JPH026421A - Production of trail-following bepheromone of termite and precursor intermediate thereof - Google Patents

Abstract

PURPOSE:To simply obtain the title compound in high yield by preparing a novel intermediate from a 3-butyne-1-halide and trans-2-hexanal as starting substances and reducing the triple bond of the intermediate in the presence of a catalyst. CONSTITUTION:Compounds shown by formula I-III (compound shown by formula III is trans-form) are used as starting substances. For example, the compound shown by formula I is reacted with PPh3 (Ph is phenyl), (a) successively reacted with a compound shown by formula II then with a compound shown by formula III or (b) condensed with the compound shown by formula III in the presence of a weak base and further condensed with the compound shown by formula II in the presence of a strong base to prepare a novel dodeca-6Z,8Z-diene-3-yne-1- ol shown by formula IV. Then the triple bond of the compound is half reduced in the presence of a first catalyst, preferably a reducing catalyst carrying Pd on CaCO3 or BaSO4 to advantageously give 3Z,6Z,8E-dodecatrienol shown by formula V having the same steric configuration as that of natural trail-following bepheromone of termite from readily obtainable raw materials.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing termite bepheromone and its precursor intermediate, and its purpose is to produce 32°6Z, 8E with the same steric configuration as natural termite bepheromone. - Only by the extremely convenient method of reducing dodecatrienol,
In other words, the goal is to create a precursor intermediate that can be synthesized in high yield, and the starting material for this intermediate is versatile and easily available.Therefore, the entire process is suitable for industrial production methods. The purpose of the present invention is to provide precursor intermediates thereof.

In addition, in this specification, termite signpost bepheromone means Yamato termite signpost bepheromone.

(Prior art) In general, Yamato termites, which belong to the family Termitidae of the order Isoptera, decompose the fibers of the wooden structural materials of wooden houses.
It is known as a type of termite that causes damage that reduces the structural strength of wood.

Organic chlorine pesticides have traditionally been used as termite exterminators, but their use was banned in 1988 due to their strong residual toxicity.

Currently, 3Z-, 6Z-, and 8E-dodecatrienol, which are signpost bepheromone produced by termites, are being researched as substances to be used for termite control in place of organochlorine pesticides.

Examples of techniques related to the synthesis of the pheromone include a)
3. Method using 4-epoxybutanol as raw material, b)
A method using butanal as a raw material is known.

[(a) J, In5ec, Physiol,
17.181-188 (1971L(b) J, Or
G, Chew, 34(7), 2180-218
2.1 However, these methods have drawbacks as shown below.

(Disadvantages of the prior art) That is, in both cases, dodecatrienol obtained by the method using 3,4-epoxybutanol as a raw material and the method using butanal as a raw material in b) is The double bonds of are each in the cis form (Z
) , )Although it is controlled by the lance form (E), the double bond at position 6 is obtained as a mixture of the cis form (Z) and the trans form (E), and in the end, it is a dodeca pheromone that has a different configuration from the natural pheromone. It contained trienol.

3Z, 6Z, 8E which are termite signpost bepheromone
Unless the double bond at position 6 of dodecatrienol is controlled by the cis form, it is not effective as a termite bepheromone (Tai et al., J.

In5ect, Physiol, 17.18H1
971), ), In the end, all of the above conventional methods always require separation of geometric isomers, and it is difficult to easily obtain the preferred termite bepheromone in high yield.

(Problems to be Solved by the Invention) Therefore, the inventors have found that 32.6Z, 8E-dodecatrienol, which has the same configuration as the natural termite signpost bepheromone, can be synthesized using only an extremely simple method of reducing, that is, in high yield. We are striving to create a precursor intermediate, and this precursor intermediate has a starting material that is versatile and easily available.
Therefore, we aimed to create a method for producing termite signpost pepheromone and its precursor intermediate, which is suitable for industrial production as a whole process.

