JPS5916897A - Production of sodium aliphatic acetylide compound - Google Patents

Abstract

PURPOSE:After reaction between propargyl halide and a Grignard reagent, the product is made to react with metallic sodium finely dispersed in an organic solvent to achieve industrially advantageous production of the titled compound used as a synthetic intermediate of a sexual pheromone for inhibiting insect pests from infesting. CONSTITUTION:The cross-coupling reaction between propargyl halide such as chloride of the formula CHidenticalCCH2X (X is halogen) and a Grignard reagent of the formula: RMgX (R is aliphatic hydrocarbon) such as n-butylmagnesium chloride is effected in a solvent such as tetrahydrofuran to form a unsaturated hydrocarbon. Then, the product is made to react with metallic sodium finely dispersed in an inert organic solvent such as xylene to give the objective compound of RCH2CidenticalCNa.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a sodium aliphatic acetylide compound which is useful as an intermediate for synthesizing various insect pheromone substances.

A ``biological pest control method'' that uses insect pheromone substances to prevent the emergence of pests is currently attracting attention around the world, and development trials are being conducted. The chemical structure of the insect pheromone substance, especially the sex pheromone substance of the insect sex pheromone substance, has one or more double bonds, and an acetyloxy group or formyl group at the end, and a carbon number a to C18. Linear hydrocarbon compounds account for more than 80%.

Therefore, the sex pheromone substance having the above structure, for example, the sex pheromone substance of Grape berry moth is Z-9-dodecenyl acetate, and 5
It is more selective for each insect, as that of pruce bud worm is g-11-tetradecenal. For this reason, in most cases, the method for synthesizing these sex pheromone compounds is to use an acetylene compound having a triple bond as an intermediate.

For the above purpose, it is natural to use easily available propargyl halide as a crude raw material, but when synthesizing acetylene compound (1) by coupling reaction of propargyl halide and Grignard reagent, the π bond is Allene compound (II) produced as a result of positional isomerization is simultaneously produced as a by-product.

2HC2CCH2X +2 RMgy RCH2G30) (+ROE(=C=CH2+ 2Mg
XY (1) El) Since the production ratio of this acetylene compound (1) and allene compound [11] is 50:50, according to this synthesis method, the yield of the target acetylene compound can be expected to be 50% or more. For this reason, the use of propargyl halide was generally not practiced.

Nevertheless, the present inventors persisted in using propargylparite and as a result of thorough research, they developed an extremely advantageous synthetic reaction method using propargylparite as a starting material.

That is, the present invention provides (a) in a solvent, the general formula 0HEOOR
An unsaturated hydrocarbon compound is produced by cross-coupling a propargyl halide represented by 2X (X is a halogen atom) and a Grignard reagent represented by the general formula RMgX (R is an aliphatic hydrocarbon group, X is a halogen atom). and then (b) reacting this unsaturated hydrocarbon compound with metallic sodium finely dispersed in an inert organic solvent to obtain the general formula RCH2CmiC.
The present invention relates to a method for producing a sodium aliphatic acetylide compound, which is characterized by producing a sodium aliphatic acetylide represented by Na (R is as described above).

According to the method of the present invention, an acetylene compound and an allene compound produced by a cross-coupling reaction with a probargylparide Tocrinard reagent can be produced by reacting the resulting mixture with finely dispersed sodium metal, using the following reaction formula: Accordingly, it was confirmed that the arene compound, like the acetylene compound, becomes the desired sodium aliphatic acetylide compound (due to positional isomerism of the π bond).

ROH2C3OH1Na +ROH2CmiG Na +
x H2RO)I =C=CH2+N a →RCH2
CmiONa + 2 H2 In this way, the arene compound, which was considered to be a by-product, is fully utilized effectively, and as a result, the yield of the sodium aliphatic acetylide compound relative to propargylparite is greatly improved.

Propargylparite, which is a reaction raw material used in the method of the present invention, includes propargyl chloride, propargyl bromide, etc., and Grignard reagents of formula RMgX include ethylmagnesium bromide, n-propylmagnesium chloride, n-butylmagnesium chloride, n-pentylmagnesium chloride, impentylmagnesium chloride, hexylmagnesium chloride, heptylmagnesium chloride, 2-
Examples include hebutenylmagnesium chloride and 8-tridecenylmagnesium bromide.

