JPS63267745A - Benzoate derivative and production thereof - Google Patents

Abstract

NEW MATERIAL:A benzoic acid ester derivative expressed by formula I (R is H, halogen or lower alkyl; n is integer of 1-4; X is halogen; R1-R3 are lower alkyl, lower haloalkyl or lower alkoxycarbonyl; XCO is substituted in meta or para position to CO). EXAMPLE:tert.-Butyl 4-chloromethyl benzoic acid. USE:An intermediate for medicine or agricultural chemical. PREPARATION:A benzoic acid halide expressed by formula II (Y is halogen) is reacted with tert. alcohols expressed by formula III in the presence or absence of an inert solvent in the presence of a base to provide the compound expressed by formula I.

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, general formula (1): (wherein R may be the same or different and represent a hydrogen atom, a halogen atom, or a lower alkyl group, n represents an integer of 1 to 4, and X represents a halogen Rh& and R3 may be the same or different and represent a lower alkyl group, a lower haloalkyl group, a lower alkoxycarbonyl group, or a phenyl group, provided that the substituent XCI (t is at the meta position with respect to the carbonyl group) The present invention provides a benzoic acid ester derivative represented by (or showing substitution at the rose position) and a method for producing the same.

The compound of the present invention is a new compound that has not yet been described in the literature, and is a compound useful as an intermediate for pharmaceuticals, agricultural chemicals, etc. A benzoic acid ester derivative is produced by selectively reacting a specific halogen atom of a halide derivative, for example, as shown below.

(II) (I) (wherein R may be the same or different and represent a hydrogen atom, a halogen atom, or a lower alkyl group, n represents an integer of 1 to 4, and X and Y are the same or different may also represent a halogen atom, R1, Rx and R3
, which may be the same or different, represent a lower alkyl group, a lower haloalkyl group, a lower alkyl dicarbonyl group, or a phenyl group, provided that the substituent XCH2 is substituted at the meta or para position with respect to the carbonyl group. ) That is, a benzoic acid halide derivative represented by the general formula (...) in the presence of a base in the presence or absence of an inert solvent,
A benzoic acid ester represented by the general formula (I) can be produced by reacting it with a tertiary alcohol represented by the general formula (In).

Solvents that can be used in the present invention may be those that do not inhibit this reaction, such as ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dioxane, dioxane, tetrachloroethane, chloroform, and carbon tetrachloride. halogenated hydrocarbons such as benzene, monochlorobenzene, nitrobenzene,
Aromatic hydrocarbons such as toluene can be mentioned.

These can be used alone or in combination.

Further, by using an excess of tertiary alcohol represented by the general formula (III), it can also be used as a solvent. As the base, an inorganic base or an organic base can be used, but it is preferable to use an organic base, for example, tertiary amines such as triethylamine, pyridine, picoline, 4NtN-dimethylaminopyridine, etc. can be used.

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

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

The amount of the 6th class alcohol represented by the general formula (III) and the base to be added may be equimolar to the benzoic acid halide derivative represented by the general formula (II), but they may be used in excess. .

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

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

(V) (fV)
(n) (wherein, Re n, para- or meta-benzoic acid halide derivatives, and the compound (I
The benzoic acid halide derivative represented by the general formula (II) can be produced by halogenating one hydrogen of the methyl group at the para or meta position in V).

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

Example t Production of t-butyl 4-chloromethylbenzoic acid A reaction solution containing C'Fb t-butyl tes, col a55 y ((LO 75 mol) and pyridine 595 y ((105 mol)) was maintained at 10°C. Then, 9.455 g (105 mol) of 4-chloromethylbenzoic acid chloride dissolved by heating was added, and the reaction was carried out with stirring at 10°C for 3 hours.
The reaction was carried out at ℃ for 2 hours. After the reaction is complete, add 20% of water,
The generated pyridine hydrochloride was dissolved, and the target compound was collected by evaporation, washed with water, and dried to obtain the target compound 1 (178 ml).

Melting point: 554°C, yield: 95.2cm.

Example 2 Production of t-butyl 4-bromomethylbenzoic acid H5 4-bromomethylbenzoic acid chloride 1.75P (1
005 mol) was added at 10°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, 10af of water was added to the reaction solution, and the target compound was extracted with ethyl acetate (3 times for 30d), washed with 10-dilute hydrochloric acid, dried, and the extract was distilled off under reduced pressure.
The residue was purified by silica gel chromatography to obtain the target compound 198P.

H3 t59 (ll+ 9H, -C-C city), 443(s
, 2H-Cfb).

Electron Hs 7.55 (d, 2H benzene ring), 7.87 (
d, 2H, Hensen ring) Yield: 72.

