DESC:FIELD
The present disclosure relates to a process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
2-nitro-4-methylsulfonyl benzoic acid (NMSBA) (I) is an intermediate used in the production of pesticides, pharmaceuticals, and dyes. Particularly, NMSBA is the key intermediate used in the synthesis of agrochemicals such as Mesotrione. Mesotrione is a triketone selective herbicide preferably used for cornfield weeding.

(I)
Conventional methods for the preparation of NMSBA provide NMSBA with impurities. Such methods require further purification of the NMSBA that makes the process uneconomical and hazardous to the environment. Further, the impurities in the NMSBA may affect the efficacy, safety, stability of the final product (Mesotrione) produced by using NMSBA. The yield/productivity of 2-nitro-4-methylsulfonyl benzoic acid, obtained from the conventional processes is considerably low.
Therefore, there is felt a need to provide a process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA) that mitigates the aforestated drawbacks.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
Yet another object of the present disclosure is to provide a process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA) with a comparatively better yield.
Still another object of the present disclosure is to provide a simple and cost-effective process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
Another object of the present disclosure is to provide an environment friendly and commercially scalable process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY
The present disclosure relates to a process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA). The process comprises the step of nitrating 1-Chloro-4-methyl sulfonyl benzene by using a nitrating agent to obtain 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB). The so obtained 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB) is reacted with methyl cyanoacetate by using a base in a fluid medium to obtain methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB). Methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB) is oxidized by using an oxidizing agent and a base to obtain 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
DETAILED DESCRIPTION
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
Benzoic acids and its substituted derivatives, are vital intermediates for the production of agricultural chemicals. Mesotrione, a well-known herbicide is obtained from the important chemical intermediate i.e., 2-Nitro-4-(methylsulfonyl) benzoic acid (NMSBA) which is synthesized by a wide variety of methodologies. However, these methods are associated with drawbacks such as low yield and/ or low purity of the product,, hazardous and have tedious process steps.
The present disclosure provides a simple, economical, and environment-friendly process for the preparation of 2-Nitro-4-methylsulfonyl benzoic acid (NMSBA).
NMSBA is represented by Formula I which is given as:

Formula I
The process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid comprises the following steps:
a) nitrating 1-Chloro-4-methyl sulfonyl benzene by reacting a nitrating agent with 1-Chloro-4-methyl sulfonyl benzene over a first predetermined time period at a first predetermined temperature to obtain 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB);
b) reacting the 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB) with methyl cyanoacetate by using a first base in a fluid medium at a second predetermined temperature for a second predetermined time period to obtain methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB); and
c) oxidizing the methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB) by using an oxidizing agent and a second base at a third predetermined temperature for a third predetermined time period to obtain 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
The process for the synthesis of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA) is described in detail as given below:
Step-a): Preparation of 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB)
In a first step, the nitration of 1-Chloro-4-methyl sulfonyl benzene is carried out by reacting a nitrating agent with 1-Chloro-4-methyl sulfonyl benzene over a first predetermined time period at a first predetermined temperature to obtain 1-Chloro-2-Nitro-4-methyl sulfonyl benzene (Chloro NMSB).
A schematic representation for the preparation of 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB), in accordance with the process of the present disclosure, is given as scheme A.

SCHEME A
In an embodiment of the present disclosure, the nitrating agent is a mixture of sulphuric acid and nitric acid.
In an embodiment of the present disclosure, the first predetermined temperature is in the range of 25 °C to 35 °C and the first predetermined time period is in the range of 2 hours to 6 hours. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 30 °C and the first predetermined time period is 4 hours.
Step-b): Preparation of methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB)
In a second step, Chloro NMSB obtained in step-a is reacted with Methyl cyano acetate by using a first base in a fluid medium at a second predetermined temperature for a second predetermined time period to obtain methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB).
A schematic representation for the preparation of methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB), in accordance with the process of the present disclosure, is given as scheme B.

