JP3511686B2 - Optically active ester derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aromatic derivative useful as a component of a liquid crystal material or a composition having excellent responsiveness of an organic electronic material, particularly an image display, and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, various compounds have been developed as constituents of liquid crystal materials. However, in order to maintain or improve a high response speed, which is one of the original characteristics of liquid crystals, especially ferroelectric liquid crystals, conventional methods have been developed. Is not yet sufficient.

[0003]

An object of the present invention is to develop an aromatic derivative useful as a component of a liquid crystal, particularly a ferroelectric liquid crystal compound and / or a ferroelectric liquid crystal composition, and a method for producing the same. .

[0004]

Means for Solving the Problems The present inventors have conducted various studies to solve the above-mentioned problems, and as a result, an aromatic derivative, which is a novel compound, is excellent as a liquid crystal composition and can be produced industrially advantageously. The inventors have found that the present invention can be performed, and have led to the present invention. That is, the present invention relates to the general formula (1) (Wherein, R ¹ represents a saturated or unsaturated alkyl group which may be substituted with a halogen atom having 1 to 10 carbon atoms, Ar represents a pyrimidyl group, and R ² represents-(A) _n -R
³ represents, E represents -CH = CH- or -C−C-, R ³ represents a saturated or unsaturated alkyl group, an alkoxyalkyl group or a substituted or unsubstituted halogen atom having 1 to 15 carbon atoms. group _{- (CH 2) r -CH (} C
H ₃ ) -Y. Here, Y represents OR ⁴ or a fluorine atom, and R ⁴ represents a saturated or unsaturated alkyl group or alkanoyl group which may be substituted with a halogen atom having 1 to 10 carbon atoms. X represents -COO-, -OCO- or a single bond, l represents an integer of 0 to 2, m and n each represent 0 or 1, and r represents an integer of 0 to 8. ) And a process for producing the same.

Hereinafter, a method for producing the compound of the present invention will be described. The aromatic derivative represented by the general formula (1) is represented by the general formula (2) (In the formula, R ¹ and Ar represent the same meaning as described above.)
A phenol represented by the general formula (3) (Wherein R ² , l and m represent the same meaning as described above,
R ⁵ represents a hydroxyl group or a halogen atom. )) To obtain a carboxylic acid.

Alternatively, general formula (4) (Wherein R ¹ , Ar and R ⁵ have the same meanings as described above) and a carboxylic acid represented by the general formula (5): (Wherein, R ² , l and m have the same meanings as described above). Furthermore, the general formula (6) (Wherein, R ¹ , Ar, X and 1 represent the same meaning as described above, and D represents a halogen atom, OCOCF ₃ or —OS
O ₂ R ′ is shown. Here, R 'represents a lower alkyl group which may be substituted by a fluorine atom, or a phenyl group which may be substituted. ) And an acetylene represented by the general formula (7) ≡-R ³ (7) (wherein R ³ has the same meaning as described above) or the general formula (8) (In the formula, R ⁸ represents a hydroxyl group, a linear, branched or cyclic alkyl group or a linear, branched or cyclic alkoxy group. In this case, R ³ is mutually bonded to form a ring. Or a benzodioxy group which may be substituted by (R ⁸ ) ₂ , wherein R ³ has the same meaning as described above) in the presence of a metal catalyst and a basic substance. The resulting compound can be further hydrogenated with unsaturated bonds using hydrogen and a hydrogenation catalyst.

First, the reaction between a phenol represented by the general formula (2) and a carboxylic acid represented by the general formula (3) will be described. Many of the phenols (2) as one raw material used in the present invention are known compounds, and can be produced according to the method described in the literature as follows.

[0008]

The phenols (2) include 2-
(4-methylcyclohexyl) -5-hydroxypyrimidine 2- (4-ethylcyclohexyl) -5-hydroxypyrimidine, 2- (4-propylcyclohexyl)-
5-hydroxypyrimidine 2- (4-butylcyclohexyl) -5-hydroxypyrimidine, 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine2-
(4-hexylcyclohexyl) -5-hydroxypyrimidine, 2- (4-heptylcyclohexyl) -5-hydroxypyrimidine 2- (4-octylcyclohexyl) -5-hydroxypyrimidine, 2- (4-nonylcyclohexyl) -5- Hydroxypyrimidine 2- (4-
Decylcyclohexyl) -5-hydroxypyrimidine,
2- (4-ethenylcyclohexyl) -5-hydroxypyrimidine, 2- (4-propenylcyclohexyl) -5
-Hydroxypyrimidine, 2- (4-butenylcyclohexyl) -5-hydroxypyrimidine, 2- (4-pentenylcyclohexyl) -5-hydroxypyrimidine,
2- (4-hexenylcyclohexyl) -5-hydroxypyrimidine, 5- (4-methylcyclohexyl) -2-
Hydroxypyrimidine, 5- (4-ethylcyclohexyl) -2-hydroxypyrimidine, 5- (4-propylcyclohexyl) -2-hydroxypyrimidine, 5-
(4-butylcyclohexyl) -2-hydroxypyrimidine, 5- (4-pentylcyclohexyl) -2-hydroxypyrimidine, 5- (4-hexylcyclohexyl) -2-hydroxypyrimidine, 5- (4-heptylcyclohexyl) -2 -Hydroxypyrimidine, 5-
(4-octylcyclohexyl) -2-hydroxypyrimidine, 5- (4-nonylcyclohexyl) -2-hydroxypyrimidine, 5- (4-decylcyclohexyl)
-2-hydroxypyrimidine, 5- (4-ethenylcyclohexyl) -2-hydroxypyrimidine, 5- (4-
Propenylcyclohexyl) -2-hydroxypyrimidine, 5- (4-butenylcyclohexyl) -2-hydroxypyrimidine, 5- (4-pentenylcyclohexyl) -2-hydroxypyrimidine, 5- (4-hexenicyclohexyl) -2 -Hydroxypyrimidines, which can also be used as metal phenolates.

The carboxylic acid (3), which is the other raw material in this reaction, can be produced from commercially available products or produced according to a known method (for example, US Pat. No. 5,019,298).

Phenols (2) and carboxylic acids (3)
Can be applied by a usual esterification method, and can be carried out by using a catalyst or a condensing agent in the presence or absence of a solvent.
When a solvent is used in this reaction, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, hexane, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide,
Solvents which are inert to the reaction, such as ethers such as dimethylsulfoxide, acetonitrile or pyridine, ketones, aliphatic or aromatic hydrocarbons, halogenated hydrocarbons, aprotic polar solvents, and organic amines, alone or in a mixture. The amount of such a solvent can be used without any particular limitation. In this reaction, since the carboxylic acid (3) is relatively expensive, it is preferable to carry out the reaction using an excess amount of the other raw material, phenol (2), in order to use the carboxylic acid effectively. The reaction is carried out using 1 to 4 equivalents, preferably 1 to 2 equivalents. Of course, when the phenol (2) is expensive, it is preferable to carry out the reaction using an excess amount of the carboxylic acid (3) as the other raw material.

When a catalyst is used, the catalyst includes
For example, organic or inorganic basic substances such as dimethylaminopyridine, tri-n-butylamine, pyridine, lysine, imidazole, sodium carbonate, sodium methylate, potassium hydrogen carbonate and the like can be mentioned. Further, an organic or inorganic acid such as toluenesulfonic acid, methanesulfonic acid or sulfuric acid can be used as a catalyst. The amount of the catalyst used depends on the type of each raw material used, the combination of the catalyst used, and the like, and is not necessarily specified. For example, when an acid halide is used, the basicity is at least 1 equivalent times the acid halide The substance is used.

Further, when the carboxylic acid (3) is a carboxylic acid, carbodiimides such as N, N'-dicyclohexylcarbodiimide and N-cyclohexyl-N '-(4-diethylamino) cyclohexylcarbodiimide are used as condensing agents. Preferably used, if necessary 4
-Dimethylaminopyridine, 4-pyrrolidinopyridine,
Organic bases such as pyridine and triethylamine can also be used in combination. In this case, the amount of the condensing agent used is usually 1 to 1.2 equivalent times based on the carboxylic acid (3). ０．２0.2 equivalent times. Carboxylic acids (3)
The reaction temperature in the reaction between phenol and the phenol (2) is usually -30C to 100C, preferably -25C to 80C.
° C. The reaction time is not particularly limited, and the reaction can be terminated when the carboxylic acid (3) as the raw material disappears. Of course, when the carboxylic acid (3) as a raw material is excessive, the reaction can be terminated by disappearance of the phenol (2). After completion of the reaction, the desired aromatic derivative represented by the general formula (1) (X = OCO) can be isolated from the reaction mixture by a usual separation means, for example, an operation such as extraction, liquid separation, and concentration. If necessary, it can be purified by column chromatography, recrystallization and the like.

Next, the reaction between the carboxylic acid represented by the general formula (4) and the phenol represented by the general formula (5) will be described. Many of the carboxylic acids (4) used as raw materials in the present invention are known compounds, and can be produced according to the method described in the literature as follows.

