JPH0977747A - Aromatic derivative and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an aromatic derivative useful for producing an intermediate for a medicine, an agrochemical, a liquid crystal, etc., especially an intermediate for a low-viscosity liquid crystal compound excellent in dielectric anisotropy. SOLUTION: This aromatic derivative is shown by formula I [R is a 1-12C alkyl, alkenyl or (substituted) benzyl; X is F; (r) is 0-3] such as 2-(4- benzyloxy-2,3-difluorophenyl)-5-(3-hydroxy-3,3,-dimethyl-1-propynyl)py rimidine. The derivative is obtained by reacting a phenylpyrimidine derivative of formula II (D is a halogen) with 1,1-dimethyl-2-propyne in the presence of a metal catalyst such as copper iodide to give an acetylene derivative of formula III and reacting the resultant substance with a basic substance such as triethylamine, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an aromatic derivative represented by the following general formula [1] which is useful as an intermediate for medicines, agricultural chemicals, liquid crystal compounds and the like, and a method for producing the same.

[0002]

The present invention is intended as an intermediate for drugs, agricultural chemicals, liquid crystals and the like having a novel acetylene skeleton, particularly as an intermediate for low viscosity liquid crystal compounds having excellent dielectric anisotropy. It is intended to provide a useful aromatic derivative [1] and an industrially advantageous production method thereof.

[0003]

Means for Solving the Problems The present inventors have completed the present invention by finding intermediates useful for the production of pharmaceuticals, agricultural chemicals, liquid crystals and the like, particularly liquid crystal compounds having excellent dielectric anisotropy. Came to.

That is, the present invention has the general formula [1] (In the formula, R represents a C _{1 to} C ₁₂ alkyl group, an alkenyl group, or a benzyl group which may have a substituent, X represents a fluorine atom, and r is an integer of 0 to 3. The present invention provides an aromatic derivative represented by (4) and a method for producing the same. Hereinafter, the present invention will be described in detail.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The aromatic compound [1] of the present invention is
General formula [3] (In the formula, X and r have the same meanings as described above, and D represents a halogen atom such as a bromine atom or an iodine atom.) And 1,1-
Dimethyl-2-propyne is reacted in the presence of a metal catalyst to give a compound of the general formula [2] (In the formula, R, X and r have the same meanings as described above.) The acetylene derivative is obtained and then obtained by reacting with a basic substance.

The phenylpyrimidine derivative [3] as a raw material can be synthesized by the method shown below. (In the formula, D, R, X and r have the same meanings as described above.)

Phenylpyrimidine derivative [3] and 1,1
In a reaction for reacting dimethyl-2-propyne in the presence of a metal catalyst to obtain an acetylene derivative [2],
The amount of 1,1-dimethyl-2-propyne used is usually 1 to 20 times equivalents, preferably 1.1 to 5 times equivalents, of the phenylpyrimidine derivative [3]. If it is used more than this, there is no problem, but an amount within this range allows the reaction to proceed sufficiently.

The metal catalyst used in the above reaction is
In the palladium system, palladium chloride, palladium acetate, palladium / carbon, triphenylphosphine palladium complex (eg, tetrakistriphenylphosphine palladium, dichloroditriphenylphosphine palladium)
And the like, and the same catalysts as described above are used for nickel-based and rhodium-based catalysts. The amount of these metal catalysts used is usually in the range of 0.001 to 0.1 times the equivalent amount of the starting phenylpyrimidine derivative [3]. Also,
In this reaction, it may be preferable to use a trivalent phosphorus compound or a trivalent arsenic compound as a co-catalyst in addition to the above-mentioned metal catalyst, as those compounds represented by the general formula [4] R ^1- (R ^2- ) M-R ³ [4] (In the formula, M represents a phosphorus atom or an arsenic atom, and R ¹ , R
² and R ³ are the same or different and each represents an alkyl group, an alkoxy group, an aryl group, an aryloxy group, a heterocyclic group or a halogen atom. ) Is a compound represented by
Specifically, tri-n-butylphosphine, triphenylphosphine, tri-o-tolylphosphine, tri-o-
Examples include tolylphosphite, trithienylphosphine, phosphorus trichloride, triphenylarsenic and the like. The amount of the phosphorus compound or arsenic compound used is usually 0.5 to 50 times equivalent, preferably 3 to 50 times, the amount of the metal catalyst.
It is 30 times equivalent.

