JPS632250B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to 2,4-dichloro-m-toluic acid and its derivatives, which have not been described in the literature, and a method for producing the same. It is useful as an intermediate in the production of derivatives, particularly pyrazole dichlorobenzoic acid derivatives useful as herbicides. More specifically, the present invention is based on the following formula (), However, in the formula, Z is a hydroxyl group, a halogen atom, e.g.
The present invention relates to 2,4-dichloro-m-toluic acid and derivatives thereof, which represent groups selected from the group consisting of Cl, Br, and lower alkoxy, such as C ₁ -C ₃ alkoxy, and their preparation. Traditionally, dichlorobenzoic acid derivatives have been used in pharmaceuticals,
It is known as a compound useful as an intermediate for agricultural chemicals, plasticizers, surfactants, flame retardants, etc. For example, 2,4-dichlorobenzoic acid is used as an intermediate for agricultural chemical production. The present inventors have conducted research on the synthesis of 2,4-dichlorobenzoic acid and its derivatives, which are useful as intermediates for agricultural chemical synthesis. As a result, 2,4-dichloro-m-toluic acid represented by the above formula () and its derivatives exist, which have not been previously described in the literature, and these compounds can be synthesized by an easy synthetic route and in good yield. I discovered something. The present inventors have discovered the following formula ()-1, in which Z is a hydroxyl group, among the compounds of the formula () that have not been previously described in the literature: However, in the formula, Z ₁ represents an OH group. In order to obtain 2,4-dichloro-m-toluic acid represented by, an attempt was made to synthesize formula ()-1 by chlorination of m-toluic acid, but In addition to the problem that chlorination itself is difficult to proceed, the carboxyl group of m-toluic acid

It is presumed that this is due to the orientational properties of [Formula], but it was found to be difficult to obtain its 2,4-dichloride. Furthermore, 2,4, which is expected to be useful as an intermediate for the synthesis of 2,4-dichloro-m-toluic acid,
An attempt to synthesize -dichloro-m-xylene by chlorination of m-xylene was made in 4.6-
It was found that this method gave a mixed chloride containing dichloride which was difficult to separate and was unsuitable for practical use. The present inventors have proposed the above formula () which has not been described in the literature so far.
As a result of further research to synthesize 2,4-dichloro-m-toluic acid represented by -1 by an easy synthetic route and in a good yield, we found that the following formula (), However, in the formula, R is a lower alkyl group selected from the group consisting of a C ₁ -C ₃ lower alkyl group such as a methyl group, an ethyl group, an isopropyl group, an acetyl group, and a functional derivative group thereof, such as -CH ₂ OH, -CHO. When a compound represented by the following is oxidized, the methyl group at the 3-position is oxidized, R is selectively oxidized and converted to a carboxyl group, and in the formula (), the compound represented by the formula ()- It has been discovered that 2,4-dichloro-m-toluic acid represented by 1 can be selectively formed in good yield. Furthermore, in the above formula (), the following formula ()
-2 However, in the formula, Z ₂ is a halogen atom such as Cl, Br
and a lower alkoxy group such as a group selected from the group consisting of C ₁ -C ₃ alkoxy groups, if desired, the derivatives of 2,4-dichloro-m-toluic acid are optionally prepared as described above. By halogenating or lower alkyl esterification of the 2,4-dichloro-m-toluic acid that can be obtained, the compound of formula ()-1 in formula () is converted to the compound of formula ()-2 in a good yield. I discovered that it is possible. Therefore, the object of the present invention is to obtain 2,4-dichloro-m, which has not been described in the literature, and which can be represented by the above formula () and is useful, for example, in the production of agricultural chemical production intermediates.
