WO2004113257A1

WO2004113257A1 - Process for the production of ethynylbenzene derivatives

Info

Publication number: WO2004113257A1
Application number: PCT/JP2004/008343
Authority: WO
Inventors: Kazuto Umezu; Hideo Ooi
Original assignee: Ihara Chemical Industry Co., Ltd.
Priority date: 2003-06-17
Filing date: 2004-06-15
Publication date: 2004-12-29
Also published as: JPWO2004113257A1

Abstract

The invention provides a process by which ethynylbenzene derivatives can be simply produced from 3-chloro-3-substituted propenal derivatives under safe and environment-friendly conditions with low effluent loading and which is suitable for the production on an industrial scale, that is, a process for the production of ethynylbenzene derivatives represented by the general formula (2): [wherein R1, R2 and R3 are each independently hydrogen, halogeno, or the like; l is an integer of 1 to 6; and m, n, o, p, and q are each independently an integer of 0 to 5 with the proviso that the sum of o and p is 5 or below and the sum of l, m, n and q is 6 or below], characterized by reacting a 3-halogeno-3-substituted propenal derivative represented by the general formula (1): [wherein X and Y are each independently halogeno; and R1, R2, R3, Z, l, m, n, o, p and q are each as defined above] with a base in the presence of a phase transfer catalyst.

Description

Specification

Method for producing ethurbenzene derivative

Technical field

The present invention relates to a novel method for producing an ethynylbenzene derivative useful in the field of pharmaceutical 'agrochemical' materials.

Background art

[0002] Conventionally, as one of the methods for producing an ethurbenzene derivative, a elimination reaction from a corresponding 3-chloro-3-substituted propenal derivative using an aqueous alkali metal hydroxide solution is known. However, all of these methods use a dioxane solvent (see Patent Document 1), a tetrahydrofuran (THF) solvent (see Non-Patent Document 1), and a solvent that can be freely mixed with water (optionally in water). In order to use a solvent which dissolves in the ratio of 1), it was necessary to use an extraction solvent separately for the post-treatment and to take out the target substance. It is difficult to sufficiently recover dioxane and THF dissolved in water.Since a large amount of dioxane and THF remains in the wastewater, it is industrial scale from the viewpoint of environmental protection and safety. Implementation was difficult.

Patent Document 1: US Pat. No. 4,125,563

Non-Patent Document 1: "Synthesis", (Germany), Georg Thieme Verlag Stuttgart-New York, 1992, pp. 735-737

[0003] These solvents are ether solvents, and there is a problem in that there is a danger of explosion due to the formation of a peroxidized product in the recovery and reuse of Z.

[0004] Therefore, in the production of an ethurbenzene derivative from a 3-chloro-3-substituted propenal derivative, there has been no simple, safe, and environmentally friendly production method with a simple process.

Disclosure of the invention

Problems the invention is trying to solve

[0005] The present invention provides a safe, low-wastewater environment suitable for industrial-scale production. It is an object of the present invention to provide a method for producing an ethynylbenzene derivative from a 3-chloro-3-substituted propenal derivative by a simple process under conditions. Means for solving the problem

[0006] In view of the above situation, the present inventor has conducted intensive studies on a method for producing an ethurbenzene derivative from a 3-chloro-3-substituted propenal derivative under safe and environmentally friendly conditions. In addition, it was found that by reacting a 3-chloro-3-substituted propenal derivative with a base in the presence of a phase transfer catalyst, an ethynylbenzene derivative can be produced in good yield. The invention has been completed.

The invention's effect

[0007] The method of the present invention provides a novel industrial method for producing an ethynylbenzene derivative. According to the method of the present invention, ethynylbenzene derivatives can be produced in a safe process under environmentally friendly conditions with a low wastewater load, so that the method of the present invention has very high industrial utility value.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail.

[0009] The present invention has solved the above-mentioned problems by providing the inventions described in the following [1] to [12].

