JPS63198637A - Production of 10-tetradecene derivative - Google Patents

Abstract

PURPOSE:To obtain the titled substance efficiently and in high yield, by subjecting a 3-heptenyl magnesium halide prepared from a 3-heptenyl halide and metallic Mg and 1,7-dihalide of heptane, etc., to coupling reaction. CONSTITUTION:A compound shown by the formula CH3(CH2)2CH=CH(CH2)2 MgX (X is Cl, Br or I) prepared from a 3-heptenyl halide and metallic Mg is coupled with a compound shown by the formula X1(CH2)7R (X1 is Br or I; R is Cl, Br or OH protected with methylsilyl group, etc.) in the presence of cuprous iodide as a catalyst in a solvent such as THF, etc., to give a compound shown by the formula CH3(CH2)2CH=CH(CH2)9R. The coupling reaction may be carried out dividedly at two stages. The method has excellent efficiency and requires no pressure device, etc. The prepared substance is useful as a synthetic intermediate for pheromone for insects.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing lO-tetradecene derivatives useful in the synthesis of insect pheromones.

[Conventional technology]

Insect pheromones have recently attracted attention as a means of controlling pests in agricultural crops. Conventionally, organic insecticides have been used to control pests, but they have a negative impact on the human bodies of farmers, increase the resistance of pests, and lead to significant destruction of biological systems such as a decrease in natural enemies, which poses social problems. It becomes. In contrast, insect pheromones are expected to be applied as a new pest control method that utilizes the mating behavior of pests. The use of synthetic pheromones to control communication disruption of Phosphoptera pests is already being put into practical use both in Japan and abroad. The sex pheromones of Lymphoptera moths vary depending on each insect pest, but the number of carbon atoms lθ~
Most of them are straight chain aliphatic compounds having 23 carbon-carbon double bonds.

10-tetradecene derivatives are very useful compounds in the field of sex pheromone synthesis. For example, Z-10-tetradecenyl acetate is known as one of the sex pheromone components of the goldenrod moth. JP-A-81-134347 discloses the use of this as an attractant.

Conventionally, methods for synthesizing carbon skeletons with double bonds such as those shown in L include a method using the Wittig reaction and a method using a coupling reaction between sodium acetylide and alkyl halide in liquid ammonia. be.

(Problems to be solved by the invention) However, the synthesis method using the Wittig reaction lacks selectivity in the geometric structure and is difficult to purify.In addition, the synthesis method using liquid ammonia requires pressure-resistant equipment for low-temperature reaction. is 0
Both methods have some problems.

The present invention solves the problems of the conventional methods and provides a method for efficiently producing lO-tetradecene derivatives.

[Means for solving problems]

The first aspect of the present invention has been made to solve the above problems.
The 10-tetradecene derivative C1h (CH2
The method for producing hCH0CHCCHz)qR is 3-hebutenyl halide C)I3(CHz)2cH=cH(CHz
hX 3 obtained by reacting dimetallic magnesium Mg
-hebutenylmagnesium halide CH3(CH2)2
0H-CH(CH2)2MgX and general formula XI(C
H2) Contains a coupling reaction with a substance called JR. That is, it includes a one-step coupling reaction.

The method of the first invention is expressed in the order of the steps by a formula.

CH3(CH2)20H-CI(CH2)2X-”
-eCH3(CH2)zcH-cH(CH2)9R. In this case, X is a chlorine atom, a bromine atom or an iodine atom; e Xl is a bromine atom or an iodine atom, preferably a bromine atom. R is a chlorine atom or a bromine atom, or a 10H group protected in the form of a trimethylsilyl group or tetrahydropyranyl ether;
Chloroheptane, 1,7-dibromohebutane, 1-chloro-7-iodohebutane, 7-bromohebutane-1-
There are all trimethylsilyl ether and 7-iodohebutan-1-ol tetrahydropyranyl ether.

The reaction conditions were Grignard reagent-
M g
~1.5 times equivalent Examples include cuprous iodide, cuprous bromide, cupric bromide, cuprous chloride, cupric chloride, copper acetate, dilithium copper tetrachloride, and -lithium copper dichloride. , especially 1
Cuprous iodide of valent copper is preferred, and the amount of catalyst is about 0.5 to 2.0 g per mol of Grignard reagent.
Examples of reaction solvents include tetrahydrofuran (THF) and diethyl ether, but the reaction proceeds even in their absence. Preferred is tetrahydrofuran.

