JPH0853371A - Bromination of methyl group bound to aromatic ring - Google Patents

Abstract

PURPOSE:To brominate a methyl group of a methylated aromatic compound in high selectivity and yield in a short time by reacting a specific methylated aromatic compound with bromine in the presence of bentonite in a specific solvent at a specific temperature, CONSTITUTION:A methyl group of (A) a compound of the formula Ar-CH3 [Ar is a (NO2, CN or halogen substituted) aromatic ring] is brominated by reacting the compound A with (D) bromine, in the presence of (B) bentonite, in (C) dichloromethane solvent, at 0-30 deg.C. Preferable compounding ratios are 0.0001-0.5 pts.wt. of the component B, and 1-500 pts.wt. of the component C based on 1 pt.wt. of the component A, and 1-10mol of the component D based on 1 mole of component A. Further, hydrogen bromide generated as a byproduct in the bromination is swept by an inert gas.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for brominating a methyl group bonded to an aromatic ring.

[0002]

Many examples of bromination of a methyl group bonded to an aromatic ring have been reported so far. However, it is known that bromination of a methylated aromatic compound which has no substituent other than a methyl group on the aromatic ring or has an electron-withdrawing substituent such as a nitro group together with the methyl group is very difficult. There is. Therefore, conventionally, for bromination of a methylated aromatic compound, it was necessary to carry out a reaction at a high temperature or to irradiate light. For example, a method of obtaining p-nitrobenzyl bromide by reacting p-nitrotoluene with bromine at a high temperature of 145 ° C to 150 ° C is known (Org. Synth., 4 P.443 (194).
2)).

However, since the reaction temperature is high, p-nitrobenzyl bromide and p-nitrobenzal bromide which is a dibromo compound are produced at the same time, and the selectivity of p-nitrobenzyl bromide is low. Further, as an improved method for brominating at a low temperature and in good yield, there is known a method of using hydrogen peroxide as a proton trap agent and refluxing p-nitrotoluene with a brominating agent in dichloromethane to obtain a corresponding p-nitrobenzyl bromide. (Japanese Patent Laid-Open No. 2-2212)
No. 33).

Further, when bentonite is added as a catalyst and refluxed in carbon disulfide, p-nitrotoluene having a methyl group in the aromatic ring and a nitro group which is an electron-withdrawing group in the para position selectively brominates the methyl group. It is also known to occur (J. Chem. Soc., Chem.
Commun. , P .; 1188 (1990)).

[0005]

In the latter two methods described above, the reaction is carried out at a relatively low temperature, but a dibromo compound is also produced as a by-product in addition to the desired monobromo compound, and the selectivity is still unsatisfactory. . On the other hand, if these reactions are carried out at a low temperature in order to increase the selectivity, the reaction rate of bromination becomes remarkably small, and it becomes difficult to efficiently obtain a monobromide.

Therefore, the present invention provides a method for brominating a methyl group bonded to an aromatic ring, which solves the problem of low selectivity of conventional monobromo compounds and at the same time obtains a bromide in a good yield in a short time. This is an issue.

[0007]

Means for Solving the Problems In order to solve this problem, the present inventors have studied in detail the bromination of a methyl group bonded to an aromatic ring using bromine and the reaction using bentonite as a catalyst. As a result, surprisingly, by using dichloromethane as a solvent and reacting at a temperature of 0 to 30 ° C., a monobromide can be obtained with extremely high selectivity, and bromination proceeds at a reaction rate that can complete the reaction in several hours. The present invention has been completed and the present invention has been completed.