As the solvent system for carrying out the cross-coupling reaction, it is desirable to use tetrahydrofuran or a mixture of tetrahydrofuran and an aromatic hydrocarbon, and benzene, toluene, xylene, etc. are used as the aromatic hydrocarbon.

A specific method for the reaction may be a method of dropping propargylparite into a Grignard reagent solution in the above-mentioned solvent, and in this case, the reaction molar ratio is 1 to 1 propargyl halide.
Desirably 05 to 2.0 moles of Grignard reagent per mole. In addition, the temperature of the reaction salt is between 0°C and 60”C.
It is recommended that the range be within the range of . Further, the above reaction may take a reaction form in which the Grignard reagent is added dropwise to a mixed solution of propargyl halide and tetrahydrofuran.

In the above cross-coupling reaction, it is desirable to use a copper-based catalyst, which includes cuprous chloride,
Copper halide compounds such as cuprous bromide are used. The amount used is 0001 to 0.1 per mole of Grignard reagent.
Preferably, the amount is in the molar range.

After the cross-coupling reaction is completed, the reaction product is poured into, for example, a 5% anthone chloride aqueous solution, and the organic layer is subjected to separate distillation to obtain an unsaturated hydrocarbon compound as a reaction product. Alternatively, the unsaturated hydrocarbon compound may be obtained by directly distilling the reaction mixture without passing through the hydrolysis step.

Next, the unsaturated hydrocarbon compound thus obtained is added dropwise or blown into an inert organic solvent in which metallic sodium is finely dispersed, and is reacted with the metallic sodium to form the desired sodium aliphatic compound. Acetylide compounds are produced in suspension. As the inert organic solvent, hydrocarbon solvents such as hechitin, benzene, toluene, and xylene, and ether solvents such as diethyl ether and tetrahydrofuran are used.

As a method of creating a finely dispersed state of metallic sodium, it is also possible to divide metallic sodium into particles of a predetermined size and add and disperse them in a solvent, but in general, it is possible to It is convenient to heat and melt metallic sodium in a solvent and then stir it to disperse it into powder. According to this method, 5μ
It can be dispersed into fine particles of about m size. The finer the particle size of the metallic sodium dispersed in the solvent, the higher the yield of the sodium acetylide compound relative to the metallic sodium, and the closer to the stoichiometric value the amount of raw material hydrocarbon used until the reaction is completed.

Next, while maintaining this dispersion system at 50 to 130°C,
A raw material hydrocarbon is added dropwise or blown into this to cause a reaction. *#Taka1-The rate of dropping or blowing this raw material hydrocarbon varies depending on the specific temperature of the reaction system, etc., but it is usually 3 to 20 per mole of sodium metal charged.
It may be mmol/min.

According to the method of the present invention, the desired sodium acetylide compound can be obtained in high yield using only two steps using the crude raw material propargylparite.

The sodium acetylide compound synthesized by the method of the present invention can be reacted with an alkyl halide in a liquid ammonia solvent and, through several steps, can be converted into various insect pheromones. For example, the forest moth Douql, a
Z-6-Hpneicosen-11-on, an insect pheromone of s-fir tussok moth
e can be easily derived by the following synthetic route.

2 (J (300) (201+2G) (30H20H2C
)(2MgO10H3(CH,), Ol-1=0=
CH2, HFCH3(C!H2)4cI(=al-T
cH2cH2 Next, a specific example will be given.

Example] Metallic magnesium 24 was placed in a reaction flask with an internal volume of 500.
J7- (1.0 mol), T) (F2O3- and 1 piece of iodine were charged, the internal temperature was raised to 40°C without replacing the system with nitrogen, and n-butyl chloride 92.5) (1,0
mol) was added dropwise. As the reaction progresses, the internal temperature rises, and when the internal temperature reaches 66°C, it is heated to 60-66°C by a water bath.
was maintained. After completion of the dropwise addition, the reaction system was aged at 66°C for 1 hour, then cooled to below 30°C, and 1 part of cuprous chloride was charged into the reaction system.
1.0 mol) was added dropwise while controlling the internal temperature to 1() to 20°C.

