JPH0786091B2 - Tetradecadienyl chloride and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention synthesizes a novel compound which has not been described in the literature, in particular, E, Z-4,10-tetradecadienylacetate, which is a sex pheromone of Physcomitrella patens. Useful as an intermediate for
The present invention relates to E, Z-4,10-tetradecadienyl chloride and a method for producing the same.

(Prior Art) Phyllonorycter ningoniela is a major pest of apples, and its larvae are known to live in the mesophyll and significantly inhibit fruit enlargement and flower bud formation. Therefore, the control is limited to the young larva having high sensitivity to the insecticide, and in order to improve the efficiency, it is required to know the time of spraying the insecticide in advance. Therefore, in recent years, a biological control method using a sex pheromone has come to the attention, for example, E, Z-4,10-tetradecadienyl acetate, which is a minor component but deeply involved in mating behavior as a sex pheromone of the goldenrod, Moth. With respect to the above, JP-A-61-134347 discloses a synthetic agent using a Wittig reaction as shown in the following formula.

(Problems to be Solved by the Invention) However, this conventional technique is a synthesis centering on the Wittig reaction, has poor stereoselectivity of the reaction product, and has a geometric isomer of any structure at any ratio. Hard to get. This complicates the process such as a separate operation for separating the E-form and the Z-form by silver nitrate column chromatography, and the yield is low, resulting in inconvenient production efficiency. Also, because chromic acid is used to synthesize the aldehyde used in the Wittig reaction,
There are also subsequent processing problems.

The present invention was carried out in order to solve these disadvantages, and to stereoselectively synthesize E, Z-4,10-tetradecadienyl chloride, an intermediate as a novel compound, using the Grignard reaction. Provide an effective means of producing the sex pheromone component of Echinochloe oryzae, E, Z-4,10-tetradecadienyl acetate.

(Means for Solving the Problems) A method for producing a novel compound, E, Z-4,10-tetradecadienyl chloride according to the present invention, is 6-chloro-E-2-hexenyl acetate and Z-4-octenyl. The gist is to react with magnesium halide in the presence of a copper catalyst.

Further, in the present invention, 6-chloro-E-2-hexenyl acetate used as a starting material for this reaction is hydrogen as a reaction product of 5-chloro-1-pentynyl magnesium halide and orthoformate triaryl ester. After addition, it is preferably obtained by hydrolyzing, reducing this, and acetylating.

Hereinafter, the details of the present invention will be described together with the reaction formula. As mentioned above, the present invention uses 6-chloro-E-2-as a starting material.
Hexenyl acetate is used.

i) A suitable method for preparing this compound is to first prepare 5-chloro-1
6-chloro-obtained by reacting pentynyl magnesium halide with orthoformate trialkyl ester represented by ethyl orthoformate and methyl orthoformate
The 2-hexinal dialkyl acetal is separated by distillation. In this reaction, both compounds are equivalent to 60 to 10 in a single solvent or a mixed solvent of tetrahydrofuran (hereinafter referred to as THF), n-butyl ether, toluene, xylene and the like.
It is carried out by heating at 0 ° C for 10 to 30 hours, preferably 90 to 95 ° C for 15 to 20 hours. As the orthoformate trialkyl ester used in the reaction, ethyl orthoformate is particularly preferable because it is easily available.

The obtained 6-chloro-2-hexinal dialkyl acetal is subjected to hydrogenation reaction in the presence of a catalyst and then hydrolyzed to give 6-chloro-2-hexenal. In the hydrogenation reaction, P-2Ni, Pd-BaSO _4, etc. are used as a catalyst in a ratio of 0.001 to 0.1 equivalent to the reaction substrate, and the hydrogen pressure is 1 to 10 kg / c.
It may be completed within 0.5 to 3 hours at m ² and a temperature of 10 to 50 ° C. After the reaction, dilute 2-3 times with a solution such as n-hexane or methylene chloride, hydrolyze with 20% hydrochloric acid water or formic acid, and lead to the corresponding aldehyde. The obtained 6-chloro-2-hexenal is medium. The solvent is removed under sexual conditions and used as it is in the next step.