[0010] [1] In the presence of a phase transfer catalyst, the general formula (1)

[0011] [Formula 3]

(Wherein, X and Y each independently represent a halogen atom,

R ² and IT each independently represent a hydrogen atom; a halogen atom; a nitro group; a hydroxyl group; an alkyl group; an alkenyl group; an alkyl group; a dialkylamino group; an aralkyl group; an alkoxy group; R ¹ and R ² may be joined together to form a ring Z is an oxygen atom; a sulfur atom; a sulfonyl group; an alkyl or aryl group may be substituted !, a methylene group; a carboxyl group Or 1 represents a single bond, 1 represents an integer of 1 to 6, m, n, o, p, and q each independently represent an integer of 0 to 5, o + p is 5 or less, and 1 + m + n + q is 6 or less. )

A general formula (2) characterized by reacting a 3-halogeno 3-substituted propenal derivative represented by the formula: with a base

[0013] [Formula 4]

[0014] (where,

R ² , R ³ , Z, 1, m, n, o, p, and q have the same meaning as described above. )

A method for producing an ethynylbenzene derivative represented by the formula:

[2] The method for producing an ethynylbenzene derivative according to [1], wherein the reaction is carried out in an aqueous solvent system.

[3] The method for producing an ethynylbenzene derivative according to [1], wherein the reaction is carried out in a solvent system that does not dissolve in water at an arbitrary ratio.

[4] The method for producing an ethynylbenzene derivative according to [1], wherein the reaction is carried out in a solvent that does not dissolve in water at an arbitrary ratio and a heterogeneous solvent system that is hydraulic.

[5] The method for producing an ethynylbenzene derivative according to [1], wherein the reaction is performed in a solvent-free system.

[6] The solvent is not soluble in water at an arbitrary ratio, and the solvent is an aromatic hydrocarbon; [3] or [4]

] A method for producing the ethynylbenzene derivative described above.

[7] The method for producing an ethynylbenzene derivative according to [1], wherein the phase transfer catalyst is a quaternary ammonium salt.

[8] The method for producing an ethurbenzene derivative according to [7], wherein the phase transfer catalyst is tetrabutylammonium bromide.

[9] The basicity of the ethynylbenzene derivative according to [1], which is an alkali metal hydroxide Production method.

[10] The method for producing an ethurbenzene derivative according to [9], which is basic sodium hydroxide.

[11] The method for producing an ethynylbenzene derivative according to [1], wherein X and Y of the 3-no, logeno-3-substituted propenal derivative represented by the general formula (1) are both chlorine atoms.

[12] The method for producing an ethynylbenzene derivative according to [1], wherein RR ² and R ³ of the 3-noperogeno-3-substituted propenal derivative represented by the general formula (1) are all alkyl groups.

Hereinafter, the present invention will be described in detail.

First, the 3-halogeno 3-substituted penal derivative represented by the general formula (1) used as a raw material of the method of the present invention will be described.

[0028] X and Y in the general formula (1) each independently represent a halogen atom, and examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

In the general formula (1), R ² and R ³ each independently represent a hydrogen atom; a nodogen atom; a nitro group; a hydroxy group; an alkyl group; an alkyl group; an alkyl group; An aralkyl group; an alkoxy group; or an alkoxyalkyl group;

R ² may be taken together to form a ring.

[0030] Examples of the halogen atom for R ² and R ³ include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

The alkyl group for R ³ is a straight-chain or straight-chain having 1 to 6 carbon atoms (hereinafter, the number of carbon atoms of the substituent is abbreviated as “C1 to C6” in this case). As long as it is a branched-chain alkyl group, specific examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, and n- A hexyl group and the like can be shown in column f.

[0032] R \ R ^2, the R ³ Aruke - The group, linear or branched C2- C6 alkenyl - More Yogu specifically if Le group Eteyuru group, 1 Purobe - group, Examples thereof include a 2-probel group, a 1-butyl group, a 2-butyl group, a 1,3-butagel group, and a 1,3,5-hexatriene group.

[0033] The alkyl group for R ² and R ³ is a linear or branched C2-C6 alkyl group. I just need.

