JPH11279123A - Production of dialkyl 2-bromo-and/or 2,5-dibromoterephthalate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain, in high yield, a dialkyl 2-bromoterephthalate and a dialkyl 2,5-dibromoterephthalate both of which are useful as industrial organic intermediates for medicines, agrochemicals, and so on, by brominating a specific dialkyl terephthalate with a specific brominating agent using a strong acid as a solvent, without using expensive and difficult-to-handle reagents, without, causing hydrolysis the raw material. SOLUTION: One of these compounds (e.g. dimethyl 2-bromoterephthalate) is obtained by brominating (A) a dialkyl terephthalate shown by the formula (R<1> and R<2> are each a 1-10C alkyl) (e.g. dimethyl terephthalate) with (C) preferably an N-bromimide-type brominating agent such as N-bromosuccinimide using (B) a strong acid such as sulfuric acid having a concentration, preferably, of 70-100 vol.% as a solvent, preferably at 10-150 deg.C. A yield of dialkyl 2- bromoterephthalate and that of a dialkyl 2,5-dibromoterephthalate can be controlled selectively by the amount of component C in this method.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing dialkyl 2-bromo and / or dialkyl 2,5-dibromoterephthalate. 2-bromo and dialkyl 2,5-dibromoterephthalates are compounds useful as industrial organic intermediates for pharmaceuticals, agricultural chemicals, synthetic resins and the like.

[0002]

2. Description of the Prior Art As a conventional method for producing 2-bromo and dialkyl 2,5-dibromoterephthalates, BrF ₃
An example in which dimethyl terephthalate is brominated with bromine in the presence to obtain 2-bromodimethyl phthalate in a yield of 53% [EP 0344936 (1989)] is known.
However, this method uses BrF ₃ which is expensive and difficult to handle, and the yield of the target product is low. An example in which terephthalic acid is brominated with bromine in an oleum solvent and then esterified with methanol to obtain dimethyl 2,5-dibromoterephthalate in a yield of 66% [SU 743989 (1980)].
Although oleum, which is also difficult to handle, is used, the yield of the target product is low.

[0003]

An object of the present invention is to provide a method for selectively brominating a target position on a benzene ring without causing hydrolysis of an ester group of dialkyl terephthalate as a raw material. It is in. In particular, it is an object of the present invention to provide a method for selectively obtaining 2-bromo or dialkyl 2,5-dibromoterephthalate in spite of using the same brominating agent.

Another object of the present invention is to provide a practical production method which avoids expensive and difficult-to-handle reagents and reaction conditions.

[0005]

That is, the present invention provides a compound represented by the general formula [I]:

[0006]

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(In the formula, R ¹ and R ² may be the same or different and represent an alkyl group having 1 to 10 carbon atoms.)
Wherein the dialkyl terephthalate represented by is brominated using a strong acid as a solvent and an N-bromoimide-type brominating agent, to produce a 2-alkyl and / or 2,5-dibromo terephthalate dialkyl. About.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. The present invention is illustrated by the following reaction scheme.

[0009]

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Alternatively,

[0011]

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(R ¹ and R ² are the same as those of the above formula [I].) The dialkyl terephthalate used in the present reaction includes:
For example, dimethyl terephthalate, diethyl terephthalate,
Di-n-propyl terephthalate, di-i-terephthalate
Propyl, di-n-butyl terephthalate, di-i-butyl terephthalate, di-s-butyl terephthalate, di-t-butyl terephthalate, di-n-amyl terephthalate,
Di-i-amyl terephthalate, di-t-amyl terephthalate, di-n-hexyl terephthalate, di-n-heptyl terephthalate, di-i-heptyl terephthalate, di-n-octyl terephthalate, terephthalic acid Di-i-octyl, di-n-nonyl terephthalate, di-terephthalate
n-decyl and the like.