(Means for Solving the Invention) That is, the inventors mainly used 3-butyne-1-halide (formula 1 below), ethylene oxide (formula 2 below), and trans-2-hexanal (formula 3 below) as starting materials to produce dodecarboxylic acid. -6Z,8E-dien-3-yn-1-ol (formula 1 below) was prepared, and this dodeca-6Z,8E-dien-3
A termite signpost characterized by half-reducing the triple bond of -yn-1-ol (formula 4 below) in the presence of a first catalyst to obtain 3Z, 6Z, 8E-dodecatrienol (formula 5 below) By providing a method for producing bepheromone and its precursor intermediate, it is possible to produce bepheromone using only an extremely simple method of reducing 3Z, 62°8E-dodecatrienol (Formula 5), which has the same configuration as the natural termite signpost bepheromone. In other words, we succeeded in creating a precursor intermediate that can be synthesized in high yield, and the starting material for this precursor intermediate is versatile and easily available.Therefore, the entire process is suitable for industrial production methods. We have succeeded in obtaining a manufacturing method and its precursor intermediate, and have completed this group of inventive methods.

(However, in the formula, X is any one of chlorine, bromine, or iodine atom) Explain in detail.

Inventive method as a preferred method for producing dodeca-6Z,8E-dien-3-yn-1-ol (formula 4 below), which is a precursor intermediate used in the main inventive method of the present invention and is an inventive substance. The two sides are listed below.

(However, in the formula, X is an atom of chlorine, bromine, or iodine.) 3-Butyne-1-halide (formula 1 below) and triphenylphosphine (formula 6 below) are mixed at 60°C or more without using a solvent. 15
3-butynyltriphenylphosphonium halide ( Equation 7) is obtained.

[First production method] 3-butynyltriphenylphosphonium (wherein, X is any of chlorine, bromine, or iodine atoms) Reason for setting the reaction temperature to 60 to 180°C in this invention This is because if the reaction temperature exceeds 180°C, the raw materials and reaction products will decompose, and if the reaction temperature is lower than 60°C, the reaction will not proceed, which is ultimately undesirable in either case.

In this invention, when a solvent is used, it may be used as long as it does not inhibit the progress of this reaction, and particularly preferably aprotic solvents (tetrahydrofuran, benzene, chlorobenzene, dimethylformamide, toluene, carbon tetrachloride, chloroform etc.) can be used.

Next, the obtained 3-butynyltriphenylphosphonium halide (Formula 7) is treated with n-butyllithium and alkali metal amide in a dry solvent under conditions of -40°C to room temperature, preferably 0°C to Q'C. Alternatively, at least two equivalents of at least one strong base among alkali metal hydrides are added to the phosphonium salt.

Ethylene oxide (formula 2 below) was added dropwise into this reaction system,
After the condensation reaction, trans-2-hexanal (formula 3 below) is added dropwise to carry out the condensation reaction.

The reaction solution is poured into water, extracted with pentane, washed with water, and the pentane is distilled off.

This residue was collected using adsorption chromatography (using silica gel as an adsorbent).
(using pentane and ether as developing solvents) to obtain dodeca-6Z, 8E-dien-3-yn-1-ol (Formula 4).

Toy Y (2) In this invention, the reason why the reaction temperature is set to 0°C to room temperature, preferably 130°C to 0°C is that below -40°C, the reaction progresses slowly, and above room temperature, the ylide decomposes. This is because

In this invention, the reason why at least 2 equivalents of at least one strong base selected from n-butyllithium, alkali metal amide, or alkali metal hydride is used with respect to the phosphonium salt is that these strong bases remove the hydrogen of the methine group of the phosphonium salt. This is because one equivalent is required to extract the phosphonium salt, and another equivalent is required to extract the hydrogen at the α-position of the phosphonium salt to form a phosphonium ylide.

The first method for producing dodeca-6Z, 8E-dien-3-yn-1-ol (Formula 4) is as described above, and next, the second method for producing it will be described below.

[Second production method] A weak base such as an alcoholate is added to 3-butynyltriphenylphosphonium halide (Formula 7) obtained by the same method as the first production method, and then trans-2-hexanal (
Formula 3) is sequentially reacted.

Deca-4Z, 6E-genyl-1 thus obtained
=yne (formula 8 below), at least one strong base selected from n-butyllithium, alkali metal amide or alkali metal hydride, and then ethylene oxide (formula 2)
) are reacted sequentially.

This reaction solution was purified by the same method as the first production method to obtain dodeca-6Z, 8E-dien-3-yn-1-
All (formula 4) is obtained.

Preferably the temperature is -30°C to 0°C.

The reason for this is that, as in the first production method, the reaction progresses slowly at temperatures below -40°C, and decomposition of the ylide occurs at temperatures higher than room temperature.