(Here X = halogen atom, R = -C ₂ H ₅ or -CH ₃
Group) ii) The product 6-chloro-2-hexenal selectively reduces its formyl group with a reducing agent such as 0.5 to 3.0 times equivalent of sodium borohydride or lithium aluminum hydride with respect to the aldehyde. After that, the resulting OH group was acetylated and 6-chloro-
E-2-hexenyl acetate. In addition, if this reduction is attempted with lithium aluminum hydride, the reducing power is too strong and the halogen group may be reduced, and the reaction at low temperature and in a short time is unavoidable. Is preferably used in 1.0 to 1.5 times equivalent and the reaction is preferably carried out in the presence of THF so as not to exceed 40 ° C.
On the other hand, acetylation uses acetyl chloride or acetic anhydride as an acetylating agent, and in the presence of an equivalent amount of a base such as pyridine or triethylamine, methylene chloride, n-hexane, or THF is used as a solvent in an amount of 300 to 600 g per mol.
And react at 0-50 ° C. After the reaction, water is added to remove the organic layer, the solvent is removed, and the product is separated by distillation to separate the above product.

iii) As described above, the method for producing E, Z-4,10-tetradecadienyl chloride according to the present invention uses the 6-chloro-E-2-hexenyl acetate obtained as described above as a starting material. It is used.

In the present invention, this compound is first reacted with a Grignard reagent prepared by a reaction of Z-4-octenyl halide and metallic magnesium in the presence of a copper catalyst to give E, Z-4,10-tetradecadienyl chloride. And For the preparation of this Grignard reagent, THF, diethyl ether, n-butyl ether, toluene, xylene and the like are used alone or as a mixed solvent at a ratio of 200 to 500 g per mol, but usually THF is used.
300 g may be used. In the reaction with 6-chloro-E-2-hexenyl acetate, the Grignard reagent is added in the system in an amount of 1.0 to 1.5 times equivalent amount. Copper catalysts used here include cuprous chloride, cuprous bromide, monovalent copper halides such as cuprous iodide, cupric chloride, cupric bromide, cupric iodide, etc. There are copper-lithium catalysts such as divalent copper halide and dilithium copper tetrachloride (Li ₂ CuCl ₄ ).
E, Z-4,1 with high yield can be obtained by reacting at -20 to + 30 ℃ in HF.
0-Tetradecadienyl chloride is obtained.

The above product is an alkali metal salt of acetic anhydride represented by anhydrous potassium acetate and anhydrous sodium acetate (CH ₃ COOM).
And 200 to 400 g per mol of the reaction substrate are reacted under heating at 140 to 180 ° C. to obtain E, Z-4,10-tetradecadienyl acetate which is the object of the present invention.

The above-obtained compound can be easily isolated and purified by usual separation operations such as distillation, column chromatography, preparative thin layer chromatography and preparative gas chromatography, and its geometric purity is at least 88%. Reach above

iv) In addition, Z-4-octenyl halide used as a raw material in the preparation of the Grignard reagent in this reaction is, for example, as shown in the following formula, 4-pentynol and propyl bromide in the presence of LiNH _2. After reacting,
It can be easily obtained by a very general synthetic method of hydrogenating and halogenating.

In addition, E, Z-4,10-tetradecadienyl chloride obtained in the present invention is an anhydrous acetic acid alkali metal salt typified by anhydrous potassium acetate and anhydrous sodium acetate (CH ₃ COO
M) is reacted with 200 to 600 g per mol of the reaction substrate under heating at 140 to 180 ° C. to obtain E, Z-4,10-tetradecadienylacetate which is a sex pheromone component of Quercus cinerea.