In addition to the above catalysts, copper catalysts can be used. Examples of such copper catalysts include copper iodide, copper bromide, copper chloride, copper oxide and copper cyanide. Is usually in the range of 0.001 to 0.1 times the equivalent of the phenylpyrimidine derivative [3].

In the above reaction, the use of a basic substance preferably promotes the reaction, and examples of such a basic substance include inorganic bases such as alkali metal carbonates, carboxylates, alkoxides and hydroxides, and organic bases. And secondary or tertiary organic bases are preferred. Examples of such organic bases include diethylamine, triethylamine, diisopropylethylamine, tri-n-butylamine, tetramethylethylenediamine, dimethylaniline, N-methylmorpholine and N-methylpiperidine.

The amount of the basic substance used is usually 1 to 5 times the equivalent amount of the phenylpyrimidine derivative [3].

In the above reaction, a suitable solvent can be used if necessary, and examples of such a solvent include toluene, pyridine, picoline, acetonitrile, tetrahydrofuran, dimethylformamide, hexamethylphosphorylamide, N-methylpyrrolidone, Methanol may be used, and the amount used is not particularly limited. Further, the above base can be used as a solvent.

The above reaction is usually carried out in an inert gas such as nitrogen or argon. In the above reaction, the reaction yield can be improved by increasing the reaction temperature, but in consideration of the increase of by-products, the reaction temperature is usually
15-160 degreeC, Preferably it is 30-140 degreeC.

After completion of the reaction, the acetylene derivative [2] can be obtained by usual means such as extraction, distillation, recrystallization and the like. If necessary, it can be purified by distillation, column chromatography, recrystallization or the like.

Next, a method for producing the aromatic derivative represented by the general formula [1], which is the object of the present invention, by reacting the acetylene derivative [2] with a basic substance will be described.
Examples of the basic substance used in this reaction include alkali metals and alkaline earth metals as well as their carbonates, carboxylates, alkoxides, hydrides and hydroxides, or DBU, triethylamine, diisopropylethylamine and tri-n-n-. Examples thereof include organic bases such as butylamine, tetramethylethylenediamine, dimethylaniline, N-methylmorpholine and N-methylpiperidine, but preferably hydroxides such as sodium hydroxide and potassium hydroxide, sodium ethylate and sodium methylate. And alkoxides.

The amount of the basic substance used is usually 0.005 to 50 times equivalent to the acetylene derivative [2].
If necessary, for example, chlorobenzene, dichlorobenzene, benzene, toluene, xylene, tetrahydrofuran, xylene, cyclohexane, decane, dimethylformamide, hexamethylphosphorylamide, N-methylpyrrolidone, dimethyl sulfoxide and the like can be used as a reaction solvent. . The use amount of these reaction solvents is not particularly limited. The reaction temperature of this reaction is usually 20 to 1.
It is 90 ° C., preferably 40 to 150 ° C.
The reaction time is not particularly limited.

In this reaction, since acetone is by-produced as the reaction progresses, it is possible to efficiently proceed by removing by-product acetone at any time during the reaction. After completion of the reaction, the aromatic derivative [1] of the present invention can be obtained by usual means such as extraction and concentration. If necessary, it can be purified by distillation, column chromatography or the like.

Specific examples of the aromatic derivative [1] obtained in the present invention are, for example, in the general formula [1], R is methyl, ethyl, propyl, butyl,
Pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, ethenyl, propenyl,
Examples thereof include alkyl groups such as butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, and further lower alkoxy groups such as methoxy, ethoxy, propoxy, butoxy, pentyloxy or methyl, ethyl, propyl, Examples thereof include a benzyl group which may be substituted with a lower alkyl group such as butyl and pentyl.