[0034] Examples of the dialkylamino group R \ R ^2, R ^3, di [(C1 one C6) alkyl] amino group, specifically Jimechiruamino group, Jechiruamino group, be exemplified dipropylamino group Wear.

Examples of the aralkyl group of R \ R ² and R ³ include, for example, benzyl group, 2-chlorophenylmethyl group, 4-chlorophenylmethyl group, 4-methylphenylmethyl group, 4-methoxyphenylmethyl group, Examples thereof include an arylalkyl group which may have a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, or the like as a substituent, such as a diphenylmethyl group.

[0036] Examples of the alkoxy group for R ² and R ³ include a [(C1-C6) alkyl] oxy group, specifically, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, and a hexyloxy group. And the like.

As the alkoxyalkyl group for R ² and R ³ , a linear or branched [(C1-C6) alkyl] oxy (C1-C6) alkyl group, specifically, a methoxymethyl group, ethoxymethyl Groups, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, hexyloxymethyl group and the like.

In the general formula (1), Z is an oxygen atom; a sulfur atom; a sulfol group; a C1-C6 alkyl group or V 基 may be substituted with an aryl group; a methylene group; a carboxyl group Or a single bond, wherein the aryl group which may be substituted with a methylene group includes one or more of a C1-C6 alkyl group, a C1-C6 alkoxy group, or a halogen atom; And a phenyl group.

[0039] In the general formula (1), 1 represents an integer of 16; m, n, o, p, and q each independently represent an integer of 0 to 5, and o + p is 5 or less. , 1 + m + n + q is 6 or less.

[0040] Specific examples of the 3-halogeno 3-substituted propenal derivatives represented by the general formula (1) as described above include, for example, 3-chloro-3-phenylpropenal, 3-chloro-3- ( 2—Black Mouth Fen-Nore), 3—Black Mouth—3— (3—Mouth Fue-Nore) Propena, 3—Black Mouth—3— (4—Mouth Mouth) Nore, 3 black mouth—3— (2-Nitrofuenore) propena nore, 3—black mouth—3— (3-—trohue-nore) propena nore, 3—black mouth—3— (4—- Trohue-Nore ) Propenal, 3—clo mouth—3— (2-hydroxyphenyl) propenal, 3—clo mouth—3— (

3-Hydroxyphenyl) propenal, 3-clonal mouth—3— (2-Methylphenyl) propenal, 3-clonal mouth—3— (3-methylphenyl) propenal, 3-clonal mouth—3— (4-Methylphenyl) propenal, 3-chloro-opening 3- 3- (3-Dimethylaminophenol) propenal, 3-chloro-opening 3--3- (4-dimethylaminoamino) propenal, 3-chloro Mouth—3— (2-Benzylphenyl) propenal, 3-Cro mouth—3— (3-Benzylphenol) propenal, 3—Cro mouth—3— (

