TW201305104A - Isopropyl 3-chloro-4-methylbenzoate and method for producing same - Google Patents

Abstract

Provided is isopropyl 3-chloro-4-methylbenzoate, which is a novel substance that is useful as an intermediate for the synthesis of functional polymer materials, agrichemicals, pharmaceuticals, and the like. Also provided is a method for producing the same. Isopropyl 3-chloro-4-methylbenzoate represented by formula (1) is produced by the method whereby 4-chloro-methylbenzoic acid chloride is subjected to nuclear chlorination in the presence of chlorine and a Lewis acid catalyst, the resulting 3-chloro-4-methylbenzoic acid chloride is esterified by isopropyl alcohol, and isopropyl 3-chloro-4-methylbenzoate is produced.

Description

Isopropyl 3-chloro-4-methylbenzoate and its production method

The present invention provides a novel substance of isopropyl 3-chloro-4-methylbenzoate, and further provides an industrially produced high yield and high purity of the 3-chloro-4-methylbenzoic acid. Process for the preparation of propyl 3-chloro-4-methylbenzoic acid isopropyl ester.

Isopropyl 3-chloro-4-methylbenzoate is a trisubstituted aromatic compound substituted with a methyl group, a chloro group and an ester group on a benzene ring, and is expected to be an aromatic polyamine or an aromatic polyester. In addition to the synthetic intermediates of functional polymer materials, it can also be used as a 6-aryloxyquinoline derivative for the synthesis of intermediates for the manufacture of pesticides or pharmaceuticals such as agricultural and horticultural insecticides or fungicides. Substance of the substance.

Here, in Patent Document 1, it can be seen that when a 6-aryloxyquinoline derivative which can be used as a synthetic intermediate for the production of a pesticide is produced, it is indicated that 5-chloro-4 represented by the following formula (4) is used. -Methyl-2-nitro-benzoic acid isopropyl ester as a description of its synthetic intermediate, or suggesting that this 5-halo-4-alkyl-2-nitro-benzoate (compound 4) is at 5 A description of the production of a nitro group by introducing a nitro group at the 2-position of a benzene nucleus of a halogen-4-alkyl-benzoate.

Then, in Patent Document 1, 5-halo-4-alkyl-benzoate which is a raw material for the production of 5-halo-4-alkyl-2-nitro-benzoate has been described. Can be purchased in general. However, Patent Document 1 does not describe how 5-halo-4-alkyl-benzoate is specifically produced, and in particular, it relates to isopropyl 3-chloro-4-methylbenzoate. Specifically, various benzoate derivatives are known, but the production method thereof is not specifically known.

When the trisubstituted aromatic compound having a methyl group, a chloro group and an ester group on the benzene ring is produced, the type of the substituent introduced into the benzene ring, the number and arrangement thereof, and the substance to be an intermediate are produced. The physical and chemical properties of physical properties, reactivity, orientation (positional selectivity) are very different, and the methods of treatment in the latter step are also very different, and a large number of products are produced or sought for the trisubstituted aromatic compounds obtained. In the high-purity industrial production, it is extremely important to select which raw materials are selected and in which order the substituents are introduced.

Then, in order to synthesize a trisubstituted aromatic compound substituted with a methyl group, a chloro group and an ester group on such a benzene ring, it is generally considered to use 4-methylbenzoic acid which is easily obtained as a starting material to make this 4- Methyl benzoic acid is dissolved in a solvent such as carbon tetrachloride, and is subjected to nuclear chlorination in a reaction solvent to synthesize 3- Chloro-4-methylbenzoic acid, then reacting the obtained 3-chloro-4-methylbenzoic acid with sulfinium chloride to synthesize 3-chloro-4-methylbenzoic acid, further chlorinating The 3-chloro-4-methylbenzoic acid was added dropwise to isopropanol to be esterified, and the synthetic route of the objective product of 3-chloro-4-methylbenzoic acid isopropyl ester was synthesized.