The aromatic derivative [1] obtained in the present invention is
A liquid crystal compound can be derived as shown in the route below. (In the formula, D, R, X and r have the same meanings as described above,
R 'represents an alkyl group of C ₁ -C _20. )

[0020]

The aromatic derivative represented by the general formula [1] of the present invention is very useful as an intermediate for medicines, agricultural chemicals, liquid crystal compounds and the like.

[0021]

EXAMPLES The present invention will now be described in more detail with reference to examples, but the present invention is not limited to these examples.

(Example 1) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was made to have a nitrogen atmosphere, 2- (4-benzyloxy-2,3-difluorophenyl)-was prepared. 7.5 g of 5-bromopyrimidine (3-1)
(20 mmol), bis (triphenylphosphine) palladium chloride 0.06 g, copper iodide 0.06 g, triphenylphosphine 0.1 g, triethylamine 40
g, 1,1-dimethyl-2-propyn-1-ol 2.
Add 5 g (30 mmol) and stir under reflux for 8 hours. After cooling to room temperature, hydrochloric acid is added to neutralize, 100 ml of toluene is added, and then the organic layer is separated and washed with water. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2- (4-benzyloxy-2,3-difluorophenyl) -5- (3-
6.7 g (yield 88%) of hydroxy-3,3-dimethyl-1-propynyl) pyrimidine (2-1) is obtained. Melting point 148-149 ° C ¹ H NMR (CDCl ₃ ) δppm: 1.6 (s, 6H), 2.8 (s, 1H),
5.25 (s, 2H), 7.0 to 8.0 (m, 7H),
8.85 (s, 2H)

The following acetylene derivative [2] is obtained according to Example 1. -2- (4- (4-methoxy) benzyloxy-2,3
-Difluorophenyl) -5- (3-hydroxy-3,
3-dimethyl-1-propynyl) pyrimidine 2- (4-methoxy-2,3-difluorophenyl)
-5- (3-Hydroxy-3,3-dimethyl-1-propynyl) pyrimidine 2- (4-pentyloxy-2,3-difluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1
-Propinyl) pyrimidine-2- (4-decyloxy-2,3-difluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1-
Propinyl) pyrimidine.2- (4-allyloxy-2,3-difluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1-)
Propynyl) pyrimidine

(Example 2) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was made to have a nitrogen atmosphere, 2- (4-benzyloxy-2-fluorophenyl) -5- Bromopyrimidine (3-2) 7.2 g (20
mmol), bis (triphenylphosphine) palladium chloride 0.06 g, copper iodide 0.06 g, triphenylphosphine 0.1 g, triethylamine 40 g, toluene 30 ml, 1,1-dimethyl-2-propyne-1.
-Add 2.5 g (30 mmol) of all and add 5 under reflux.
Stir for hours. After cooling to room temperature, hydrochloric acid is added to neutralize, 100 ml of toluene is added, and then the organic layer is separated and washed with water. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2-
(4-benzyloxy-2-fluorophenyl) -5-
6.4 g (yield 89%) of (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine (2-2) is obtained. Melting point 158-161 ° C ¹ H NMR (CDCl ₃ ) δppm: 1.6 (s, 6H), 2.8 (s, 1H),
5.25 (s, 2H), 7.0 to 8.0 (m, 7H),
8.8 (s, 2H)

The following acetylene derivative [2] is obtained according to Example 2. 2- (4- (4-methyl) benzyloxy-2-fluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine 2- (4-ethoxy-2-fluorophenyl) ) -5
(3-Hydroxy-3,3-dimethyl-1-propynyl) pyrimidine.2- (4-hexyloxy-2-fluorophenyl)
-5- (3-Hydroxy-3,3-dimethyl-1-propynyl) pyrimidine-2- (4-decyloxy-2-fluorophenyl)-
5- (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine.2- (4- (3-hexenyloxy) -2-fluorophenyl) -5- (3-hydroxy-3,3-dimethyl- 1-propynyl) pyrimidine

