2-nonenal is, for example, (1)
A method of esterifying an α,β-unsaturated carboxylic acid, protecting the substituent at the 9-position, reducing it to an alcohol, and oxidizing this again to an aldehyde, and (2) a method with the general formula CH=C(CH2)11 Using 8-halo-1-octyne represented by 1-octyn-i-ylmagnesium halide, and then orthozaric acid alkyl ester (R20) 3CH (R" is a methyl group or an ethyl group)
2) Ho When the latter method is combined with the method for producing an alkadiene compound according to the present invention, it is possible to obtain functional There is no fear that -X2, which must remain as a group, changes during this series of steps, and the same solvent system can be used, which is advantageous in production.

This method involves reacting the 8-hello-1-octyne with an alkylmagnesium halide as a Grignard reagent in tetrahydrofuran at 40-80°C, and then reacting at 80-80°C.
At 100°C, orthoformic acid alkyl ester was added dropwise to approx.
After reacting for 0 hours to form 9-halo-2-noninal dialkyl acetal, it is hydrogenated and hydrolyzed, and the hydrogenation catalyst used at this time is Lindlar catalyst, Pd-C
A Pd-based catalyst such as P-2Ni or a Ni-based catalyst such as P-2Ni is preferable. Hydrogen pressure is 0.5-10 Kg/
cm', a temperature range of 0 to 70°C is preferred. Hydrolysis is carried out in various organic solvents containing 20% hydrochloric acid.
As this solvent, aliphatic or aromatic hydrocarbons such as n-hexane and toluene, and chlorine solvents such as dichloromethane are used. Considering the recovery of the solvent, n-hexane or toluene is preferable, but if dichloromethane is used, the reaction will be completed instantly. 20% hydrochloric acid is 0.5 to 2.0 times the volume of acetal, and the reaction temperature is 0 to 4.
0°C is desirable.

The thus obtained 9-halo-(E)-2-nonenal is converted into 1-halo-(E,Z")-7,
A 9-alkadiene compound can be used, but this reaction can use the solvent used for phospholarinide formation, and is usually carried out in the range of -78 to 80°C, but can be heated or cooled if necessary. . The reaction time is several minutes to 3 hours, but the reaction is usually completed in 30 minutes to 1 hour. Preferably, all of these operations are carried out in a stream of inert gas, including nitrogen and argon.

The crude product obtained as described above is subjected to vacuum fractional distillation,
It can be easily isolated and purified by column chromatography, thin layer chromatography, etc.

1-Heguchi-(E) obtained by this method.

In the Z)-7,9-alkadiene, the E form at the 7th position is guaranteed, but 10 to 30% of the E form at the 9th position is simultaneously produced. However, in order to give priority to cis-form generation, “5”
alt free” condition (J, 3m.

Chew, Sac, 104.5821 (1982
)), and a stereocontrol method such as reaction can be applied to improve the geometric purity.

(Example) Hereinafter, specific aspects of the present invention will be explained using examples.
The present invention is not limited thereby.

Example 1 Synthesis of 1-chloro-(E,Z)-7,9-dodecadiene (intermediate of the grape sex pheromone, E,Z-7,9-tochashenyl acetate).

Preparation of 9-chloro-(E)-2-nonen-1-al (raw material) First, 2.1 mol of Grignard reagent: methylmagnesium chloride was prepared in 400 ml of tetrahydrofuran under a nitrogen atmosphere. In this preparation, 8-chloro-
289 g of 1-octyne was added dropwise at 50 to 60°C, and 70°C
The mixture was stirred for 1 hour. Next, 200 ml of toluene was added and 325 g of orthoformic acid ethyl ester was added dropwise at 80 to 90°C, and the reaction was carried out at 90 to 100°C for about 20 hours. After the reaction, the reaction solution was poured into ammonium chloride water to separate the organic layer. When the solvent is removed and distilled, 9-chloro-
2-Nonene-1-ar diethyl acetal (boiling point 15
250 g of 0-b was obtained.

On the other hand, P-2Ni equivalent to 0.03 mol was prepared in ethyl alcohol 300a+1, and 1 g of ethylenediamine was added thereto, and the above 9-chloro-2-nonene-
250 g of 1-ar diethyl acetal was added, and hydrogenation was carried out in an autoclave at 20 to 40°C and a hydrogen pressure of 5 kg/cm'. After confirming by gas chromatography that the peak of the raw material had completely disappeared, 300 ml each of water and hexane were added to separate the mixture. The hexane in the organic layer was removed, and 400 ml of dichloromethane and 300 ml of 20% hydrochloric acid were added instead.
Hydrolysis was carried out at °C. After confirming that the acetal had completely disappeared by gas chromatography, it was washed successively with saturated saline and 2% sodium carbonate water. Next, take the organic layer and remove dichloromethane, resulting in 9
-Chloro-(E)-2-nonen-1-al was obtained.