In the process of this invention, as described above, 3-butynyltriphenylphosphonium halide (Formula 7) is reacted with a weak base such as an alcoholate, but the reason for using a weak base instead of a strong base is that the phosphonium salt At least one of n-butyllithium, an alkali metal amide, or an alkali metal hydride to be subsequently reacted in order to selectively extract hydrogen at the α-position of the phosphonium salt and form a phosphonium halide without extracting hydrogen from the methine group of the phosphonium salt. This is because a weaker base is initially required than a strong base.

Therefore, as long as it is a weak base that satisfies these conditions, it is not particularly limited to alcoholates.

Next, the method of the present invention uses dodeca-6Z,8E-dien-3-yn-1-ol (
Using formula 4), this starting material is dissolved in a solvent and subjected to catalytic half-reduction in the presence of the first catalyst at a reaction temperature below ice temperature and with stirring in a hydrogen atmosphere.

The reaction solution is filtered, the filtrate is concentrated, and then ether is added.

Next, the mixture is washed with hydrochloric acid, a saturated aqueous sodium bicarbonate solution, water, and brine (1), and the ether layer is distilled off to obtain a residue.

This residue was purified by adsorption chromatography (using silica gel as an adsorbent and hexane and ether as developing solvents).
Z, 6Z, 8E-dodecatrienol (formula 5 below) is obtained.

In this main method of the invention, the solvents preferably used include hydrocarbon solvents such as pentane and hexane;
Examples include alcohol solvents such as methanol and ethanol.

The first catalyst used in the present invention is at least one type of reduction catalyst in which palladium is supported on calcium carbonate or barium sulfate as a carrier,
Depending on the case, a catalyst obtained by mixing this catalyst with quinoline can be preferably used, and in short, any catalyst having relatively weak activity as a reduction catalyst can be suitably used without particular limitation.

The reason for this is that by using a reduction catalyst in which palladium is supported on calcium carbonate or barium sulfate as a carrier, reduction can be carried out with high reaction efficiency in industrial production.

Furthermore, the reason why a mixture of quinolines is employed in this invention is to weaken the function of the quinoline as a catalyst poison, that is, to weaken the activity of the reduction catalyst, and to eliminate the possibility of the quinoline becoming a saturated compound in which the triple bond is completely reduced.

In this invention, the reason why the reaction temperature during catalytic half-reduction is set to below freezing temperature is because if the temperature exceeds freezing temperature, there is a high possibility that a trans isomer will be produced when the triple bond is reduced, which is undesirable. It is.

Finally, a preferred method for producing 3-butyne-1-halide (Formula 1) used in the present invention will be described.

To 3-butyn-1-ol (formula 9 below), in the presence of at least the same amount of pyridine and at a reaction temperature below ice temperature, p-)luenesulfonyl chloride (tosyl chloride) is added dropwise to cause a substitution reaction.

After concentrating the reaction solution, it is washed with ether and water.

After washing this ether layer successively with a saturated aqueous copper sulfate solution and a saturated saline solution, the ether is distilled off to obtain 0-tosyl-3-butyn-1-ol (formula 10 below).

The reason for keeping the reaction temperature below ice temperature in this step is
At temperatures higher than ice temperature, after tosylation, the reaction product is chlorinated by the chlorine anions contained in the reaction system, and the desired 0-tosyl-3-butyn-1-ol (formula 10
) is difficult to obtain.

The reason why at least the same amount of pyridine as 3-butyn-1-ol (Formula 9) is required in this step is to neutralize hydrogen chloride generated as the reaction progresses and promote the progress of the reaction.

Therefore, as long as it is a base, it is not limited to pyridine as described above.

Next, the obtained O-tosyl-3-butyn-1-ol (
Sodium hydrogen carbonate and lithium halide (formula 11 below) are added to 210), and a substitution reaction is carried out at a reaction temperature of 40°C to 50°C.

This reaction solution is poured into water, and after extraction with ether, the ether layer is washed with saturated saline.

After concentrating this, it is purified by adsorption chromatography (using silica gel as an adsorbent and hexane and ether as developing solvents) to obtain 3-butyne-1-halide (21).

LiX
(11) (However, in the formula, X is any one of chlorine, bromine, and iodine atoms.) The reason why lithium halide (Formula 11) is added in this step is to convert tosyl ester into halide.