(Example 3) The inside of a four-necked flask equipped with a stirrer, a reflux condenser, and a thermometer was placed in a nitrogen atmosphere, and then 2- (4-benzyloxy-3-fluorophenyl) -5- Bromopyrimidine (3-3) 7.2 g (20
mmol), tetrakis (triphenylphosphine) palladium 0.08 g, copper iodide 0.06 g, triphenylphosphine 0.12 g, triethylamine 40 g, toluene 30 ml, 1,1-dimethyl-2-propyne-1.
-Add 2.5 g (30 mmol) of all and add 5 under reflux.
Stir for hours. After cooling to room temperature, hydrochloric acid is added to neutralize, 100 ml of toluene is added, and then the organic layer is separated and washed with water. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2-
(4-benzyloxy-3-fluorophenyl) -5-
6.6 g (yield 91%) of (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine (2-3) is obtained. Melting point 154-157 ° C ¹ H NMR (CDCl ₃ ) δppm: 1.6 (s, 6H), 2.8 (s, 1H),
5.25 (s, 2H), 7.0 to 8.0 (m, 7H),
8.85 (s, 2H)

The following acetylene derivative [2] is obtained according to Example 3. 2- (4- (4-methoxy) benzyloxy-3-fluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine 2- (4-methoxy-3-fluorophenyl) ) -5
(3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine.2- (4-hexyloxy-3-fluorophenyl)
-5- (3-Hydroxy-3,3-dimethyl-1-propynyl) pyrimidine 2- (4-decyloxy-3-fluorophenyl)-
5- (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine 2- (4- (6-heptynyloxy) -3-fluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1 -Propynyl) pyrimidine

(Example 4) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was placed in a nitrogen atmosphere, the 2- (4-benzyloxy-) obtained in Example 1 was obtained.
2,3-Difluorophenyl) -5- (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine (2
-1) 1.9 g (5 mmol), sodium hydroxide 0.
2 g (5 mmol) and 25 ml of toluene are stirred under reflux for 1 hour. The solvent is distilled off during the reaction. After the reaction was completed, the mixture was cooled to room temperature, 10 ml of water was added, the layers were separated, and the organic layer was washed with water.
Wash twice and dry with anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography to give 1.5 g of 2- (4-benzyloxy-2,3-difluorophenyl) -5-ethynylpyrimidine (1-4) (yield 94 %). Melting point 133-134 ° C. Elemental analysis: C ₁₉ H ₁₂ N ₂ OF ₂ CHN Theoretical value (%) 70.80 3.75 8.69 Analytical value (%) 70.62 3.68 8.77 ¹ H NMR (CDCl ₃ ) δppm: 3.5 (s, 1H), 5.25 (s, 2)
H), 6.9 to 8.0 (m, 7H), 8.85 (s, 2)
H)

The following aromatic derivative [1] is obtained in the same manner as in Example 4. -2- (4- (4-methoxy) benzyloxy-2,3
-Difluorophenyl) -5-ethynylpyrimidine 2- (4-pentyloxy-2,3-difluorophenyl) -5-ethynylpyrimidine 2- (4-decyloxy-2,3-difluorophenyl) -5-ethynylpyrimidine -2- (4-allyloxy-2,3-difluorophenyl) -5-ethynylpyrimidine