4-Benzylphenyl) propenal, 3-chloro mouth— [3- (3-diphenylmethyl) phenyl] —2-propenal, 3-chloromouth— [3- (4-diphenylmethyl) phenyl] — 2 propenal, 3 clo mouth—3- (2-methoxyphenyl) propenal, 3—clo mouth—3— (3-methoxyphenyl) propenal, 3—clo mouth—3— (4-methoxyphenyl) Propenal, 3-chloro-mouth 3 — (2-methoxymethylphenyl) propenal, 3-chloro-mouth 3- (3-methoxymethylphenyl) propenal, 3-chloro-3- (4-methoxymethylphenyl) Le) propenal, 3-black mouth-3-[3-(1 black mouth-3 oxoprober) phenol] propenal, 3-black mouth-3-[4-(1 black mouth-3-year old xopro (Bale) fel] propenal, 3 black mouth [3,5 bis (1-black mouth 1-3-oxoprodini) Nore) Hue-Nore] 1-3-Black-mouth propena, 3- 3-Mouth-prop 3-[4,-(1 Black-mouth-3 oxoprober) bihue-ru 3 yl] -3 Black-mouth propenal, 3—Black mouth—3— [4, — (1 Black mouth—3 oxoprozinyl) bihu-ru 4-yl] propenal ゝ 3—Black mouth—3— {3— [4— (1—Black mouth—3 —Oxopropyl) benzyl] phenyl} probenal, 3-chloro-3- (4— [4- (1-chloroproxyl-3-benzyl) phenyl) phenyl} propenal, 3 —Black mouth— 3— {3— [4— (1-Black mouth—3-oxoproberyl) benzoyl] phenyl} propenal, 3 Black mouth— 3— {4— [4— (1 Black mouth— 3-oxoprober) benzoyl] propenal, 3-black mouth—3— {3- (4- (1-black mouth—3-oxopropenyl) phenoxy] phenyl} propenal 3— B mouth 3— {4— [4— (1-black mouth 3-oxoprophenyl) phenoxy] phenyl} propenal, 3-black mouth—3— {3-—4— (1— Black mouth—3-oxoprole) phenylsulfur]} Feel} propenal, 3-black mouth—3— {4- (4- (1-chloro-3-oxoprobe) phenylsulfur) ] Fer} propenal, 3-chloro-port—3— {3- (4- (1-chloro-3—oxopropenyl) benzenesulfonyl) phenyl} propenal, 3-chloro-port—3— {4— [4— (1 black mouth—3-oxoprobe) Nsensulfol] phenyl} propenal, 3-chloro-3— (2, benzyloxy-4, -methoxyphenyl) propenal, 3-chloro-3naphthalene 2-ylooppanal, 3-chloro-3—phenanthrene-9 3-loop penal, 3-bromo-penal, 3-bromo-penal, 3-bromo-3- (2-methylphenyl) propenal, 3-bromo-3- (3-methylphenyl) propenal, 3-bromo-3 — (4 Methylphenyl) propenal etc. can be listed.

[0041] The method for obtaining the 3-halogeno-3-substituted propenal derivative represented by the general formula (1) is not particularly limited, and examples thereof include, for example, Journal of Chemical Society, Perkin Transaction and Chem. Soc. Perkin Trans .; It can be easily prepared by the Vilsmeier Haack reaction from the corresponding acetofphenone derivative described in Vol. I, pp. 355-358 (1994). The double bond part of propenal may be E-form, Z-form, or a mixture of E-form and Z-form.

[0042] As the phase transfer catalyst used in the method of the present invention, any of cationic, neutral, and anionic phase transfer catalysts can be used. For example, tetramethylammonium bromide, tetrabutylammonium bromide, trioctylmethylammonium bromide, trioctylpropylammonium bromide, cetyltrimethylammonium bromide, etc. Quaternary phosphonium salts such as tetramethyl phospho-bromo bromide, tetrabutyl phospho-bromo bromide, cetyl tributyl phospho-bromo bromide, tetraphenyl phospho-bromo bromide, etc. Salts; Cationic phase transfer catalysts including pyridium salts such as butylpyridinium bromide, heptylpyridinium bromide, dodecylpyridinium bromide, etc .; dibenzo-18 crown 6, dicyclohexyl Crown crowns such as 18 crown 6, 18 crown 6; polyethylene glycols such as polyethylene glycol 400 and polyethylene glycol dimethyl ether 500 Phase transfer catalysts include triton-X100 (a registered trademark of Union Force-Vide Co., Ltd.), and ionic phase transfer catalysts including polyethylene glycols such as polyoxyethylene (20) sorbitan monooleate. Can be Preferred is a cationic phase transfer catalyst, and particularly preferred is a quaternary ammonium salt, such as tetrabutylammonium bromide.

[0043] The amount of the phase transfer catalyst used is determined by the amount of the 3-halogeno 3-substituted propenaner represented by the general formula (1). The range may be 0.001 to 1 mol, preferably 0.01 to 0.30 mol, per 1 mol of the metal derivative.

