JPH0118059B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a system represented by the general formula RCH=CHCH ₂ CH ₂ (CH ₂ ) _o Br (R in the formula represents an alkyl group having 1 to 8 carbon atoms, and n is an integer of 3 to 10). -Regarding an improved method for producing alkenyl bromides. This cis-alkenyl bromide is considered to be very useful as an intermediate for synthesizing sex pheromone substances for various pests, which have recently been applied as sex pheromone concentrates for the control of pests. In other words, when this intermediate is treated as it is with anhydrous sodium acetate or potassium acetate, it easily becomes a sexual pheromone substance (including pseudopheromone substances) of Lepidoptera insect pests such as moths and moths.
Cis-alkenyl acetate represented by the general formula RCH=CHCH ₂ CH ₂ (CH ₂ ) _o OCOCH ₃ , which is well-known as or cis-alkenal. Furthermore, by reacting this intermediate as a raw material, it is also possible to synthesize other sex pheromone substances with an increased number of carbon atoms. Conventionally, as a method for synthesizing the above-mentioned sex pheromone substances, Tetrahedron Vol. 33, page 1845 (1977) discloses a method using the following reaction steps. RC≡CM+X(CH ₂ ) _n Y→ RC≡C(CH ₂ ) _n Y+MX RC≡C(CH ₂ ) _n Y+H ₂ →RCH=CH(CH ₂ ) _n Y RCH=CH(CH ₂ ) _n Y →RCH =CH( _CH2 ) _n AR: Alkyl group having 1 to 8 carbon atoms M: Li or Na X: Br or I Y: Cl or pyranyl ether group A: _-OCOCH3 , -OH, -CHO m:5 An integer of ~12 However, the above method (1) requires the use of raw materials and solvents such as butyllithium, sodium amide, liquid ammonia, hexamethylphosphoric triamide, etc. to make RC≡CM, and also requires low-temperature reaction ( -40°C to -20°C), which requires a pressure-resistant device.
(2) X(CH ₂ ) _n Y is produced by a complicated method, which is economically and industrially disadvantageous;
It has the disadvantage that Br(CH ₂ ) _n Br cannot be used instead. As a result of intensive research to solve these problems, the present inventors discovered a useful synthesis method for cis-alkenyl bromide, which is extremely useful as an intermediate for the synthesis of sex pheromone substances, and completed the present invention. It was time to do it. That is, the present invention is based on the general formula RCH=CHCH ₂ CH ₂ Cl () (R in the formula is an alkyl group having 1 to 8 carbon atoms)
Grignard reagent of cis-3-alkenyl chloride represented by and α, ω represented by the general formula Br(CH ₂ ) _o Br ……() (in the formula, n is an integer from 3 to 10)
- General formula characterized by reacting with dibromoalkane in the presence of lithium copper dichloride and/or dilithium copper tetrachloride RCH=CHCH ₂ CH ₂ (CH ₂ ) _o Br ... () (R and n are as described above). The above method of the present invention has the following advantages. (1) α,ω-Dibromoalkane is easily available and is an economically inexpensive raw material. (2) The Grignard reaction described above does not require the use of industrially disadvantageous raw materials such as butyl lithium and sodium amide, or difficult-to-handle solvents such as liquid ammonia, and it There is no need to conduct a low-temperature reaction. In the present invention, the reaction can be carried out easily and in high yield using common raw materials such as magnesium and tetrahydrofuran, and at a normal reaction temperature of 0 to 66° C. and using equipment. (3) As mentioned above, the obtained cis-alkenyl bromide is extremely important as an advantageous intermediate from which various sex pheromone substances can be easily derived. The method of the present invention will be explained in detail below. The method of the present invention uses readily available () as the main raw material.
It is characterized in that it uses cis-3-alkenyl chloride of the formula. Examples of the alkyl group having 1 to 8 carbon atoms represented by R in formula () include methyl group, ethyl group, n-propyl group, n-butyl group, n-hexyl group, and n-octyl group. Sis-3 like this
- For the alkenyl chloride, prepare a tetrahydrofuran solution of methylmagnesium chloride in a conventional manner, add an alkyl acetylene dropwise to the solution while stirring, react the obtained alkyl acetylene magnesium chloride with ethylene oxide, and then perform a hydrolysis reaction. Accordingly, 3-
Generate alkyn-1-ol. By hydrogenating this product using a Lindlar catalyst and then chlorinating it with a chlorinating agent such as thionyl chloride, cis-3-alkenyl chloride can be obtained in high yield. What can be considered here is that α,ω
-This method involves reacting dibromoalkane (cross-coupling reaction), but this reaction hardly progresses. Furthermore, the Grignard reagent represented by RC≡CCH ₂ CH ₂ MgCl cannot be produced using RC≡CCH ₂ CH ₂ Cl as a raw material. Furthermore, when RCH=CHCH ₂ Cl, which has one fewer carbon number, is used as a raw material, a homocoupling reaction occurs in addition to the cross-coupling reaction, resulting in poor yield. The other reaction raw material, α,ω-dibromoalkane of formula (), includes 1,3-dibromopropane, 1,4-dibromobutane, 1,5-dibromopentane, 1,6-dibromohexane, 1,8-
Examples include dibromooctane and 1,10-dibromodecane. These are the corresponding α, ω―
They can be easily obtained in high yield by reacting alkanediols with hydrobromic acid, and many of them are commercially available at low cost as general-purpose industrial raw materials. As a Grignard reagent for cis-3-alkenyl chloride, cis-3-alkenyl chloride is reacted with metallic magnesium at 40 to 66°C in an ordinary method in anhydrous tetrahydrofuran.