2.1-chloro-(E,Z)-7,9-dodecadiene (
Synthesis of n-propyltriphenylphosphonium bromide 27 (product of the present invention)
0 g was suspended in 600 ml of anhydrous tetrahydrofuran, and 78 g of 1-BuOK was added little by little at 15 to 20° C. under a nitrogen atmosphere to form a phosphoranylidene (the reaction solution turned dark red). After stirring for about 30 minutes, 9-chloro-(E)-2-nonen-1-al obtained by the above method! 22g was added dropwise while maintaining the temperature at 15-20°C, and the mixture was stirred for 1 hour at 20°C. After the reaction, the pressure was reduced to remove tetrahydrofuran, and 200ml each of water and hexane were added.
The resulting triphenylphosphine oxyto was filtered off. The obtained hexane layer was concentrated and the crude product was distilled under reduced pressure to obtain 1-chloro-(E,Z)-7,9 with a geometric purity of 75% or more.
-85 g of dodecadiene were obtained. This is MS, NMR
, IR analysis gave the following results.

(^) MS: m/e (spectral intensity) ratio 39 (16%
), 41 (34%), 55 (30%), 67 (1
00%), aa (42%), 81 (50%), 82
(78%), 9.5 (83%), 109 (17%), 1
23 (68%), 1440 (12%), 167◆ (1
0%), 171 min (10%), 200 min (M”, 34
%) The Kojirushi peak is accompanied by the isotope peak of chlorine 37.

(B) NMR: δppm CHsCH2CH, -CHbCHc-CHdCH2(C
H2) 4CH2(:11.0 (t, 3H, J-7H
2), 1.20-1.75 (broad, 8) 1) 2.25
(m, 4H, -CH3CN-CH-).

3.50 (t, 2H, J=6.5Hz, -C)12C
1).

5.20(td,l)I,-Ha,J-7,5Hz).

5.50 (td, IH, -Hd, J-7H2).

5.80 (dd, 1)1. -Hb, J (Ha-Hb
)-10,5H2).

6.25(dd,l)I, -Hc,J(Hc-Hd)-
15Hz, J(Hc-)1b)-6,5)1z) (C) IR (ffla+): cm-13020,
2960, 2925, 2875, 2850, 1690°1B50. 1470. 1415. 1380. 9
80. ! 145. 7303, (E,Z)-7
Synthesis of ,9-dodecagenyl acetate (applied product) This 1-chloro-(E,Z)-7,9-dodecadiene 8
5 g was stirred with 1508 potassium acetate anhydride and 100 g of acetic acid at 160°C for 5 hours under a nitrogen atmosphere, and then poured into reaction condensate. The organic layer was distilled under reduced pressure to obtain (E) with a geometric purity of 75% or more.

Z) −7° 9-dodecagenyl acetate 80g was gotten.

Example 2゜ 1-bromo- (E.

Z)-7 Synthesis of 9-dodecadiene CH3CHxCH-CHCH-CHICH2) earl
, 9-bromo-(E)-2-nonen-1-al (
Preparation of 8-bromo-1-in place of 8-chloro-1-octyne
1 of Example 1 except that 378 g of octyne was used.
When the same operation as above was performed, 9-bromo-2-nonine-! with a purity of 90% or more was obtained. 292 g of -R diethyl acetal (boiling point 158-165 t/3 mmHg) was obtained, and the same operation as 1 of Example 1 was performed to obtain 9-bromo-(E)-2-nonen-1-R.

2. Synthesis of 1-bromo-(E,Z)-7,9 dodecadiene (product of the present invention) 9-bromo-(E)-2 instead of 9-chloro-(E)-2-nonen-1-al The same operation as in Example 1-2 was performed except for using -nonene-1-al.
1-Bromo-(E,Z)-7,9 with geometric purity of 75% or more
-90 g of dodecadiene were obtained. MS, N
The results of analysis by MR and IH are shown below.

(A) MS: m/e (spectral intensity ratio) 39
(12%), 41 (29%), 55 (29%)
, 67 (100%), 68 (38%), 81 (
53%), 82 (83%), 95 (96%), 109
(21%), 123 (10%), 135I (5%), 1
88* (8%), 215◆ (3%), 2440
(Ml, 24%) The middle mark peak is accompanied by the isotope peak of bromine 81.

(B) NMR: δppm CH3C)12CHa-CHbCHc-CI (dtl:
H2(CI(2) 4(1:)12Br1.0 (t,
3H, J-7Hz), 1.20-1.75 (bro
ad, 8) 1).