Thus, such a synthetic route is easy to establish in a laboratory, but it is produced in large quantities, or in the industrial production for seeking high purity of the obtained trisubstituted aromatic compound, using 4-methyl as a raw material. 3-Chloro-4-methylbenzoic acid of benzoic acid or its nuclear chlorination product is a high melting point substance, so it must be useful in the synthesis reaction of such a substance as a raw material to dissolve the substance. In addition to the operation of removing the solvent to be used from the reaction mixture, the melting point, the boiling point, and the sublimation point between the reaction raw material and the reaction product are close to each other, and the separation and purification of the reaction product become difficult and the purity is high. A lot of troubles and costs are required, and at the same time, it is easy to solidify when the intermediate is temporarily stored between the respective reaction steps, and there is a problem that it is necessary to be remelted when the subsequent reaction step is performed. Furthermore, it is envisaged that sulfinium chloride must be used in the synthesis of 3-chloro-4-methylbenzoic acid from 3-chloro-4-methylbenzoic acid, so the resulting 3-chloro-4-methyl chloride is obtained. A sulfur-based substance in benzoic acid is present as an impurity, and a sulfur-based substance is used in the isopropyl 3-chloro-4-methylbenzoate of the target compound synthesized using the 3-chloro-4-methylbenzoic acid. Mixing into impurities.

Further, in Patent Document 2, it is described that chlorochlorinated 4-methylbenzoic acid is subjected to nuclear chlorination in the presence of chlorine and a Lewis acid catalyst to produce 3-chloro-4-methylbenzoic acid chloride.

[Previous Technical Literature] [Patent Literature]

[Patent Document 1] WO 2010/007,964

[Patent Document 2] Japanese Patent Publication No. 07-330,663

[Summary of the Invention]

Therefore, the inventors of the present invention are industrially advantageous in the production of a novel substance which can be used as a functional polymer material or a synthetic intermediate of a pesticide, a pharmaceutical, or the like, isopropyl 3-chloro-4-methylbenzoate. By accumulating the results of intensive studies, it was found that the use of 4-methylbenzoic acid ruthenium chloride such as trichlorotoluene or sulfinium chloride is industrially readily available for the chlorination of 4-methylbenzoic acid. The nucleation of the 4-methylbenzoic acid chloride produces 3-chloro-4-methylbenzoic acid chloride, and the isochlorohydrin is added dropwise to the obtained 3-chloro-4-methylbenzoic acid chloride. By esterification, hydrazine can be easily produced industrially in high yield of isopropyl 3-chloro-4-methylbenzoate in high yield, and the present invention has been completed.

Accordingly, an object of the present invention is to provide a novel substance which can be used as a functional polymer material or a synthetic intermediate of a pesticide, a pharmaceutical or the like, and an isopropyl 3-chloro-4-methylbenzoate.

Further, it is an object of the present invention to provide a reaction of 3-chloro-4-methylbenzoic acid with isopropanol to produce a high-purity 3-chloro-4-methyl group in high yield and industrially advantageous. Process for the preparation of isopropyl 3-benzo-4-methylbenzoate isopropyl benzoate.

Further, the object of the present invention is to provide a high-purity 3-isopropyl 4-methylbenzoic acid isopropyl ester in a high yield and industrially advantageous manner using 4-methylbenzoic acid chloride as a raw material. A method for producing isopropyl 4-methylbenzoic acid isopropyl ester.

That is, the present invention is isopropyl 3-chloro-4-methylbenzoate represented by the following formula (1).

Further, the method for producing 3-chloro-4-methylbenzoic acid isopropyl ester of the present invention is characterized in that it is stirred under 3-chloro-4-methylbenzoic acid represented by the following formula (2) The reaction was carried out by dropping isopropyl alcohol, and the obtained reaction product was separated and purified.

Further, the method for producing isopropyl 3-chloro-4-methylbenzoate of the present invention is characterized in that 4-methylbenzyl chloride is represented by the following formula (3) The acid is subjected to nuclear chlorination in the presence of chlorine and a Lewis acid catalyst, and the obtained chlorinated 3-chloro-4-methylbenzoic acid is added dropwise with isopropanol under stirring to react, and then isolated and purified. Reaction product.

