JPS63275537A - Production of alkynyl alcohol - Google Patents

Abstract

PURPOSE:To obtain the titled compound in one pot reaction at a low cost without requiring detaching treatment of a protecting group, by using acetylene, omega-haloalkyl alcohol, alkali metal amide and alkylhalide readily available as raw materials. CONSTITUTION:Acetylene is reacted with an excess amount (preferably 2-2.5 equivalent excess amount) of a alkali metal amide in a solvent at low temperature to provide alkali metal acetylide, which is then is reacted with a halogenated alcohol expressed by formula I (X is halogen; n is 4-12) to afford an acetylenealkoxide expressed by formula II (M is alkali metal) and an alkali metal amide is successively added to a reaction mixture containing the resultant halogenated alcohol and the resultant product is reacted with an alkylhalide expressed by formula III (R is 1-8C alkyl; X' is halogen) at a low temperature to provide the compound expressed by formula IV.

Description

[Detailed Description of the Invention] The present invention relates to the general formula % (formula %) which is an important intermediate for producing the sex pheromone substance of the Rinshimoku insect (wherein R is 1 carbon number) ~8 alkyl group, n is 4
Indicates an integer between ~12. ) It relates to a method for easily producing an alkynyl alcohol represented by:

Due to the toxicity and persistence of the insecticide, a method of controlling pests that uses sex pheromone substances is attracting attention instead of a method of controlling pests that uses agricultural chemicals such as insecticides. Communication disruption methods and mass trapping methods have been widely studied for agricultural crops and garden plants.

, For example, the chemistry of the sex pheromone substance of the lint moth +
The 14 structures differ depending on each pest, but in common, they are all compounds that have an acetyloxy group, formyl group, or hydroxyl group at the end of a long-chain hydrocarbon group,
Moreover, almost all of them have one or two double bonds in the molecule.

Conventionally, a typical method for producing a sex pheromone substance having such a chemical structure is to obtain a precursor alkynyl alcohol, half-reduce it, and modify the alcohol moiety, as shown below. It is being

RX + Cl44CH+χ-(Cut)n-OR'
-RC== C-(C1lz) n-OR' →RCH
= CH-(Cllz) n-OR' (However, R is an alkyl group, and Ro represents a 1g retention group.) However, when using this method, it is necessary to protect the hydroxyl group with a protecting group in a series of steps, and therefore , for dejuvenation of the protecting group,
This not only increases the number of steps but also increases manufacturing costs.

As a result of intensive research in order to solve the above-mentioned problems in the production of alkynyl alcohol, the present inventors discovered that by reacting an excessive amount of alkali metal amide with acetylene in a solvent, A reaction mixture containing an alkali metal amide and an acetylide is prepared, a halogenated alcohol in approximately the same amount as the acetylide is added thereto, an alkali metal amide is added again to the reaction mixture containing the acetylene alkoxide produced, and then a halogenated alkyl amide is prepared. The present invention was achieved based on the discovery that the desired alkynyl alcohol can be easily obtained without using a protecting group in a so-called pot reaction.

In the present invention, acetylene is reacted with an excess amount of alkali metal amide in a solvent, and the resulting alkali metal acetylide is added to the general formula % (%) (where X represents a halogen atom). , n represents an integer of 4 to 12) to form an acetylene alkoxide represented by the general formula % formula %) (where M represents an alkali metal), and then, Without isolating this, an alkali metal amide was added to the reaction mixture containing this to give the corresponding acetylide, and then the general formula (wherein R represents an alkyl group having 1 to 8 carbon atoms, X' represents a halogen atom.) A general formula characterized by reacting a halogenated alkyl represented by %) (wherein, R represents an alkyl group having 1 to 8 carbon atoms, and n is 4
Indicates an integer between ~12. ) to obtain an alkynyl alcohol represented by

The method according to the invention is represented by the following scheme.

Excess 51(7)MNHHz + HC=CHHC=C
MHC=CM+X-(CHg)n-OH-He
-=C-(CI2)n-0M Each of the above steps will be explained in detail below.

First, in the reaction for preparing an alkali metal acetylide, sodium, lithium or potassium amide is usually preferably used as the alkali metal amide. The alkali metal amide may be prepared in advance or may be prepared in liquid ammonia immediately before the reaction.

The reaction between the alkali metal amide and acetylene to obtain the alkali metal acetylide is carried out in a solvent at low temperature. In the present invention, the alkali metal amide is used in an excess of 2 equivalents or more, preferably in an excess of 2 to 2.5 equivalents, relative to acetylene. As the solvent, liquid ammonia, diethyl ether, tetrahydrofuran, dioxane, dimethylformamide, dimethyl sulfoxide, etc. can be used, and liquid ammonia is particularly preferably used. The reaction temperature is usually 50
℃ or less, preferably -30℃ or less.

Next, ω-haloalkyl alcohol is added to the reaction mixture containing the alkali metal acetylide and the alkali metal amide, and a coupling reaction is performed to produce acetylene represented by the general formula % (where M represents an alkali metal). Generates alkoxides.

As the ω-haloalkyl alcohol, for example, chloride, bromide or iodide can be used, and iodide or bromide is particularly preferred. These ω-haloalkyl alcohols can be prepared by mixing, as is already known, for example, in the case of ω-bromoalkyl alcohols, α,ω-alkanediol with hydrobromic acid in a suitable solvent such as heptane or toluene. After stirring under reflux, the organic layer is separated and distilled under reduced pressure.