- Toluic acid and its derivatives are provided. An object of the present invention is to provide a method for producing the formula () compound which can be industrially advantageously produced. In the present invention, among the compounds of the formula (), the compound in which R is a lower alkyl group is, for example, 2.6
- dichlorotoluene in the presence of an acidic catalyst by means known per se, lower alkyl chlorides such as methyl chloride, ethyl chloride, isopropyl chloride etc., lower alcohols such as methanol, ethanol, i-propanol and ethylene, propylene; It can be easily obtained by alkylating using the same as an alkylating agent. This reaction can be carried out, for example, by bringing 2,6-dichlorotoluene and an alkylating agent into contact in the presence of a catalyst, in the presence or absence of a solvent. Examples of the solvent include lower nitroalkanes such as nitromethane and nitroethane, aliphatic nitriles such as acetonitrile and propionitrile, halogenated hydrocarbons such as dichloromethane and tetrachloroethane, carbon disulfide, etc. Examples include solvents. The amount of alkylating agent used can be selected as appropriate, for example,
Approximately 0.1 per mole of 2,6-dichlorotoluene
Examples include amounts of from about 1 mole to about 1 mole. The amount of solvent to be used can also be selected as appropriate; for example,
The amount used may be from about 0.5 to about 20 in terms of weight ratio to the raw material 2,6-dichlorotoluene. Examples of acid catalysts used in this reaction include:
Examples include Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, and titanium tetrachloride, and protonic acids such as hydrogen fluoride, sulfuric acid, and phosphoric acid. The amount of these catalysts used varies depending on the type and amount of the alkylating agent, but can be exemplified in an amount of about 0.01 to about 0.5 mol per 1 mol of 2,6-dichlorotoluene. As the reaction temperature, for example,
Examples include temperature conditions of about 0 to about 200°C, and reaction times of about 1 to about 24 hours. Furthermore, the above formula ()
In the compound, 2,4-dichloro-m-xylene in which R is a methyl group can also be produced in good yield from m-xylene, which is an inexpensive and easily available petrochemical product. According to this preferred embodiment, 5-t-butyl-m-xylene, which can be easily obtained by the reaction of m-xylene and isobutene, is
Utilizing the steric hindrance of the t-butyl group at the -position, 2,4-dichloride is selectively formed, for example, by iodine-catalyzed benzene nucleus substitution chlorination, and then, for example, 2,4-dichloride is formed by anhydrous aluminum chloride. 2,4-dichloro-m-xylene can be produced in good yield by carrying out a transalkylation reaction with m-xylene using a Lewis acid such as the above as a catalyst. This reaction consists of a chlorination reaction and a transalkylation reaction. The chlorination reaction can be carried out, for example, by bringing 5-t-butyl-m-xylene into contact with chlorine gas in the presence of a catalyst, in the presence or absence of a solvent. Examples of the solvent include halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, and chloroform. The amount of the solvent to be used can be selected as appropriate, for example, from about 0.5 to about
An example of a usage amount is 10. As a catalyst, for example, aluminum chloride, dichloride
Examples include iron, Lewis acids such as tin tetrachloride, and iodine. The amount of these catalysts used is 5
-For 1 mole of -t-butyl-m-xylene,
Examples include amounts of about 0.5 mmol to 20 mmol. The reaction temperature may be, for example, about 0 DEG to 50 DEG C., and the reaction time may be, for example, about 1 to 10 hours. The transalkylation reaction can be carried out by bringing the obtained 2,4-dichloro-5-t-butyl-m-xylene into contact with a t-butyl group acceptor in the presence of an acid catalyst.
Examples of t-butyl group acceptors include benzene,
Examples include aromatic hydrocarbons such as toluene and xylene, but in particular when m-xylene is used,
This is advantageous because it is recovered into the starting material 5-t-butyl-m-xylene. The amount of these receptors to be used can be selected as appropriate, and an example of the amount used is about 1 to 20 mol per 1 mol of raw material 2,4-dichloro-5-t-butyl-m-xylene. can. Examples of acid catalysts used in this reaction include aluminum chloride, ferric chloride,
Lewis acids such as antimony pentachloride and titanium tetrachloride can be exemplified. The amount of these catalysts used is 2,4-dichloro-5-t-butyl-m-
An example of the amount used is about 0.01 to about 1 mole per mole of xylene. The reaction temperature may be, for example, about 0° to 100°C, and the reaction time may be, for example, about 1 to 10 hours. In the present invention, the compound in which R is an acetyl group in the compound of formula () can be obtained, for example, by acetylating 2,6-dichlorotoluene in the presence of an acidic catalyst by a method known per se. Can be done. This reaction can be carried out by bringing 2,6-dichlorotoluene and an acetylating agent into contact in the presence of a catalyst in the presence or absence of a solvent. Examples of the solvent include lower nitroalkanes such as nitromethane and nitroethane, halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, and tetrachloroethane, carbon disulfide, and nitrobenzene. .