(Embodiment 5) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was made to have a nitrogen atmosphere, the 2- (4-benzyloxy-2) obtained in Embodiment 2 was obtained.
-Fluorophenyl) -5- (3-hydroxy-3,3
-Dimethyl-1-propynyl) pyrimidine (2-2)
1.8 g (5 mmol), sodium hydroxide 0.08 g
(2 mmol) and 25 ml of toluene are stirred under reflux for 2 hours. The solvent is distilled off during the reaction. After completion of the reaction, the mixture is cooled to room temperature, 10 ml of water is added, liquid separation and the organic layer are washed twice with water, and dried using anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2- (4-benzyloxy-
2-fluorophenyl) -5-ethynylpyrimidine (1
-5) Obtain 1.5 g (96% yield). Melting point 147-
149 ° C Elemental analysis: C ₁₉ H ₁₃ N ₂ OF CHN theoretical value (%) 74.99 4.31 9.21 analytical value (%) 74.87 4.51 9.13 ¹ H NMR (CDCl ₃ ). δppm: 3.5 (s, 1H), 5.3 (s, 2H),
6.9 to 8.0 (m, 8H), 8.8 (s, 2H)

The following aromatic derivative [1] is obtained according to Example 5. 2- (4- (4-methyl) benzyloxy-2-fluorophenyl) -5-ethynylpyrimidine 2- (4-ethoxy-2-fluorophenyl) -5-
Ethynylpyrimidine 2- (4-hexyloxy-2-fluorophenyl)
-5-ethynylpyrimidine-2- (4-decyloxy-2-fluorophenyl)-
5-ethynylpyrimidine 2- (4- (3-hexenyloxy) -2-fluorophenyl) -5-ethynylpyrimidine

(Example 6) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was made to have a nitrogen atmosphere, the 2- (4-benzyloxy-3) obtained in Example 3 was obtained.
-Fluorophenyl) -5- (3-hydroxy-3,3
-Dimethyl-1-propynyl) pyrimidine (2-3)
1.8 g (5 mmol), sodium hydroxide 0.01 g
(0.02 mmol) and 25 ml of toluene are stirred under reflux for 2 hours. The solvent is distilled off during the reaction. After the reaction,
After cooling to room temperature, 10 ml of water is added, liquid separation and the organic layer are washed twice with water and dried using anhydrous magnesium sulfate.
After distilling off the solvent, the residue was purified by silica gel column chromatography to give 2- (4-benzyloxy-3-fluorophenyl) -5-ethynylpyrimidine (1-6) 1.4 g (yield 95%). To get Melting point 1
Forty-two to one hundred forty-four ° C. Elemental _{analysis: C 19 H 13 N 2 OF} C H N Theoretical value (%) 74.99 4.31 9.21 Analytical values ^{(%) 74.87 4.51 9.13 1 H} NMR (CDCl ₃ ) δppm: 3.5 (s, 1H), 5.3 (s, 2H),
6.9 to 8.0 (m, 8H), 8.8 (s, 2H)

The following aromatic derivative [1] is obtained according to Example 6. 2- (4- (4-methoxy) benzyloxy-3-fluorophenyl) -5-ethynylpyrimidine 2- (4-methoxy-3-fluorophenyl) -5
Ethynylpyrimidine 2- (4-hexyloxy-3-fluorophenyl)
-5-ethynylpyrimidine-2- (4-decyloxy-3-fluorophenyl)-
5-ethynylpyrimidine-2- (4- (6-heptynyloxy) -3-fluorophenyl) -5-ethynylpyrimidine

(Example 7) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser, and a thermometer was made to have a nitrogen atmosphere, the 2- (4-methoxy-2,3) obtained in Example 3 was obtained. −
Difluorophenyl) -5- (3-hydroxy-3,3
-Dimethyl-1-propynyl) pyrimidine (2-7)
1.5 g (5 mmol), sodium hydroxide 0.01 g
(0.02 mmol) and 25 ml of toluene are stirred under reflux for 2 hours. The solvent is distilled off during the reaction. After the reaction,
After cooling to room temperature, 10 ml of water is added, liquid separation and the organic layer are washed twice with water and dried using anhydrous magnesium sulfate.
After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2- (4-methoxy-).
1.2 g (yield 96%) of 2,3-difluorophenyl) -5-ethynylpyrimidine (1-7) is obtained. Elemental analysis: C ₁₃ H ₈ N ₂ OF ₂ CHN theoretical value (%) 63.42 3.28 11.38 analytical value (%) 63.37 3.46 11.19

(Examples 8 to 14) The aromatic derivative [1] shown in Table 2 was obtained by sequentially carrying out the reaction and post-treatment according to Examples 1 and 4 except that the starting materials shown in Table 1 were used. can get.