In the present invention, 4-methylbenzoic acid chlorinated using the compound 3 as a raw material for production, for example, by the air oxidation reaction of p-xylene to produce 4-methylbenzoic acid by trichlorochloride. The ruthenium chloride can be easily produced by toluene or sulfinium chloride, and can be easily and inexpensively obtained.

Then, in the present invention, by the nucleation reaction of 4-methylbenzoic acid (Compound 3) to produce 3-chloro-4-methylbenzoic acid (Compound 2) according to the following reaction mechanism Then, the esterification reaction of Compound 2 with isopropyl alcohol was carried out to produce the object of 3-chloro-4-methylbenzoic acid isopropyl ester (Compound 1).

In the present invention, first, 4-methylbenzoic acid (compound) is carried out. 3) Nuclear chlorination reaction to produce 3-chloro-4-methylbenzoic acid chloride (Compound 2). This nuclear chlorination reaction is carried out in a solvent-free liquid phase reaction, and is carried out by blowing chlorine gas into the raw material of 4-methylbenzoic acid under stirring in the presence of a Lewis acid catalyst such as chlorinated second iron.

The reaction conditions of the nuclear chlorination reaction are generally a reaction temperature of 20 ° C or more and 160 ° C or less, preferably 40 ° C or more and 60 ° C or less. If the reaction temperature is lower than 20 ° C, the reaction rate is lowered and the yield is deteriorated, and the load for recovering the raw material is increased. Further, when the reaction temperature is higher than 160 ° C, the amount of perchlorinated product such as dichlorobenzene increases, and the selectivity of the target product of 3-chloro-4-methylbenzoic acid decreases. Since the nuclear chlorination reaction is a reaction of 4-methylbenzoic acid chloride as a liquid, it is preferably carried out in a solvent-free manner without using a solvent.

The separation and purification of the chlorinated 3-chloro-4-methylbenzoic acid derived from the reaction mixture is generally carried out by distillation under reduced pressure of 5 mmHg or more and 30 mmHg or less, preferably 5 mmHg or more and 10 mmHg or less. Further, the temperature at the bottom of the distillation column of the vacuum distillation is carried out in the range of 120 to 150 ° C, whereby the 4-methylbenzoic acid of the unreacted raw material and the 3-chloro chloride of the product are distilled under reduced pressure. 4-methylbenzoic acid was recovered as a distillate. Then, in the vacuum distillation, the chlorinated 4-methylbenzoic acid of the raw material is recovered as a preliminary distillation, and is circulated in a reaction vessel of the nuclear chlorination reaction, and can be reused in the nuclear chlorination reaction, and further produced by the reaction. The perchlorate such as dichloro is formed into a high boiling point compound and is removed from the bottom of the column.

The above-mentioned nuclear chlorination reaction of 4-methylbenzoic acid (compound 3) is successively carried out, but in this nuclear chlorination reaction, second iron (FeCl ₃ ) is used as a Lewis acid catalyst, so that The amount of the second iron chloride to be used is 0.1% by weight or more and 1.0% by weight or less based on the chlorinated 4-methylbenzoic acid (compound 3) of the raw material, and is preferably in the range of 0.2% by weight or more and 0.4% by weight or less. And the chlorine introduction amount is 0.5 times or more with respect to the chlorinated 4-methylbenzoic acid of the raw material, preferably 0.9 times or more and 1.1 moles or less, and further, the nitrogen substitution is rapidly performed after the reaction is completed to cause the reaction. The unreacted chlorine in the vessel is quickly discharged to the outside of the reaction system, and the chlorination degree of the reaction end point is controlled to be 0.88 or more and 0.91 or less, and the formation ratio of the monochlorobenzene/dichlorobenzene is obviously increased, and the nuclear chlorination reaction is enhanced. The yield of the product of 3-chloro-4-methylbenzoic acid (Compound 2) is even higher, and the object obtained by using 4-methylbenzoic acid (Compound 3) as a raw material is obviously improved. Yield of -chloro-4-methylbenzoic acid isopropyl ester (Compound 1). For example, in the examples described in JP-A-2007-330,663, the formation ratio of the monochlorobenzene/dichlorobenzene is 31.0, and the reaction conditions of the present invention are used, and the monochlorobenzene is used as shown in the examples. The formation ratio of dichloro is increased to 38.6. Further, the degree of chlorination used in the nuclear chlorination reaction for controlling 4-methylbenzoic acid (compound 3) is such that some of the four hydrogen atoms bonded to the benzene nucleus of the compound 3 are substituted into chlorine atoms to average The value shown by the value.