Examples of the acetylating agent include reactive derivatives of acetic acid such as acetyl chloride, acetyl bromide, and acetic anhydride. The amount of these acetylating agents to be used can be selected as appropriate, and is approximately 0.5 to 2,6-dichlorotoluene.
An example of the amount used is 1.5 mol to 1.5 mol, but usually around 1 mol is used. The amount of the solvent to be used can also be selected as appropriate, and for example, the amount used can be 0.5 to 20 in weight ratio to 2,6-dichlorotoluene. Examples of the acid catalyst used in this reaction include Lewis acids such as aluminum chloride, aluminum bromide, zinc chloride, and titanium tetrachloride. The amount of these catalysts used varies depending on the amount of acetylating agent used, but is approximately 2.6
- The amount used may be about 0.5 to 2.5 mol per mol of dichlorotoluene. The reaction temperature may be, for example, about 20 to about 100°C, and the reaction time may be, for example, about 1 to about 100°C.
Mention may be made of reaction times such as 10 hours. Furthermore, in the present invention, in the compound of formula (), R is a functional derivative group of the group R as described above.
Compounds such as CH ₂ OH and -CHO can be obtained as intermediate products of the oxidation reaction of compounds of formula () described below, and can also be obtained by partially chlorinating 2,4-dichloro-m-xylene and hydrolyzing it. can also be obtained and used in the method of the present invention. Examples of such compounds include, for example, 2,4-dichloro-
Examples include 3-methylbenzyl alcohol and 2,4-dichloro-m-tolualdehyde. According to the present invention, in the formula (), the formula ()-
2,4-dichloro-m-toluic acid represented by 1 can be obtained, for example, by converting the compound of formula () which can be obtained as described above or by any other method.
It can be produced by oxidation. Such oxidation means can be selected as appropriate, but according to a preferred embodiment when R in the compound of formula () is a lower alkyl group, for example, the molecule is oxidized in a lower fatty acid solvent in the presence of an oxidation catalyst and a co-catalyst. This can be carried out by a liquid phase autoxidation reaction using oxygen. Examples of the solvent include _C2 to _C6 lower fatty acids such as acetic acid, propionic acid, butyric acid, and among these, acetic acid is more preferred. Further, as the above-mentioned oxidation catalyst, for example, carboxylates, halides, acetylacetonates, etc. of transition metals such as cobalt, manganese, chromium, or iron can be used alone or in a mixture of two or more. can. Examples of the carboxylic acid of the carboxylate include the same carboxylic acids as exemplified for the above solvent. In addition, as the halogen of the above halide,
For example, chlorine, bromine, etc. can be used. Among the above-exemplified oxidation catalysts, cobalt acetate or a combination of cobalt acetate and manganese acetate is more preferred from the viewpoint of solubility in the reaction solvent. Further, examples of the co-catalyst include bromine-containing compounds or carbonyl compounds such as bromine, hydrogen bromide, metal bromides, organic bromides, etc., and examples of the metals include alkali metals such as sodium, potassium, and lithium. Examples include metals such as cobalt, manganese, iron, and cum. Further, examples of organic bromides include compounds such as acetyl bromide, benzyl bromide, and bromoform. Examples of carbonyl compounds include acetaldehyde and methyl ethyl ketone. Among these, it is more preferable to use sodium bromide and/or potassium bromide. Examples of molecular oxygen include oxygen gas, air, mixtures thereof, and other molecular oxygen-containing gases. When carrying out the above liquid phase autooxidation reaction, the concentration of the starting compound (formula ()) can be selected as appropriate, and for example, a concentration of about 1 to about 90% by weight, preferably about 5 to about 50% by weight can be exemplified. . Further, the amount of the oxidation catalyst to be used can be selected as appropriate, for example, from about 0.5 to about 50% by weight based on the raw material formula () compound. More preferably, the amount used is about 2 to about 25% by weight. According to the preferred embodiment, when cobalt acetate or a combination of cobalt acetate and manganese acetate is employed, the Mn/Co (atomic ratio) is preferably in the range of 0 to about 10. Further, the amount of the co-catalyst to be used may be about 0.005 to about 50% by weight, more preferably about 0.01 to about 20% by weight, based on the starting compound of formula (). According to the preferred embodiment, when sodium bromide and/or potassium bromide is used as a cocatalyst, about 0.01 to
About 5% by weight, more preferably about 0.1 to about 2% by weight