[0036]

[Table 1]

[0037]

[Table 2]

[0038]

[Table 3]

(Example 15) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was made to have a nitrogen atmosphere, 2- (4-benzyloxyphenyl) -5-bromopyrimidine (3 -15) 6.8 g (20 mmol),
Bis (triphenylphosphine) palladium chloride 0.05 g, copper iodide 0.05 g, triphenylphosphine 0.1 g, triethylamine 15 g, toluene 30
ml, 3.3 g (40 mmol) of 1,1-dimethyl-2-propyn-1-ol are added, and the mixture is stirred under reflux for 8 hours. After cooling to room temperature, hydrochloric acid is added to neutralize, 100 ml of toluene is added, and then the organic layer is separated and washed with water. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2- (4-benzyloxyphenyl) -5- (3-hydroxy-3,3).
-Dimethyl-1-propynyl) pyrimidine (2-15)
6.2 g (yield 90%) are obtained. Mp 166-168 ° C. Elemental _{analysis: C 22 H 20 N 2 O} 2 C H N Theoretical value (%) 76.72 5.85 8.13 Analytical values ^{(%) 76.51 5.66 8.37 1 H} NMR (CDCl ₃ ) δppm: 1.6 (s, 6H), 2.7 (s, 1H),
5.25 (s, 2H), 7.0 to 8.0 (m, 7H),
8.85 (s, 2H)

(Example 16) After the inside of a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer was made to have a nitrogen atmosphere, the 2- (4-benzyloxyphenyl) -obtained in Example 15 was obtained. 5- (3-hydroxy-3,3-dimethyl-1-propynyl) pyrimidine (2-15) 1.7 g
(5 mmol), 0.02 g of potassium hydroxide (5 mmo
1) and 25 ml of toluene are stirred under reflux for 1 hour. The solvent is distilled off during the reaction. After completion of the reaction, the mixture is cooled to room temperature, 10 ml of water is added, liquid separation and the organic layer are washed twice with water, and dried using anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2- (4-benzyloxyphenyl)-
1.3 g of 5-ethynylpyrimidine (1-16) (yield 9
5%). Melting point 169-171 ° C Elemental analysis: C ₁₉ H ₁₄ N ₂ O CHN theoretical value (%) 84.42 5.22 10.36 Analytical value (%) 84.16 4.98 10.51 ¹ H NMR ( CDCl ₃ ) δppm: 3.6 (s, 1H), 5.25 (s, 2)
H), 6.9 to 8.0 (m, 9H), 8.85 (s, 2)
H)

Claims (4)

[Claims] 1. The general formula [1] (In the formula, R represents a C _{1 to} C ₁₂ alkyl group, an alkenyl group, or a benzyl group which may have a substituent, X represents a fluorine atom, and r is an integer of 0 to 3. ) An aromatic derivative represented by. 2. The general formula [2] (In the formula, R, X and r have the same meanings as described above.) The acetylene derivative represented by the formula and the basic substance are reacted with each other to obtain the aromatic derivative represented by the general formula [1]. Manufacturing method. 3. A general formula [3] (In the formula, r and X have the same meanings as described above. D
Represents a halogen atom. ) Is reacted with 1,1-dimethyl-2-propyne in the presence of a metal catalyst to obtain an acetylene derivative represented by the general formula [2], which is further reacted with a basic substance. A method for producing the aromatic derivative represented by the above general formula [1]. 4. An acetylene derivative represented by the general formula [2].