Example 5 Preparation of 2-chloro-1,3-dimethylethyl 4-chloromethylbenzoic acid CHZ 1.1-X))Tyl-2-chloroethyl alcohol &1
3p ((1075 mol) and pyridine & 95 jlF
4-chloromethylbenzoic acid chloride dissolved under heating in a reaction solution containing (1105 mol)? , 45p (5 moles of CLO) were added at 10°C, and the reaction was carried out with stirring at that temperature for 3 hours, and then the reaction was further carried out at 30°C for 2 hours. After the reaction was completed, 50% of water was added to the reaction solution, and the target compound was extracted with ethyl acetate (3 times with 50% of water), washed with 50 sJ of diluted hydrochloric acid, dried, and the extract was distilled off under reduced pressure to remove the residue. Purify by silica gel chromatography to obtain 1α
I got 6.

MS NMR' cDcl, (ppm)t t44(s, 6H, -C), A37(s, 2H,
-CHz). N454 (s, 2He CHz )-Z53 (
d, 2H, benzene ring) 7.88 (d, 2H, benzene ring) Yield 81%.

Example Production of 1-methoxycarbonyl-1-methylethyl 4-chloromethylbenzoic acid Methyl 2-methyl-2-hydroxypropionic acid a85
p((L075-E#) and pyridi71957(105
9.45 P (α05 mol) of 4-chloromethylbenzoic acid chloride dissolved under heating in a reaction solution containing 10
The mixture was added at 30° C., and the reaction was carried out at that temperature for 5 hours with stirring, and the reaction was further carried out at 30° C. for 2 hours. After the reaction was completed, 50 d of water was added to the reaction solution, and the target product was extracted with ethyl acetate (3 times of 3 od), washed with 50 d of diluted hydrochloric acid, dried, the extract was distilled off under reduced pressure, and the residue was chromatographed on silica gel. The target product 11S9y was obtained by graphical purification.

MS NMR#cI)c1. (ppm) 1.67 (s
, 6H, -C-) + 155(s, 3H-OCHs
)L 458(s, 2H, -CH2)-7'8(d, 2H
, benzene ring) 7.78 (d, 2H, benzene ring) Yield 62.

Example 5 Production of tl-dimethylethyl 3-chloromethylbenzoic acid 0 and 1,1-dimethylpropyl alcohol &6F (α075
9.457 mol of 3-chloromethylbenzoic acid chloride was added to a reaction solution containing pyridine 595F (α05 mol).
(105 mol) was added at 10°C, the reaction was carried out at that temperature for 3 hours with stirring, and the reaction was further carried out at 50°C for 2 hours. After the reaction was completed, 20 mm of water was added to the reaction solution, the target product was extracted with ethyl acetate (3 times 50 mm each), and 50 mm of dilute hydrochloric acid was added.
After washing with m and drying, the extract was distilled off under reduced pressure, and the residue was purified by silica gel chromatography to obtain the target compound ICL2.

MS NMRI CDC13 (PPhl) 0 coins (L95 (t, 3He-c city), 1.52 (s,
6H* C) + CC1 0,89 (q, 2H, -CR2-), 459 (s
, 2H, -〇Hs)7,15~7.85 (m,
4H, benzene ring) yield 85%.

Patent applicant: Nihon Nohyaku Co., Ltd. rlη12 names

Claims (2)

[Claims] (1) General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R may be the same or different and represents a hydrogen atom, a halogen atom, or a lower alkyl group, and n represents an integer from 1 to 4, X represents a halogen atom, R_1, R_2 and R_3 may be the same or different,
Indicates a lower alkyl group, lower haloalkyl group, lower alkoxycarbonyl group, or phenyl group, provided that substituent X
CH_2 shows substitution at the meta or para position with respect to the carbonyl group. ) A benzoic acid ester derivative represented by (2) General formula (II): ▲Mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R may be the same or different and represents a hydrogen atom, a halogen atom, or a lower alkyl group, and n represents an integer from 1 to 4, X and Y may be the same or different, and represent a halogen atom, provided that the substituent XCH_2 represents substitution at the meta or para position relative to the carbonyl group. General formula (III): ▲Mathematical formula, chemical formula, table, etc.▼(III) (In the formula, R_1, R_2 and R_3 may be the same or different,
It represents a lower alkyl group, a lower haloalkyl group, a lower alkoxycarbonyl group, or a phenyl group. ) General formula (I) characterized by reacting with a tertiary alcohol represented by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R, R_1, R_2, R_3, X and (n has the same meaning as defined above.) A method for producing a benzoic acid ester derivative represented by: