JP2527961B2 - Benzoic acid ester derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel benzoic acid ester derivative and a method for producing the same.

More specifically, the general formula (I): (In the formula, R may be the same or different and represents a hydrogen atom, a halogen atom, or a lower alkyl group, n represents an integer of 1 to 4, X represents a halogen atom, and R ₁ and R ₂ R ₃ and R _{3, which} may be the same or different, each represents a lower alkyl group, a lower haloalkyl group, a lower alkoxycarbonyl group or a phenyl group, and the substituent XCH ₂ represents a meta-position or a para-position substitution with respect to the carbonyl group. However, the substituent XCH ₂
Represents para-position substitution with respect to the carbonyl group, and R represents a hydrogen atom, X excludes a bromine atom. ) And a method for producing the same.

The compound of the present invention is a novel compound that has not been described in the literature yet, and is a compound useful as an intermediate for medicines, agricultural chemicals and the like.

The method for producing the compound of the present invention is to selectively react a specific halogen atom of a benzoic acid halide derivative having two active halogen atoms to give a benzoic acid ester derivative. It can be illustrated as follows.

(In the formula, R may be the same or different and represents a hydrogen atom, a halogen atom or a lower alkyl group, n represents an integer of 1 to 4, X and Y may be the same or different, and a halogen atom. R ₁ , R ₂ and R _{3, which} may be the same or different, each represents a lower alkyl group, a lower haloalkyl group, a lower alkoxycarbonyl group or a phenyl group, and the substituent XCH ₂ is a meta group to the carbonyl group. Position or para position substitution, provided that the substituent XCH ₂
Represents para-position substitution with respect to the carbonyl group, and R represents a hydrogen atom, X excludes a bromine atom. ) That is, by reacting a benzoic acid halide derivative represented by the general formula (II) with a tertiary alcohol represented by the general formula (III) in the presence of a base in the presence or absence of an inert solvent. The benzoic acid ester represented by the general formula (I) can be produced.

The solvent that can be used in the present invention may be any solvent that does not inhibit this reaction, for example, diethyl ether, diisopropyl ether, tetrahydrofuran, ethers such as dioxane, dichloroethane, tetrachloroethane,
Halogenated hydrocarbons such as chloroform and carbon tetrachloride,
Aromatic hydrocarbons such as benzene, monochlorobenzene, nitrobenzene and toluene can be mentioned. These can be used alone or in a mixture. Further, the solvent can be used by using the tertiary alcohol represented by the general formula (III) in excess.
As the base, an inorganic base or an organic base can be used, but the use of an organic base is preferable, and for example, a tertiary amine such as triethylamine, pyridine, picoline, and 4-N, N-dimethylaminopyridine may be used. it can.

The reaction temperature may be selected from a temperature in the range of 0 ° C. to the boiling point of the solvent, but it is preferable to carry out the reaction at a temperature near room temperature.

The reaction time is not constant depending on the reaction temperature and the reaction scale, but it may be selected as long as the reaction is completed and selected from the range of several minutes to 48 hours.

The tertiary alcohols represented by the general formula (III) and the base may be added in equimolar amounts to the benzoic acid halide derivative represented by the general formula (II), but may be used in excess. .

After completion of the reaction, it can be treated by a conventional method and used as it is in the next reaction, or can be purified and used in the next reaction.

The benzoic acid halide derivative represented by the general formula (II), which is the starting material of the present invention, can be produced by the method shown below.

(In the formula, R, n, X and Y have the same meanings as defined above.) That is, the para or metabenzoic acid derivative represented by the general formula (V) is halogenated to obtain the para represented by the general formula (IV). Alternatively, the compound (I
By halogenating one hydrogen of the methyl group at the para or meta position of V), the benzoic acid halide derivative represented by the general formula (II) can be produced.

Typical examples of the compound of the present invention are shown below, but the present invention is not limited thereto.

Example 1. Preparation of t-butyl 4-chloromethylbenzoic acid A reaction solution containing 5.55 g (0.075 mol) of t-butyl alcohol and 3.95 g (0.05 mol) of pyridine was kept at 10 ° C,
9.45 g of 4-chloromethylbenzoic acid chloride dissolved by heating
(0.05 mol) was added, the reaction was carried out at 10 ° C. for 3 hours with stirring, and then the reaction was further carried out at 30 ° C. for 2 hours. Water after reaction
20 ml was added, the produced pyridine hydrochloride was dissolved, the target compound was collected, washed with water, and dried to obtain 10.78 g of the target compound.

Melting point 53.4 ° C, yield 95.2%.