SCHEME B
In an embodiment of the present disclosure, the fluid medium is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethyl formamide (DMF) and dimethylacetamide (DMAC). In an exemplary embodiment of the present disclosure, the fluid medium is DMSO.
In an embodiment of the present disclosure, the first base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate. In an exemplary embodiment of the present disclosure, the first base is sodium hydroxide.
In an embodiment of the present disclosure, the second predetermined temperature is in the range of 25 °C to 35 °C and the second predetermined time period is in the range of 1 hour to 4 hours. In an exemplary embodiment of the present disclosure, the second predetermined temperature is 30 °C and the second predetermined time period is 1.5 hours.
In an embodiment of the present disclosure, a molar ratio of the 1-Chloro-2-nitro-4-methyl sulfonyl benzene to the methyl cyanoacetate is in the range of 1:1 to 1:1.2. In an exemplary embodiment of the present disclosure, the molar ratio of the 1-Chloro-2-nitro-4-methyl sulfonyl benzene to the methyl cyanoacetate is 1:1.05.
In accordance with the present disclosure, the yield of Na-cyano NMSB obtained is greater than 80%.
Step-c): Preparation of NMSBA
In a third step, methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB) obtained in step-b is subjected to oxidation by using an oxidizing agent and a base at a third predetermined temperature for a third predetermined time period to obtain 2-Nitro-4-methyl sulfonyl benzoic acid (NMSBA).
A schematic representation for the preparation of NMSBA, in accordance with the process of the present disclosure, is given as scheme C.

SCHEME C
In an embodiment of the present disclosure, the oxidizing agent is selected from hydrogen peroxide (H2O2) and sodium percarbonate. In an exemplary embodiment of the present disclosure, the oxidizing agent is hydrogen peroxide (H2O2). In another exemplary embodiment of the present disclosure, the oxidizing agent is sodium percarbonate.
In an embodiment, the second base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate. In an exemplary embodiment of the present disclosure, the second base is sodium hydroxide.
In an embodiment of the present disclosure, the third predetermined temperature is in the range of 40 °C to 60 °C and the third predetermined time period is in the range of 30 minutes to 120 minutes. In an exemplary embodiment of the present disclosure, the third predetermined temperature is 45 °C and the third predetermined time period is 1 hour.
In accordance with the present disclosure, a yield of NMSBA obtained is greater than 75% and the purity is greater than 98%.
The present disclosure provides a simple process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA) which provides a higher yield of the product with greater purity while also being cost-efficient and economical.
The formation of sodium salt of 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate (Na-cyano NMSB) attributes to the higher yield and greater purity of the final product (NMSBA). Further, the formation of Na-cyano NMSB leads to lower consumtion of raw material, thus, making the process of the present disclosure cost effective. Due to the formation of Na-cyano NMSB, less byproduct and less effluent are formed, thus, the process of the present disclosure is environment friendly.
The process of the present disclosure is simple and employs inexpensive and easily available reagents. Thus, the process of the present disclosure is economical.
The process of the present disclosure doesn’t require any further purification step. Thus, the process of the present disclosure is simple and environment friendly.
The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
EXPERIMENTAL DETAILS
Example 1: Preparaion of NMSAB in accordance with the present disclosure:
Step-a): Preparation of 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB)
400 g of sulphuric acid was charged into a reactor followed by the addition of 1-chloro-4-methyl sulfonyl benzene 190.5g to obtain a reaction mixture in the form of a clear light yellow color solution. The reaction mixture was cooled to 30 °C to obtain a cooled reaction mixture. To the cooled reaction mixture, nitric acid (1.1 m) was added slowly over a period of 4 hours by maintaining the reaction temperature at 30 °C to obtain a reaction mass. The reaction mass was stirred by maintaining the temperature at 30°C for 2 hours to obtain a product mixture. After 2 hours, the reaction was stopped and the product mixture was drowned in 500 ml water to obtain a residue. The residue was filtered to obtain a wet mass. The wet mass was dried to obtain 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB). The yield of chloro NMSB was 98% and purity was 98%.
Step-b): Preparation of methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB)
534 g of dimethyl sulfoxide (DMSO) was charged into a reactor followed by the addition of NaOH flakes (2.1m) under stirring to obtain a clear solution. The solution was cooled to 28°C. To the clear solution, methyl cyano acetate (1.05 m) was added slowly over a period of 1 hour by maintaining the reaction temperature at 28°C to 30°C to obtain a reaction mixture. To the reaction mixture, a solution of Chloro NMSB 235.5g that was dissolved in 600 g of dimethyl sulfoxide (DMSO) was added under stirring to obtain a reaction mass. The reaction mass was maintained at 30°C for 1.5 hours to obtain a product mass. After 1.5 hours, the product mass was distilled at 100°C under reduced pressure to distilled out (remove) 900-950 g DMSO, and then the product mass was mixed with water (2630 ml) followed by distilling water and DMSO. Further, traces of DMSO were distilled out with water at 100°C under 10mm Hg pressure to obtain a resultant mass. After distillation, the resultant mass was cooled to 20°C to obtain a cake. The cake was washed with 50 ml water followed by 50 ml ethylene dichloride (EDC) to obtain a residue. The residue was subjected to a displacement wash such that the obtained residue was soaked in EDC for 15 minutes and filtered by applying vacuum (for complete filtration) followed by drying to obtain a purified Na-Cyano NMSB (Sodium salt of Cyano NMSB). The yield of Na-Cyano NMSB was 80%.
Step-c): Preparation of NMSBA
Example 1
Sodium salt of Cyano NMSB (322 g; 1 mole) obtained in step b, was mixed with 4000 ml water to obtain a slurry. NaOH flakes (1.33 m) were added to the slurry under stirring to obtain a reaction mixture. The reaction mixture was equilibrated for 1 hour to obtain a clear solution. The clear solution was heated to 45°C followed by the gradual addition of H2O2 (5.5 m) over a period of 1 hour and maintained at 45°C for 1 hour to obtain a reaction mass. The reaction mass was cooled to 25°C and excess H2O2 was destroyed by the addition of sodium thiosulfate followed by acidifying the reaction mass by using 300 ml of 5N HCl to obtain a precipitate which was isolated by filtration to obtain NMSBA. The yield of NMSBA was 76%.
Example 2
Sodium salt of Cyano NMSB (322 g; 1 mole) obtained in step b, was mixed with 4000 ml water to obtain a slurry. NaOH flakes (1 m) were added to the slurry under stirring to obtain a reaction mixture. The reaction mixture was equilibrated for 1 hour to obtain a clear solution. The clear solution was heated to 45°C followed by the gradual addition of clear solution of Sodium percarbonate in water (4 m) over a period of 1 hour and maintained at 45°C for 1 hour to obtain a reaction mass. The reaction mass was cooled to 25°C. The reaction mass was acidified by using 300 ml of 5N HCl to obtain a precipitate which was isolated by filtration to obtain NMSBA crop 1. The filtrate was extracted with butyl acetate to get NMSBA crop 2. The yield of NMSBA was 75% with 98.5% purity
TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid, which:
- is simple and environment-friendly;
- produces product (NMSBA) in high yield and high purity; and
- involves shorter reaction time and simple work up methodology giving high productivity of NMSBA.
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The foregoing description of the specific embodiments so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