That is, the present invention is as follows. 1. When brominating a methyl group of a methylated aromatic compound represented by the general formula (I) with bromine, an aromatic compound characterized by reacting in a dichloromethane solvent at a temperature of 0 ° C to 30 ° C in the presence of bentonite. A method for brominating a methyl group bonded to a ring. Ar-CH ₃ (I) (wherein Ar has no substituent or is a nitro group,
It represents an aromatic ring having at least one substituent selected from a cyano group and a halogen atom. ) 2. 1 to 1 mol of bromine for 1 mol of the methylated aromatic compound
A method for brominating a methyl group bonded to an aromatic ring according to the above 1, which is characterized by using 10 mol. 3. The method for brominating a methyl group bonded to an aromatic ring according to the above 1, wherein the dichloromethane solvent is used in an amount of 1 to 500 parts by weight with respect to 1 part by weight of the methylated aromatic compound. 4. Bentonite is used in an amount of 0.0001 to 0.5 part by weight, based on 1 part by weight of the methylated aromatic compound. 5. A method for brominating a methyl group bonded to an aromatic ring according to the above 1, wherein hydrogen bromide produced as a by-product is removed with an inert gas.

The present invention will be described in more detail below. In the method of the present invention, the aromatic compound having a methyl group used as a raw material has no substituent other than a methyl group, or at least one substituent selected from a nitro group, a cyano group, and a halogen atom. Have. There is no particular limitation on the number of substituents bonded to the aromatic ring. The substituent bonded to the aromatic ring is preferably the above-mentioned electron-withdrawing group. This is because the presence of the electron-donating group causes bromination of the aromatic ring in addition to bromination of the methyl group.

Examples of the halogen atom include fluorine, chlorine, bromine and iodine. The following is a specific example.
If the aromatic ring is a benzene ring, toluene, (o
-, M-, p-) nitrotoluene, 2,3-dinitrotoluene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 3,4-dinitrotoluene, (o-, m-,
p-) tolunitrile, 2,6-dicyanotoluene, (o
-, M-, p-) fluorotoluene, 2,4-difluorotoluene, 2,5-difluorotoluene, 2,6-difluorotoluene, 3,4-difluorotoluene, 2,
3,4-trifluorotoluene, (o-, m-, p-)
Chlorotoluene, 2,3-dichlorotoluene, 2,4-
Dichlorotoluene, 2,5-dichlorotoluene, 2,6
-Dichlorotoluene, 3,4-dichlorotoluene, (o
-, M-, p-) bromotoluene, 2,5-dibromotoluene, 3,5-dibromotoluene, (o-, m-, p
-) Iodotoluene, 2-fluoro-4-nitrotoluene, 2-fluoro-5-nitrotoluene, 2-fluoro-6-nitrotoluene, 3-fluoro-4-nitrotoluene, 4-fluoro-2-nitrotoluene, 4-fluoro- 3-nitrotoluene, 5-fluoro-2-nitrotoluene, 2-chloro-3-nitrotoluene, 2-chloro-6-nitrotoluene, 4-chloro-2-nitrotoluene, 4-chloro-3-nitrotoluene, 2-bromo-4.
-Nitrotoluene, 2-bromo-5-nitrotoluene,
2-bromo-6-nitrotoluene, 2-methyl-6-nitrobenzonitrile, 2-fluoro-5-methylbenzonitrile, 5-fluoro-2-methylbenzonitrile,
3-chloro-4-methylbenzonitrile, 2-chloro-
6-methylbenzonitrile, 2-chloro-4-fluorotoluene, 2-chloro-6-fluorotoluene, 3-chloro-4-fluorotoluene, 4-chloro-2-fluorotoluene, 2-bromo-4-fluorotoluene. , 2-
Bromo-5-fluorotoluene, 3-bromo-4-fluorotoluene, 4-bromo-2-fluorotoluene, 5
-Bromo-2-fluorotoluene, 2-fluoro-4-
Iodotoluene, 2-bromo-5-chlorotoluene, 4
-Chloro-2-fluoro-5-nitrotoluene, 2-bromo-4-chloro-5-nitrotoluene and the like are included.
Further, those having a naphthalene ring include 1-bromo-2-methylnaphthalene, 1-bromo-4-methylnaphthalene,
2-Methyl-1-nitronaphthalene and the like are included, and those having an anthracene ring include 1-methyl anthracene, 2-
Includes methylanthracene and 9-methylanthracene.