The thus obtained chlorinated 3-chloro-4-methylbenzoic acid (Compound 2) is followed by esterification with isopropanol to give the desired 3-chloro-4-methylbenzoic acid isopropyl ester ( Compound 1). Here, in the esterification reaction in the production of the isopropyl 3-chloro-4-methylbenzoate, it is necessary to add isopropanol to the 3-chloro-4-methylbenzoic acid chloride under stirring. The reaction.

In the esterification reaction in which the acid chloride is reacted with an alcohol, the acid chloride is generally added dropwise in an excess amount of the alcohol, but in an excess amount of isopropanol. When esterified with 3-chloro-4-methylbenzoic acid by dropwise addition, the hydrogen chloride gas generated by the esterification reaction reacts with isopropyl alcohol to form impurities such as water or an olefin compound, and the resulting water system The hydrolysis of the chlorinated 3-chloro-4-methylbenzoic acid of the starting material results in the formation of impurities derived from the olefin compound, in addition to the significant reduction in the yield of the objective product, isopropyl 3-chloro-4-methylbenzoate. In the present invention, the formation of impurities such as water or an olefin compound can be suppressed by dropwise addition of isopropanol under stirring in 3-chloro-4-methylbenzoic acid chloride, in the reaction mixture after the completion of the reaction. Almost no impurities are observed, and a high-purity target substance can be easily obtained from the reaction mixture by distillation purification.

In the esterification reaction of isopropyl alcohol of 3-chloro-4-methylbenzoic acid (Compound 2), the amount of isopropanol used is relative to 3-chloro-4-methylbenzene chloride. The formic acid is 0.9 times the molar amount of 1.2 times the molar amount or less, preferably 1.0 times the molar amount or less and 1.05 times the molar amount. If less than 0.9 times the molar amount, the raw material is 3-chloro-4-methylbenzoic acid chloride. Will remain, and if more than 1.2 times Mo, the water produced by the hydrolysis of 3-chloro-4-methylbenzoic acid from the raw material will be hydrolyzed to produce the impurity 3-chloro-4-methylbenzoic acid. . Further, in the ester reaction, it is not necessary to use an excessive amount of isopropanol, and isopropanol is added dropwise to the 3-chloro-4-methylbenzoic acid chloride, so that the volumetric efficiency of the reaction vessel is high and economical. .

Further, the reaction temperature in the esterification reaction is generally 60 ° C or higher and 140 ° C or lower, preferably 80 ° C or higher and 120 ° C or lower. If the temperature is lower than 60 ° C, the reactivity is lowered, and the time required for the reaction to be terminated becomes long. On the other hand, if it is higher than 140 ° C, a high boiling point compound is formed and the yield is lowered.

Then, the reaction mixture is separated and purified from the end of the esterification reaction 3- The method of isopropyl chloro-4-methylbenzoate (Compound 1) is generally carried out by distillation. The distillation purification is generally 5 mmHg or more and 30 mmHg or less, and is preferably carried out at a column bottom temperature of 150 ° C or more and 190 ° C or less, preferably at 160 ° C or more and 180 ° C or less, under a reduced pressure of 5 mmHg or more and 10 mmHg or less. This was purified by distillation, and the chlorinated 3-chloro-4-methylbenzoic acid and isopropyl alcohol of the unreacted raw material and the product of 3-chloro-4-methylbenzoic acid isopropyl ester were distilled to form a distillate. Then, in this distillation purification, 3-chloro-4-methylbenzoic acid and isopropanol which form the raw material which is initially distilled and recovered are recycled to the reaction vessel of the esterification reaction and can be reused in the esterification reaction. Further, high-boiling compounds such as impurities can be easily removed from the bottom of the column.