It is preferable to use an amount of about 30%. The reaction temperature for the above-mentioned liquid phase autooxidation can be exemplified by a temperature of about 50° to about 180°C, preferably about 60° to about 130°C. Further, the reaction pressure can be any appropriate pressure that can maintain the reaction system in a liquid phase, and examples thereof include atmospheric pressure conditions to about 20 atmospheres. Furthermore, the flow rate of the molecular oxygen-containing gas supplied to the reaction system can be adjusted as appropriate;
A slightly excess flow rate is sufficient. Although the reaction time can be changed as appropriate depending on the reaction temperature, reaction pressure, and other reaction conditions, for example, about 1
It can be carried out for a period of ~10 hours. From the reaction mixture obtained in the above manner, the reaction solvent, water produced by the reaction, unreacted raw material, catalyst, by-products, etc. are separated, and 2,4-dichloro- m-Toluic acid can be obtained. For example, the reaction mixture is directly distilled under reduced pressure to separate the reaction solvent, unreacted raw materials, low-boiling byproducts, etc., and then the distillation residue is thermally extracted with an appropriate organic solvent, such as toluene, and then recrystallized. For example, 2,4-dichloro-m-toluic acid can be obtained. In addition, if you want to obtain even higher purity 2,4-dichloro-m-toluic acid, for example,
2,4-dichloro-m-toluic acid in the above-mentioned distillation residue is converted into methyl ester by a well-known esterification method, for example, by using concentrated sulfuric acid and methanol, and after recovering this ester by distillation, it is treated with an aqueous alkali solution, for example, an aqueous sodium hydroxide solution. heat, hydrolyze,
When the 2,4-dichloro-m-toluic acid alkali salt aqueous solution obtained in this way is acidified with hydrochloric acid etc.,
Extremely pure 2,4-dichloro-m-toluic acid can be obtained. According to a preferred embodiment where R in the compound of formula () is an acetyl group or a functional derivative group thereof, the oxidation can be carried out, for example, by nitric acid oxidation using dilute nitric acid. At this time, the concentration of nitric acid is preferably about 5 to about 60% by weight, and as the diluent, for example, water and/or acetic acid can be used. When a combination of water and acetic acid is used, the higher the proportion of acetic acid used, the more the reaction system becomes a homogeneous system, and therefore the reaction progresses faster. In this oxidation mode, the amount of nitric acid used relative to the starting compound of formula () can be changed as appropriate, but for example, the molar ratio to the compound of formula () is about 1 to about 10, more preferably about 3.
A molar ratio of about 6 to about 6 can be exemplified. As the reaction temperature, a temperature around about 100° C. is most often used, and as the reaction time, a reaction time of about 1 to about 10 hours, more preferably about 2 to about 8 hours, can be exemplified. From the reaction mixture obtained as above, the reaction solvent, unreacted raw materials, by-products, etc. are separated by an appropriate method to obtain 2,4-dichloro-m-toluic acid. be able to. For example, by filtering the reaction mixture, 2,4-dichloro-m
- Recrystallization of a mixture consisting of toluic acid, unreacted raw materials, by-products, etc. from an organic solvent such as toluene results in highly pure 2,4-dichloro-m
- Toluic acid can be obtained. In the production of 2,4-dichloro-m-toluic acid represented by formula ()-1 in formula () from the compound of formula () which can be carried out in the various embodiments exemplified above, any reaction type can be used. For example, a batch type, a semi-continuous type, or a continuous type may be adopted. Furthermore, it is also possible to obtain 2,4-dichloro-m-toluic acid by hydrolysis of 2,4-dichloro-3-methylbenzonitrile or 2,4-dichloro-3-methylbenzotrichloride. . For example, nitration of 2,6-dichlorotoluene,
2,4-dichloro-3-methylbenzonitrile is obtained by reduction and cyanation by Sandmeyer reaction, and 2,4-dichloro-3-methylbenzotrichloride is obtained by radical chlorination of 2,4-dichloro-m-xylene. is obtained. The 2,4-dichloro-3-methylbenzonitrile and 2,4-dichloro-3-methylbenzotrichloride thus obtained are easily hydrolyzed in the presence of acid or alkali, resulting in 2,4-dichloro-3-methylbenzonitrile and 2,4-dichloro-3-methylbenzonitrile. -converted to m-toluic acid. This reaction can be carried out by contacting with an acid or alkaline aqueous solution in the presence or absence of a solvent. Examples of acceptable solvents include lower fatty acids such as formic acid, acetic acid, and propionic acid, and lower alcohols such as methanol, ethanol, and propanol. Examples of acids used include mineral acids such as hydrochloric acid and sulfuric acid; examples of alkalis include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; calcium hydroxide; and barium hydroxide. As for the reaction temperature, temperature conditions such as room temperature to about 1,500 ℃ are used.