Example 2 Preparation of 2-chloro-1,3-dimethylethyl 4-chloromethylbenzoic acid 8.1-g 1,1-dimethyl-2-chloroethyl alcohol
(0.075 mol) and 4.95 g (0.05 mol) of pyridine were added to 9.45 g (0.05 mol) of 4-chloromethylbenzoic acid chloride heated and dissolved at 10 ° C., and the mixture was stirred at that temperature for 3 hours and reacted. Then, the reaction was carried out at 30 ° C. for 2 hours. After the reaction was completed, 50 ml of water was added to the reaction solution, the target compound was extracted with ethyl acetate (3 times with 30 ml each), and diluted hydrochloric acid was added.
After washing with 50 ml and drying, the extract was distilled off under reduced pressure, and the residue was purified by silica gel chromatography to obtain 10.6 g of the desired compound.

_{3.87 (s.2H, -CH 2 -)} 4.54 (s.2H, -CH 2 -), 7.33 (d.2H, benzene ring) 7.88 (d.2H, benzene ring) 81% yield.

Example 3 Preparation of 1-methoxycarbonyl-1-methylethyl 4-chloromethylbenzoic acid Methyl 2-methyl-2-hydroxypropionic acid 8.85g
(0.075 mol) and 4.95 g (0.05 mol) of pyridine were added to 9.45 g (0.05 mol) of 4-chloromethylbenzoic acid chloride heated and dissolved at 10 ° C., and the mixture was stirred at that temperature for 3 hours and reacted. Then, the reaction was carried out at 30 ° C. for 2 hours. After completion of the reaction, 50 ml of water was added to the reaction solution, the target product was extracted with ethyl acetate (30 ml, three times), and 50 ml of dilute hydrochloric acid was added.
The extract was distilled off under reduced pressure, and the residue was purified by silica gel chromatography to give 8.39 g of the desired product.
Obtained.

_{3.55 (s.3H-OCH 3) 4.58} (s.2H, -CH 2 -), 7.08 (d.2H, benzene ring) 7.78 (d.2H, benzene ring) 62% yield.

Example 4 Preparation of 1,1-dimethylpropyl 3-chloromethylbenzoic acid 1,1-Dimethylpropyl alcohol 6.6g (0.075mol)
And 3.95 g (0.05 mol) of pyridine in a reaction solution containing 3-
Chloromethylbenzoyl chloride 9.45 g (0.05 mol) 10
The mixture was added at 0 ° C, the reaction was carried out at that temperature for 3 hours with stirring, and the reaction was further carried out at 30 ° C for 2 hours. After the reaction was completed, 20 ml of water was added to the reaction solution, and the target product was ethyl acetate (30 ml, three times)
The extract was distilled off under reduced pressure, and the residue was purified by silica gel chromatography to obtain 10.2 g of the desired compound.

0.95 (t.3H, -CH _{3), 1.89 (q.2H, -CH 2 -)} , 4.59 (s.2H, -CH 2 -) 7.15~7.85 (m.4H, benzene ring) 85% yield.

Claims (2)

(57) [Claims] 1. General formula (I): (In the formula, R may be the same or different and each represents a hydrogen atom, a halogen atom or a lower alkyl group, n represents an integer of 1 to 4, X represents a halogen atom, R ₁ , R ₂ and R _{3's, which} may be the same or different, each represents a lower alkyl group, a lower haloalkyl group, a lower alkoxycarbonyl group or a phenyl group, and the substituent XCH ₂ represents a meta-position or a para-position with respect to the carbonyl group. Group XCH ₂
Represents para-position substitution with respect to the carbonyl group, and R represents a hydrogen atom, X excludes a bromine atom. ) A benzoic acid ester derivative represented by 2. General formula (II): (In the formula, R may be the same or different and represents a hydrogen atom, a halogen atom or a lower alkyl group, n represents an integer of 1 to 4, X and Y may be the same or different, and a halogen atom The substituent XCH ₂ represents a meta-position or a para-position substitution with respect to the carbonyl group, provided that when the substituent XCH ₂ represents a para-position substitution with respect to the carbonyl group and R represents a hydrogen atom, X represents bromine. A benzoic acid halide derivative represented by the general formula (III): (In the formula, R ₁ , R ₂ and R ₃ may be the same or different and each represents a lower alkyl group, a lower haloalkyl group, a lower alkoxycarbonyl group or a phenyl group.) General formula (I) characterized by (In the formula, R, R ₁ , R ₂ , R ₃ , X and n have the same meanings as defined above.) A process for producing a benzoic acid ester derivative.