The isopropyl 3-chloro-4-methylbenzoate of the present invention can be used as a novel substance for synthesizing intermediates of functional polymer materials, pesticides, pharmaceuticals, etc., and in particular, can be used as an intermediate for medical pesticides. An important intermediate for the synthesis of 5-chloro-4-methyl-2-nitro-benzoic acid isopropyl ester (Compound 4) in the case of an aryloxyquinoline derivative.

Further, according to the method of the present invention, 4-methylbenzoic acid chloride which is inexpensive and easily obtainable is used, and a second iron which is easily obtained and easy to handle is used as a Lewis acid catalyst, and a solvent-free liquid phase is used. The reaction and high-purity isopropyl 3-chloro-4-methylbenzoate can be produced in a high yield, which is industrially advantageous from the viewpoints of raw materials, reaction equipment, and economy.

[Formation for implementing the invention]

Hereinafter, the contents of the present invention will be specifically described based on examples and reference examples.

[Examples] [Manufacture of 3-chloro-4-methylbenzoic acid]

In a 1000 ml brown reaction flask equipped with a reflux condenser and a waste water washing device, a gas chromatographic analysis of 99.7% of a concentration of 99.7% of 4-methylbenzoic acid 927.6 g (6.0 mol), and a second iron chloride 2.9 g (0.3% by weight), the reaction temperature was maintained at 50 to 55 ° C while introducing chlorine gas at a flow rate of 18.9 g/hr under stirring, and the reaction was carried out for 22 hours. At this time, the introduction amount of chlorine was 1.0, and after the completion of the reaction, nitrogen substitution was rapidly performed, and unreacted chlorine in the reaction vessel was quickly discharged to the outside of the reaction system, and the degree of chlorination at the end of the reaction was controlled to 0.90.

The yield of the reaction mixture obtained after the completion of the reaction was 1113.0 g, and the composition was based on the analysis of the gas chromatography layer, the unreacted 4-methylbenzoic acid 12.4%, and the intended chlorinated 3-chloro-4- 84.9% of methylbenzoic acid, 0.1% of 2-chloro-4-methylbenzoic acid of the isomer of the target substance, 2.2% of dichloro-4-methylbenzoic acid of the side reaction product, monochloro The body/dichloro formation ratio (84.9/2.2) was 38.6. Further, the amount of hydrogen chloride recovered in the waste water washing apparatus was 196.4 g (5.4 mol), and the amount of unreacted chlorine was 33.3 g (0.5 mol).

The reaction mixture was distilled under reduced pressure at a pressure of 10 mmHg and a bottom temperature of 165 ° C to obtain 3-chloro-4-methylbenzyl chloride as a colorless liquid. Acid 775.1g. The purity of the obtained 3-chloro-4-methylbenzoic acid chloride was 99.8% by gas chromatographic analysis, and the yield was 70.4%.

[Method for producing 3-chloro-4-methylbenzoic acid isopropyl ester]

775.1 g (4.1 mol) of 3-chloro-4-methylbenzoic acid obtained by the above method was fed into a reaction container while maintaining the reaction temperature at 78 to 80 ° C while stirring at 86 g / The speed of hr was dropped into 258.7 g of isopropanol (4.3 mol, 1.05 times the molar ratio of chlorinated to 3-chloro-4-methylbenzoic acid) for about 3 hours, and the temperature was gradually increased to 120 after the reaction was completed. Maintain and mature for 10 hours at °C.