Bromine is used as the brominating agent, and the addition amount is preferably 1 to 10 mol, and more preferably 2 to 5 mol, per 1 mol of the methylated aromatic compound. If the amount is less than 1 mol, the addition ratio of the raw material methylated aromatic compound cannot reach 100%, and a means for separating from the reaction mixture is required. It also has an unfavorable effect on the selectivity. Even if the amount is 10 mol or more, the desired monobromide can be obtained, but the selectivity is lowered and the amount of the dibromide by-product is increased. Bromine may be added to the reaction system all at once or in small portions.

The reaction temperature is required to be 0 to 30 ° C. Further, it is preferably 5 to 20 ° C. If the temperature is lower than 0 ° C, a sufficient reaction rate cannot be obtained, and the reaction requires a long time of several tens of hours. On the other hand, when the temperature is 30 ° C. or higher, the selectivity of the target monobromide is remarkably lowered.
In the present invention, it is necessary to use dichloromethane as the inert organic solvent. Although the details of the effect of dichloromethane on the reaction selectivity are not clear, it is considered that it has the most suitable polarity for the reaction. As a result of various studies, such effects could not be obtained with other solvents such as carbon disulfide and chloroform. The amount of dichloromethane used is preferably 1 to 500 parts by weight, more preferably 2 to 200 parts by weight, based on 1 part by weight of the methylated aromatic compound. When the amount is 1 part by weight or less, the above effects cannot be sufficiently obtained, and the selectivity of the reaction decreases. If the amount is more than 500 parts by weight, there is no great difference in the effect on the selectivity and the amount of dichloromethane recovered after the reaction increases, which is not preferable.

Further, in the present invention, a vent is used as a catalyst.
It is necessary to add knight. Bentonite is S
iO₂, Al₂O₃With SiO as the main component₂/ Al
₂O ₃Has a molar ratio of 4.4 to 7.7 and an average of 5.9,
It is a clay mainly composed of montmorillonite stones. Main component mineral
In addition to Nmorillon stone, protein stone, buffalo, butterfly
It may include stone, fluorspar, volcanic glass, and the like. Bentona
The amount of iron added is based on 1 part by weight of the methylated aromatic compound.
0.0001 to 0.5 part by weight is preferable, and more preferable.
It is preferably 0.001 to 0.1 part by weight, particularly preferably
Or 0.001 to 0.05 parts by weight. 0.0001
If it is less than parts by weight, the reaction not involving the bentonite catalyst will occur.
The reaction mainly becomes less selective. More than 0.5 parts by weight
Target product monobromide adsorbed on the catalyst after cousin reaction
Is increased, and a troublesome process is required for recovery, which is not preferable.
Yes.

In the present invention, hydrogen bromide is by-produced during the reaction. As a result of investigation, it was revealed that hydrogen bromide inhibits the reaction system of the present invention. In the present invention, nitrogen,
It is preferable to supply an inert gas such as argon or helium to the reaction solution in or on the reaction solution to remove hydrogen bromide produced as a by-product from the reaction system. The reaction mode may be a complete mixing type in which a methylated aromatic compound and bromine or bentonite are stirred in dichloromethane, a fixed bed type in which bentonite is supported on any carrier, or a fluidized bed type.

[0015]

EXAMPLES Next, the present invention will be described in more detail with reference to examples.