[0044] The base used in the method of the present invention may be any alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal hydride, alkaline earth metal hydride, alkali metal carbonate, or the like. Potassium hydroxide, sodium hydroxide and the like are used as metal hydroxides, calcium hydroxide and barium hydroxide are used as alkaline earth metal hydroxides, and sodium hydride is used as alkali metal hydrides. , Lithium hydride and the like, alkaline earth metal hydrides include calcium hydride and the like, and alkali metal carbonates include lithium carbonate, lithium carbonate and sodium carbonate. Among them, it is preferable to use an alkali metal hydroxide such as sodium hydroxide.

The amount of the base used is usually 1.0 to 7.0 with respect to 1 equivalent of 1 chloro-3-oxopropenyl group in the 3 halogeno 3-substituted propenal derivative molecule represented by the general formula (1). An equivalent, preferably in the range of 2.0 to 6.0 moles can be exemplified.

[0046] However, in the case where the raw material, ie, the 3-ino or logeno 3-substituted propenal derivative represented by the general formula (1) has a hydroxyl group in the molecule, the progress of the reaction may be insufficient. In such a case, it is preferable to use an excess of the base in an amount corresponding to the number of hydroxyl groups in the raw material molecule for the reaction.

[0047] In the method of the present invention, a solvent that can be carried out without a solvent and that does not dissolve in water at an arbitrary ratio can be used, or can be carried out in a heterogeneous system using water. Accordingly, the solvent system of the method of the present invention includes: A) an aqueous solvent system (forming a heterogeneous reaction system), B) a solvent system that is not soluble in water at an arbitrary ratio, and C) a solvent system that is not soluble in water at an arbitrary ratio. It may be either a heterogeneous solvent system consisting of a solvent and water which is not used, or D) a solventless system (forming a heterogeneous reaction system).

[0048] As the "solvent that does not dissolve in water at any ratio", a solvent that is inert to the reaction can be used, and an aprotic solvent that separates easily with water and reduces wastewater load can be used. The use of a neutral solvent is preferred. Examples of such “solvents that do not dissolve in water at any ratio” include, for example, aromatic hydrocarbon solvents, specifically, toluene, xylene, cyclobenzene, orthocyclobenzene, etc .; aliphatic Z or alicyclic Hydrocarbon solvents, specifically n-hexane Sun, n-heptane, n-decane, cyclohexane and the like; ether solvents, specifically, propyl ether, diisopropyl ether, dibutyl ether and the like. It is preferable to use an aromatic hydrocarbon solvent represented by toluene, which is easy and safe to use in industrial settings. The “solvent that does not dissolve in water at an arbitrary ratio” can be used alone or as a mixed solvent having an arbitrary mixing ratio.

[0049] When a solvent and water are used, the amount used may be any amount that can sufficiently stir the reaction system, but 1 mole of the 3 halogeno 3-substituted propenal derivative represented by the general formula (1) is used. On the other hand, the total amount of the solvent system can be, for example, 5000 ml or less, preferably 3000 ml or less.

[0050] The reaction temperature of the above reaction is 10-arbitrary temperature up to the reflux temperature in the reaction system, preferably in the range of 30-80 ° C, and the reaction time is in the range of 0.1-12 hours. The reaction can be carried out under normal pressure, and usually does not require pressurization.