The yield of the obtained reaction mixture was 926.7 g, and the composition was in terms of gas chromatographic analysis, the unreacted isopropanol was 1.3%, and the intended 3-chloro-4-methylbenzoic acid isopropyl ester was 98.3%. Further, the amount of hydrogen chloride recovered in the waste water washing apparatus was 156.9 g.

The reaction mixture was subjected to distillation under reduced pressure at a pressure of 10 mmHg and a bottom temperature of 180 ° C to afford 685.8 g of 3-chloro-4-methylbenzoic acid isopropyl ester as a colorless liquid. The purity of the obtained isopropyl 3-chloro-4-methylbenzoate was 99.8% in terms of gas chromatography, and the yield was 74.0%.

[Structural analysis of [3-chloro-4-methylbenzoic acid isopropyl ester]

For the isopropyl 3-chloro-4-methylbenzoate obtained in this example, the following physicochemical properties were determined.

(1) Infrared absorption spectrum

An infrared spectroscopic device (manufactured by HORIBA Co., Ltd.: FT-720) was used as a measuring device.

Further, in terms of characteristic absorption, absorption (cm ^-1 ) as follows was observed.

1716, 1606, 1490, 1387, 1182, 833

(2) Mass spectrometry

A mass spectrometer (manufactured by Shimadzu Corporation: GCMS-QP5050A) was used as a measuring device.

Further, in terms of characteristic peaks, the following peaks (m/e) were observed.

212(M ⁺ ),170,153(base)

(3) ¹ H-NMR spectrum (σ ppm from TMS, in CDCl ₃ )

A nuclear magnetic resonance apparatus (manufactured by Bruker: DRX-500) was used as a measuring device.

Further, in terms of characteristic peaks, the following peaks (ppm) were observed.

1.36ppm (6H, d), 2, 41ppm (3H, s), 5.24ppm (1H, m), 7.27ppm (1H, d), 7.81ppm (1H, m), 7.98ppm (1H, d)

(4) ¹³ C-NMR spectrum (σ ppm from TMS, in CDCl ₃ )

20.285 ppm, 21.927 ppm, 68.662 ppm, 127.696 ppm, 130.082 ppm, 130.223 ppm, 130.792 ppm, 134.454 ppm, 141.168 ppm

[Comparative example]

98.0 g of isopropanol (1.6 mol; 2.0 times the molar ratio of chlorinated 3-chloro-4-methylbenzoic acid) was fed to the reaction vessel while maintaining the reaction temperature at 78 to 80 ° C. 152.1 g (0.8 mol) of 3-chloro-4-methylbenzoic acid chloride prepared in the above example was added dropwise at a rate of 50.7 g/hr under stirring for about 3 hours, and the temperature was maintained at 140 ° C after the completion of the reaction. And cooked for 4 hours.

The yield of the obtained reaction mixture was 228.0 g, and the composition was in terms of gas chromatographic analysis, the unreacted isopropanol was 21.7%, and the intended 3-chloro-4-methylbenzoic acid isopropyl ester was 77.5%. In addition to these impurities, 3-chloro-4-methylbenzoic acid was found to be 0.6%. Further, the amount of hydrogen chloride recovered in the exhaust gas water washing device was 15.2 g (0.4 mol).

The reaction mixture was subjected to distillation under reduced pressure at a pressure of 60 mmHg and a bottom temperature of 60 ° C, and excess isopropyl alcohol was distilled off to obtain 161.0 g of 3-chloro-4-methylbenzoic acid isopropyl ester as a colorless liquid. The purity of the obtained isopropyl 3-chloro-4-methylbenzoate was 99.2% in terms of gas chromatography, and the yield was 70.6%. Further, the isopropyl 3-chloro-4-methylbenzoate obtained in this comparative example precipitated 3-chloro-4-methylbenzoic acid during storage.