,CLAIMS:WE CLAIM:
1. A process for the preparation of 2-nitro-4-methylsulfonyl benzoic acid (NMSBA), said process comprising the following steps:
a) nitrating 1-Chloro-4-methyl sulfonyl benzene by reacting a nitrating agent with 1-Chloro-4-methyl sulfonyl benzene over a first predetermined time period at a first predetermined temperature to obtain 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB);
b) reacting the 1-Chloro-2-nitro-4-methyl sulfonyl benzene (Chloro NMSB) with methyl cyanoacetate by using a first base in a fluid medium at a second predetermined temperature for a second predetermined time period to obtain methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB); and
c) oxidizing the methyl 2-cyano-2-(4-(methylsulfonyl)-2-nitrophenyl)acetate sodium salt (Na-Cyano NMSB) by using an oxidizing agent and a second base at a third predetermined temperature for a third predetermined time period to obtain 2-nitro-4-methylsulfonyl benzoic acid (NMSBA).
2. The process as claimed in claim 1, wherein said nitrating agent is a mixture of sulphuric acid and nitric acid.
3. The process as claimed in claim 1, wherein said first predetermined temperature is in the range of 25 °C to 35 °C and said first predetermined time period is in the range of 2 hours to 6 hours.
4. The process as claimed in claim 1, wherein said first base and said second base are independently selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.
5. The process as claimed in claim 1, wherein said fluid medium is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethyl formamide (DMF) and dimethylacetamide (DMAC).
6. The process as claimed in claim 1, wherein said second predetermined temperature is in the range of 25 °C to 35 °C and said second predetermined time period is in the range of 1 hour to 4 hours.
7. The process as claimed in claim 1, wherein a molar ratio of the 1-Chloro-2-nitro-4-methyl sulfonyl benzene to the methyl cyanoacetate is in the range of 1:1 to 1:1.2.
8. The process as claimed in claim 1, wherein said oxidizing agent is selected from hydrogen peroxide (H2O2) and sodium percarbonate.
9. The process as claimed in claim 1, wherein said third predetermined temperature is in the range of 40 °C to 60 °C and said third predetermined time period is in the range of 30 minutes to 120 minutes.
10. The process as claimed in claim 1, wherein a yield of 2-Nitro-4-methyl sulfonyl benzoic acid is greater than 75% and a purity is greater than 98 %.