[0015]

The carboxylic acids (4) include 2-
(4-methylcyclohexyl) -5-carboxypyrimidine, 2- (4-ethylcyclohexyl) -5-carboxypyrimidine, 2- (4-propylcyclohexyl)
-5-carboxypyrimidine, 2- (4-butylcyclohexyl) -5-carboxypyrimidine, 2- (4-pentylcyclohexyl) -5-carboxypyrimidine,
2- (4-hexylcyclohexyl) -5-carboxypyrimidine, 2- (4-heptylcyclohexyl) -5
-Carboxypyrimidine, 2- (4-octylcyclohexyl) -5-carboxypyrimidine, 2- (4-nonylcyclohexyl) -5-carboxypyrimidine, 2-
(4-decylcyclohexyl) -5-carboxypyrimidine, 2- (4-ethenylcyclohexyl) -5-carboxypyrimidine, 2- (4-propenylcyclohexyl) -5-carboxypyrimidine, 2- (4-butenylcyclohexyl) ) -5-Carboxypyrimidine, 2-
(4-pentenylcyclohexyl) -5-carboxypyrimidine, 2- (4-hexenylcyclohexyl) -5-
Carboxypyrimidine, 5- (4-methylcyclohexyl) -2-carboxypyrimidine, 5- (4-ethylcyclohexyl) -2-carboxypyrimidine, 5- (4
-Propylcyclohexyl) -2-carboxypyrimidine, 5- (4-butylcyclohexyl) -2-carboxypyrimidine, 5- (4-pentylcyclohexyl)-
2-carboxypyrimidine, 5- (4-hexylcyclohexyl) -2-carboxypyrimidine, 5- (4-heptylcyclohexyl) -2-carboxypyrimidine,
5- (4-octylcyclohexyl) -2-carboxypyrimidine, 5- (4-nonylcyclohexyl) -2-
Carboxypyrimidine, 5- (4-decylcyclohexyl) -2-carboxypyrimidine, 5- (4-ethenylcyclohexyl) -2-carboxypyrimidine, 5-
(4-propenylcyclohexyl) -2-carboxypyrimidine, 5- (4-butenylcyclohexyl) -2-carboxypyrimidine, 5- (4-pentenylcyclohexyl) -2-carboxypyrimidine, 5- (4-hexenylcyclohexyl) ) -2-carboxypyrimidines, which can also be used as acid halides, free acids or metal salts.

The phenol (5), which is the other starting material in this reaction, can be a commercially available product or can be produced according to a known method (eg, US Pat. No. 4,985,590). The reaction between the carboxylic acids (4) and the phenols (5) can be carried out by applying the above-mentioned esterification method and reacting with a catalyst or a condensing agent in the presence or absence of a solvent. Can be. When a solvent is used in this reaction, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, hexane, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, and dimethylsulfoxide. , Acetonitrile or pyridine; ethers, ketones; aliphatic or aromatic hydrocarbons; halogenated hydrocarbons; aprotic polar solvents; The amount of such a solvent can be used without any particular limitation.

In this reaction, phenols (5)
Is relatively expensive, and in order to use it effectively, it is preferable to carry out the reaction using an excess amount of the carboxylic acid (4) as the other raw material, usually 1 to 4 equivalents, preferably 1 to 4 equivalents. The reaction is performed using two equivalents. Of course, when the carboxylic acids (4) are expensive, the reaction is preferably performed using an excess amount of the other raw material, phenols (5). When a catalyst is used, examples of such a catalyst include organic or inorganic basic substances such as dimethylaminopyridine, tri-n-butylamine, pyridine, lysine, imidazole, sodium carbonate, sodium methylate, and potassium hydrogen carbonate. Further, an organic or inorganic acid such as toluenesulfonic acid, methanesulfonic acid or sulfuric acid can be used as a catalyst. The amount of the catalyst used depends on the type of each raw material used and the combination of the catalyst used, etc., and cannot always be specified.
For example, when an acid halide is used, a basic substance is used in an amount equivalent to or more than one equivalent of the acid halide.

Further, when the carboxylic acid (4) is a carboxylic acid, carbodiimides such as N, N'-dicyclohexylcarbodiimide and N-cyclohexyl-N '-(4-diethylamino) cyclohexylcarbodiimide are used as condensing agents. Preferably used, if necessary 4
-Dimethylaminopyridine, 4-pyrrolidinopyridine,
Organic bases such as pyridine and triethylamine can also be used in combination. In this case, the amount of the condensing agent used is usually 1 to 1.2 equivalent times with respect to the carboxylic acids (4). ０．２0.2 equivalent times.

Phenols (5) and carboxylic acids (4)
The reaction temperature in the reaction with is usually -30C to 100C, preferably -25C to 80C. The reaction time is not particularly limited, and the reaction can be terminated when the raw material phenol (5) disappears. Of course, when the phenol (5) is in excess, the reaction is terminated when the carboxylic acid (5) disappears. After completion of the reaction, the desired aromatic derivative represented by the general formula (1) (X = COO) can be isolated from the reaction mixture by a usual separation means, for example, an operation such as extraction, liquid separation, and concentration. If necessary, it can be purified by column chromatography, recrystallization and the like.

Next, a halide represented by the general formula (6), an acetylene represented by the general formula (7) or a boron represented by the general formula (8) and a palladium catalyst are mixed in the presence of a basic substance. A method for causing the reaction will be described.
The halide (6) as a raw material used in the present invention can be produced, for example, by the following method.

[0022]

[0023]

[0024]

As the halide (6), 2- (4-
Methylcyclohexyl) -5- (4-bromophenyl)
Pyrimidine, 2- (4-ethylcyclohexyl) -5
(4-bromophenyl) pyrimidine, 2- (4-propylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-butylcyclohexyl) -5- (4
-Bromophenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-hexylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-heptylcyclohexyl) -5- ( 4-bromophenyl) pyrimidine, 2- (4-octylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-nonylcyclohexyl) -5- (4-bromophenyl) pyrimidine,
2- (4-decylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-ethenylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2-
(4-propenylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-butenylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2-
(4-pentenylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 2- (4-hexenylcyclohexyl) -5- (4-bromophenyl) pyrimidine, 5-
(4-methylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-ethylcyclohexyl)
-2- (4-bromophenyl) pyrimidine, 5- (4-
Propylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-butylcyclohexyl)-
2- (4-bromophenyl) pyrimidine, 5- (4-pentylcyclohexyl) -2- (4-bromophenyl)
Pyrimidine, 5- (4-hexylcyclohexyl) -2
-(4-bromophenyl) pyrimidine, 5- (4-heptylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-octylcyclohexyl) -2-
(4-bromophenyl) pyrimidine, 5- (4-nonylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-decylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-ethenylcyclohexyl)- 2- (4-bromophenyl) pyrimidine, 5- (4-propenylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-butenylcyclohexyl) -2- (4-bromophenyl) pyrimidine, 5- (4-pentenyl) Cyclohexyl) -2- (4
-Bromophenyl) pyrimidine, 5- (4-hexenylcyclohexyl) -2- (4-bromophenyl) pyrimidine, further, a compound in which the above bromine atom is replaced by an iodine atom or a trifluoromethanesulfonyloxy group, and furthermore, the above phenyl group is Compounds substituted by 3-fluorophenyl group, 2-fluorophenyl group, and 2,3-difluorophenyl group can be mentioned.

The acetylenes (7) or borons (8), which are the other raw materials in this reaction, are commercially available, or the borons (8) are prepared according to a known method, for example, by the following method. Can be manufactured.

Halide (6) and acetylenes (7)
Alternatively, in a reaction to obtain an aromatic derivative (1) (where E is —CHＣＨCH—, —C≡C—) from the boron (8), the acetylene (7) or the boron (8) ) Is usually 0.9 to 10 equivalents, preferably 1 to 3 equivalents, to the halide (2). As the metal catalyst, palladium chloride, palladium acetate, triphenylphosphine palladium complex, palladium / carbon and the like are used in the case of palladium, and the same catalysts as in the above-mentioned palladium are used in the case of nickel and rhodium. The amount of these metal catalysts used is in the range of 0.001 to 0.1 times equivalent to the starting halide (2). In this reaction, a trivalent phosphorus compound or a trivalent arsenic compound is used as a co-catalyst in addition to the above-mentioned metal catalyst, and these are represented by the general formula (7): R ^6- (R ^7- ) Y-R ¹⁰ (7) (wherein, Y represents a phosphorus atom or arsenic atom, R ^6, R
⁷ and R ¹⁰ are the same or different alkyl group, an aryl group, an alkoxy group, an aryloxy group or a halogen atom. ), Specifically, tri-n-butylphosphine, triphenylphosphine, tri-o-tolylphosphine, tri-o-tolylphosphite, phosphorus trichloride, triphenylarsenic and the like. You. The amount of the phosphorus compound or the arsenic compound to be used is 0.5 to 50 equivalents, preferably 10 to 30 equivalents to the above metal catalyst. Further, in addition to these catalysts, a copper catalyst is preferably used. As such a copper catalyst, copper iodide, copper bromide, copper chloride, copper oxide, copper cyanide, or the like is used. Compound (2) in the range of 0.001 to 0.1 equivalent. Of course, it is possible to use more, but there is no merit of using it in large quantities.

Examples of the basic substance include alkali metal carbonates, carboxylate salts, alkoxides, hydroxides, and organic bases. Preferred examples include diethylamine, triethylamine, diisopropylethylamine, and tri-n-butylamine. Amine, tetramethylethylenediamine, dimethylaniline, piperidine, piperazine, morpholine, N-methylmorpholine,
Tertiary or secondary amines (organic bases) such as N-methylpiperidine, or hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide are preferably used. The amount of the base to be used is generally 1 to 5 equivalents to the halide (2). If necessary, a suitable solvent such as acetonitrile, toluene, pyridine, picoline, tetrahydrofuran, dimethylformamide, hexamethylphosphorylamide, N-methylpyrrolidone,
Methanol or the like can also be used as a reaction solvent. Further, the above base can be used as a solvent. The use amount of these reaction solvents is not particularly limited.