The reaction time may include a reaction time of about 1 to 20 hours. Among the compounds of the formula () of the present invention that can be obtained as described above for several embodiments, 2,4-dichloro-m-toluic acid represented by the formula ()-1 is a compound that has not been previously described in the literature. It is a compound. The compound of formula ()-1 is a white crystal with a melting point of 169.5 to 173.5 degrees, and is soluble in organic solvents such as ethanol, ether, and chloroform. In addition, in the infrared spectrum, characteristic absorption of carboxyl groups is shown in the vicinity of 3000 to 2500 cm ^-1 and 1700 cm ^-1 , and in the mass spectrum, the parent peak of m/e204 and m/e187
shows a characteristic peak. In addition, in the NMR spectrum, the chemical shift of the methyl group at the 3-position on the benzene ring was observed as a single line at δ2.48 ppm, and the positional isomers of the methyl group (5-methyl form: 2.37 ppm, 6
-Methyl form: 2.40ppm). Among the above formula () compounds, the formula ()-1 compound is
By halogenation or lower alkyl esterification, it can be easily converted into the above formula ()-2 compound in which Z represents a group selected from the group consisting of a halogen atom and lower alkoxy. , these compounds are also compounds that have not been previously described in any literature. For example, a compound in which Z is a halogen atom in formula ()-1 is 2,4-dichloro-m of formula ()-1.
- Can be formed by halogenating toluic acid with thionyl halide in the presence or absence of a non-polar solvent. Preferred examples of the thionyl halide include thionyl chloride and thionyl bromide. Furthermore, examples of the non-polar solvent include aromatic hydrocarbon solvents such as benzene and toluene. The reaction is preferably carried out using an excess of thionyl halide, for example 2,4-dichloro-m
- The amount of thionyl halide to be used is about 2 to about 5 times the molar amount of toluic acid. The reaction can be carried out, for example, under reflux temperature conditions at a temperature and time of about 1 to about 5 hours. After completion of the reaction, excess thionyl halide is distilled off under reduced pressure to obtain a crude target product, which can be further purified by a method such as vacuum distillation to obtain a highly pure product. In addition, among the compounds of formula (), the compound in which Z is a lower alkoxy group can be obtained by esterifying 2,4-dichloro-m-toluic acid of formula ()-1 by a known alkyl esterification means. It can be easily manufactured. In this reaction, 2,4-dichloro-m-toluic acid is mixed with a large excess of lower alcohol in the presence of an acid catalyst such as concentrated sulfuric acid for about 1 to about 5 hours.
This can be carried out by heating the reaction under reflux conditions. After the reaction is completed, the reaction mixture is cooled, poured into a large amount of ice water, extracted and recovered with a solvent such as chloroform, and the solvent is distilled off to obtain a crude target product. Furthermore, it can be purified by methods such as vacuum distillation. Preferred examples of the lower alcohol include _C1 to _C3 lower alcohols such as methanol, ethanol, and n- or iso-propanol. In addition, in the above formula () compound, 2,4-dichloro-m-toluic acid of formula ()-1 is represented by formula ()-
It is also useful for forming derivatives other than 2. Examples of such derivatives include alkali metal salts, alkaline earth metal salts, ammonium salts, acid anhydrides, amides, hydrazides, thiol esters, and the like. The compound of formula () of the present invention has a methyl group at the 3-position, thereby making an excellent contribution to herbicidal activity, and is a compound that is extremely useful as an intermediate for herbicide synthesis. Furthermore, according to the production method of the present invention, 2,4-dichloro-m-toluic acid and its derivatives of the formula () can be obtained using an industrially easily available and inexpensive compound such as m-xylene as a starting material. It can be manufactured at a high rate. Incidentally, examples of compounds of formula () of the present invention are as follows. 2,4-dichloro-m-toluic acid 2,4-dichloro-m-toluoyl chloride 2,4-dichloro-m-toluoyl bromide 2,4-dichloro-m-toluoyl methyl 2,4-dichloro-m -Ethyl toluate n-propyl 2,4-dichloro-m-toluate i-propyl 2,4-dichloro-m-toluate Allyl 2,4-dichloro-m-toluate Next, the present invention will be described in Examples. Therefore, the following examples will be described in more detail, but they are intended to illustrate embodiments of the present invention, and are not intended to limit the present invention in any way. Reference Example 1 A 200ml three-necked flat-bottomed flask equipped with a gas blowing tube thermometer and a Teflon stirrer inside was filled with 5-t.