Similarly, the method for producing an IO-tetradecene derivative according to the second invention of the present invention includes 3-hebutykolmagnesium halide obtained by reacting 3-hebutenyl halide with metallic magnesium and a compound having the general formula X+ (CHz)ynRx. CH3CCH2)2 obtained by a coupling reaction with a substance
CH3(CH2)20H-OH(C
H2) 9-nMgRx and general formula X2(CH2)IIR
In other words, it includes a multi-step coupling reaction.

When the method of the second invention is expressed in the formula in order of steps, CH3C
CH2)2 Cl-0H(CH2)2 X l-CH3
(CH2)zcH-(J(GHz)9-nRx-→CH
3(CH2)zCH-OH(CH2)9R. X and R are the same as in the first invention. Rx is the first
It is the same as X in the invention and is a chlorine atom, a bromine atom or an iodine atom.* Xi and X2 are the same as xl in the first invention and are a bromine atom or an iodine atom. n is an integer from 2 to 5. X
Preferred combinations of +(GHz)y-nRx and X2(CH2)nR are shown in Table 1 below.

Table 1 Ding HP is a tetrahydropyranyl group.

The reaction conditions are the same as in the first invention, but the nm2
In this case, the efficiency is slightly low, so a combination of nm3 and nm4 is preferable.

Similarly, the method for producing a 10-tetradecene derivative according to the third invention of the present invention is to use 3-hebutenyl magnesium halide obtained by reacting 3-hebutenyl/\ride with metallic magnesium and the general formula X+ (CHz)7-nRo+ CHz CCH obtained by coupling reaction with a substance
2) CH3CCHz) 2cH-CHCCHz obtained by halogenating 2cH-CHCCHz)q-nROM
)q-nRx, CH3CCH2)2 CH-(H(CH2) 9- obtained by reacting metallic magnesium
It includes a coupling reaction between n MgRx and a substance of the general formula X2 (CH2) n R.

When the method of the third invention is expressed by a formula in the order of steps, CH3(
CH2)2CH-CI(CH2)2X -halogenation
-Rx CH3(CH2)2 CIhCH(CH2)9-11R
OMg CH3CCHz)2cHmcH(CH2)q-nRx-
In addition to the 10H group protected in the form of CH3 (CH2) 20H gastric CH (CH2) 9R ranyl ether, ethylene oxide is a good eRx for X of the first invention and second invention (7)
Same as Rx. CH3(GHz)2cH-OH(C
Hz) When halogenating 9-nROM, if ROH is trimethylsili-0H3i or ethylene oxide, use thionyl chloride, thionyl bromide,
Use phosphorus tribromide and phosphorus trichloride. n is the same as in the second invention.

Xl(CH2)y-nRoH and X2(CH2)nR (preferred combinations are shown in Table 2 below).

Table 2 THP is a tetrahydropyranyl group.

Restrictions on reaction conditions are the same as in the case of the second invention.

From the 10-tetradecene derivatives obtained according to the first to third inventions, for example, z-10-tetradecenyl acetate, which is one of the sex pheromone components of the goldenrod, can be derived according to the following formula.

CH3CCH2)2 CHMaroCH(CH2)90cOc
h or CH3GOCI CH3(CHzhCH-CH(CH2)90HCH3C
CH2)2 CI-CM (GHz)90COCH3 [
Examples] (1) One-step synthesis example of cis-10-tetradecenyl chloride (Example of the first invention) 24.3 g (1 mol) of metallic magnesium and T
Add 300 g of HF and add 128 g (0.95 mol) of cis-3-hebutenyl chloride to 60 to 8
Prepare a THF solution of cis-3-heptenylmagnesium chloride by dropwise addition at 5°C. Next, in another dry flask, add 1 g (0,005 mol) of cupric iodide and 200 g THF.
, 213.5 g (1 mol) of 1-bromo-7-chloroheptane are added and stirred vigorously for several minutes under N2 atmosphere. 1
cis-3, which had been cooled to 0 °C and prepared as above.
- THF solution of hebutenylmagnesium chloride at 25%
Drop at below ℃ 0 After completion of dropping, add 5% NHaCI water 3
If 001 is added, hydrolyzed, and then separated, and the THF of the organic layer is removed and the residue is distilled, 184.5 g of cis-1O-tetradecenyl chloride (bp-105~b two-step synthesis example ( Example of the second invention) ■First stage 24.3 g (1 mol) of metallic magnesium and 300 g of THF in the cis-8-decenyl chloride reactor
and add 12g (0.95 mol) of cis-3-heptenyl chloride dropwise at 60 to 65°C under N2 atmosphere to prepare a THF solution of cis-3-heptenylmagnesium chloride. Next, another drying step is carried out. 1 cuprous chloride in a flask
g (0.01 mol) THF200g, 1-bromo-3
- Add 157.5 g (1 mol) of chloropropane and add N2
After stirring vigorously for several minutes in an atmosphere, cool to 10°C, and dropwise add the THF solution of cis-3-heptenylmagnesium chloride prepared as described above at 25°C or below. 3001 is added, hydrolyzed and separated, and the organic layer after removing THF is distilled to obtain cis-8-decenyl chloride 12.
4g (b, p, = ElO ~ 64℃ 12 mHg, yield 7
1%) is obtained.