2.25 (m, 4H, -CH2C)I-C)I-)
, 3.40 (t, 2H, J-6, 5Hz,
-CH2Br)5.20 (td, IH, -Ha,
J=7.5Hz), 5.45 (td, IH,
-Hd, J=7Hz).

5.80(dd, LH, -41b, J(Ha-Hb)-
10Hz).

6.20 (dd, 1) 1. -Hc, J()Ic-Hd)
・15Hz, J (He-)1b)・8)1z)(C)
IR (film): cm-1 3020, 29B0.2925.2875.2850.
1695.1650°1470, 1415.1380.
980.945.7203, Synthesis of (E,Z)-7,9-dodecadienyl acetate (applied product) 1-chloro-(E,Z)-7,9-dodecadiene 85g
When the same operation as in Example 1-3 was performed except that 90 g of 1-bromo-(E,Z)-7°9-dodecadiene was used instead, (E,Z)-7 with a geometric purity of 75% or more was obtained.
, 62 g of 9-dodecagenyl acetate were obtained.

Ac0)1 (Z) (E) CH3C1hC)I-CHCH”CH(CH2) 60
COCH3 Example 3 Synthesis of 1-chloro-(E,Z)-7,9-dodecadiene (intermediate of the crab sex pheromone, E,Z-10°12-hexadodecadien-1-ol).

-BuOK 2) 204kNaOH n-propyltriphenylphosphonium bromide 27
The same procedure as in Example 1-2 was performed except that 300 g of n-butyltriphenylphosphonium bromide was used instead of 0 g, and 1-chloro(E,Z) was obtained.
87 g of -7,9-tridodecadiene was obtained with a geometric purity of more than 75%.

When this compound was further subjected to the above reaction, 61 g of E,Z-10,12-hexadecadien-1-ol (boiling point 162-165°C/3 mmH8) was obtained.
was obtained with a geometric purity of 75% or more.

Example 4 Synthesis of 1-chloro-(E)-7,9-decadiene (sex pheromone component of Kanshanoshin Ihamaki, intermediate of E-7,9-decadienyl acetate) (E) (E) CH2 -C)ICH-C)I(CH21sc11.9-
Preparation of chloro-(E)-2-nonenal (raw material) First, 2.1 mol of Grignard reagent: methylmagnesium chloride was prepared in 400 ml of tetrahydrofuran under a nitrogen atmosphere. In this preparation, 8-chloro-
289 g of 1-octyne was added dropwise at 50 to 60°C, and 70°C
The mixture was stirred for 1 hour. Next, 200 ml of toluene was added, 325 g of orthoformic acid ethyl ester was added dropwise at 80 to 90°C, and the mixture was reacted at 90 to 100°C for about 20 hours. After the reaction, the reaction solution is poured into ammonium chloride water to separate the layers, and the solvent of the organic layer is removed and distilled to obtain 9-chloro- with a purity of over 96%.
2-nonenal diethyl acetal (boiling point 150-16
0° C./3 mmg) 250 g was obtained.

On the other hand, P-2Ni equivalent to 0.03 mol was prepared in 300 ml of ethyl alcohol, 1 g of ethylenediamine was added thereto, 250 g of the above 9-chloro-2-nonenal diethyl acetal was added, and the mixture was placed in an autoclave for 20 to 30 minutes. Hydrogenation was carried out at 40° C. and a hydrogen pressure of 5 kg/cm. After confirming by gas chromatography that the peak of the raw material had completely disappeared, 300 ml each of water and hexane were added to separate the mixture. The hexane in the organic layer was removed, and 400 ml of dichloromethane and 300 ml of 20% hydrochloric acid were added instead, and hydrolysis was performed at 0 to 30°C.Complete disappearance of acetal was confirmed by gas chromatography. Thereafter, the organic layer was washed successively with saturated brine and 2% sodium carbonate water.Then, the organic layer was taken and dichloromethane was removed to obtain 9-chloro-(E)-2-nonenal.

2. Synthesis of 1-chloro-(E)-7,9-decadiene (product of the present invention) 250 g of methyltriphenylphosphonium bromide was suspended in 600 ml of anhydrous tetrahydrofuran, and a small amount of 76 g of t-BuOK was added at 15 to 20°C under a nitrogen atmosphere. phosphoranylidene was added (the reaction solution turned dark red).
. After stirring for about 30 minutes, 122 g of 9-chloro-(E)-2-nonenal obtained by the above method was mixed with 15
The mixture was added dropwise while maintaining the temperature at ~20°C, and the mixture was stirred at 20°C for 1 hour. After the reaction, the pressure was reduced to remove tetrahydrofuran, 200 ml each of water and hexane were added, and the resulting triphenylphosphine oxyto was filtered off.