[0016]

Example 1 500 mg of p-nitrotoluene (3.65)
(mmol) was dissolved in 30 ml (39.8 g) of dichloromethane, and 5 mg of bentonite (manufactured by Wako Pure Chemical Industries, Ltd.) was added at 10 ° C. To 20 ml (26.5 g) of dichloromethane 1.
A solution in which 75 g (10.95 mmol) of bromine was dissolved was added dropwise with stirring over 1 hour. The progress of the reaction was monitored by liquid chromatography and 1.
The reaction was completed in 5 hours. Nitrogen gas was slowly and continuously supplied into the liquid at the time of dropping bromine and the subsequent reaction to remove by-product hydrogen bromide. The reaction solution was washed with 10% aqueous sodium thiosulfate solution to remove excess bromine. The organic layer was separated and dried over sodium sulfate. After drying, the reaction solution was analyzed by liquid chromatography. As a result, the reaction rate of p-nitrotoluene was 97.9%, the yield of p-nitrobenzyl bromide was 91.2%, and the selectivity of p-nitrobenzyl bromide was 93.2%. there were.

[0017]

Example 2 500 mg of p-chlorotoluene (3.95)
Mmol) was dissolved in 30 ml of dichloromethane (39.8 g) and cooled to 10 ° C. Bentonite 5 with stirring
mg was added. 20 ml of dichloromethane (26.5 g)
A solution having 1.89 g (11.85 mmol) of bromine dissolved therein was added dropwise over 1 hour while stirring. The reaction was completed 1 hour after the completion of the dropping. Nitrogen gas was slowly and continuously supplied into the liquid at the time of dropping bromine and at the subsequent reaction to remove by-product hydrogen bromide. After carrying out the same operation as in Example 1, the reaction solution was analyzed by liquid chromatography. As a result, the reaction rate of p-chlorotoluene was 99.5%, the yield of p-chlorobenzyl bromide was 93.7%, and p-chlorobenzyl. The bromide selectivity was 94.2%.

[0018]

Example 3 p-Bromotoluene 500 mg (2.92)
Mmol) was dissolved in 30 ml of dichloromethane (39.8 g) and cooled to 10 ° C. Bentonite 5 with stirring
mg was added. 20 ml of dichloromethane (26.5 g)
A solution having 1.40 g (8.77 mmol) of bromine dissolved therein was added dropwise over 1 hour with stirring. After the dropping is completed,
The reaction was completed in 1 hour. Nitrogen gas was slowly and continuously supplied into the liquid when bromine was dropped and during the subsequent reaction. After carrying out the same operation as in Example 1, the reaction solution was analyzed by liquid chromatography. As a result, the reaction rate of p-bromotoluene was 99.3%, and the yield of p-bromobenzyl bromide was 93.
5%, p-bromobenzyl bromide selectivity 94.2
%Met.

[0019]

Example 4 500 mg of p-tolunitrile (4.27 m)
Mol) was dissolved in 30 ml of dichloromethane (39.8 g) and cooled to 10 ° C. Bentonite 5m with stirring
g was added. A solution in which 2.05 g (12.80 mmol) of bromine was dissolved in 20 ml (26.5 g) of dichloromethane was added dropwise over 1 hour while stirring. After the dropping is completed,
The reaction was completed in 1.5 hours. Nitrogen gas was slowly and continuously supplied into the liquid when bromine was dropped and during the subsequent reaction. After performing the same operation as in Example 1, the reaction solution was analyzed by liquid chromatography. As a result, the reaction rate of p-tolunitrile was 98.0%, and the yield of p-cyanobenzyl bromide was 9.
1.8%, p-cyanobenzyl bromide selectivity 9
It was 3.7%.

[0020]

Example 5 Toluene (500 mg, 5.43 mmol) was dissolved in dichloromethane (30 ml, 39.8 g) to give 10
Cooled to ° C. Bentonite 5 mg was added with stirring. 2.60 in 20 ml (26.5 g) of dichloromethane
A solution in which g (16.29 mmol) of bromine was dissolved was added dropwise over 1 hour while stirring. The reaction was completed 1 hour after the completion of the dropping. Nitrogen gas was slowly and continuously supplied into the liquid when bromine was dropped and during the subsequent reaction. After performing the same operation as in Example 1, the reaction solution was analyzed by liquid chromatography. As a result, the toluene conversion rate was 99.1%, the benzyl bromide yield was 90.0%, and the benzyl bromide selectivity was 90.8%. Met.

