JPH03170450A - Production of alkynylketone derivative - Google Patents

Abstract

PURPOSE:To safety obtain the subject compound useful as an intermediate for perfumes, etc., in high purity and yield all at once using an inexpensive catalyst by reacting 1-alkyenes corresponding to the objective compound with an acid halide in the presence of a copper halide catalyst. CONSTITUTION:1-Alkynes expressed by formula 2 (R<1> is alkyl, alkenyl, alkynyl, aryl or heterocyclic group) are made to react with an acid halide expressed by formula 3 (R<2> is respective groups in R<1>; X is halogen) in the presence of a copper halide catalyst, e.g. copper chloride, copper iodine or copper bromide in an organic solvent, as necessary, using a base to industrially and advantageously afford the objective compound, expressed by formula 1 and capable of providing a raw material for producing furanones useful also as an intermediate for medicines or agricultural chemicals in a simple process and operation with high safety without using an expensive palladium-based catalyst or virulently poisonous and dangerous carbon monoxide.

Description

[Detailed Description of the Invention] (Industrial Application Field) The present invention relates to a novel method for producing alkynyl ketone derivatives,
More specifically, ■ - an alkynyl ketone derivative represented by the following formula (1) n in which an alkyne and an acid halide are reacted in the presence of a copper halide catalyst, where Rl and R2 have the same meanings as above; Regarding new manufacturing methods.

(Prior Art) Alkynyl ketones are an important group of compounds that serve as raw materials for producing furanones, which are important intermediates for fragrances, pharmaceuticals, agricultural chemicals, and the like.

Conventionally, as a means of synthesizing this type of compound, for example, a method of synthesizing an alkynyl ketone by reacting a copper salt of an alkyne with an acylnolide has often been used [
Org. React. ．． 22.380 (1975)].

However, industrial preparation of copper acetylides is fraught with trouble and is not practical.

As an improvement to the conventional method, l-alkynes can be easily converted into alkynyl compounds in a one-step reaction by reacting l-alkynes with acyl halides in triethylamine in the presence of a copper(I) iodide/tri7enylphosphine-palladium dichloride catalyst. Ketone (R2-alkyl, styryl, allyl, 2
- frills) [Synt
hesis, 777 (1977)].

(Left below) However, the metal catalytic reactions proposed so far as described above have a serious drawback in that they use expensive palladium catalysts, resulting in high costs for industrial production.

Furthermore, in the process diagram below, the formula (A) organic halide, the formula (B) terminal acetylene compound, and carbon monoxide,
A method has been proposed in which alkynyl ketones of formula (C) are synthesized by reaction in the presence of a palladium compound (Japanese Patent Publication No. 16376/1983).

Cat. R'X + HCmiCR"+CO----→(A)
(B) R'-C-CmiC-R"1 (C) O In the above formula, R1 and R2 represent an organic group, and X represents a halogen atom.

This proposed method is based on the combination of an organic group Rl- from a halogen compound R'-X, an acetylene group R2-CmiC- from which the terminal hydrogen has been removed from a terminal acetylene compound Hz-CmiCH, and carbon monoxide. are directly bonded at the same time to obtain the compound of formula (C) above.

However, even this proposal could not be called an industrial method because it used an expensive palladium compound and highly toxic carbon monoxide, and hydrogen chloride was produced in the reaction.

(Problems to be Solved by the Invention) As described above, the conventionally proposed manufacturing methods have had various problems. An object of the present invention is to provide a novel and efficient method for producing alkynyl ketones that eliminates many of these drawbacks.

(Means for Solving the Problems) The present inventors have conducted intensive studies on a method for combining the conventionally proposed reactions described above, which does not require the use of expensive palladium catalysts, is simple in process and operation, and is free from danger. did.

As a result, the l-alkynes of the above formula (2), which are easily available or easily synthesized on the market, and the acid halides of the above formula (3) are reacted in an organic solvent in the presence of an inexpensive copper halide catalyst. By doing so, surprisingly, the above formula (1
The present invention was achieved by discovering that the alkynyl ketone derivatives of ) can be synthesized all at once with high yield and high purity.

That is, according to the present invention, the following formula (2) HCmiC-R
' (2) In the formula, Rl represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, or a heterocyclic group. group, an aryl group, or a heterocyclic group, and X represents a halogen atom. 1) ○ 2111 R - C - C - C - R (1) However, in the formula, R1 and R2 have the same meanings as above, and the alkynyl ketone derivative represented by A very advantageous manufacturing method can be provided.

The reaction of the present invention can be expressed as shown below in a process diagram.

(2) (3)
(1) The method for producing the alkynyl ketone derivative of the above formula (1) of the present invention will be explained in detail below according to the above process diagram.

Examples of the organic group Rl in the 1=alkynes of formula (2) HCmiC-R' used in the present invention include C.I. -C2. Alkyl group, phenyl, naphthyl,
Aryl groups such as dimethylphenyl and ethyl 7enyl, C1 to C, such as vinyl, propenyl, allyl, butadienyl, pentadienyl, etc. alkenyl group, benzyl, a-
Aralkyl groups such as 722-ethyl, cyclohexyl,
Cycloalkyl groups such as cyclooctyl, C1-C2 such as ethynyl, phenylethynyl, etc. This includes organic groups such as alkynyl groups and heterocyclic groups such as chenyl, furyl, and pyridyl, and these organic groups may have substituents that are inert to the reaction. Examples of the substituent include dialkylamino group, carbamoyl group, acyl group, alkoxyl group, alkoxyl group, halogen atom, sulfonyl group, sulfinyl group,
Sul7enyl group, cyano group, acyloxy group, silyl group,
Examples include a nitro group, formyl group, hydroxyl group, alkylthio group, alkoxyalkyl group, and organosilyl group.