Further, in this comparative example, if the reaction mixture obtained by distillation purification is obtained Distilled to isopropyl 3-chloro-4-methylbenzoate, which is subjected to distillation to purify hydrogen chloride dissolved in excess isopropanol to corrode the vacuum pump, or to prevent corrosion of the vacuum pump, hydrogen chloride must be attached In addition to the equipment, if the residual amount of the pot is reduced during the distillation purification process, 3-chloro-4-methylbenzoic acid will precipitate and adhere to the wall of the distillation pot, and the maintenance of the distillation apparatus requires a large cost, if desired This problem is avoided, the amount of the pot is increased and the yield is lowered, and there is a problem that the productivity deteriorates during the distillation purification of the reaction mixture, but according to the above embodiment of the present invention, the reaction mixture as described above can be avoided. The problem of the distillation purification process.

[Reference example] [Manufacture of [5-chloro-4-methyl-2-nitrobenzoic acid isopropyl ester]

50.0 (0.24 mol) of 3-chloro-4-methylbenzoic acid isopropyl ester obtained in the above example was fed into a reaction vessel while maintaining the reaction temperature at 10 to 12 ° C while stirring about 0.5 Adding mixed acid in an hour [concentrated nitric acid 25.7g (0.28mol, 1.2 times molar ratio of 3-chloro-4-methylbenzoic acid isopropyl ester), concentrated sulfuric acid 55.3g (0.56mol, p-chloro-4-) The molar ratio of isopropyl methacrylate (3.0 times) was 81.0 g, and the mixture was aged at 20 ° C for 2 hours.

The yield of the obtained reaction mixture was 139.1 g, and the composition was in terms of gas chromatographic analysis, and the unreacted isopropyl 3-chloro-4-methylbenzoate was 3.5%, and the objective was 5-chloro-4. - Isopropyl methyl-2-nitrobenzoate was 73.8%. The isomers of the target (2 species) were 11.1% and 11.6%, respectively.

Then, 60.0 g of dichloromethane was added to the above reaction mixture, followed by extraction and separation to obtain 117.4 g of an organic phase. After adding 60.0 g of water to the organic phase, the water was washed for the first time. Then, while confirming the value by a pH meter, 27.7 g of a 10% sodium carbonate aqueous solution and 79.5 g of water were added to neutralize the acid, and 60.0 g of water was further added. The second washing was carried out to obtain 121.6 g of an organic phase.

To 121.6 g of the organic phase obtained in this manner, 15.0 g of sodium sulfate was added thereto, and the mixture was allowed to stand and filtered. Then, the obtained filtrate was distilled, and dichloromethane was distilled off to obtain 52.9 g of crude 5-chloro-4-methyl-2-nitrobenzoate as a crude crystal. The purity of isopropyl 5-chloro-4-methyl-2-nitrobenzoate was 74.3% by gas chromatographic analysis, and the yield was 87.3%.

19 g of methylcyclohexane was added as a recrystallization solvent to 5 g of crude isopropyl 5-chloro-4-methyl-2-nitrobenzoate obtained above, and it was heated and dissolved at 60 ° C, and then air-cooled. And crystallization. The obtained solid liquid was filtered under reduced pressure to give 2.6 g of 5-chloro-4-methyl-2-nitrobenzoic acid isopropyl ester as a pale yellow crystal. The obtained 5-chloro-4-methyl-2-nitrobenzoic acid isopropyl ester had a purity of 99.5% by gas chromatographic analysis and a yield of 42.1% upon recrystallization.

Claims (3)

An isopropyl 3-chloro-4-methylbenzoate, which is represented by the following formula (1); A process for producing isopropyl 3-chloro-4-methylbenzoate characterized by dropwise addition of isopropylidene to 3-chloro-4-methylbenzoic acid represented by the following formula (2) Reacting with an alcohol, separating and purifying the obtained reaction product; A process for producing isopropyl 3-chloro-4-methylbenzoate characterized by 4-methylbenzoic acid represented by the following formula (3) in the presence of chlorine and a Lewis acid catalyst Performing nuclear chlorination, reacting the obtained chlorinated 3-chloro-4-methylbenzoic acid with isopropanol under stirring, and then separating and purifying the obtained reaction product;