The above reaction is usually carried out in an inert gas such as nitrogen or argon. In the reaction, the yield of the intended ester derivative can be improved by increasing the reaction temperature, but since the by-products increase at an excessively high temperature, the reaction temperature is usually 15 to 160 ° C., preferably 30-140 ° C. There is no particular limitation on the reaction time. After completion of the reaction, the aromatic derivative (1) can be obtained by ordinary means such as extraction, concentration, and recrystallization. Further, if necessary, it can be purified by column chromatography or recrystallization. further,
Instead of the acetylenes represented by the general formula (7) or the borons represented by the general formula (8), the general formula (7 ′)）-(CH ₂ ) _r —CH (CH ₃ ) —OH (7 ′) (Wherein, r represents the same meaning as described above) or an acetylene represented by the general formula (8 ′) (Wherein, R ⁸ and r have the same meanings as described above), and reacting a halide represented by the general formula (6) with a metal catalyst in the presence of a basic substance to obtain a general compound. Equation (9) (Wherein, R ¹ , Ar, X, E, n, r and l represent the same meaning as described above).
Formula (10) R ⁴ COR ′ (10) (wherein, R ⁴ is a saturated or unsaturated alkyl group having 1 to 20 carbon atoms, which may be substituted with a halogen atom, or an alkoxyalkyl having 2 to 20 carbon atoms) R ′ represents a hydroxyl group, a halogen atom or OCOR ⁵ ) to react with a carboxylic acid represented by the following formula:
m is 0, n is 0) or a compound represented by the general formula (11) R ⁴ —Z (11) (wherein R ⁴ has the same meaning as described above, and Z represents a halogen atom or —OSO ₂ R ⁹ ) Wherein R ⁹ represents a lower alkyl group or an optionally substituted phenyl group) to obtain an aromatic derivative (where m is 0 and n is 0). Furthermore, the alcohols represented by the general formula (9) are hydrogenated using hydrogen and a hydrogenation catalyst to obtain a compound represented by the general formula (12): (Wherein, R ¹ , Ar, X, r, and 1 represent the same meaning as described above), and then a carboxylic acid represented by the general formula (10) or a carboxylic acid represented by the general formula (11) ) To obtain an aromatic derivative (1) (where m is 0 and n is 0).

The reaction between the acetylene (7 ') or boron (8') and the halide (6) is carried out by the above-mentioned acetylene (7) or boron (8) and the halide (6).
The reaction for obtaining the aromatic derivative (1) from the above is applied as it is, and after completion of the reaction, the alcohol (9) can be obtained by ordinary means such as extraction, concentration, and recrystallization. Also,
If necessary, it can be purified by column chromatography or recrystallization. In the reaction between the alcohols (9) and the carboxylic acids (10), the carboxylic acids (10) include carboxylic acids represented by R ⁴ , acid anhydrides or acid chlorides thereof, and acid halides such as acid bromides. Is done. In addition, these carboxylic acids (10) may be any of a racemic form and an optically active form.

In the above reaction, when a solvent is used,
As the solvent, for example, tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene,
Solvents that are inert to the reaction such as ethers such as benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, and hexane, ketones, aliphatic or aromatic carbons, hydrogen halides, and aprotic polar solvents. Alone or a mixture can be mentioned. The amount used is not particularly limited.

In the above reaction, when an acid anhydride or an acid halide of an aliphatic carboxylic acid is used, the amount of the acid anhydride must be at least one equivalent of the alcohol (9), and the upper limit is not particularly limited. But not preferably 1.
1 to 4 equivalent times.

Examples of the catalyst used in the above reaction include organic or organic catalysts such as dimethylaminopyridine, 4-pyrrolidinopyridine, triethylamine, tri-n-butylamine, pyridine, collidine, sodium imidazole carbonate, sodium methylate and potassium hydrogen carbonate. And inorganic basic substances. Further, an organic or inorganic acid such as toluenesulfonic acid, methanesulfonic acid or sulfuric acid can be used as a catalyst. In using such a catalyst, for example, when an acid halide of a carboxylic acid is used as a raw material, pyridine and triethylamine are preferably used. The amount of the catalyst used varies depending on the combination of the acid anhydride or acid halide of the carboxylic acids and the catalyst to be used, and is not necessarily specified. For example, when the acid halide is used, it is 1 equivalent times as large as the acid halide. That is all.

In the above reaction, when a carboxylic acid is used, the carboxylic acid is usually used in an amount of 1 to 2 equivalents to the alcohol (9) in the presence of a condensing agent to effect dehydration condensation. Obtainable. Examples of the condensing agent include N, N′-dicyclohexylcarbodiimide,
Carbodiimides such as N-cyclohexyl-N '-(4-diethylamino) cyclohexylcarbodiimide are preferably used, and if necessary, organic bases such as 4-dimethylaminopyridine, 4-pyrrolidinopyridine, pyridine and triethylamine are used in combination. The amount of the condensing agent used is 1 to 1.5 equivalent times the carboxylic acid,
When the organic base is used in combination, the amount used is 0.01 to 0.2 equivalent times as much as the condensing agent. The reaction temperature is usually -30
-100 ° C, preferably 0-80 ° C. The reaction time is not particularly limited, and the time when the raw material (9) has disappeared can be the end point of the reaction. After the completion of the reaction, by ordinary separation means, for example, extraction, separation, concentration and other operations,
The aromatic derivative (1) can be obtained in good yield, and if necessary, can be purified by column chromatography, recrystallization and the like.

Next, the alcohol (9) and the general formula (1)
In the reaction with the alkylating agent shown in 1), the alkylating agent used is a halogenated or sulfonated ester having a substituent R ⁴ , and can be produced from the corresponding alcohol by a known method.
The substituent R ⁴ in the alkylating agent may be an optically active substance. This reaction is usually performed in the presence of a basic substance. The amount of the alkylating agent to be used is optionally 1 equivalent or more times the amount of the acetylene phenol (9), but is usually in the range of 1 to 5 equivalents.

The above reaction is usually carried out in the presence of a solvent. Examples of the solvent used include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, and carbon tetrachloride. Solvents which are inert to the reaction of ethers, ketones, aliphatic or aromatic hydrocarbons, halogenated hydrocarbons, aprotic polar solvents, etc. And mixtures thereof. The amount of the solvent used is not particularly limited.

Examples of the basic substance include alkali metal hydrides such as sodium hydride and potassium hydride, alkali metals such as lithium, sodium and potassium, alkali metal alcoholates such as sodium ethylate and sodium methylate, and sodium carbonate. And alkali metal carbonates such as potassium carbonate, butyllithium and the like. Such a basic substance is required to be at least 1 equivalent times the alcohol (9), and the upper limit is not particularly limited, but is usually 1.1 to 5 equivalent times. The reaction temperature is usually
The range is from -50 to 120C, preferably from -30 to 100C. The reaction time is not particularly limited, and the reaction can be terminated by the disappearance of the starting alcohol (9). After completion of the reaction, the desired aromatic derivative represented by the general formula (1) can be isolated from the reaction mixture by a usual separation means, for example, extraction, liquid separation, concentration, etc., and if necessary, a column. It can also be purified by chromatography, recrystallization and the like.

In the above alkylation reaction, when the substituent Z of the alkylating agent is an iodine atom, silver oxide can be used instead of the above-mentioned basic substance.
In this case, the silver oxide is required to be at least 1 equivalent times the acetylene phenols (9), and the upper limit is not particularly limited, but is preferably at least 5 equivalent times. When performing an alkylation reaction in the presence of silver oxide, the amount of the alkylating agent (provided that the substituent Z is an iodine atom) is as follows:
It is optionally 1 equivalent or more times the amount of the raw material (9), but preferably 2 to 10 times the equivalent.

As a reaction solvent, an excess of an alkylating agent (substituted by an iodine atom) can be used as a solvent, and tetrahydrofuran, ethyl ether, dioxane, acetone, methyl ethyl ketone, benzene,
Solvents that are inert to the reaction, such as ethers such as toluene and hexane, ketones, and hydrocarbon solvents, may be used alone or as a mixture. The reaction temperature is usually in the range of 0 to 150 ° C, preferably 20 to 100 ° C. The reaction time is
Usually 1 hour to 20 days. Aromatic derivatives (1)
The reaction mixture is removed from the reaction mixture by removing the silver salt by filtration, and then performing a usual post-treatment operation such as extraction, liquid separation, and concentration. Further, if necessary, it can be purified by column chromatography or the like. The method for obtaining the aromatic derivative (1) from the alcohol (9) has been described above. As the substituent R ⁴ in the carboxylic acid (10) and the alkylating agent (11), the following are exemplified. Is done.

Methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, propenyl, 2-butenyl, 3-butenyl 3,3-hexenyl, 2-butynyl, 3-hexynyl, cyclopropyl, 2,2-dimethylcyclopropyl, cyclopentyl, cyclohexyl,
Octadecyl, nonadecyl, eicosyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, methoxynonyl, methoxydecyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, Ethoxyhexyl, ethoxyheptyl, ethoxyoctyl, ethoxynonyl, ethoxydecyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl,
Propoxypentyl, propoxyhexyl, propoxyheptyl, propoxyoctyl, propoxynonyl,
Propoxydecyl, butoxybutoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, butoxyhexyl, butoxyheptyl, butoxyoctyl, butoxynonyl, butoxydecyl, pentyloxymethyl, pentyloxyethyl, pentyloxypropyl, pentyloxybutyl, Pentyloxypentyl, pentyloxyhexyl, pentyloxyoctyl, pentyloxynonyl, pentyloxydecyl, hexyloxymethyl, hexyloxyethyl, hexyloxypropyl, hexyloxybutyl, hexyloxypentyl, hexyloxyhexyl, hexyloxyheptyl, hexyloxy Octyl, hexyloxynonyl, hexyloxydecyl, heptyloxymethyl, heptyloxy Siethyl, heptyloxypropyl, heptyloxybutyl, heptyloxypentyl,
Heptyloxyhexyl, heptyloxyheptyl, heptyloxyoctyl, heptyloxynonyl, heptyloxydecyl, octyloxymethyl, octyloxyethyl, octyloxypropyl, octyloxybutyl, octyloxypentyl, octyloxyhexyl, octyloxyheptyl, octyloxy Nonyl,
Octyloxyoctyl, decyloxymethyl, decyloxyethyl, decyloxypropyl, decyloxybutyl, decyloxypentyl, decyloxyhexyl,
Decyloxyheptyl, 1-methylethyl, 1-methylpropyl, 1-methylbutyl, 1-methylpentyl, 1
-Methylhexyl, 1-methylheptyl, 1-methyloctyl, 1-methylnonyl, 1-methyldecyl, 2-methylpropyl, 2-methylbutyl, 2-methylpentyl, 2-methylhexyl, 2-methylheptyl, 2-methyloctyl, 2,3-dimethylbutyl, 2,3,3-trimethylbutyl, 3-methylpentyl, 3,3-dimethylpentyl, 2,4-dimethylpentyl, 2,3,
3,4-tetramethylpentyl, 3-methylhexyl,
2,5-dimethylhexyl, 2-trihalomethylpropyl, 2-trihalomethylbutyl, 2-trihalomethylpentyl, 2-trihalomethylhexyl, 2-trihalomethylheptyl, 2-haloethyl, 2-halopropyl,
3-halopropyl, 3-halo-2-methylpropyl,
2,3-dihalopropyl, 2-halobutyl, 3-halobutyl, 4-halobutyl, 2,3-dihalobutyl, 2,4
Dihalobutyl, 3,4 Dihalobutyl, 2-Halo 3
-Methylbutyl, 2-halo3,3-dimethylbutyl,
2-halopentyl, 3-halopentyl, 4-halopentyl, 5-halopentyl, 2,4-dihalopentyl, 2,
5-dihalopentyl, 2-halo-3-methylpentyl,
2-halo-4-methylpentyl, 2-halo-3-monohalomethyl-4-methylpentyl, 2-halohexyl, 3
-Halohexyl, 4-halohexyl, 5-halohexyl, 6-halohexyl, 2-haloheptyl, 2-halooctyl, (in the above examples, halo represents fluorine, chlorine or bromine) and the like. Examples of the carboxylic acids include, in addition to the above examples, halomethyl, 1-haloethyl, 1-halopropyl, 1-halobutyl, 1-halopentyl, 1-halohexyl, 1-haloheptyl, 1-halooctyl, and the like. These alkyl groups or certain alkoxyalkyl groups are linear, branched or cyclic, and when branched or cyclic, they may be optically active groups.

Among the above exemplified carboxylic acids having a substituent R ⁴ , those which are optically active are obtained by oxidation of the corresponding alcohols and reductive deamination of amino acids, and some are naturally occurring or Alternatively, it can be derived from the following optically active amino acids and optically active oxyacids obtained by resolution. Further, among the alkylating agents having a substituent R ⁴ , those which are optically active can be easily produced from the corresponding alcohol by a known method, and some of these alcohols are asymmetric metal catalysts of the corresponding ketone or Obtained by asymmetric reduction with microorganisms or oxygen. Some are naturally occurring or can be derived from optically active amino acids or optically active oxyacids obtained by optical resolution, such as: Alanine, valine, leucine, isoleucine, phenylalanine, threonine, alosreonine, homoserine, alloisoleucine, tert-leucine, 2-aminobutyric acid, norvaline, norleucine, ornithine, lysine, hydroxylysine, phenylglycine, aspartic acid, glutamic acid, mandelic acid , Tropic acid, 3-hydroxybutyric acid, malic acid, tartaric acid or isopropyl malic acid.
Among the aromatic derivatives (1) thus obtained, E
However, the unsaturated compound showing —CH ＝ CH— or —C≡C— can further reduce this unsaturated bond to obtain a saturated aromatic derivative (1).

Such a reduction reaction can be carried out by hydrogenation using hydrogen and a hydrogenation catalyst. As the hydrogenation catalyst in the above reaction, Raney nickel, palladium or a platinum-based metal catalyst usually used as a hydrogenation catalyst is preferably used, and specific examples thereof are palladium-carbon, palladium oxide, palladium black, palladium chloride or platinum-. And carbon. Such a hydrogenation catalyst is used usually in an amount of 0.001 to 0.5 times by weight, preferably 0.005 to 0.3 times by weight of the raw material. The reaction is usually
The reaction is performed in a solvent, for example, water, dioxane, tetrahydrofuran, methanol, ethanol, n
Hydrocarbons such as propyl alcohol, acetone, dimethylformamide, toluene, dichloromethane or ethyl acetate, alcohols, ethers, ketones, esters,
A single solvent or a mixture of solvents inert to the reaction such as halogenated hydrocarbons or amides is used.

The above reaction is carried out at a hydrogen pressure of normal pressure or under pressure, and it is preferable that the reaction end point is reached when the amount of absorbed hydrogen becomes 2 to 2.4 equivalent times the raw material. The reaction is carried out at a temperature of -10 to 130C, preferably 10 to 100C. After completion of the reaction, the desired saturated aromatic derivative (1) can be obtained by removing the catalyst from the reaction mixture by filtration or the like and then concentrating it. It can also be purified by chromatography or the like. The saturated aromatic derivative (1) was separately hydrogenated with an alcohol represented by the general formula (9) using hydrogen and a hydrogenation catalyst to obtain a saturated alcohol represented by the general formula (12). Thereafter, it can be obtained by further reacting with a carboxylic acid represented by the general formula (10) or separately with an alkylating agent represented by the general formula (11). The reduction reaction used here can be carried out in the same manner according to the method of obtaining hydrogen of the general formula (1) by hydrogenation using the above hydrogen and a hydrogenation catalyst. Esterification and alkylation conditions and purification can be carried out in the same manner as in the case of the alcohols (9).

The intermediate (13-a) or (13-b), which is a synthetic intermediate of the halide represented by the general formula (6), is prepared separately from the general formula (14) R ³ -Z (14) ( In the formula, R ³ and Z have the same meanings as described above), whereby an aromatic derivative (m = 1) can be obtained. Alkylation conditions and purification can be carried out in the same manner as in the case of the alcohols (9). The alkylating agent can be a commercially available product or can be synthesized according to a known method.

The alcohols represented by the general formula (9) or the saturated alcohols represented by the general formula (12) are obtained by substituting a hydroxyl group with a fluorine atom by using a fluorinating agent to obtain a fluorinated aromatic compound. A derivative (provided that Y is a fluorine atom) can be used. Examples of the fluorinating agent used herein include hydrogen fluoride, a complex compound thereof, a sulfur fluoride-based compound, a fluorinated olefin, and the like. Specifically, hydrogen fluoride-pyridine, hydrogen fluoride-triethylamine,
Sulfur fluoride, diethylamino sulfur trifluoride (DAS
T), morpholino sulfur trifluoride (morph-DAS)
T), 2-chloro-1,1,2-trifluoroethylene, hexafluoropropene and the like. These alone,
It can be used as a mixture or in combination with diethylamine, diisopropylamine and morpholine.

The formula (9) or (12)
In the reaction between the alcohol and the fluorinating agent represented by the formula (I), the amount of the fluorinating agent is usually 1.0 to 5 equivalents, preferably 1.0 to 2 equivalents to the alcohol. is there. In this reaction, a solvent is usually preferably used, and halogenated hydrocarbons or hydrocarbons are preferably used. Specifically, hexane, benzene, toluene, dichloromethane, dichloroethane, chlorobenzene and the like are used alone or in a mixture. The use amount of these reaction solvents is not particularly limited. The reaction temperature of this reaction is usually-
70 to 100 ° C, preferably -40 to 50 ° C
It is. After the completion of the reaction, the fluorinated aromatic derivative (1) can be obtained by ordinary post-treatment methods such as extraction, distillation, recrystallization, and column chromatography.

[0047]

Thus, according to the method of the present invention, an aromatic derivative effective for the development of an optical switching element or a liquid crystal display element material can be produced industrially and advantageously.

[0048]

EXAMPLES The present invention will be described below with reference to examples.
The invention is not limited to these. Example 1 In a four-necked flask equipped with a stirrer and thermometer, add 2-
(4-pentylcyclohexyl) -5- (4-bromofur
Phenyl) pyrimidine (6-1) 11.6 g (0.03
), Optically active 1-heptin-6-ol (7-1)
4.0 g (0.036 mol) of bis (triphenylphosphine)
N) 0.15 g of palladium chloride, 0.20 g of copper iodide,
0.9 g of phenylphosphine and 60 of triethylamine
ml, and put in a nitrogen stream at 60 to 65 ° C. for 13 hours.
Let react. After the reaction is completed, the reaction mixture is made up to 200 ml of water.
Pour and extract with 200 ml of ethyl acetate. Acetic acid obtained
The chill layer is washed with 3% HCl aqueous solution and then concentrated under reduced pressure.
Obtain the residue. This is silica gel column chromatography
(Eluent: toluene-ethyl acetate)
Biologically active (-)-2- (4-pentylcyclohexyl)
-5- (4- (6-hydroxy-1-heptynyl) fe
Nyl) pyrimidine (9-1) (9.9 g, 79% yield)
obtain. Optical rotation [α]_D ²⁰−2.9 ° (C = 1.0, CHCl
 _Three). Next, 4.2 g (1) of (9-1) obtained here was obtained.
0 mmol), 10 ml of methanol, 30 ml of ethyl acetate
And a 0.4% mixed solution of 5% palladium on carbon
10kg / cm^TwoAt 30 to 40 ° C. End of reaction
After that, the catalyst is filtered off, the filtrate is concentrated under reduced pressure, and the optically active
(-)-2- (4-pentylcyclohexyl) -5
(4- (6-hydroxy-1-heptyl) phenyl) pi
4.1 g (98.0% yield) of limidine (12-1) was obtained.
You. Optical rotation [α]_D ²⁰−2.7 ° (C = 1.0, CHCl_Three).
(Melting point 78-79 ° C) Further, (12-1) 0.84 g (2 mM) was added to pyridine.
A salt solution is added to a mixed solution of 5 ml and 8 ml of toluene at 20 to 25 ° C.
0.24 g (3 mmol) of acetyl chloride (10-1)
You. Thereafter, the reaction is carried out at the same temperature for 2 hours. End of reaction
Thereafter, the reaction solution is poured into ice water and extracted with 30 ml of toluene.
You. The organic layer was washed with aqueous hydrochloric acid, water, and aqueous sodium bicarbonate, and then concentrated.
Further purification by chromatography allows for optically active
(-)-2- (4-pentylcyclohexyl) -5
(4- (6-acetoxy-1-heptyl) phenyl) pi
0.9 g (97% yield) of limidine (1-1) is obtained. Turning
Luminous intensity [α] _D ²⁰−3.1 ° (C = 1.0, CHCl_Three)