A solution of 3-alkenylmagnesium chloride prepared in tetrahydrofuran is used. Cis-alkenyl bromide is produced by reacting the Grignard reagent of cis-3-alkenyl chloride prepared as described above with α,ω-dibromoalkane.In this reaction, α, It is best to prepare a solution in which ω-dibromoalkane is dissolved in tetrahydrofuran in advance, and the Grignard reagent is added dropwise to this solution while controlling the reaction temperature to 0 to 40°C to form cis-3-alkenyl chloride. The Grignard reagent and α,ω-dibromoalkane undergo a cross-coupling reaction to obtain the cis-alkenyl bromide of the formula () in high yield. In the above reaction, the reaction molar ratio is preferably 1 to 2 moles of α,ω-dibromoalkane per 1 mole of Grignard reagent of cis-3-alkenyl chloride, and in order to promote the cross-coupling reaction, LiCuCl ₂ (lithium copper dichloride) or Li ₂ CuCl ₄ (dilithium copper tetrachloride) is used as a catalyst. The above-mentioned lithium copper dichloride can be obtained by adding and mixing lithium chloride and cuprous chloride in tetrahydrofuran at a ratio of 1:1 (molar ratio). By adding and mixing these catalysts in tetrahydrofuran at a ratio of 2:1 (molar ratio), they can be easily obtained as tetrahydrofuran solutions.
- It can be added in advance to a solution of dibromoalkane in tetrahydrofuran. In both cases of lithium copper dichloride and dilithium copper tetrachloride, the amount used is preferably 0.001 mol to 0.1 mol per mol of Grignard reagent of cis-3-alkenyl chloride.
It is desirable that the amount is 0.003 mol to 0.02 mol. Tetrahydrofuran as a solvent used in this reaction is required in an amount equivalent to or more than the equivalent mole of magnesium metal when preparing the Grignard reagent for cis-3-alkenyl chloride, and is necessary for preparing the Grignard reagent for cis-3-alkenyl chloride. However, this yield is 2.0% per mole of cis-3-alkenyl chloride initially used in the entire reaction system.
It is desirable that the amount is at least 3 moles, preferably 3 to 20 moles. The reaction solution obtained by the cross-coupling reaction as described above is filtered or washed with water to remove by-product salts, and the solvent tetrahydrofuran is distilled off and then distilled to produce cis-alkenyl bromide. obtained in high yield. This cis-alkenyl bromide can be heated with anhydrous sodium acetate or anhydrous potassium acetate to obtain the corresponding cis-alkenyl acetate, which can be further hydrolyzed to give a cis-alkenyl alcohol, and then oxidized to give the corresponding cis-alkenyl acetate. It can be easily led to cis-alkenal. These are useful as sex pheromone substances. Next, specific examples will be given. Example 1 24.3 g of metallic magnesium in a reactor with a capacity of 1,
Charge 360 g of anhydrous tetrahydrofuran and 1 piece of iodine, drop 2 g of ethyl bromide while stirring, and add 118.5 g of cis-3-hexene-1-chloride while keeping the internal temperature at 50°C.
(1 mol) was added dropwise and reacted over 2 hours. After the dropwise addition was completed, the mixture was stirred at this temperature for an additional hour to complete the reaction, and then cooled to 20°C. Transfer this material to the dropping funnel and add the 1,6-
A solution of 293 g (1.2 mol) of dibromohexane and LiCuCl ₂ in tetrahydrofuran (1424 mg of LiCl)
(1990 mg of CuCl dissolved in 200 g of THF) was charged, and the Grignard reagent was reacted with stirring while cooling on ice and maintaining the internal temperature at 15 to 20°C. The dropping process took about 2 hours. After the dropwise addition was completed, the reaction was further maintained at 40°C for 1 hour to complete the reaction. After cooling to room temperature, the reaction solution was filtered to remove the resulting salt and catalyst. Next, after distilling off the solvent tetrahydrofuran, distillation was carried out under reduced pressure, resulting in 195 g of a colorless and transparent fraction with a boiling point of 118-120°C under 4 mmHg.
was gotten. When this substance was identified by gas chromatography mass spectrum, the parent peak
246 and 248 (intensity ratio 1:1), and it was confirmed that it was cis-9-docene-1-bromide (yield 79%). Cis-9-dodecene-1 obtained in this way
- Charge 195 g of bromide with 120 g of glacial acetic acid and 100 g of anhydrous sodium acetate into a reactor with a capacity of 1,
The reaction was carried out at reflux temperature (164° C.) for 5 hours while stirring. After the reaction was completed, the mixture was cooled to 50°C, 300ml of water was added, and the organic layer was separated and distilled under reduced pressure.
169g (95%) of cis-9-dodecenyl acetate
yield) was obtained. This is the sex pheromone of Grape berry moth. Examples 2 to 7 Cis-3-alkenyl chloride 1 shown in Table-1
_{Li 2 CuCl 4} (LiCl 430 mg and
When the reaction was carried out in the same manner as in the previous example except that 676 mg of CuCl ₂ dissolved in 200 g of THF was used, various cis-alkenyl bromides and cis-alkenyl acetates as shown in Table 1 were obtained. The physical properties of the obtained cis-alkenyl bromide are shown in Table 2.

【table】

【table】

[Table] *: Based on gas chromatography mass spectrum

Claims (1)

[Claims] 1 A Grignard reagent of cis-3-alkenyl chloride represented by the general formula RCH=CHCH ₂ CH ₂ Cl (R in the formula is an alkyl group having 1 to 8 carbon atoms) and a Grignard reagent of the general formula Br ( CH ₂ ) _o Br (n in the formula is an integer from 3 to 10) α, ω
-dibromoalkane in the presence of lithium copper dichloride and/or dilithium copper tetrachloride, using the general formula RCH=CHCH ₂ CH ₂ (CH ₂ ) _o Br (R in the formula and n is as defined above).