Although lithium halide was described as a suitable substituent in the above examples, the substituent is not necessarily limited to lithium halide, and any compound from which a halide anion can be obtained can be suitably used in the method of this invention. .

The reason why the reaction temperature is 40°C to 50°C is as follows.
If the temperature is lower than 40°C, the reaction progresses extremely slowly, and 5
This is because intermediates and reaction products decompose when the temperature is higher than 0°C.

The main inventive method of the present invention, the precursor intermediate according to the present invention, and all steps of the manufacturing method thereof are illustrated below.

(Space below) (First production method) ↓ (Main invention method) (Second production method) (Invention substance) (However, in the formula, X is any of chlorine, bromine, or iodine atoms) Main invention in this invention method In the method, Dodeka-6Z
, 8E-dien-3-yn-1-ol (formula 4), termite signpost bepheromone 3Z, 6Z, 8
E-dodecatrienol (Formula 5) is obtained with a yield of about 95%.

(Effects of the Invention) As detailed above, the method for producing termite signpost bepheromone according to the present invention includes 3-butyne-1-halide (formula 1
), dodeca-6Z,8 starting from ethylene oxide (formula 2) and trans-2-hexanal (formula 3)
Prepare E-dien-3-yn-1-ol (formula 4),
The triple bond of dodeca-6Z, 8E-dien-3-yn-1-ol (Formula 4) is semi-reduced in the presence of the first catalyst to form 3Z, 6Z, 8E-dodecatrienol (Formula 5).
) The main feature of this method for producing termite bepheromone is to obtain termite bepheromone using only an extremely simple method of reducing 3Z, 6Z, and 8B-dodecatrienol, which has the same configuration as natural termite bepheromone. In other words, we have created a precursor intermediate that can be synthesized in high yield, and the starting material for this intermediate is versatile and easily available.Therefore, the entire process is suitable for industrial production methods. It has the effect of being a precursor intermediate.

By showing Examples, Comparative Examples, and Reference Examples below, the effects of this invention will be made clearer.

[Example and Comparative Example of Synthesizing 3-butynyltriphenylphosphonium halide from 3-butyn-1-halide (Example 1) 104 g (780 mmol) of 3-butyn-1-bromide
and triphenylphosphine 215g (820mmo
1) were mixed and heated at 100°C for about 3 hours.

The ether was distilled off to obtain 277 g of 3-butyltriphenylphosphonium bromide. The yield was 90%.

(Comparative Examples 1 and 2) The reaction temperature was set at 200°C (Comparative Example 1) and 40°C (Comparative Example 2).
) The yield of 3-butyltriphenylphosphonium bromide obtained by the same treatment as in Example 1 is shown in Table 1 below.

Table 1 (Examples 2 and 3) Example 1 and all (3- The yield of butyltriphenylphosphonium bromide is also shown in Table 2 below.

(The following is a blank space) Table 2 (However, 1N was added to the solvent.) Examples and comparative examples of the manufacturing method (Example 4) 3-butynyltriphenylphosphonium halide 270
g (680 mmol) in dry tetrahydrofuran (T
) IF) 31 and dry hexamethylphosphoric triamide (HMP8) 31, and n-butyllithium (1,6N 940ml 11.5mol) (2.2 equivalents relative to the phosphonium salt) was added dropwise at -40°C. The mixture was reacted at -30°C for 1 hour.

To this reaction system, 50 g of ethylene oxide (1,1 mo
200 ml of the T liver solution of 1) was added dropwise at -30°C, and after reacting for 2 hours, 67 g of trans-2-hexanal was added.
(680 mmol) was added to the mixture.

After the temperature was slowly raised from -30°C to room temperature and the disappearance of trans-2-hexanal was confirmed by thin layer chromatography, the reaction solution was poured into water and extracted with pentane.

This pentane layer was washed with water, dried, concentrated, and purified by adsorption chromatography (using silica gel as an adsorbent and pentane and ether as developing solvents) to obtain a reaction product.

The results of elemental analysis of this reaction product by mass spectrometry are shown in Table 3 below.

From the results shown in Table 3, it was found that dodeca-6Z, 8E dien-3-yn-1-ol was obtained as the reaction product.

The weight of the reaction product was 85 g, and the yield was 71%.

Incidentally, an infrared absorption spectrum diagram is shown in FIG.