Example 2 The optically active (-)-2- (4-pentylcyclohexyl) -5- (4- (6-hydroxy-) obtained in Example 1 was obtained.
1-heptyl) phenyl) pyrimidine (12-1)
84 g (2 mM), 20 g of ethyl iodide (11-2),
A mixed solution of 15 g of silver oxide is reacted at 30 to 35 ° C. for 48 hours. After the completion of the reaction, the reaction solution was separated by filtration, and the filtrate was concentrated and further purified by chromatography to obtain optically active (-)-2- (4-pentylcyclohexyl) -5-.
0.54 g (63% yield) of (4- (6-ethoxy-1-heptyl) phenyl) pyrimidine (1-2) is obtained. Optical rotation [α] _D ²⁰ −2.4 ° (C = 1.0, CHCl ₃ )

Embodiment 3 Example 1 was obtained in a reactor equipped with a stirrer and a thermometer.
Optically active (-)-2- (4-pentylcyclohexyl)
) -5- (4- (6-Hydroxy-1-heptyl) phenyl
0.84 g (2 mM) of phenyl) pyrimidine (12-1)
And dichloromethane (30 ml).
Add 0.5 g of tylamino sulfur trifluoride and stir for 30 minutes
You. Thereafter, the reaction mixture was poured into water and toluene 100 m
The organic layer is washed with water and concentrated under reduced pressure. Get
Residues are separated by silica gel column chromatography (elution
Liquid: toluene-hexane) to give (+)-2
-(4-pentylcyclohexyl) -5- (4- (6-
(Fluoro-1-heptyl) phenyl) pyrimidine (1-
3) 0.74 g (84% yield) is obtained. Optical rotation [α] _D
²⁰+ 2.8 ° (C = 1.0, CHCl_Three).

Example 4 The optically active (-)-2- (4-pentylcyclohexyl) -5- (4- (6-hydroxy-) obtained in Example 1 was obtained.
1-heptynyl) phenyl) pyrimidine (9-1)
84 g (2 mM) of acetic anhydride (10-4) was added to a mixed solution of 5 ml of pyridine and 8 ml of toluene at 20 to 25 ° C.
5 g (5 mmol) are added. Thereafter, the reaction is carried out at the same temperature for 2 hours. After completion of the reaction, the reaction solution is poured into ice water and extracted with 30 ml of toluene. The organic layer is washed with aqueous hydrochloric acid, water and aqueous sodium bicarbonate, concentrated, and then purified by chromatography to obtain optically active (-)-2- (4-pentylcyclohexyl) -5- (4- (6 0.9 g (yield 98%) of -acetoxy-1-heptynyl) phenyl) pyrimidine (1-4) is obtained. Optical rotation [α] _D ²⁰ −3.3 ° (C = 1.0
, CHCl ₃ ).

Embodiment 5 Optically active (-)-2- (4-pen) obtained in Example 1
Tylcyclohexyl) -5- (4- (6-hydroxy-
1-heptynyl) phenyl) pyrimidine (9-1)
84 g (2 mM), 25 g of methyl iodide (11-2),
A mixed solution of 15 g of silver oxide is reacted at 30 ° C. for 48 hours.
You. After completion of the reaction, the reaction solution was separated by filtration, and the filtrate was concentrated.
By purifying by chromatography, the optically active (-)
-2- (4-pentylcyclohexyl) -5- (4-
(6-methoxy-1-heptyl) phenyl) pyrimidine
(1-5) 0.62 g (yield 72%) is obtained. Optical rotation
[Α] _D ²⁰−2.6 ° (C = 1.0, CHCl_Three). Got here
(1-5) 0.43 g (1 mmol), methanol
10 ml, tetrahydrofuran 10 ml and 5%
A mixed solution of 0.05 g of carbon dioxide is hydrogen pressure of 10 kg / cm2.
 Hydrogenation under the condition of 30-35 ° C, (-)-2-
(4-pentylcyclohexyl) -5- (4- (6-me
(Toxiheptinyl) phenyl) pyrimidine is obtained.

Example 6 The optically active (-)-2- (4-pentylcyclohexyl) -5- (4- (6-hydroxy-) obtained in Example 1 was placed in a reactor equipped with a stirrer and a thermometer. 1-heptynyl)
0.84 g (2 mM) of phenyl) pyrimidine (9-1)
And 30 ml of dichloromethane, 0.4 g of diethylaminosulfur trifluoride was added at −45 ° C., and the mixture was stirred for 30 minutes. Thereafter, the reaction mixture was poured into water and toluene (50 ml) was added.
, And the organic layer was washed with water and concentrated under reduced pressure. The obtained residue is subjected to silica gel column chromatography (eluent:
(Toluene-hexane) to give (+)-2- (4-
Pentylcyclohexyl) -5- (4- (6-fluoro-
1-heptynyl) phenyl) pyrimidine (1-6)
74 g (84% yield) are obtained. Optical rotation [α] _D ²⁰ +2.9
° (C = 1.0, CHCl ₃ ). (1-6) obtained here
0.44 g (1 mmol), methanol 10 ml, tetrahydrofuran 10 ml and 5% palladium on carbon 0.05
g of the mixed solution was hydrogenated at a hydrogen pressure of 10 kg / cm ² and a temperature of 30 to 35 ° C. to obtain (+)-2- (4-pentylcyclohexyl) -5- (4- (6-fluoroheptinyl) phenyl) pyrimidine. Get

Example 7 A four-necked flask equipped with a stirrer, a reflux condenser and a thermometer and purged with nitrogen in the system was charged with 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4). -Trifluoromethanesulfonyloxyphenyl) pyrimidine (6-7)
5.9 g (12 mmol), tetrakistriphenylphosphine palladium 0.23 g (0.2 mmol),
After adding 2.4 g (60 mmol) of sodium hydroxide and 60 ml of tetrahydrofuran, 50 ml of a solution of E-1-heptenylcatecholborane (8-7) (20 mmol) in tetrahydrofuran is added dropwise at room temperature. Thereafter, the mixture is heated and refluxed for 6 hours while stirring. After cooling to room temperature, 5 ml of a 10% aqueous sodium hydroxide solution and 2 ml of a 30% aqueous hydrogen peroxide solution are added, followed by stirring for 1 hour. Ether was added for extraction, and the organic layer was washed twice with 20 ml of a saturated saline solution.
Dry using anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography to give 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4- (1-trans).
4.7 g of (-heptenyl) phenyl) pyrimidine (1-
7) (83% yield). (1-
7) 0.49 g (1 mmol), 10 ml of methanol, 10 ml of tetrahydrofuran and 0.5% palladium on carbon.
05 g of the mixed solution was subjected to a hydrogen pressure of 10 kg / cm ² at 30 to 35 ° C.
Hydrogenate under the conditions. After completion of the reaction, the catalyst is filtered off, and the filtrate is concentrated under reduced pressure to give 2- (4-pentylcyclohexyl).
-5- (2,3-difluoro-4-heptenylphenyl)
0.45 g (96% yield) of pyrimidine are obtained.

Example 8 A four-necked flask equipped with a stirrer and a thermometer was charged with 2-
(4-propylcyclohexyl) -5- (4-bromobenzoyloxy) pyrimidine (6-8) 4.0 g (0.01
Mol), 1.4 g (0.02 mol) of 1-pentyne (7-8), 0.1 g of bis (triphenylphosphine) palladium chloride, 0.2 g of copper iodide, triphenylphosphine
0.5 g and 40 ml of triethylamine are charged and reacted at 70 to 75 ° C. for 13 hours under a nitrogen stream. After completion of the reaction, the reaction mixture was poured into 400 ml of water, and toluene 20
Extract with 0 ml. The resulting toluene layer is 3% HCl aqueous,
After washing with water, the mixture is concentrated under reduced pressure to obtain a brown residue. The residue was purified by silica gel column chromatography (eluent: toluene-hexane), and 2.0 g of 2- (4-propylcyclohexyl) -5- (4- (1-pentynyl) benzoyloxy) pyrimidine (1-8) was used. (51% yield). 0.4 g (1 mmol) of (1-8) obtained here, 10 ml of methanol, 30 ml of ethyl acetate and 5
Hydrogen pressure of 10 kg
/ Cm ² at 30 to 35 ° C. After the reaction,
The catalyst is removed by filtration, and the filtrate is concentrated under reduced pressure to obtain 2.0 g of 2- (4-propylcyclohexyl) -5- (4-pentylbenzoyloxy) pyrimidine (yield: 95%).