The above ω-haloalkyl alcohol is usually used in an amount of 0.2 to 0.8 equivalents, preferably 0.3 to 0.7 equivalents, based on the amount of alkali metal amide charged in the preparation of the metal acetylide. It will be done. This coupling reaction is usually carried out at 0°C or lower, preferably at -30°C or lower.

The alkali metal amide is then re-added to the reaction mixture thus obtained. The amount added here is preferably 0.3 to 0.7 equivalents of the initial amount of alkali metal amide charged. The reaction temperature is 0°C or lower, preferably -3
The temperature is below 0°C. According to the method of the present invention, the hydroxyl group of the ω-haloalkyl alcohol is protected with an alkali metal, so protection with a protecting group is not required.

In the method of the present invention, the acetylene alkoxide thus obtained is directly added to the reaction mixture containing the acetylene alkoxide without isolating the acetylene alkoxide having the general formula (wherein R has 1 carbon number
~8 alkyl group, X'' represents a halogen atom,
) is added and a coupling reaction is carried out to obtain the target alkynyl alcohol represented by the general formula % (wherein R is the same as above).

In this coupling reaction, chloride, bromide, iodide, etc. are suitable as the alkyl halide, and bromide such as ethyl bromide is particularly preferably used from the viewpoint of reactivity and cost. In this reaction, the amount of alkyl halide used is usually 0.5 to 2 equivalents, preferably 0.8 to 1 equivalent, based on the amount of acetylene initially charged.
It is 2 equivalents.

This reaction is carried out at a low temperature in its initial stage, and the reaction temperature is usually below 0°C.

However, as the reaction progresses, the reaction temperature may be increased to room temperature.

After the reaction is completed, the target alkynyl alcohol can be isolated by distilling off the solvent from the reaction mixture and then distilling the reaction residue.

The alkynyl alcohol obtained in the above manner can be semi-reduced using a Lindlar catalyst or a nickel catalyst to obtain cis-alkenyl alcohol (a) as shown below. Transalkenyl alcohol (b) can be obtained by half-reduction with an alkali metal or the like.

The alkenyl alcohol obtained in this way is an insect pheromone substance in itself, and can be further converted into various sex pheromones by, for example, being acetylated or aldehyded, as shown below. .

(d) The above compounds (a), (C) and (d) are insect sex pheromone substances shown in the table below.

(Note) *: The number of carbon atoms in the alkyl group R is 4 to 4. As mentioned above, according to the method of the present invention, acetylene, ω-haloalkyl alcohol, alkali metal amide, and alkyl halide, which are easily available as raw materials, can be used. By using , an alkynyl alcohol can be obtained at low cost by a -pot reaction without desorption of a protecting group.

castration± The present invention will be explained below with reference to Examples.

Example 1 A suspension of sodium amide prepared by adding 2.32 g of metallic sodium to liquid ammonia was cooled to -70°C, acetylene gas (50 ms+ol) was gradually blown into the suspension, and the suspension was vigorously stirred. Then, 10-promo-1-decanol (11.9 g) was added dropwise to this reaction mixture, and the mixture was reacted at a temperature of -40 to -33°C for 6 hours.

Next, sodium amide (2,
After adding 0g) and stirring vigorously at the same temperature as above, ethyl bromide (5.4g) was added dropwise to give a temperature of -40 to -33
The reaction was allowed to proceed for 3 hours while stirring vigorously at a temperature of .degree. Thereafter, the temperature was gradually returned to room temperature over one night to evaporate the ammonia. Water was added to the resulting residue, extracted with ether, and the extract was concentrated and distilled under reduced pressure to obtain 11-tetradecynyl alcohol (8.4 g, yield s 0%).

Example 2 A suspension of sodium amide prepared by adding 1.16 g of sodium metal to liquid ammonia was cooled to -70°C,
After gradually blowing acetylene gas (25+u+ol) into this, the mixture was vigorously stirred. Then, 8-promo l-octatool (5.0 g) was added dropwise to the reaction mixture.
The reaction was carried out at a temperature of -40 to -33°C for 7 hours.

Next, sodium amide (1,
After adding 0g) and stirring vigorously at the same temperature as above, butyl bromide (5.0g) was added dropwise to give a temperature of -40 to -33
The reaction was allowed to proceed for 3 hours while stirring vigorously at a temperature of .degree. Thereafter, the temperature was gradually returned to room temperature over one night to evaporate the ammonia. Water was added to the resulting residue, extracted with ether, and the extract was concentrated and distilled under reduced pressure to obtain 9-tetradecynyl alcohol (4.2 g, yield 80%).

Claims (2)

[Claims] (1) Acetylene is reacted with an excess amount of alkali metal amide in a solvent, and the resulting alkali metal acetylide has the general formula (indicates an integer from 12 to 12) is reacted to form an acetylene alkoxide represented by the general formula HC≡C(CH_2)_n-OM (where M represents an alkali metal), and then , without isolating it, add an alkali metal amide to the reaction mixture containing it to give the corresponding acetylide, and then form the corresponding acetylide with the general formula R-X' (wherein R is an alkyl group having 1 to 8 carbon atoms). and X' represents a halogen atom. group, n is 4
Indicates an integer between ~12. ) A method for producing an alkynyl alcohol represented by (2) The method for producing an alkynyl alcohol according to claim 1, characterized in that in the reaction to obtain the alkali metal acetylide, the alkali metal amide is used in an amount of 2 or more equivalents based on acetylene.