The obtained hexane layer was concentrated and the crude product was distilled under reduced pressure to obtain 1-chloro-(E)-7,9- with a geometric purity of 75% or more.
Decadiene (boiling point 110-116℃/3 mmHg)
69 g was obtained. MS this.

When analyzed by NMR and IR, the following results were obtained.

(1) Mass spectrum: M/Z (attribution) 172 and 174
("Molecular ion peak derived from CI and 37C1") See Figure 1 (a) (2) Nuclear magnetic resonance spectrum "Structural formula" 2)
4) 6) "Attribution""Remarks" Unit: 699m Solvent: Deuterium chloroform standard 1! '
H-NMR is 7.26 ppm of CHC13, “C
-NMR is 77.5 ppm of CDCl3.

(3) Infrared (IR) absorption spectrum Figure 1 (b) Reference Example 5 1-chloro-(E,Z)-7,9-undecadiene (F
ilbert worm sex pheromone, E, Z-8,
Synthesis of 10-dodecagenyl acetate intermediate) Example 4-2 except that 260 g of ethyltriphenylphosphonium bromide was used instead of 250 g of methylphenylphosphonium bromide in Example 4-2.
When the same operation as 2 was performed, 1-chloro-(E,Z
') -7,9-undecadiene 72g (boiling point 116~
118° C./2.5 mmHg), and the geometric purity of the EZ form was 78% or more. This is M31NMR%
When analyzed by fR, the following results were obtained.

(1) Mass spectrum: M/Z (attribution) 186 and 188
(Molecular ion beak from which 35C1 and 37cl originate) See Figure 2 (a) (2) Nuclear magnetic resonance spectrum "Structural formula"2>
4) 8) "Attribution""Remarks" Unit = δppm Solvent double chloroform standard: H
-NMR is 7.25 ppm of CHC13, 13C
-NMR is 77.5 ppm of CDC1s.

(3) Infrared absorption spectrum (see Fig. 2(b)) Application example 1 (E) Synthesis of -7,9-decadienyl acetate (cooperative component of the sex pheromone of C. chinensis) Obtained in Example 4-2 1-chloro-(E)-7,9-
69 g of decadiene was reacted with 210 g each of acetic anhydride or glacial acetic acid at 170° C. for 6 hours under a nitrogen atmosphere. After the reaction, 200 mA of pure water was added to separate the layers, and the organic layer was distilled under reduced pressure to obtain 71 g of (E)-7,9-decadienyl acetate.

Application example 2 (E,Z)-8,10-dodecagenyl acetate (F
Synthesis of ilbert worm sex pheromone) 72 g of 1-chloro-(E,Z)-7,9-undecadiene obtained in Example 5 was stirred with 18 g of magnesium in THF to prepare a Grignard reagent, then 68- 7
At 0°C, add 21g of paraformaldehyde and dilute with THFHF.
The following reaction was performed. Dilute HCj2 water was added into the reactor to stop the reaction, and the organic layer was separated and dehydrated by adding anhydrous magnesium sulfate.

Then add 75 g of triethylamine as an acid binder,
76 g of acetic anhydride was added dropwise, and the mixture was stirred at 70°C for 2 hours. After the reaction, 150 ml of water was added, the layers were separated, and the organic layer was distilled under reduced pressure to obtain 61 g of an oily liquid. Gas chromatography revealed that this product was 89% E,Z-8,10-dodecagenyl acetate and contained 10% EE.

[Brief explanation of drawings]

The drawings are all related to Examples of the present invention, and Fig. 1(a) and (b) respectively show the mass spectrum and infrared absorption spectrum of the product in Example 4-2, and Fig. 2(a) shows the mass spectrum and infrared absorption spectrum of the product in Example 4-2. , (b) show the mass spectrum and infrared absorption spectrum of the product in Example 5, respectively.

Claims (1)

[Claims] 1. General formula R^5CH=CHCH=CH(CH_2)_
6X^2 (R^5 in the formula is a hydrogen atom or a methyl group,
^2 is a bromine or chlorine atom) 1-halo-(E,Z)-7,9-alkadiene compound. 2. General formula R^3CH_2PR^4_3・X^1 (R^3 in the formula is a hydrogen atom or an alkyl group having 1 to 15 carbon atoms, and R^4 is a phenyl group or an alkyl group having 1 to 10 carbon atoms. , X^1 is a bromine, iodine, or chlorine atom) is reacted with a base, and then the general formula OHCCH=CH(CH_2)_6X^2 (where X^
The general formula R^3CH=CHCH=CH(CH_2)_6X^2(
R^3 and X^2 in the formula are the same as above) 1
-Production method of halo-(E,Z)-7,9-alkadiene compound.