Example 9 An acid chloride prepared from 2.4 g (10 mmol) of (+)-4- (1-butyryloxyethyl) phenylcarboxylic acid (3-9) and oxalyl chloride was treated with 2- (4- Pentylcyclohexyl) -5-hydroxypyrimidine (2-9) 3.0 g (12 mmol), pyridine 20 g
And 30 g of dichloromethane at room temperature. Stir at the same temperature for 2 hours. After completion of the reaction, the reaction solution is extracted with 100 ml of toluene, and washed successively with water, dilute hydrochloric acid, 7% aqueous sodium bicarbonate and water. The organic layer was concentrated under reduced pressure, and the obtained pale yellow solid was purified by silica gel column chromatography to obtain 2- (4-pentylcyclohexyl) of (+)-4- (1-butyryloxyethyl) phenylcarboxylic acid. ) Esters of 5-hydroxypyrimidine (1-9)
4.3 g (93% yield) are obtained. Optical rotation [α] _D ²⁰ +2.
3 ° (C = 1.0, CHCl ₃ ). As in the present embodiment,
2- (4-pentylcyclohexyl) of (+)-4 ′-(1-hexanoyloxyethyl) phenylcarboxylic acid
Esters of -5-hydroxypyrimidine, (+)-4 '
Ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of-(1-decanoyloxyethyl) phenylcarboxylic acid, 2- (4-)-4 '-(1-butyryloxyethyl) phenylcarboxylic acid Ester of (4-pentylcyclohexyl) -5-hydroxypyrimidine, (+)-4 ′-(1-butyryloxyethyl)
Esters of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of phenylcarboxylic acid can be synthesized.

Example 10 4-hexyloxyphenylcarboxylic acid (3-10)
An acid chloride prepared from 2.2 g and oxalyl chloride was mixed with 3.0 g (12 mmol) of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine (2-10).
l), at room temperature in a solution consisting of 20 g of pyridine and 30 g of dichloromethane. Stir at the same temperature for 2 hours. After completion of the reaction, the reaction solution is extracted with 100 ml of toluene, and washed successively with water, dilute hydrochloric acid, 7% aqueous sodium bicarbonate and water. The organic layer was concentrated under reduced pressure, and the obtained pale yellow solid was purified by silica gel column chromatography to obtain 2- (4-pentylcyclohexyl) of 4-hexyloxyphenylcarboxylic acid.
Esters of -5-hydroxypyrimidine (1-10)
4.3 g (95% yield) are obtained. In the same manner as in this example, 4- (4-pentyloxyphenylcarboxylic acid) 2- (4
-Pentylcyclohexyl) -5-hydroxypyrimidine ester, 4-heptyloxyphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester, 4-octyloxyphenylcarboxylic acid 2- (4-pentyl) Cyclohexyl) -5
-Hydroxypyrimidine ester, 4-nonyloxyphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester, 4-decyloxyphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxy Esters of pyrimidines,
An ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 4-dodecyloxyphenylcarboxylic acid can be synthesized. Further, an ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 4-hexylphenylcarboxylic acid, an ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 4-heptylphenylcarboxylic acid, 4
Esters of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of octylphenylcarboxylic acid, esters of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 4-nonylphenylcarboxylic acid, 4-decylphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester of acid, 2- (4-pentylcyclohexyl) ester of 4-dodecylphenylcarboxylic acid
An ester of (pentylcyclohexyl) -5-hydroxypyrimidine can be synthesized.

Example 11 2.6 g (10 mmol) of 2,3-difluoro-4-hexyloxyphenylcarboxylic acid (3-11) and acid chloride prepared from oxalyl chloride were combined with 2- (4-pentylcyclohexyl) -5- Hydroxypyrimidine (2
-11) It is added at room temperature to a solution consisting of 3.0 g (12 mmol), 20 g of pyridine and 30 g of dichloromethane. Stir at the same temperature for 2 hours. After completion of the reaction, the reaction solution is extracted with 100 ml of toluene, and washed successively with water, dilute hydrochloric acid, 7% aqueous sodium bicarbonate and water. The organic layer was concentrated under reduced pressure, and the obtained pale yellow solid was purified by silica gel column chromatography to give 2,3-difluoro-4-hexyloxyphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5.
-Hydroxypyrimidine ester (1-11) 4.6
g (yield 94%), ester of 2,3-difluoro-4-pentyloxyphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine 2,3 difluoro-4- Ester 2,3- (4-pentylcyclohexyl) -5-hydroxypyrimidine of heptyloxyphenylcarboxylic acid 2,3- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester 2,3-difluoro-4-octyloxyphenylcarboxylic acid Ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 3-difluoro-4-nonyloxyphenylcarboxylic acid 2,2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 3,3-difluoro-4-decyloxyphenylcarboxylic acid Es 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester of 2,3-difluoro-4-dodecyloxyphenylcarboxylic acid 3- (4-pentylcyclohexyl) -5-hydroxy ester of 3-fluoro-4-hexyloxyphenylcarboxylic acid Pyrimidine ester 3-Fluoro 4-heptyloxyphenyl carboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester 3-Fluoro 4-octyloxyphenyl carboxylic acid 2- (4-pentylcyclohexyl)
Ester of 5-hydroxypyrimidine 3-Fluoro-4
Ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of nonyloxyphenylcarboxylic acid 3-Fluoroester of 3- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 4-decyloxyphenylcarboxylic acid 3-Fluoro-4 Esters of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of dodecyloxyphenylcarboxylic acid, 2,3
2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester of difluoro-4-pentylphenylcarboxylic acid 2- (4-pentylcyclohexyl) of 3-difluoro-4-heptylphenylcarboxylic acid
2-Hydroxypyrimidine ester 2,3-difluoro-4-octylphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester 2,3-difluoro-4-nonylphenylcarboxylic acid 2- (4-pentyl) Cyclohexyl) -5-hydroxypyrimidine ester 2,3-difluoro-4-decylphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester 2,3, difluoro-4-dodecylphenylcarboxylic acid 2- (4
-Pentylcyclohexyl) -5-hydroxypyrimidine ester 3-Fluoro-4-hexylphenylcarboxylic acid 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester, 3-Fluoro4-heptylphenylcarboxylic acid 2- (4- Ester of pentylcyclohexyl) -5-hydroxypyrimidine, 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester of 3-fluoro-4-octylphenylcarboxylic acid, 2- (4- of 4-fluoro-4-nonylphenylcarboxylic acid Pentylcyclohexyl) -5-hydroxypyrimidine ester, 3-fluoro-4-decylphenylcarboxylic acid 2- (4-pentylcyclohexyl)
An ester of 5-hydroxypyrimidine and an ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 3-fluoro-4-dodecylphenylcarboxylic acid can be synthesized.

Example 12 An acid chloride prepared from 2.9 g (10 mmol) of (+)-4- (4-butyryloxypentyl) phenylcarboxylic acid (3-12) and oxalyl chloride was added to 2- (4
-Pentylcyclohexyl) -5-hydroxypyrimidine (2-12) 3.0 g (12 mmol), pyridine 2
Add at room temperature into a solution consisting of 0 g and 30 g of dichloromethane. Stir at the same temperature for 2 hours. After the reaction,
The mixture is extracted with 100 ml of toluene and washed successively with water, dilute hydrochloric acid, 7% aqueous sodium bicarbonate and water. The organic layer was concentrated under reduced pressure, and the obtained pale yellow solid was purified by silica gel column chromatography to obtain 2- (4-pentylcyclohexyl) of (+)-4- (4-butyryloxypentyl) phenylcarboxylic acid. ) -5-Hydroxypyrimidine ester (1
-12) 4.8 g (93% yield) are obtained. Optical rotation [α]
_D ²⁰ + 2.6 ° (C = 1.0, CHCl ₃ ). In the same manner as in this example, 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester of (+)-4- (2-butyryloxypropyl) phenylcarboxylic acid, (+)-
Ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 4- (3-butyryloxybutyl) phenylcarboxylic acid 2- (4- (5-butyryloxyhexyl) phenylcarboxylic acid) Ester of 4-pentylcyclohexyl) -5-hydroxypyrimidine 2- (4-pentylcyclohexyl) of (+)-4- (6-butyryloxyheptyl) phenylcarboxylic acid
An ester of -5-hydroxypyrimidine can be synthesized.

Example 13 An acid chloride prepared from 2.9 g of (-)-4- (4-hexyloxypentyl) phenylcarboxylic acid (3-13) and oxalyl chloride was converted into 2- (4-propylcyclohexyl)- 5-hydroxypyrimidine (2-13)
It is added at room temperature to a solution consisting of 2.6 g (12 mmol), 20 g of pyridine and 30 g of dichloromethane. Stir at the same temperature for 2 hours. After completion of the reaction, toluene 100
The mixture is extracted with water, washed with water, diluted hydrochloric acid, 7% aqueous sodium bicarbonate and water in that order. The organic layer was concentrated under reduced pressure, and the obtained pale yellow solid was purified by silica gel column chromatography.
2- (4-Propylcyclohexyl) -5 of (-)-4- (4-hexyloxypentyl) phenylcarboxylic acid
-Hydroxypyrimidine ester (1-13) 4.7
g (95% yield). Optical rotation [α] _D ²⁰ −2.4 °
(C = 1.0, CHCl ₃ ) In the same manner as in this example, 2- (4-propylcyclohexyl) -5-hydroxypyrimidine ester of (−)-4- (2-hexyloxypropyl) phenylcarboxylic acid, -)-2- (4-Propylcyclohexyl) -4- (3-hexyloxybutyl) phenylcarboxylic acid
-5-hydroxypyrimidine ester, (-)-4-
Ester of 2- (4-propylcyclohexyl) -5-hydroxypyrimidine of (5-hexyloxyhexyl) phenylcarboxylic acid, 2- (4-propyl) of (-)-4- (6-hexyloxyheptyl) phenylcarboxylic acid Cyclohexyl) -5-hydroxypyrimidine ester can be synthesized.