64.9 g (0.4 mol) of -butyl-m-xylene, 20 ml of carbon tetrachloride, and 0.075 g of iodine as a catalyst were added, and while stirring well, chlorine gas was blown in at a flow rate of about 4/hr. During this time, the reaction temperature was maintained at 10 to 20° C. by external cooling, and the reaction was carried out for 5 hours. After the reaction was completed, 150ml of n-hexane was added to the reaction mixture.
A small amount of insoluble material was separated. n-hexane solution
Washed twice with 100 ml of saturated aqueous sodium bicarbonate solution and then twice with 100 ml of water. After drying over anhydrous sodium sulfate, n-hexane was distilled off using a rotary evaporator, and the mixture was dried under reduced pressure at room temperature to obtain 98 g of an oily substance. Analysis by gas chromatography revealed that this crude product was 2,4-dichloro-
It was found that it contained 86% by weight of 5-t-butyl-m-xylene. Next, the crude 2.4-
Dichloro-5-t-butyl-m-xylene 98g
(0.365 mol in terms of purity) and 500 g of m-xylene were added. While flowing nitrogen gas into the reaction system, add 13.3 g of anhydrous aluminum chloride from one neck of the flask.
(0.1 mol) was added. During this time, the mixture was thoroughly stirred and externally cooled to maintain the reaction temperature at 15 to 25°C, and the reaction was carried out at this temperature for 2 hours. After the reaction was completed, the reaction mixture was poured into about 1 kg of ice water and stirred for 1 hour. After standing still, the upper organic layer was separated, washed twice with 500 ml of water, dried over anhydrous sodium sulfate, and m-xylene was distilled off under reduced pressure to obtain 123 g of an oily substance. As a result of gas chromatographic analysis, this oily substance contained 53% of 2,4-dichloro-m-xylene.
It was found that it contains g. Distillation under reduced pressure is performed using a packed column type rectification tube to achieve a boiling point of 87-91℃/10mm.
50.3 g of an almost colorless liquid was obtained as a Hg fraction. This liquid was 2,4-dichloro-m-xylene with a purity of 95% by weight. The actual yield in terms of purity was 47.8 g, and the yield based on 5-t-butyl-m-xylene was 63 mol%. Example 1 10 g of acetic acid and 0.25 g of cobalt acetate (tetrahydrate) were placed in a 25 ml four-neck flat bottom flask equipped with a reflux condenser, a thermometer, a gas blowing tube, and a Teflon stirrer inside.
(14.3% by weight based on raw materials), sodium bromide 0.01
g (0.57% by weight based on the raw material) and 1.75 g (0.01 mol) of 2,4-dichloro-m-xylene,
After purging the system with nitrogen, the flask was placed in an oil bath controlled at 100°C. After the reaction solution reaches 100℃, add oxygen gas for about 1 hour while stirring well.
was blown into the liquid at a flow rate of /hr. After carrying out the reaction for 6 hours, the reaction solution was cooled and the unreacted 2.4
-Dichloro-m-xylene was analyzed by gas chromatography, and 2,4-dichloro-m-toluic acid was analyzed by high performance liquid chromatography. As a result, the conversion rate of 2,4-dichloro-m-xylene was
The yield of 2,4-dichloro-m-toluic acid was 47 mol%. Example 2 In a 500ml three-necked flat bottom flask equipped with a reflux condenser, a thermometer and an internal Teflon stirrer, 2.4
-dichloro-3-methylacetophenone 48.7g
(0.24 mol), 66 g of water, 200 g of acetic acid, and 129 g (1.25 mol) of 61% by weight concentrated nitric acid were added, and the reaction was carried out at 100° C. for 7 hours with thorough stirring. After cooling the reaction mixture, it was poured into about 1 kg of ice water, stirred for 30 minutes, and then the crystals were filtered off by suction. The obtained crude crystals were added to 500 ml of a saturated aqueous sodium bicarbonate solution, and after stirring and dissolving for about 30 minutes, a small amount of insoluble matter was separated. After washing the sodium bicarbonate aqueous solution with 100 ml of toluene and acidifying it by adding hydrochloric acid dropwise under ice cooling, 2.4-
Dichloro-m-toluic acid precipitated out as a white powder. This was filtered under suction, washed with water, and then dried under reduced pressure at 50°C. The yield of 2,4-dichloro-m-toluic acid was 38.0 g (yield 77 mol%). The obtained 2,4-dichloro-m-toluic acid was purified by recrystallization from toluene and had a melting point of 169.5 to 173.5.