[0051] Examples of the ethynyl benzene derivative represented by the general formula (2) that can be produced by the method of the present invention include, for example, ethyninolebenzene, 2 ethyninolecroc benzene, 4 ethyninolecroc benzene, 4 ethyninolecroc benzene, and 2-ethyninole nitrobenzene 3 —Ethyninolenitrobenzene, 4-ethynylnitrobenzene, 2-ethynylphenol-3-ethynylphenol, 2-ethynyltoluene-3-ethynyltoluene, 4-ethynyltoluene 3-ethynyl-N, N-dimethyla -Phosphorus, 4-Ethyl-L N, N Dimethyl-phosphorus, 2-Benzylphenyl-acetylene, 3-Benzylphenyl-acetylene, 4-Benzylphenyl-acetylene, (3-Ethynylphenyl) diphenylmethane , (4-Ethurfueru) diphenyl methane, 2-Ethurmethoxy benzene 3-Echininolemethod Cybenzene, 4-ethyninolemethoxybenzene, 2-ethynylmethoxymethylbenzene-3-ethynylmethoxymethylbenzene, 4-ethynylmethoxymethylbenzene, 1-3-ethynylbenzene, 1,4-ethynyl Benzene, 1,3,5-triethylbenzene, 4,4'-detjurdiphenyl, 3,3'-detjurdiphenyl, (3-etulfur), (4-etulfur) methane, bis (4-ethyulfer) methane, 3,4'-Jetynylbenzophenone, 4,4'-Jethynylbenzophenone, 3,4'-Jetynyldiphenyl ether, 4,4'Jetini Ludiphenyl ether, 3, 4'-Jetuldiphenol-sulfide, 4, 4 'Detci-Rudiphenyl-sulfide, 3, 4' Detti Nyldiphenylsulfone, 4,4 'ethynyldiphenylsulfone, 2-benzyloxy-4-methoxyphenylacetylene, 2-ethynylnaphthalene, 9-ethynylphenanthrene, 1-eturpyrene and the like can be exemplified. .

Example

Next, the ability to specifically explain the method for producing the compound of the present invention with reference to Examples, Comparative Examples and Reference Examples is not intended to limit the present invention.

Reference Example 1: Synthesis of getyl 3′-methylbenzoylmamate

10. Charge 80 g (0.84 mol) of anhydrous magnesium chloride and 800 ml of toluene, and cool in an ice bath. Under C or lower, 128.lg (0.80 mol) of getyl malonate and 170.0 g (1.68 mol) of triethylamine were successively added and aged at room temperature for 2 hours. Subsequently, 123.7 g (0.80 mol) of 3-methylbenzoyl chloride was added dropwise at 10 ° C. or lower while cooling the reaction solution in an ice bath. After completion of the dropwise addition, the mixture was aged at room temperature for 12 hours, and while cooling the reaction solution in an ice bath, 480 ml of an aqueous 18% hydrochloric acid solution was added dropwise at 25 ° C or lower. After separating the toluene layer, the aqueous layer was re-extracted with 40 Oml of toluene. The obtained toluene extract was washed successively with an aqueous 18% hydrochloric acid solution, water and a saturated saline solution, dried over anhydrous sodium sulfate, and the toluene layer was concentrated under reduced pressure to obtain the desired getyl 3, -methylbenzoylmalonate. 221.30 g (0.795 mol) was obtained in a yield of 99.4%.

Reference Example 2: Synthesis of 3, -methylacetophenone

22.30 g (0.795 mol) of 3, -methylbenzoylmalonate, 502.2 g (5.12 mol) of concentrated sulfuric acid and 800 ml of water were charged, and the mixture was aged under heating and reflux for 12 hours. After aging, 500 ml of toluene was added at room temperature to separate the layers. The obtained toluene extract was washed successively with water and a saturated saline solution, dried over anhydrous sodium sulfate, and the toluene layer was concentrated under reduced pressure to obtain 99.6 g (0%) of the desired 3′-methylacetophenone. .74 mol) with a yield of 93.4%.

Reference Example 3: Production of 3-chloro-3- (3-methylphenyl) propenal

800 ml of N, N-dimethylformamide (DMF) was charged, and while cooling in an ice bath, 271.3 g (l. 77 mol) of oxychloride was added dropwise at 10 ° C. or lower. After completion of the dropwise addition, the mixture was aged at room temperature for 30 minutes. Subsequently, 107.3 g (0.80 mol) of 3,1-methylacetophenone was added, the temperature was raised to 60 ° C, and the mixture was aged at 60 ° C for 6 hours. After aging, cool the reaction mixture to room temperature and Injected into 2 L of water. After neutralization with sodium hydrogen carbonate, 500 ml of toluene was added and the layers were separated. The obtained toluene solution was washed with water, dried over anhydrous sodium sulfate, and concentrated. Then, 114.3 g (0.63 mol) of the desired 3-chloro-3- (3-methylphenyl) propenal was obtained in a yield of 79.1. %.