Embodiment 14 2- (4-pentylcyclohexyl) -5-carboxy
2.9 g (10 mmol) of pyrimidine (4-14),
(+)-4- (1-butyryloxyethyl) phenol
(5-14) 2.1 g (10 mmol), dicyclohexyl
2.2 g (10 mmol) of silcarbodiimide, dimethyl
0.5 g of laminopyridine and 30 g of dichloromethane
Is stirred at room temperature for 12 hours. End of reaction
Thereafter, the precipitated crystals are removed by filtration and the organic layer is removed under reduced pressure.
The light yellow solid obtained by concentration was concentrated by silica gel column chromatography.
Purified by chromatography, 2- (4-pentylcyclohexane)
(+)-4- of xyl) -5-carboxypyrimidine
(1-butyryloxyethyl) phenol ester (1
-14) 4.2 g (95% yield) are obtained. Optical rotation [α]
_D ²⁰+ 12.4 ° (C = 1.0, CHCl_Three). This embodiment and
Similarly, 2- (4-pentylcyclohexyl) -5
(+)-4- (5-hexano-carboxypyrimidine
Yloxyhexyl) phenol ester, 2- (4-
Pentylcyclohexyl) -5-carboxypyrimidine
(+)-4- (3-decanoyloxybutyl) pheno
Ester, 2- (4-pentylcyclohexyl)-
(+)-4- (2-butylyl) of 5-carboxypyrimidine
2-hydroxypropyl) phenol ester, 2- (4-pe
N-cyclohexyl) -5-carboxypyrimidine
(+)-4- (5-butyryloxyhexyl) pheno
Ester, 2- (4-pentylcyclohexyl) -5
(+)-4- (6-propio) -carboxypyrimidine
Nyl-1-trans-heptenyl) phenol ester, 2
-(4-pentylcyclohexyl) -5-carboxypi
(+)-4- (6-propionyl-1-hepta of limidine
(Tinyl) phenol ester.

Embodiment 15 2- (4-pentylcyclohexyl) -5-carboxy
2.9 g (10 mmol) of pyrimidine (4-15),
(-)-4- (1-butoxyethyl) phenol (5-
15) 2.0 g (10 mmol), dicyclohexylka
2.2 g (10 mmol) of rubodiimide, dimethylamido
0.5 g of pyridine and 30 g of dichloromethane.
The solution is stirred at room temperature for 12 hours. After completion of the reaction, precipitation
The crystals formed are removed by filtration and the organic layer is concentrated under reduced pressure.
The obtained pale yellow solid is subjected to silica gel column chromatography.
2- (4-pentylcyclohexyl)
(-)-4- (1-buto) of -5-carboxypyrimidine
4.3 g of (xyethyl) phenol ester (yield 92
%). Optical rotation [α]_D ²⁰+ 18.3 ° (C = 1.0, CHC
l _Three). In the same manner as in this embodiment, 2- (4-pen
Of tylcyclohexyl) -5-carboxypyrimidine
(-)-4- (5-Propyloxyhexyl) pheno
Ester, 2- (4-pentylcyclohexyl) -5
-Carboxypyrimidine of (-)-4- (3-hexyl)
Oxybutyl) phenol ester, 2- (4-pliers)
Rucyclohexyl) -5-carboxypyrimidine
(-)-4- (2-butyloxypropyl) phenol
Ester, 2- (4-pentylcyclohexyl) -5-
(−)-4- (5-hexylio) of carboxypyrimidine
(Xyhexyl) phenol ester, 2- (4-pentyl)
Rucyclohexyl) -5-carboxypyrimidine
(-)-4- (6-ethoxy-1-trans-heptenyl)
Phenol ester, 2- (4-pentylcyclohexyl)
Ru) -5-carboxypyrimidine of (+)-4- (6-
Methoxy-1-heptynyl) phenol ester, 2-
(4-pentylcyclohexyl) -5-carboxypyri
Midine's (-)-4- (6-butoxy-1-trans-pen)
(Tenyl) phenol ester, 2- (4-pentylshik)
(+)-4 of Rohexyl) -5-carboxypyrimidine
-(6-ethoxy-1-pentynyl) phenol ester
Can be synthesized.

Example 16 2.9 g (10 mmol) of 2- (4-pentylcyclohexyl) -5-carboxypyrimidine (4-16)
-(1-trans-nonenyl) phenol (5-16)
A solution consisting of 2.2 g (10 mmol), 2.2 g (10 mmol) of dicyclohexylcarbodiimide, 0.5 g of dimethylaminopyridine and 30 g of chloroform is stirred at room temperature for 15 hours. After completion of the reaction, the precipitated crystals were removed by filtration and the organic layer was concentrated under reduced pressure. The obtained pale yellow solid was purified by silica gel column chromatography to give 2- (4-pentylcyclohexyl) -5-carboxy. 4.3 g of 4- (1-trans-nonenyl) phenol ester of pyrimidine (1-16) (90% yield)
Get.

Example 17 2.9 g (10 mmol) of 2- (4-pentylcyclohexyl) -5-carboxypyrimidine (4-17)
-(1-heptynyl) phenol (5-17) 2.0 g
(10 mmol), 1.9 g (10 mmol) of dicyclohexylcarbodiimide, 0.5 g of dimethylaminopyridine and 30 g of dichloromethane are stirred at room temperature for 12 hours. After completion of the reaction, the precipitated crystals were removed by filtration and the organic layer was concentrated under reduced pressure. The obtained pale yellow solid was purified by silica gel column chromatography to give 2- (4-pentylcyclohexyl) -5-carboxy. 4.1 g (91% yield) of pyrimidine (-)-4- (1-heptynyl) phenol ester (1-17)
Get.

Example 18 2.9 g (10 mmol) of 2- (4-pentylcyclohexyl) -5-carboxypyrimidine (4-18), 4
-(2-butoxyethyl) phenol (5-18) 2.
A solution consisting of 0 g (10 mmol), 2.2 g (10 mmol) of dicyclohexylcarbodiimide, 0.5 g of dimethylaminopyridine and 30 g of dichloromethane is stirred at room temperature for 14 hours. After completion of the reaction, the precipitated crystals were removed by filtration and the organic layer was concentrated under reduced pressure. The obtained pale yellow solid was purified by silica gel column chromatography to give 2- (4-pentylcyclohexyl) -5-carboxy. 4.3 g of (-)-4- (1-butoxyethyl) phenol ester of pyrimidine (1-18) (yield 9
2%).

Example 19 (+)-4- (1- (2-Chloro-3-methyl) pentanoyloxyethyl) phenylcarboxylic acid (3-19)
An acid chloride prepared from 3.0 g and oxalyl chloride was combined with 2.2 g (10 mmol) of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine (2-19).
l), at room temperature in a solution consisting of 20 g of pyridine and 30 g of dichloromethane. Stir at the same temperature for 2 hours. After completion of the reaction, the reaction solution is extracted with 100 ml of toluene, and washed successively with water, dilute hydrochloric acid, 7% aqueous sodium bicarbonate and water. The organic layer was concentrated under reduced pressure, and the obtained pale yellow solid was purified by silica gel column chromatography to obtain (+)-4- (1- (2
2- (4-pentylcyclohexyl) -5-hydroxypyrimidine ester of -chloro-3-methyl) pentanoyloxyethyl) phenylcarboxylic acid (1-19)
4.3 g (87% yield) are obtained.

Example 20 2.9 g (10 mmol) of 2- (4-pentylcyclohexyl) -5-carboxypyrimidine (4-20)
-(1-pentynyl) -3-fluorophenol (5-2)
0) A solution consisting of 1.8 g (10 mmol), 1.9 g (10 mmol) of dicyclohexylcarbodiimide, 0.5 g of dimethylaminopyridine and 30 g of dichloromethane is stirred at room temperature for 12 hours. After completion of the reaction, the precipitated crystals were removed by filtration and the organic layer was concentrated under reduced pressure. The obtained pale yellow solid was purified by silica gel column chromatography to give 2- (4-pentylcyclohexyl) -5-carboxy. 3.9 g of 4- (1-pentynyl) -3-fluorophenol ester of pyrimidine (1-20)
(90% yield).