Specific examples of alkynes commonly used in the present invention include:
Examples include propylene, phenylacetylene, 1-pentyne, 3-methyl-l-butyn-3ol, l-butyn-3-ol, 3-(1'ethoxyethoxy)-3-methyl-1-butyne, and the like.

Furthermore, examples of the organic group R2 in the acid halide of formula (3) used in the present invention include, for example, the same groups as R1 described above. As the halogen atom X,
Mention may be made of chlorine, bromine and iodine. Specific examples of such acid halides include benzoyl chloride, acetyl chloride, butyric acid chloride, invaleric acid chloride, cinnamic acid chloride, L-butyroyl chloride, crotyl chloride, p-methoxybenzoyl chloride, p-amylbenzoyl Examples include acid chlorides such as chloride and p-dimethylaminobenzoyl chloride, and bromides and iodides of these organic acids.

Specific examples of the copper halide catalyst CuX used in the present invention include copper chloride, copper iodide, copper bromide, and the like.

Furthermore, the organic solvents used in the present invention include, for example, lower alkylamines such as trimethylamine, triethylamine, and n-tributylamine, pyridine, acetonitrile, hexane, tetrahydrofuran, hexamethylphosphotriamide, dimethylformamide, acetone, benzol, Toluene etc. are preferably used, alcohols,
Any commonly used solvent can be used as long as it is not a solvent that serves as an active proton source such as carboxylic acids.

Preferred embodiments of the present invention include acid halides,
The reaction is carried out by adding a terminal alkyne compound and a catalyst to the organic solvent and reacting with stirring.

The molar ratio of the acid halide to the terminal alkynes is usually selected from the range of 50:1 to 1:50, even if either is in excess, the reaction does not occur. Further, the amount of the base used as necessary may be at least equimolar to the acid halide, and is generally used in a range of about 1 to 50 moles per mole of the acid halide. Of course, it is possible to use a larger amount of base than this, but this does not bring about particularly beneficial results in terms of the reaction.

The amount of copper halide catalyst to be used is not particularly limited and can be selected arbitrarily, but generally, the amount of copper halide catalyst used is 1
1/10 mole or less, especially 1/10,000 mole
-1/100 mole range is preferred.

The reaction of the present invention may proceed at room temperature depending on the structure of the acid halide, but in order to obtain a preferable reaction rate, the reaction may be carried out at 200°C.
It can be heated up to

In order to separate and purify the target alkynyl ketones from the reaction solution obtained by the reaction of the present invention, first, the solvent is recovered from the reaction solution under reduced pressure, or extracted with an appropriate extraction solvent, and then washed. This can be carried out by drying and purifying using any conventional method such as distillation or column chromatography.

Hereinafter, embodiments of the present invention will be explained in more detail with reference to Examples.

Example l 4-Hydroxy-4-methyl-1-7enyl-2-butyn-1-one was added to a reaction flask containing 3-methyl-1-butyn-3-ol8
- 49 (0.10 mol), benzoyl chloride 14.
1 g (0.10 mol), copper(I) iodide 0.19 and triethylamine 100 ml2,
Heat and stir at O for 2.5 hours. After the reaction was completed, the mixture was cooled and triethylamine was recovered. The residue was diluted with 100 ml of toluene, washed with dilute aqueous hydrochloric acid, saturated brine, and aqueous sodium bicarbonate, further washed with saturated brine, and then dried over magnesium sulfate. . Collecting the solvent gave 19.19 of the crude title compound. This crude product was distilled under reduced pressure to give a boiling point of 139-141'o/3mmH.
15.59 g of the target product was obtained (yield 82.4%).

Examples 2 to 12 In the same manner as in Example 1, various ketones were combined using predetermined acid halides and terminal acetylene compounds under the conditions shown in the following table. The results are summarized in Table 1 and Table 2. Note that the yield was measured by gas chromatography. Moreover, the results of Example 1 are also shown in this table.

In addition, No. in the table. represents the example number (the same applies below).

Table 1 (Starting materials) Table 2 (Raw materials) (Effects of the invention) According to the present invention, the following formula (2) HCmiC-R' (2) In the formula, Rl has the same meaning as above, l-alkynes represented by the following formula (3), where R2
is the same as described above, and by reacting the acid halide represented by in the presence of an inexpensive copper halide catalyst, an alkynyl ketone derivative can be synthesized at once with high purity and high yield. .

Furthermore, it is possible to provide an innovative synthesis method that is simple in process and operation, and is non-hazardous, without using the expensive palladium-based catalyst or highly poisonous and dangerous carbon monoxide that has been proposed in the past. .

The alkynyl ketones obtained by the present invention are useful as fragrant substances.
hydroxy-3(2H) monofuranone] and bratenone [
It is extremely important as a synthetic compound of furanones including 2,2-dimethyl-5-7enyl-2(IO-3-furanone), and the present invention has great industrial significance.

Claims (1)

[Claims] The following formula (2) HC≡C-R^1 (2) where R^1 represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, or a heterocyclic group. 1-alkynes and the following formula (3) ▲ Numerical formula, chemical formula, table, etc. ▼ (3) However, in the formula, R^2 represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group. , and X represents a halogen atom, and is characterized by reacting an acid halide represented by in the presence of a copper halide catalyst ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) However, A method for producing an alkynyl ketone derivative represented by the formula, where R^1 and R^2 have the same meanings as above.