After completion of the dropwise addition, the mixture was aged at 30° C. for 1 hour, and then the reaction solution was poured into a 5% aqueous hydrochloric acid solution, and the separated organic layer was separated by distillation, yielding 768 fractions of 95 to b am+Hg. As a result of gas chromatography analysis, this was found to be 49% 1-heptine, 1.2
-Hebutagene was 51%.

Next, 11.5 n (o, 5 moles) of metallic sodium, 200 g of xylene, and 0.05 g of oleic acid were placed in a reaction flask with an internal volume of 500 mm, and the internal temperature was lowered to 110 g without purging the system with nitrogen. I
Jum'Y was dispersed to a particle size of 50 to 100 μm.

Add the previously obtained mixture of 1-heptine and 12-hebutadiene to this dispersion while adjusting the reaction temperature to 100-110°C. P (0.5 mol) was reacted dropwise to produce sodium heptinilide.

In order to check the yield of IJ umheptinilide, this reaction mixture was distilled under reduced pressure to remove low-boiling components (unreacted l-heptyne and 1,2-hebutadiene), and then the concentrated residue was By adding water and causing a hydrolysis reaction of butynylide to sodium, 1-heptine was obtained, which was then distilled to obtain 37.4y-heptine. From this, it was confirmed that the yield was 77.9% (based on sodium metal).

Example 2 Same as Example 1, but instead of n-butyl chloride, n-pentyl chloride xo65jiI-(1,.

The mixture was reacted with propargyl chloride in the same manner except that 1-octyne (mol) was used, and 90.2 g (20~b) of a mixture consisting of 48% of 1-octyne and 52% of 1,2-octadiene was obtained.

Next, 55 g of this mixture was reacted with metallic sodium in the same manner as in the previous example, and sodium octinylide was obtained as a reaction mixture.

In order to determine the yield of sodium octinylide, the reaction mixture was concentrated under reduced pressure, the concentrated residue was hydrolyzed and separated by distillation, and 43.2 g of 1-octyne was obtained. From this, it was confirmed that the yield was 78.5% (based on sodium metal).

Example 3 In Example 1, Z-butyl chloride was replaced with
8-tridecenyl bromide (26111.0 mol) was used in the same manner, but the reaction was carried out with propargyl chloride, and 49% of Z-11-hexadecen-1-yne and Z-1
, 2,8-hexadecatriene 51% mixture 1
67.2. p (110-120℃ 15 neck Hg fraction)
I got it.

Next, 110 g of this mixture was reacted with metallic sodium in the same manner as in Example 1.
3-11-hexadecen-1-ynilide was obtained as a reaction mixture.

This reaction mixture was charged into a 21 autoclave, the atmosphere was purged with nitrogen, the internal temperature was cooled to -40°C, and 500 ml of liquid ammonia and 38.9 ml of ethylene oxide (0.8
After charging 6 mol), the internal temperature was gradually raised while stirring, and the reaction was carried out at an internal temperature of -10°C and an internal pressure of 3 and 9/crI for 6 hours. After the completion of the reaction, ammonia was distilled off, and the reaction residue was diluted with 10% aqueous hydrochloric acid (after hydrolysis,
When the organic layer was distilled under reduced pressure, 865 g of Z-13-octadecen-3-yn-1-ol was obtained. Yield is 8
It was 6.5% (based on sodium metal).

This Z-13-octadecen-3-yn-1-ol is z,Z-
It is considered to be an important intermediate for 3,13-octadecagenyl acetate.

Patent applicant 1 Shin-Etsu Chemical Co., Ltd.

Claims (1)

[Claims] 1. (a) In a solvent, propargyl halide represented by the general formula CHEOOH,X (X is a halogen atom) and RMgX (R is an aliphatic hydrocarbon group, X is a halogen atom) Produce an unsaturated hydrocarbon compound by cross-coupling with the Grignard reagent shown, and then (b) react this unsaturated hydrocarbon compound with metallic sodium finely dispersed in an inert organic solvent. Method 2 for producing a sodium aliphatic acetylide compound, characterized by producing a sodium aliphatic acetylide represented by the general formula ROH20YocNa (R is as described above), as the solvent in step (a), tetrahydrofuran or tetrahydrofuran. A method 3 for producing a sodium aliphatic acetylide compound according to claim 1, characterized in that a mixture of 1 and an aromatic hydrocarbon is used. A method for producing a sodium aliphatic acetylide compound characterized by using a copper halide compound