Example 21 3.9 g (0.01 mol) of 2- (4-pentylcyclohexyl) -5- (4-bromophenyl) pyrimidine (6-21) was placed in a four-necked flask equipped with a stirrer and a thermometer. -Hexine (7-21) 1.6 g (0.02 mol), bis (triphenylphosphine) palladium chloride 0.1 g, copper iodide 0.2 g, triphenylphosphine
0.5 g and 40 ml of triethylamine are charged and reacted at 70 to 75 ° C. for 13 hours under a nitrogen stream. After completion of the reaction, the reaction mixture was poured into 400 ml of water, and toluene 20
Extract with 0 ml. The resulting toluene layer is 3% HCl aqueous,
After washing with water, the mixture is concentrated under reduced pressure to obtain a brown residue. The residue was purified by silica gel column chromatography (eluent: toluene-hexane), and 3.0 g of 2- (4-pentylcyclohexyl) -5- (4- (1-hexynyl) phenyl) pyrimidine (1-21) was obtained. A mixture of 0.39 g (1 mmol) of (1-21) obtained above, 10 ml of methanol, 30 ml of ethyl acetate and 0.08 g of 5% palladium on carbon was treated with a hydrogen pressure of 5 kg / cm ² , 30 to 30%.
Hydrogenate at 35 ° C. After completion of the reaction, the catalyst is filtered off,
The filtrate was concentrated under reduced pressure to give 2- (4-pentylcyclohexyl) -5- (4-hexylphenyl) pyrimidine.
37 g (96% yield). As in the present embodiment, 2-
(4-pentylcyclohexyl) -5- (4- (1-butynyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4- (1-pentynyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) )
-5- (4- (1-Heptynyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4- (1-octynyl) phenyl) pyrimidine, 2- (4-
Pentylcyclohexyl) -5- (4- (1-nonyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4- (1-decyl) phenyl) pyrimidine 2- (4-pentylcyclohexyl) -5- ( 2,3-difluoro-4-hexynylphenyl) pyrimidine 2- (4-pentylcyclohexyl) -5- (2,
3-difluoro-4-heptynylphenyl) pyrimidine 2
-(4-pentylcyclohexyl) -5- (2,3-difluoro-4-octynylphenyl) pyrimidine 2- (4
-Pentylcyclohexyl) -5- (4- (1-butyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4- (1-pentyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5 -(4- (1-heptyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4- (1-octyl) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4- (1 -Nonyl) phenyl)
Pyrimidine, 2- (4-pentylcyclohexyl) -5
-(4- (1-decyl) phenyl) pyrimidine 2- (4
-Pentylcyclohexyl) -5- (2,3-difluoro-4-hexylphenyl) pyrimidine 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4-heptylphenyl) pyrimidine 2- (4-pentylcyclohexyl) -5 1- (2,3-difluoro-4-octylphenyl) pyrimidine can be synthesized.

Example 22 In a four-necked flask equipped with a stirrer and a thermometer, 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4-hydroxyphenyl) pyrimidine (13-2)
2) 3.6 g (0.01 mol) of 1-bromoheptin (14
-22) 2.7 g (0.015 mol), sodium carbonate 5 g
And 40 ml of methyl isobutyl ketone, and reacted at 100 to 110 ° C. for 10 hours under a nitrogen stream.
After the reaction has ended, the reaction mixture is poured into 50 ml of water and extracted with 100 ml of methyl isobutyl ketone. The resulting organic layer is 3
After washing with aqueous% HCl and water, the mixture is concentrated under reduced pressure to obtain a residue.
The residue was subjected to silica gel column chromatography (eluent:
Purification with toluene-hexane) and 4.2 g of 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4-heptyloxyphenyl) pyrimidine (1-22)
(92% yield). In the same manner as in this example, 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4-hexyloxyphenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4- Octyloxyphenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (2,3 difluoro-4-decyloxyoxyphenyl) pyrimidine,
2- (4-pentylcyclohexyl) -5- (2,3-difluoro-4- (3-hexenyloxy) phenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4-pentyloxyphenyl) pyrimidine 2- ( 4-
Pentylcyclohexyl) -5- (4-heptyloxyphenyl) pyrimidine, 2- (4-pentylcyclohexyl) -5- (4-octyloxyphenyl) pyrimidine 2- (4-pentylcyclohexyl) -5- (4- (2 -Propynyloxy) phenyl) pyrimidine,

Example 23 Table 1 shows the phase changes of the following compounds synthesized above. (a) 2- (4-pentylcyclohexyl) -5- (4-pentyloxyphenyl) pyrimidine (b) 2- (4-pentylcyclohexyl) -5- (2,
3-difluoro-4-pentyloxyphenyl) pyrimidine (c) Ester of 2- (4-pentylcyclohexyl) -5-hydroxypyrimidine of 2,3-difluoro-4-octylphenylcarboxylic acid (d) 2,3-difluoro-4- 2- (4-pentylcyclohexyl-5-hydroxypyrimidine ester of octyloxyphenylcarboxylic acid (e) 2- (4-pentylcyclohexyl) -5- (4-hexylphenyl) pyrimidine (f) 2- (4-pentyl Cyclohexyl) -5- (2,
3-difluoro-4-hexylphenyl) pyrimidine

[Table 1]

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-6-9960 (JP, A) JP-A-4-299308 (JP, A) JP-A-4-253971 (JP, A) 117343 (JP, A) JP-A-2-118618 (JP, A) JP-A-60-199880 (JP, A) JP-A-59-98065 (JP, A) JP-A-57-95965 (JP, A) British Patent Application Publication 2270913 (GB, A) German Patent Application Publication 4029897 (DE, A1) Molecular Crystals and Liquid Crystals, (1991), 209, p. 225-235 Molecular Crystals and Liquid Crystals (1985) , 128 (1-2), p. 45-63 (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 239/26 C07D 239/28 C07D 239/34 C09K 19/34 CA (STN) REGISTRY (STN)

Claims (9)

(57) [Claims] 1. The general formula (1) (Wherein, R ¹ represents a saturated or unsaturated alkyl group which may be substituted with a halogen atom having 1 to 10 carbon atoms, Ar represents a pyrimidyl group, and R ² represents-(E) n-R
³ , E represents —CH ＝ CH— or —C≡C—, and R ³ represents a saturated or unsaturated alkyl group, an alkoxyalkyl group or a substituted or unsubstituted halogen atom having 1 to 15 carbon atoms. group _{- (CH 2) r -CH (} C
H ₃₎ shows the -Y. Here, Y represents OR ⁴ or a fluorine atom, and R ⁴ represents a saturated or unsaturated alkyl group or alkanoyl group which may be substituted with a halogen atom having 1 to 10 carbon atoms. X is -COO -, - OCO- or a single bond, l is an integer of 0 to 2, m and 0 indicates
And n represents 1, and r represents an integer of 0 to 8. ). 2. The general formula (2) (Wherein R ¹ and Ar have the same meaning as in claim 1 ) and a phenol represented by the general formula (3) (Wherein R ² , l and m have the same meanings as in claim 1 , and R ⁵ represents a hydroxyl group or a halogen atom). 1. The aromatic derivative according to 1, wherein X is -O
CO- is shown. ) Manufacturing method. 3. The formula (4) (Wherein R ¹ and Ar have the same meanings as in claim 1)
R ⁵ represents the same meaning as in claim 2 . ) And a carboxylic acid represented by the general formula (5) (Wherein, R ² , l and m have the same meanings as defined in claim 1 ), and are reacted with a phenol represented by the formula ( 1 ). Represents -COO-). 4. The general formula (6) (Wherein R ¹ , Ar, X and 1 have the same meanings as those in claim 1 , D is a halogen atom, OCOCF
₃ or an -OSO ₂ R '. Here, R 'represents a lower alkyl group which may be substituted by a fluorine atom, or a phenyl group which may be substituted. ) And an acetylene represented by the general formula (7) ≡-R ³ (7) (wherein R ³ has the same meaning as described in claim 1 ) or a general formula (8) _{^{(R 8) 2 B-CH}} = CH-R 3 (8) ( trans form) (wherein, ^{R 3} represents the same meaning as in claim 1 wherein, ^{R 8} is hydroxyl, straight-chain, branched or cyclic indicates an alkyl group or a linear, branched or cyclic alkoxy group. in this case, each other R ⁸ is optionally substituted with interconnected to the may form a ring. Alternatively (R ⁸⁾ ₂ 2. The aromatic derivative according to claim 1, wherein a boron represented by a good benzodioxy group is reacted with a metal catalyst in the presence of a basic substance.
Indicates 1. ) Manufacturing method. 5. The compound represented by the general formula (6) according to claim 4.
Logenide and general formula (7 ') (Wherein, r represents the same meaning as in claim 1)
You. ) Or an acetylene represented by the general formula (8 ′) (Wherein R ⁸ has the same meaning as in claim 4)
And r has the same meaning as in claim 1. )so
Boron shown in the presence of a metal catalyst and a basic substance
Reacting general formula (9) (Wherein R ¹ , Ar, X, l, n and r are as defined in claim 1)
Represents the same meaning as listed. ) Alcohols shown
, R ⁴ COR ″ (10) (wherein R ⁴ is a carbon atom which may be substituted with a halogen atom )
A saturated or unsaturated alkyl group having a prime number of 1 to 20 or
R 2 represents an alkoxyalkyl group having 2 to 20 carbon atoms;
Hydroxyl, a halogen atom or OCOR ^5. here
R ⁵ has the same meaning as in claim 2. )
A carboxylic acid to be reacted
The aromatic derivative according to claim 1, wherein m is 0 and n is 1.
You. ) Manufacturing method. 6. The method according to claim 5, wherein
Alcohols and the general formula (11) R ⁴ -Z (11) (wherein R ⁴ has the same meaning as in claim 5;
Z represents a halogen atom or -OSO ₂ R ^9. here
R ⁹ is a lower alkyl group or an optionally substituted
Represents a nyl group. ) With an alkylating agent
2. The aromatic derivative according to claim 1, wherein
And m represents 0 and n represents 1. ) Manufacturing method. 7. An optically active substance according to claim 7.
2. The aromatic derivative according to 1. 8. The general formula (7) according to claim 4 or claim
5. Optical properties of acetylenes represented by general formula (7 ′) described in 5.
Activator, general formula (8) according to claim 4 or claim 5
The optically active boron compound represented by the general formula (8 ′)
And an aromatic derivative represented by the general formula (1) according to claim 1.
The production according to claim 4 or 5, wherein an optically active body of a conductor is obtained.
Law. 9. The compound represented by the general formula (9) according to claim 5
Fluorination of alcohols with fluorinating agents
The aromatic derivative according to claim 1, wherein Y is fluorinated.
Represents a nitrogen atom. ) Manufacturing method.