(Examples 5-8 and Comparative Examples 3-4) The samples were treated and identified in exactly the same manner as in Example 4, except that the temperature during the reaction after addition of trans-2-hexanal was changed as shown in Table 4 below. Dodeka-62゜8E-diene-
The yield of 3-yn-1-ol is also shown in Table 4.

(C+zH+aOF, W, = 178.26) The absorption wave number (cm-') of the infrared absorption spectrum of this reactant is 3
320 (S), 3000 (W), 1460 (m)
, 1040(S).

The measurement was performed by preparing a sample using the film method.

(Examples 9 and 10 and Comparative Example 5) Dodeca-6Z, 8B- obtained by processing in exactly the same manner as in Example 4 except that n-butyllithium added as a strong base was changed as shown in Table 5 below. The yield of diene-3-yne thermo-ol is also shown in Table 5.

Table 5 (however, each base is 1, 5 as in Example 4)
Added mo 1. ) (Comparative Example 6) Dodeca-6Z obtained by processing and identifying in exactly the same manner as in Example 4, except that the amount of n-butyllithium added as a strong base was changed to 1 equivalent relative to the phosphonium salt. BB
The yield of -dien-3-yn-1-ol was 0%.

[Example and comparative example of the second production method for synthesizing dodeca-6Z, 8E-dien-3-yn-1-ol from 3-butynyltriphenylphosphonium halide] (Example 11) 3-butynyltriphenylphosphonium halide Nyltriphenylphosphonium halide 270
g (680+nmol) was dissolved in dry THF3A and dry HMA2.71, and after cooling at -40°C, t-
Butyloxypotassium 76 g (680 mmol) aqueous solution (300 ml) was slowly added dropwise.

= TII in which 67 g (680 mmol) of trans-2-hexanal was dissolved after stirring at 30 °C for about 1 hour.
Mixed solution of P and HFIPA (volume mixing ratio 1:1) 3
00ml was added all at once.

Slowly raise the temperature from -30°C to room temperature,
After confirming that trans-2-hexanal had disappeared by thin layer chromatography, the reaction solution was poured into water and extracted with pentane.

This pentane layer was washed with water, dried, concentrated, and purified by adsorption chromatography (using silica gel as an adsorbent and pentane and ether as developing solvents).
E-genyl-1-yne was obtained. The yield was 71%.

60 g of the obtained deca-42,6E-genyl-1-yne
(450 mmo+) was dissolved in dry TI (F6) and cooled to -30<0>C.

This melt? At night n-゛Tythyllithium, 6N 280m
After slowly dropping 1450mm of water, it was heated to -30℃ for about 1
After stirring for an hour, 29.7 g of ethylene oxide (675
300 ml of a dry THF solution in which mmol) was dissolved was slowly added dropwise.

After the addition was completed, the reaction temperature was slowly raised from -30°C to room temperature, and the mixture was stirred overnight.

After the reaction was completed, the reaction solution was poured into water and extracted with pentane.

This pentane layer was washed with water, dried, concentrated, purified by adsorption chromatography (using silica gel as an adsorbent, and pentane and ether as developing solvents), and identified in the same manner as in the first production method. It was found that 6Z, 8E-dien-3-yn-1-ol was obtained.

The yield was 80%.

(Examples 12 and 13 and Comparative Example 7) Deca-42 obtained by the same treatment and identification as in Example 11 except that t-butyloxypotassium added as a weak base was changed as shown in Table 6 below. , 6E-genyl-1-yne are also shown in Table 6.

Table 6 (however, each base is 68 as in Example 11)
0 mmol was added. ) [Examples and comparative examples of synthesizing 3Z, 6Z, 8E-dodecatrienol from dodeca-6Z, 8E-dien-3-yn-1-ol according to the main invention method]
(Example 14) Dodeca-6Z,8B-dien-3-yn-1-ol 6
Catalyst 3 in which 4 g (360 mmol) was dissolved in methanol 11 and palladium was supported using barium sulfate as a carrier.
2 g of quinoline and 3.2 g of quinoline were added thereto, and the mixture was vigorously stirred in a hydrogen atmosphere below ice temperature.

After about 5 hours, completion of the reaction was confirmed by gas chromatography, and the reaction solution was filtered through Celite, and the filtrate was concentrated.

Add ether 1β to this, add ice-cooled 0.5N hydrochloric acid,
It was washed successively with a saturated aqueous sodium bicarbonate solution, water and brine, and dried over sodium sulfate.