It was warm at ℃. The structure of 2,4-dichloro-m-toluic acid was confirmed by infrared spectrum, mass spectrum, NMR spectrum, and elemental analysis. The elemental analysis results are shown below.

[Table] Example 3 A 500 ml three-necked flat bottom flask equipped with a reflux condenser, a thermometer and a Teflon stirrer inside had 2.4-
205 g (1.0 mol) of dichloro-m-toluic acid and 300 g (2.5 mol) of thionyl chloride were added, and the reaction was carried out at about 80° C. for 2 hours with stirring. After the reaction solution was cooled to room temperature, excess thionyl chloride was distilled off using a rotary evaporator and dried under reduced pressure to obtain crude 2,4-dichloro-m-toluoyl as a yellow crystalline substance containing a small amount of yellowish brown liquid. Chloride was obtained. This is distilled under reduced pressure,
A highly pure target product was obtained by collecting a fraction with a boiling point of 125-128°C/6 mmHg. 2,4-dichloro-m
-The yield of toluoyl chloride was 176.2g (yield
79 mol%). Also, the melting point of this thing is 43.2
The temperature was ~47.2℃. In addition, 2,4-dichloro-m
- The structure of toluoyl chloride was confirmed by infrared spectrum, mass spectrum, NMR spectrum and elemental analysis. The elemental analysis results are shown below.

[Table] Example 4 In a 200ml eggplant-shaped flask equipped with a reflux condenser,
2,4-dichloro-m-toluic acid 2.05g (0.01
mol), 100 ml of dry methanol, and 1 ml of concentrated sulfuric acid were added, and the reaction was carried out under reflux for 8 hours. After cooling the reaction liquid, it was concentrated under reduced pressure until the liquid volume became about 1/3. The concentrated solution was ice-cooled, poured into 200 g of ice water, and extracted three times with 50 ml of cold chloroform. The extract was washed twice with 50 ml of cold water, dried over anhydrous sodium sulfate, and the chloroform was distilled off under reduced pressure to obtain crude 2.4
-Methyl dichloro-m-toluate was obtained as crystals. Purification by silica gel column chromatography using ethyl acetate as a developing solvent yielded a crystalline product of even higher purity. 2,4-dichloro-
The yield of m-toluic acid was 2.1g (yield 96 mol%)
It was hot. The melting point of this product was 51.6-52.7°C. The structure of methyl 2,4-dichloro-m-toluate can be determined by infrared spectrum, mass spectrum,
Confirmed by NMR spectrum and elemental analysis. The elemental analysis results are shown below.

[Table] Example 5 The reaction was carried out in the same manner as in Example 4 except that isopropanol was used instead of methanol, and the reaction was purified by silica gel-chloroform column chromatography, and 2,4-dichloro-m- Toluic acid isopropyl ester was obtained. n ^20.5 _D 1.5298

Claims (1)

[Claims] 1. The following formula (), 2,4-dichloro-m-toluic acid and its derivatives represented by the following formula, where Z represents a group selected from the group consisting of a hydroxyl group, a halogen atom, and lower alkoxy. 2 The following formula (), However, in the formula, R represents a group selected from the group consisting of a lower alkyl group, an acetyl group, and a functional derivative group thereof; However, in the formula, Z ₁ represents a hydroxyl group. A method for producing 2,4-dichloro-m-toluic acid represented by: 3 The following formula ()-1 However, in the formula, Z ₁ represents a hydroxyl group, and the following formula ()-2 is characterized by halogenating or lower alkyl esterification of 2,4-dichloro-m-toluic acid represented by However, in the formula, Z ₂ represents a group selected from the group consisting of a halogen atom and lower alkoxy.