The N-bromoimide type brominating agents used in the present invention include, for example, N-bromosuccinimide, N, N ', N "-tribromoisocyanuric acid, N, N'-dibromoisocyanuric acid Sodium, monosodium N-bromoisocyanurate, N
Disodium bromoisocyanurate, N-bromoisocyanuric acid, potassium N, N'-dibromoisocyanurate, N, N'-dibromoisocyanuric acid,
N, N'-dibromohydantoin, N-bromohydantoin sodium, N-bromohydantoin potassium, N
-Bromhydantoin, N-bromo-N'-methylhydantoin, 1,3-dibromo-5,5-dimethylhydantoin, 1-bromo-5,5-dimethylhydantoin, 3-bromo-5,5-dimethylhydantoin, −
Bromo-5,5-dimethylhydantoin sodium, 1
-Bromo-5,5-dimethylhydantoin potassium, 3
-Bromo-5,5-dimethylhydantoin sodium,
Examples thereof include 3-bromo-5,5-dimethylhydantoin potassium and N-bromoglutarimide.
Preferred are N-bromosuccinimide, N, N ', N "-tribromoisocyanuric acid, 1,3-dibromo-5,5-dimethylhydantoin and monosodium N-bromoisocyanurate.

A feature of the present invention is that 2-bromo or dialkyl 2,5-dibromoterephthalate can be selectively obtained depending on the amount of the bromimide type brominating agent used. That is, with respect to the reaction substrate, 0.1 per bromine atom.
When 7 to 1.3 equivalents, particularly 0.9 to 1.2 equivalents, of the brominating agent is used, dialkyl 2-bromoterephthalate can be obtained with high selectivity. On the other hand, the brominating agent is used in an amount of 1.7 to 2.5 equivalents, especially 1.9, per bromine atom with respect to the reaction substrate.
When ~ 2.2 equivalents are used, dialkyl 2,5-dibromoterephthalate can be obtained with high selectivity.

In the present invention, a strong acid represented by sulfuric acid is used as a solvent. Commercially available sulfuric acid can be used as it is. Basically, the presence of water is not preferable because it promotes acid hydrolysis of the ester group, but the effect can be suppressed by selecting reaction conditions. That is, the sulfuric acid concentration can be used in the range of 70 to 100%.
0-100% is preferred. The amount of the solvent to be used can be about 1 to 20 times by weight, particularly preferably 2 to 8 times by weight, based on the reaction substrate.

The reaction temperature is preferably in the range of 0 to 150 ° C., but is preferably 20 to 150 ° C. in view of the reaction rate and the selectivity of the target compound.
Preferably between 100 ° C. The reaction time can be determined by sampling the reaction solution and analyzing by liquid chromatography. Further, the reaction can be carried out under normal pressure or under pressure, and can be carried out in a batch system or a continuous system.

After the reaction, the reaction solution is diluted with water, extracted and concentrated with an organic solvent, and the dialkyl 2-bromoterephthalate is isolated from the resulting concentrate by distillation under reduced pressure to give 2,5-diphthalate. In the case of dialkyl bromoterephthalate, it can be isolated by crystallization. further,
The desired product is purified by distillation of the crude product under reduced pressure in the case of dialkyl 2-bromoterephthalate, and in the case of dialkyl 2,5-dibromoterephthalate in alcohols: 1,2.
-By recrystallization from dichloroethane (3: 1, w / w).

[0018]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. Example 1 A 1 L reaction vessel was charged with 1,000 g of 95% sulfuric acid and 233 g (1.20 mol) of dimethyl terephthalate, and stirred at room temperature for 30 minutes to dissolve. To this solution at room temperature was added 213.6 g (1.20 mol) of NBS in half-hourly increments. After the addition of NBS, the mixture was further stirred at room temperature for 12 hours.

In a separate container, 500 g of water, 500 g of 1,2-dichloroethane (EDC) and 200 g of methanol
, And the above reaction mixture was added little by little to the mixed solution to perform extraction and liquid separation. The separated organic layer was sequentially washed with 300 g of a 5% aqueous sodium bicarbonate solution and 200 g of water, and the solvent was distilled off. The residue was distilled under reduced pressure to give a white solid
2.5 g were obtained. 80% bp 113-114 ° C /
0.1 mm This solid was obtained from MASS and ¹ H-NMR by
-It was confirmed to be dimethyl bromoterephthalate.

Example 2 A 2 L reaction vessel was charged with 2000 g of 95% sulfuric acid and 500 g (2.25 mol) of terephthalic acid diethyl ester, and stirred at room temperature for 30 minutes. Most of the ester dissolved and the solution turned pale brown. At room temperature, add NB
400.5 g (2.25 mol) of S were added half-hourly every hour. After the addition of NBS, add another 12 at room temperature.
Stirred for hours.