The ether was distilled off, and the residue was purified by adsorption chromatography (using silica gel as an adsorbent and hexane and ether as developing solvents) to obtain a reaction product.

The results of elemental analysis of this reaction product by mass spectrometry are shown in Table 7 below.

Table 7 (C1□H2°OF, W, = 180.29) The absorption wavenumber of the infrared absorption spectrum of this reaction product is (cm-')
are 3340 (br, s), 3020 (s), 2
955(s), 2920(s), 2860(s)
, 1645 (enemy) , 1455 (m), 1435 (m)
, 1400 (m) , 1380 (m) , 1335 (
tsuba), 1260 (fuu, 1045(s), 980(s)
), 945(s).

The measurement was performed by preparing a sample using the film method.

Furthermore, the resonance frequency (H
z) is 0.903 (3H, t, J=7.3)1z)
, 1.410 (2H, tq, J=7.3, 7.3 Hz
), 2.078(2)1. ddt, J=6.7,1.
4,6.7Hz), 2.364 (2H, ddtt, J
=6.4, 1.5, 6.4, 0.7 Hz), 2.96
0(2H, dddd, J=7.3.7.3.1.5.1
．． 5 Hz), 3.654 (2H, t, J=6.6H
z), 5.243(1)1. dt, J = 10.6 Hz
), 5°406 (IH, dtt, J = 11.0, 7.3
, 1.5 Hz) , 5.552 (18, dttJ=1
0.6, 7.3, 1.5 Hz), 5.685(I)I
, dt, J=15.0.7.7Hz) , 5.965(
IH, dd, J=10.6, 10.6 Hz), 6.
308 (LH.

ddddt, J=11.0, 15.0, 1.5, 1.5
Hz).

For measurement, the sample was dissolved in chloroform-d and the frequency was set to 4.
The measurement was performed using a proton nuclear magnetic resonance spectrum at 00 MHz.

From the above results, the reaction products are 3Z, 6Z, 8E
It was found that dodecatrienol was obtained.

The weight of the reaction product was 62 g, and the yield was 96%.

Note that FIG. 2 shows an infrared absorption spectrum diagram, and FIG. 3 shows a proton nuclear magnetic resonance spectrum diagram.

(Example 15) 3Z and 6Z were obtained by processing and identifying in exactly the same manner as in Example 14, except that the reduction catalyst was changed to a catalyst in which palladium was supported using calcium carbonate as a carrier.

The yield of 8E-dodecatrienol was 90%.

(Example 16) 3Z, 6 obtained by treatment and identification in exactly the same manner as in Example 14 except that quinoline as a catalyst poison was not added.
The yield of Z, 8E-dodecatrienol was 80%.

(Comparative Example 8) The yield of 3Z, 6Z, and 8E-dodecatrienol obtained by processing and identifying in exactly the same manner as in Example 14 except that the reaction temperature was set to room temperature was 62%.

(Examples 17 and 18 and Comparative Example 9) The solvent was
Table 8 also shows the yields of 3Z, 6Z, and 8E-dodecatrienols obtained by processing and identifying in exactly the same manner as in Example 14, except for the changes shown in the table.

Table 8 [Reference example when synthesizing 3-butyn-1-halide from 3-butyn-1-ol] (Reference example 1) 70 g (1 mol) of 3-butyn-1-ol and 70 g (1 mol) of pyridine A dry TIIF solution of 210 g (1.1 mol) of p-)luenesulfonyl chloride was dissolved in 700 ml of dry THF and stirred at below ice temperature.
0ml was gradually added dropwise.

After the dropwise addition was completed, the reaction solution was raised to room temperature, and it was confirmed by thin layer chromatography that 3-butyn-1-ol had disappeared.

After concentrating the reaction solution, add 700 ml of ether and 700 ml of water.
The ether layer was further washed successively with saturated aqueous copper sulfate solution and saturated brine.

This ether layer was dried over anhydrous sodium sulfate and the ether was distilled off, resulting in 220 g of 0-tosyl-3-
Butyn-1-ol was obtained.

220 g of O-tosyl-3-butyn-1-ol obtained
(980 mmol) was dissolved in 2.51 g of dry acetone, and 168 g (2 mo 1 ) of sodium hydrogen carbonate and 131 g (1.5 mol) of lithium bromide were added.
The reaction was carried out at 50°C for 7 hours.