■Second stage 18.3g (0.75 mol) of metallic magnesium, T
Add 300g of HF, and under 82 atmosphere, cis-6-
124 g (0.71 mol) of decenyl chloride from 60 to 7
Prepare a THF solution of cis-6-zocenylmagnesium chloride by dropwise addition at 0°C. Next, add 0.7 g (0,005 mol) of cupric iodide in THF 150 to another dry flask.
g, 1-bromo-4-chlorobutane 120.0 g (0,
After stirring vigorously under N2 atmosphere,
A THF solution of cis-6-zocenylmagnesium chloride prepared in advance as described above is added dropwise at a temperature below 25°C.

After the dropwise addition, 2601 g of 5XNHaCI water is added to perform hydrolysis, followed by liquid separation, and the residue obtained by removing THF from the organic layer is distilled to obtain 131.0 g of cis-10-tetradecenyl chloride (b, p ,=105-110℃/2m
mHg, yield 8 oz).

(2) Synthesis of cis-1O-tetradecen-1-ol One-step synthesis example (Example of the first invention) A THF solution of 1 mole of cis-3-heptenylmagnesium chloride was prepared in the same manner as in (1) above. adjust 0
Next, in another dry flask, 1 g of copper iodide (0,
oo5 mol) T HF 200 g, 7-bromo-hebutan-1-ol trimethylsilyl ether 287 g (
After stirring vigorously, the THF solution of cis-3-heptenylmagnesium chloride prepared as described above was added dropwise at 25°C or below.
After the dropwise addition, 300 g of 5-ton NHaC1-HCI water is added for hydrolysis, the liquid is separated, and the organic layer after removing THF is distilled to obtain cis-10-tetradecene-1.
-Oh, +1/ 178g (b, p, -111-114
℃/2mmHg, yield 83%).

Two-step synthesis example (Example of the third invention) ■First step: cis-3-heptenylmagnesium equivalent to 1 mole was obtained by the same operation as in ■First step of cis-8-dodecenyl bromide (1). Preparing a THF solution of chloride Next, add 1 g (0,005 mol) of cupric iodide, 200 ml of THF, and 1 g (1.2 mol) of 1,5-dibromopentane to another dry flask, and stir vigorously. After adding 9 drops of the THF solution of cis-3-hebutenylmagnesium chloride prepared as described above at 20 to 25°C, the mixture was diluted with 300 g of 5% NH4Cl water and then separated into layers. If the residue after removing THF from the organic layer is distilled, cis-8-dodecenyl bromide 188
g (b, p, -114 to b yield 68z) is obtained.

■Second stage cis-10-tetradecen-1-ol 17.5 g (0.71 mol) of metallic magnesium and 250 g of THF were placed in a cis-10-tetradecen-1-ol reactor, and cis-8-
188 g (0.88 mol) of dodecenyl bromide from 60 to
Prepare a THF solution of cis-8-dodecenylmagnesium bromide by dropwise addition at 70°C. 5. Cuprous bromide by cooling to 0°C. After adding Ig (0,038 mol) and stirring for several minutes, 47 g (1.1 mol) of ethylene oxide was added at 0°C.
After the reaction is completed, add 5% NH4
If hydrolysis does not occur with 300 g of Cl water, and the residue obtained by separating the organic layer and removing THF is distilled, cis-10-
Tetradecen-1-ol 34g (b, p, proverb 108
~114°C/2simHg, yield 24z).

(3) Synthesis of cis-10-tetradecenyl chloride Two-step synthesis example (Example of the second invention) 0 m 1 stage ■ of cis-7-unzocenyl chloride (1)
Prepare a THF solution of cis-3-hebutenylmagnesium chloride equivalent to 1 mole in the same manner as in the first step. Next, put 1 g of cupric iodide (0,005
After adding 171.5 g (1 mol) of 1-bromo-4-chlorobutane and stirring vigorously, the THF solution of cis-3-heptenylmagnesium chloride prepared as described above was added to 20 to 25 ml of THF. After the completion of 0 dropwise addition at ℃, hydrolyze with 300 g of 5% NHAC1 water, separate the layers, remove THF from the organic layer, and distill the residue to obtain 153 g of cis-7-unzocenyl chloride (b , p, fog 71-72℃/two-layer Hg yield 8
1$) is obtained.

■Second stage 20.8g (0.85 mol) of metallic magnesium and T
HF2EiOg was added, and 153 g (0.81 mol) of the cis-7-unzocenyl chloride obtained above was added dropwise at 60 to 70°C under an N2 atmosphere to form a THF solution of cis-7-unzocenylmagnesium chloride. Next, add 0.81 g of cupric iodide (0.00 g) to another dry flask.
After adding 150 g of THF and 127 g (0.81 mol) of 1-bromo-3-chloropropane and stirring vigorously, the THF solution of cis-7-unzocenylmagnesium chloride prepared in advance as described above was added. After 0 drops at 20-25°C, 51 NHa
After hydrolyzing with 300 g of C1 water, the organic layer is separated and the THF is removed. The residue is cis-10
-tetradecenyl chloride.

(Synthesis of 0 cis-1O-tetradecenyl acetate (sex pheromone of the goldenrod moth), Part 1 From the cis-10-tetradecenyl chloride obtained above, cis-10-
Synthesize tetradecenyl acetate. Add 300% potassium acetate to the above residue. , add 300g of acetic acid and heat at 170℃ for 5~6
After heating for 0 hours and stirring under N2 atmosphere, pure water 8
By adding 001 and separating the layers, and distilling the organic layer, cis-
10-tetradecenyl acetate 193g (bp-1
20-125℃/2mm1g, yield 7
6$) is obtained.

(5) Synthesis of cis-10-tetradecenyl acetate,
Part 2 Cis-10-tetradecene-1 obtained above in the reactor
-ol 21.2 g (0.1 mol), n-hexane 100 ml, triethylamine 11. After cooling and stirring at 10-20°C, add 8 g of acetyl chloride dropwise and stir for several minutes. Next, add pure water 1501 to separate the layers, and remove n-hexane from the organic layer. Remove. Distillation of this residue yields 23 g (120~b) of cis-1O-tetradecenyl acetate (yield: 91K).

〔Effect of the invention〕

As explained above, according to the production method of the present invention, 10-tetradecene derivatives, which are useful compounds in the field of insect pheromone synthesis, can be synthesized extremely efficiently. It has a better yield than the conventional synthesis applying the Wittig reaction, and is optimal as a method for producing conventional sodium acetylide and furkyl halide. Furthermore, Z-10-tetradecenyl acetate, which is used for biological control using insect pheromones, can be obtained in extremely high yield.

Claims (3)

[Claims] (1) 3-hebutenylmagnesium halide obtained by reacting 3-hebutenyl halide with metallic magnesium and the general formula A method for producing a 10-tetradecene derivative, which includes a coupling reaction with a substance (a bromine atom or a hydroxyl group protected with a protective group). (2) 3-hebutenylmagnesium halide obtained by reacting 3-hebutenyl halide with metallic magnesium and the general formula X_1(CH_2)_7_-_nR_x (wherein, , bromine atom or iodine, n = an integer of 2 to 5).
)_2CH=CH(CH_2)_9_-_nR_x (in the formula, R_x is a chlorine atom, a bromine atom or an iodine atom),
CH_3 (CH
_2)_2CH=CH(CH_2)_9_-_nMgR
_x and the general formula X_2(CH_2)_nR (wherein, X_2
is a bromine atom or an iodine atom, R is a chlorine atom or a bromine atom, or a hydroxyl group protected with a protective group, n = an integer of 2 to 5). (3) 3-hebutenylmagnesium halide obtained by reacting 3-hebutenyl halide with metallic magnesium and the general formula CH_3 (CH_
2)_2CH=CH(CH_2)_9_-_nR_O_
CH_3(CH_2)_2 obtained by halogenating M
CH=CH(CH_2)_9_-_nR_x (in the formula, R
_x is CH_3 (CH_2) obtained by reacting metallic magnesium with chlorine atom, bromine atom or iodine atom)
_2CH=CH(CH_2)_9_-_nM_gR_x
Coupling with a substance of the general formula A method for producing a 10-tetradecene derivative including a reaction.