[0021]

Comparative Example 1 p-nitrotoluene 1.37 g (0.01
(mol) was dissolved in 20 ml of carbon disulfide, and bentonite (0.050 g, 0.036 wt%) was added with stirring. Under heating under reflux (reaction solution temperature 45 ° C), 3.36 g of bromine
(0.021 mmol) was added dropwise. The progress of the reaction was monitored by liquid chromatography, and the reaction was completed after 4 hours. After performing the same operation as in Example 1, the reaction solution was analyzed by liquid chromatography. As a result, the p-nitrotoluene conversion rate was 97.8%, the p-nitrobenzyl bromide yield was 76.4%, and the p-nitrobenzyl bromide was obtained. Has a selection rate of 7
It was 8.1%.

[0022]

Comparative Example 2 p-nitrotoluene 30.0 g (0.22
(mol) was placed in a 200 ml three-necked flask and heated to 145 to 150 ° C. in an oil bath. Bromine 36.8
g (0.23 mol) was added dropwise over 30 minutes. After completion of the dropping, heating and stirring were continued for 10 minutes. While the content was liquid, it was poured into 400 ml of hot ligroin, 1.5 g of activated carbon was added, and the mixture was stirred for 10 minutes and then filtered. After cooling to 20 ° C., the crystals were filtered off and washed with 20 cc of cold ligroin. The reaction rate of p-nitrotoluene was 93.4%, the yield of p-nitrobenzyl bromide was 68.1%, and the selectivity of p-nitrobenzyl bromide was 72.9%.

[0023]

Comparative Example 3 p-nitrotoluene 15.0 g (0.11
mol) in 180 ml of dichloromethane, and while stirring, 56 ml (0.05 mol) of 30% hydrogen peroxide solution.
Was added. Under reflux (reaction temperature 40 ° C.), 8.8 g of bromine
15 ml of a dichloromethane solution of (0.055 mol) was added dropwise over 30 minutes. The progress of the reaction was monitored by liquid chromatography, and the reaction was completed 2.5 hours after the completion of the dropping. As a result of analyzing the reaction solution by liquid chromatography, the reaction rate of p-nitrotoluene was 87.3%, the yield of p-nitrobenzyl bromide was 71.2%, and the selectivity of p-nitrobenzyl bromide was 81.6%.

[0024]

EFFECTS OF THE INVENTION According to the method of the present invention, the methyl group of a methylated aromatic compound can be brominated with high selectivity and high yield, and the bromination at a low temperature but the reaction rate is also high. Since it is sufficiently satisfactory, it is very useful for the production of monobromo compounds.

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Claims (5)

[Claims] 1. When brominating a methyl group of a methylated aromatic compound represented by the general formula (I) with bromine, the presence of bentonite in a dichloromethane solvent at 0 ° C. to 30 ° C.
A method for brominating a methyl group bonded to an aromatic ring, which comprises reacting at a temperature of Ar-CH ₃ (I) (wherein Ar has no substituent or is a nitro group,
It represents an aromatic ring having at least one substituent selected from a cyano group and a halogen atom. ) 2. The method for brominating a methyl group bonded to an aromatic ring according to claim 1, wherein 1 to 10 mol of bromine is used per 1 mol of the methylated aromatic compound. 3. The method for brominating a methyl group bonded to an aromatic ring according to claim 1, wherein 1 to 500 parts by weight of a dichloromethane solvent is used with respect to 1 part by weight of the methylated aromatic compound. 4. A bentonite-methylated aromatic compound 1
The method for brominating a methyl group bonded to an aromatic ring according to claim 1, wherein 0.0001 to 0.5 part by weight is used with respect to parts by weight. 5. The method for brominating a methyl group bonded to an aromatic ring according to claim 1, wherein hydrogen bromide produced as a by-product is removed by an inert gas.