Example 1: Production of 3-Ethyltoluene

Charge 25% sodium hydroxide aqueous solution 192.Og (l.20mol), 50% tetrabutylammonium-bromobromide aqueous solution 19.34g (0.03mol), toluene 300ml, and water 300ml, and heat to 80 ° C Then, 108.4 g (0.60 mol) of 3-chloro-3- (3-methylphenyl) propenal was added to the rice cake and aged at 80 ° C for 3 hours. After completion of aging, the mixture was separated at room temperature, washed with water, and dried over anhydrous sodium sulfate. The obtained toluene solution was analyzed by gas chromatography (GC). As a result, the target 3-ethyl toluene was produced in a yield of 91.0%. Subsequently, rectification yielded 47.6 g (0.41 mol) of the desired 3-ethyltoluene 3-chloro-3- (3-methylphenol) propenal in a yield of 68.3%. . Boiling point 86. CZ933 lPa (70mmHg).

Example 2 Production of 3-Etultoluene

25% aqueous sodium hydroxide solution 6.40 g (0.04 mol), 50% tetrabutylammonium bromide aqueous solution 0.64 g (lmmol) and water 10 ml were charged, and the temperature was raised to 75 ° C. — 3.61 g (0.02 mol) of 3- (3-methylphenyl) propenal was added, and the mixture was aged at 75 ° C for 3 hours. After the ripening, the toluene layer was analyzed by GC. As a result, it was found that the desired 3-ethynyltoluene was produced in a yield of 82.0.

Reference Example 4: Production of 3-chloro-3- (3-hydroxyphenyl) propenal

100 ml of N, N-dimethylformamide (DMF) was charged, and 61.4 g (0.40 mol) of oxychloride was added dropwise at 10 ° C. or lower while cooling in an ice bath. After completion of the dropwise addition, the mixture was aged at room temperature for 30 minutes. Subsequently, 3-hydroxyacetophenone (27.2 g, 0.20 mol) was added, the temperature was raised to 60 ° C, and the mixture was aged at 60 ° C for 5 hours. After aging, the reaction solution was cooled to room temperature and poured into ice-water (500 ml). After neutralization with sodium hydrogen carbonate, 100 ml of toluene was added and the layers were separated. The obtained toluene solution was washed with water, dried over anhydrous sodium sulfate, and concentrated. Then, 23.4 g (0.13 mol) of the desired 3-chloro-3- (3-hydroxyphenyl) propenal was collected. Obtained at a rate of 64.1%.

Example 3 Production of 3-Echulphenol

25% aqueous sodium hydroxide solution 102.lg (0.64mol), 50% tetrabutylammonium bromide aqueous solution 4. Charge lg (0.0064mol), water 300ml, heat up to 80 ° C, Black mouth —3— (3-Hydroxyphenyl) propenal 23.4 g (0.13 mol) was added, and 80. Aged at C for 2 hours. After completion of aging, the mixture was cooled to room temperature and acidified with a 5% hydrochloric acid aqueous solution. After separation and extraction with 300 ml of toluene, the mixture was washed with water and dried over anhydrous sodium sulfate. The obtained toluene solution was concentrated and distilled to obtain 4.84 g (0.04 lmol) of the desired 3-ethynylphenol in a yield of 32.0%. Boiling point 99. CZ1066. 4Pa (8mmHg).

Example 4 Production of 1,3-Jetulbenzene

Charge 76.8 g (0.48 mol) of a 25% aqueous sodium hydroxide solution, 3.9 g (0.0060 mol) of a 50% aqueous solution of tetrabutylammonium bromide, 100 ml of toluene, and 100 ml of water, and heat to 80 ° C. Add 3 g (0.1-mol-3 oxoprobe) fel] propenal 31. lg (0.12 mol) to the flask and add 2 hours at 80 ° C Matured. After completion of aging, the mixture was separated at room temperature, washed with water, and dried over anhydrous sodium sulfate. The obtained toluene solution was concentrated and then distilled to obtain 8.24 g (0.065 mol) of the objective 1,3-methylbenzene in a yield of 53.6%. Boiling point 80. CZ1999. 5Pa (15mmHg).