After the reaction was completed, the reaction system was poured into water, extracted with ether, washed with saturated brine, and dried over anhydrous sodium sulfate.

This was filtered, concentrated, and purified by adsorption chromatography (using silica gel as an adsorbent and hexane and ether as developing solvents) to obtain 104 g of 3-butyne-1-bromide.

The yield was 78%.

(Reference Examples 2 and 3) Table 9 shows the yield of 3-butyne-1-bromide obtained by the same procedure as in Reference Example 1 except that pyridine was changed to the base listed in Table 9 below. I will also write down.

Table 9 (Reference Example 4) The yield of 3-butyne-1-bromide obtained by the same treatment as in Reference Example 1 except that the reaction temperature was 5°C was 72.
%Met.

(Reference Examples 5 and 6) Table 10 shows the yields of 3-butyne-1-bromide obtained by treating in exactly the same manner as in Reference Example 1 except that lithium bromide was changed as shown in Table 10 below. It is written as follows.

As is clear from the results in Table 10 and above, the method for producing termite signpost bepheromone and its precursor intermediate according to the method of this invention are as follows:
The main invention method is the creation of a precursor intermediate that can be synthesized in high yield by reducing 3Z, 6Z, and 8E-dodecatrienol, which has the same configuration as the natural termite bepheromone. It can be seen that this intermediate is a method for producing termite signpost bepheromone and its precursor intermediate, whose starting materials are versatile and easily available, and therefore the entire process is suitable for industrial production methods.

[Brief explanation of the drawing]

Figure 1 shows dodeca-6Z,8E-diene-3-yne-1-
Figures 2 and 3 show the infrared absorption spectrum and proton nuclear magnetic resonance spectrum of 3Z, 6Z, and 8E-dodecatrienol, respectively. Agent Patent Attorney Yoshihiro Kiyohara

Claims (8)

[Claims] (1) Using 3-butyne-1-halide (formula 1 below), ethylene oxide (formula 2) and trans-2-hexanal (formula 3) as starting materials, dodeca-6Z,8E-dien-3-yn 1-ol (formula 4 below) is prepared, the triple bond of this dodeca-6Z,8E-dien-3-yn-1-ol (formula 4) is semi-reduced in the presence of the first catalyst, and 3Z
, 6Z, 8E-dodecatrienol (formula 5 below) is obtained. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1) (However, in the formula, X is an atom of chlorine, bromine, or iodine) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) ▲Mathematical formulas, chemical formulas, tables, etc. There are ▼ (3) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (5) (2) The dodeca-6Z,8E-dien-3-yne-1
-ol (Formula 4) is replaced by 3-butyne-1-halide (Formula 1
) is reacted with triphenylphosphine (formula 6 below), and then ethylene oxide (formula 2) is first reacted with ethylene oxide (formula 2) in the presence of a strong base.
The method for producing termite marker bepheromone according to claim 1, characterized in that it is obtained by sequentially reacting with and then trans-2-hexanal (Formula 3). PPh_3 (6) (3) The dodeca-6Z,8E-dien-3-yne-1
-ol (Formula 4) is replaced by 3-butyne-1-halide (Formula 1
) with triphenylphosphine (formula 6),
The termite guidepost according to claim 1, characterized in that first, trans-2-hexanal (Formula 3) is condensed in the presence of a weak base, and then ethylene oxide (Formula 2) is condensed in the presence of a strong base. Method for producing pheromones. (4) The method for producing termite signpost bepheromone according to any one of claims 1 to 3, characterized in that the first catalyst uses at least one type of reduction catalyst in which palladium is supported on calcium carbonate or barium sulfate as a carrier. . (5) The method for producing termite marker bepheromone according to any one of claims 1 to 4, characterized in that quinoline is added to the first catalyst. (6) The method for producing termite marker bepheromone according to any of claims 2 to 3, wherein the strong base is at least one of n-butyllithium, an alkali metal amide, or an alkali metal hydride. (7) The method for producing termite marker bepheromone according to claim 3, wherein the weak base is an alcoholate. (8) 3Z,6Z,8E-dodecatrienol (Formula 5)
dodeca-6Z,8E-diene-3- which is a precursor intermediate of
In-1-ol (formula 4 below). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(4)