In another container, 500 g of water and 500 g of EDC
And 300 g of ethanol, and the reaction solution was added little by little to the mixed solution to carry out extraction and liquid separation. The separated organic layer was washed sequentially with 300 g of a 5% aqueous sodium bicarbonate solution and 300 g of water, and the solvent was distilled off. The residue was distilled under reduced pressure to obtain 555.6 g of a colorless oil. 82% yield
bp 136 ° C / 0.5mm This solid is MASS and ¹
H-NMR confirmed that the substance was diethyl 2-bromoterephthalate.

Example 3 A reaction was carried out in the same manner as in Example 1 except that NBS was changed to 438.9 g (1.20 mol) of N, N ', N "-tribromoisocyanuric acid. As a result,
24 dimethyl 2-bromoterephthalate as a white solid
5.7 g were obtained. 75% yield

Example 4 A reaction was carried out in the same manner as in Example 1 except that NBS was changed to 275.9 g (1.20 mol) of monosodium N-bromoisocyanurate. As a result, a white solid was obtained. Dimethyl 2-bromoterephthalate as 255.
6 g were obtained. 78% yield

Example 5 A 100 mL reaction vessel was charged with 50.0 g of 95% sulfuric acid and 10.0 g (45.0 mmol) of terephthalic acid diethyl ester, and stirred at room temperature for 30 minutes. To this solution at room temperature, 16.0 g (90.0 mmol) of NBS were added in half-hourly increments. After the addition of NBS, the mixture was further stirred at room temperature for 2 hours.

In another container, 50 g of water, 50 g of EDC and 30 g of ethanol were charged, and the reaction solution was added little by little to this mixed solution to carry out extraction and liquid separation. The separated organic layer was washed sequentially with 30 g of a 5% aqueous solution of sodium bicarbonate and 30 g of water, and the solvent was distilled off. The residue was recrystallized from ethanol: 1,2-dichloroethane (3: 1, w / w) to give 14.9 g of colorless crystals. 87% mp yield
128 ° C. This solid was confirmed to be diethyl 2,5-dibromoterephthalate by MASS, ¹ H-NMR and ¹³ C-NMR.

[0026]

According to the method of the present invention, a brominated dialkyl terephthalate can be obtained in a high yield by brominating a dialkyl terephthalate using a strong acid as a solvent and an N-bromoimide type brominating agent. Further, by controlling the amount of the brominating agent used, 2-bromo or 2,5-
Dialkyl dibromoterephthalate can be selectively produced.

Claims (6)

[Claims] 1. A compound of the general formula [I] (Wherein, R ¹ and R ² may be the same or different and represent an alkyl group having 1 to 10 carbon atoms), and a dialkyl terephthalate represented by the following formula: A process for producing dialkyl 2-bromo and / or dialkyl 2,5-dibromoterephthalate, which comprises brominating with a brominating agent. 2. An N-bromoimide type brominating agent,
-Bromosuccinimide, N, N ', N "-tribromoisocyanuric acid, monosodium N-bromoisocyanurate, N-bromoglutarimide, N, N'-dibromohydantoin and 1,3-dibromo-5 The method for producing dialkyl 2-bromo and / or 2,5-dibromoterephthalate according to claim 1, which is 2,5-dimethylhydantoin. 3. The 2-bromo and / or 2,5- acid according to claim 1, wherein the strong acid is sulfuric acid having a concentration of 70 to 100%.
A method for producing a dialkyl dibromoterephthalate. 4. The process for producing dialkyl 2-bromo and / or 2,5-dibromoterephthalate according to claim 1, wherein the reaction temperature is between 10 ° C. and 150 ° C. 5. The brominated agent according to claim 1, wherein the amount of the N-bromoimide type brominating agent is 0.7 to 1.3 equivalents per bromine atom with respect to the dialkyl terephthalate represented by the general formula [I]. 3. The method for producing a dialkyl 2-bromoterephthalate described in 1. above. 6. The bromating agent according to claim 1, wherein the amount of the N-bromoimide type brominating agent is 1.7 to 2.5 equivalents per bromine atom with respect to the dialkyl terephthalate represented by the general formula [I]. 2. The method for producing a dialkyl 2,5-bromoterephthalate described in 1. above.