Example 5 Production of 4,4,4-Jetjurjifir

A 25% aqueous sodium hydroxide solution 29.lg (0.282 mol), a 50% aqueous solution of tetrabutylammonium-bromo bromide 1.49 g (2.3 mmol), toluene 50 ml, and water 50 ml were charged, and the temperature was raised to 80 ° C. Warm and add 3-cloth—3— [4, — (1—cloth—3 oxoprober) bihue-ru 4-yl] propenal 15.3 g (0.0462 mol) and add at 80 ° C. Aged for hours. After completion of aging, the mixture was separated at room temperature, washed with water, and dried over anhydrous sodium sulfate. The obtained toluene solution was concentrated, and the residue was recrystallized from ethanol to give 4.10 g (0.020 mol) of the target 4,4'-ethynyldiphenyl in a yield of 43.9%. Melting point 80. CZl999.5Pa (15mmHg)

Example 6: Production of ethinylbenzene

In a 300 ml four-necked flask equipped with a stirrer, reflux condenser, and thermometer, —3—Ferpropenal 8.33 g (0.05 mol), 99% sodium hydroxide 4.44 g (0.1 lmol), 50% tetrabutylammonium bromide aqueous solution 0.97 g (l .5 mmol) and 125 ml of toluene were added, the temperature was raised to 60 ° C, and the mixture was stirred at 60 ° C for 2 hours. After completion of the reaction, 25 ml of water was added, and the mixture was separated at room temperature to obtain an organic layer. After the obtained organic layer was washed with water, it was dried over anhydrous sodium sulfate. The obtained organic layer was analyzed by gas chromatography, and it was found that ethylbenzene yield was 69.4%.

Claims

(In the formula, X and Y each independently represent a halogen atom,

R ² and R ³ each independently represent a hydrogen atom; a halogen atom; a nitro group; a hydroxyl group; an alkyl group; an alkenyl group; an alkyl group; a dialkylamino group; an aralkyl group; an alkoxy group; ,

R ¹ and R ² may join together to form a ring Z is an oxygen atom; a sulfur atom; a sulfonyl group; an alkyl or aryl group may be substituted !, a methylene group; Or 1 represents a single bond, 1 represents an integer of 1 to 6, m, n, o, p, and q each independently represent an integer of 0 to 5, o + p is 5 or less, and 1 + m + n + q is 6 or less. )

Reacting a 3-halogeno 3-substituted propenal derivative represented by the formula with a base, characterized by the general formula (2)

[Formula 2]

(Where:

A method for producing an ethurbenzene derivative represented by the formula:

[2] The method for producing an ethynylbenzene derivative according to claim 1, wherein the reaction is carried out in an aqueous solvent system.

[3] The reaction according to claim 1, wherein the reaction is carried out in a solvent system that does not dissolve in water at any ratio. A method for producing an ethynylbenzene derivative.

[4] The method for producing an ethynylbenzene derivative according to claim 1, wherein the reaction is carried out in a heterogeneous solvent system comprising a solvent insoluble in water at an arbitrary ratio and water.

[5] The method for producing an ethynylbenzene derivative according to claim 1, wherein the reaction is carried out in a solvent-free system.

6. The method for producing an ethynylbenzene derivative according to claim 3, wherein the solvent that does not dissolve in water at an arbitrary ratio is an aromatic hydrocarbon.

[7] The method for producing an ethurbenzene derivative according to claim 1, wherein the phase transfer catalyst is a quaternary ammonium salt.

[8] The method for producing an ethynylbenzene derivative according to claim 1, wherein the base is an alkali metal hydroxide.

[9] The method for producing an ethurbenzene derivative according to claim 1, wherein X and Y of the 3-halogeno 3-substituted propenal derivative represented by the general formula (1) are both chlorine atoms.

[10] The method for producing an ethurbenzene derivative according to claim ¹ , wherein R ¹ R ² and R ^{3 of the} 3-nodogeno-3-substituted propenal derivative represented by the general formula (1) are all alkyl groups.