This E, Z-4,10-tetradecadienyl acetate has a Z-form at the 10-position, which is produced by cis-hydrogenation of 4-octynyl, as shown in the above reaction formula. The hydrogenated E-form of 6-chloro-2-hexinal dialkyl acetal is hydrolyzed to take the form of α · β-unsaturated aldehyde with respect to the double bond, and specifically 6-chloro- ( E) -2-Hexenal can be produced, and its stereostructure is retained even after the coupling reaction is performed through the subsequent reduction and acetylation of the formyl group.

Hereinafter, specific examples of the present invention will be shown, but the present invention is not limited thereto.

(Example) I. Synthesis of 6-chloro-E-2-hexenal (i): Methyl chloride is blown into 300 ml of THF containing 24.3 g of magnesium to prepare 1 mol of methylmagnesium chloride. 5-chloro-1-pentyl in it
102.5 g (1 mol) was added dropwise at 40-60 ° C, and after completion 1 hour at 80 ° C
Stir for hours to give 5-chloro-1-pentynyl magnesium halide.

Next, 148 g (1 mol) of ethyl orthoformate is added dropwise thereto at 80 ° C., and the mixture is stirred at 90 ° C. for 20 hours. After reaction 5% NH ₄ Cl water 300
When hydrolyzed with g, the organic layer was distilled after liquid separation,
151-g of 6-chloro-2-hexinal diethyl acetal
Was obtained with a yield of 75%. To this was added P-2Ni catalyst prepared from 6.8 g of nickel acetate, 1.0 g of sodium borohydride and 150 g of ethanol, and hydrogenated in an autoclave at a hydrogen pressure of 5 kg. After the reaction, the catalyst was filtered and ethanol was removed, to the residue was added 150 g of methylene chloride and 100 g of 20% hydrochloric acid water, and the mixture was stirred at room temperature for several minutes. When the methylene chloride layer was washed with water and then removed, 89 g of 6-chloro-E-2-hexenal was obtained with a yield of 90%.

II. Synthesis of 6-chloro-E-2-hexenyl acetate (ii): 200 ml of THF and 6-chloro-E-2-hexenal in a reactor.
24 g was added, and 50 ml of a 1% NaOH solution containing 6.9 g of sodium borohydride was added dropwise while maintaining the temperature at 20 to 30 ° C. 25 ℃ after completion
It was stirred for 1 hour. After the reaction, it was extracted with 400 ml of n-hexane, dried over anhydrous sodium sulfate, transferred to another reactor and added with 31 g of triethylamine, and further added to 15 to 25
23 g of acetyl chloride was slowly added dropwise at ℃. After the end 2
After stirring at 5 ° C for 1 hour, 400 ml of pure water was added to separate the liquid and n-
Hexane was removed. When the residue was distilled, 6-chloro-E-2-hexenyl acetate (bp = 103 to 109 ° C.)
/ 10 mmHg) 20 g was obtained with a yield of 64%.

III. Synthesis of Z-4-octenyl chloride (iv): 1000 ml of liquid ammonia containing 0.24 mol equivalent of LiNH _2.
The suspension was maintained at -33 ° C and 51 g of 4-pentynol was added dropwise thereto over 1 hour. 74 g of n-propyl bromide diluted with 250 ml of THF was slowly added dropwise to the resulting dark gray solution over 1 hour. After the completion, the mixture was stirred at −33 ° C. for 3 hours, 500 ml of cold water was added to the residue from which ammonia was removed, the mixture was extracted with ether, the ether layer was washed with an aqueous solution of ammonium chloride, the ether was removed, and the residue was distilled. 54 g of 4-octinol was obtained with a yield of 70%.

Next, 54 g of 4-octinol, 2 g of Lindlar's catalyst and 80 ml of n-hexane were added to the autoclave at 40 ° C.
At this time, hydrogen of 5 kg / cm ² pressure was introduced. After the reaction yield, the catalyst was filtered off and the residue from which n-hexane had been removed was transferred to another reactor,
To this, 43 g of triethylamine and 400 ml of methylene chloride were added, and thionyl chloride 55 while cooling so as not to exceed 20 ° C
g was added dropwise. After the completion, the temperature was gradually raised and the mixture was stirred at 50 ° C for 2 hours. After the reaction, the methylene chloride was removed by washing twice with 300 ml of a 5% NaOH aqueous solution, and the residue was distilled.
45 g of 4-octenyl chloride was obtained with a yield of 72%.

Synthesis of IV.E, Z-4,10-tetradecadienyl chloride (iii): After adding 4 g of metallic magnesium in 130 g of THF and further adding a small amount of methyl magnesium chloride as an initiator,
22 g of Z-4-octenyl chloride obtained in Section III was added and reacted to prepare a Grignard reagent. Next, in the reactor, THF 100g, anhydrous cupric chloride 0.5g, lithium chloride 0.3g
To prepare dilithium tetrachloride (Li ₂ CuCl ₄ ), the solution was cooled to 0 ° C., and 18 g of 6-chloro-E-2-hexenyl acetate obtained in Section II was added,
The Grignard reagent described above was added dropwise while maintaining the temperature at -10 ° C, and after the completion, the mixture was stirred at 0 ° C for 2 hours. After the reaction, 200 ml of 5% ammonium chloride-5% hydrochloric acid water was added for hydrolysis, and the residue of the organic layer from which THF had been removed was distilled. As a result, E, Z-4,10-tetradecadienyl chloride (bp = 120 ~ 127 ℃ / 2mmHg)
25 g was obtained with a purity of 93% and a yield of 68%.

This was analyzed by MS, NMR and IR to confirm the compound.

(A) MS; m / z (spectral intensity ratio) 228 * (0.8) 171 (2) 158 (2) 138 (9) 130 (10) 12
4 (11) 109 (6) 96 (18) 95 (36) 82 (51) 81 (78) 67
(76) 55 (64) 54 (42) 41 (100) 39 (29) 29 (21) 27
(23) * The peak marked with isotope peak of chlorine 37.

(B) NMR δ (ppm) 0.90 (3H, t, J = 7Hz), 1.12 to 1.60 (8H, broad, s) 1.70 to
2.30 (8H, m), 3.42 (2H, t, J = 6.5Hz), 5.10 ~ 5.47 (4H,
m) (C) (film) cm ^-1 3005,2920,2860,1650,1450,1380,970,720 25 g of E, Z-4,10-tetradecadienyl chloride thus obtained was mixed with potassium acetate anhydrous. 60 g and 60 g of acetic acid were added, and the mixture was stirred at 160 ° C for 7 hours. After the reaction, 400 ml of pure water and 5%
After washing with 400 ml of sodium hydrogen carbonate and distilling the organic layer, 24 g of E, Z-4,10-tetradecadienyl acetate (bp = 135-140 ° C./3 mmHg) was obtained with a yield of 87%.

(Effects of the Invention) According to the method of the present invention, the obtained E, Z-4,10-tetradecadienyl chloride becomes a reaction product that is sterically structurally selectable. Efficient production is possible without the need for separation operation or post-treatment.

Claims (3)

[Claims] 1. E, Z-4,10-tetradecadienyl chloride represented by: 2. A 6-chloro-E-2-hexenyl acetate and Z-4-octenyl magnesium halide,
E, Z-4,1 characterized by reacting in the presence of a copper catalyst
Process for producing 0-tetradecadienyl chloride. 3. 6-Chloro-E-2-hexenyl acetate is hydrogenated and hydrolyzed to the reaction product of 5-chloro-1-pentynyl magnesium halide and trialkyl orthoformate, which is hydrolyzed. The E, Z-4,10 according to claim 2, which is obtained by reducing and then acetylating.
-A method for producing tetradecadienyl chloride.