DESC:FIELD
The present disclosure relates to a process for the synthesis of 4-methyl sulfonyl toluene.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
4-Methyl sulfonyl toluene is used as a starting material in the preparation of medicines, dyes and pesticides. Particularly, 4-methyl sulfonyl toluene is a useful intermediate in the preparation of mesotrione. Mesotrione is a herbicide which allows to control a wide spectrum of broad leaf weeds and some grass weeds.
4-Methyl sulfonyl toluene is generally synthesized by reducing p-toluenesulfonyl chloride with sodium sulfite under weak alkaline conditions followed by methylating with dimethyl sulfate or sodium methyl sulfate to obtain 4-methyl sulfonyl toluene. The disadvantages of this method is the use of dimethyl sulfate, which is highly toxic chemical, and is dangerous during operation and hazardous for the environment. Further, long production cycles, poor product quality, and low yield of the product resulting in high production costs was observed.
Moreover, the conventional process for synthesis of 4-methyl sulfonyl toluene is carried out at high pressures which is not industrially feasible. The literature is replete in various other methods for the synthesis of 4-methyl sulfonyl toluene by various other routes.
However, these conventional methods are associated with drawbacks such as low yield and/ or low purity of 4-methyl sulfonyl toluene. Further, these methods require tedious purification steps, thereby resulting in an expensive process.
There is, therefore, felt a need to provide an alternative process for the synthesis of 4-methyl sulfonyl toluene, which mitigates the drawbacks mentioned herein above.
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.
An object of the present disclosure is to provide a process for the synthesis of 4-methyl sulfonyl toluene.
Another object of the present disclosure is to provide a simple, economical and environment-friendly process for the synthesis of 4-methyl sulfonyl toluene.
Still another object of the present disclosure is to provide a process for the synthesis of 4-methyl sulfonyl toluene with high purity and high yield.
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 synthesis of 4-methyl sulfonyl toluene. The process comprises reacting 4-toluene sulfonyl chloride with an aqueous solution of sodium sulfite and a base at a first predetermined temperature for a first predetermined time period to obtain a sodium salt of 4-toluene sulfinic acid. The sodium salt of 4-toluene sulfinic acid is methylated by using methyl chloride in the presence of a catalyst at a second predetermined temperature for a second predetermined time period in an autoclave by maintaining a pressure in the range of 2 to 4.5 Kg/cm2 to obtain 4-methyl sulfonyl toluene.
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.
4-methyl sulfonyl toluene is used in the preparation of agrochemicals and pharmaceuticals. 4-methyl sulfonyl toluene is an intermediate for the synthesis of well-known herbicide, mesotrione. Conventional processes for the synthesis of 4-methyl sulfonyl toluene has drawbacks such as use of highly toxic chemical (dimetheyl sulfate) which is dangerous during operation and hazardous for the environment. Further, long production cycles, poor product quality, and low yield of the product resulting in high production costs was also observed with the conventionally known processes. Moreover, the conventional process for synthesis of 4-methyl sulfonyl toluene is carried out at high pressures which is not industrially feasible and provides low yield and/ or low purity of 4-methyl sulfonyl toluene.
The present disclosure provides a simple, economical and environment-friendly process for the synthesis of 4-methyl sulfonyl toluene. 4-methyl sulfonyl toluene is represented by Formula I:

(I)
The synthesis of 4-methyl sulfonyl toluene (I), in accordance with the process of the present disclosure, is shown as scheme 1 given below:

The process for preparing 4-methyl sulfonyl toluene is described in detail herein below.
Step (a) Preparation of sodium salt of 4-toluene sulfinic acid:
4-toluene sulfonyl chloride is reacted with an aqueous solution of sodium sulfite and a base at a first predetermined temperature for a first predetermined time period to obtain a sodium salt of 4-toluene sulfinic acid.
In accordance with the present disclosure, 4-toluene sulfonyl chloride is slowly added in the aqueous solution of sodium sulfite over a time period in the range of 3 hours to 7 hours. In one embodiment, 4-toluene sulfonyl chloride is slowly added in the aqueous solution of sodium sulfite in lots over a period of 5 hours. In another embodiment, 4-toluene sulfonyl chloride is slowly added in the aqueous solution of sodium sulfite in a continuous manner over a time period of 5 hours.
The base is selected from sodium bicarbonate, sodium carbonate, potassium carbonate and potassium bicarbonate. In an exemplary embodiment of the present disclosure, the base is sodium bicarbonate.
In accordance with the present disclosure, the first predetermined temperature is in the range of 60 °C to 80 °C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 75 °C.
In accordance with the present disclosure, the first predetermined time period is in the range of 2 hours to 10 hours. In an embodiment of the present disclosure, the first predetermined time period is in the range of 5 hours.
In accordance with the present disclosure, a mole ratio of 4-toluene sulfonyl chloride to the sodium sulphite is in the range of 1:1 to 1:1.5. In an exemplary embodiment of the present disclosure, the mole ratio of 4-toluene sulfonyl chloride to the sodium sulphite is 1:1.3.
In accordance with the present disclosure, a mole ratio of 4-toluene sulfonyl chloride to the base is in the range of 1:2 to 1:2.3. In an exemplary embodiment of the present disclosure, the mole ratio of 4-toluene sulfonyl chloride to the base is 1:2.1.
In an exemplary embodiment of the present disclosure, sodium sulfite and sodium bicarbonate are mixed in water, followed by heating at 75°C to obtain a first mixture. 4-toluene sulfonyl chloride is slowly added to the first mixture over a period of 5 hours, followed by further maintaining the mixture at 75 °C for 3 hours to obtain the sodium salt of 4-toluene sulfinic acid.
Step (b) Preparation of 4-methyl sulfonyl toluene:
In this step, the sodium salt of 4-toluene sulfinic acid is methylated by using methyl chloride in the presence of a catalyst at a second predetermined temperature for a second predetermined time period in an autoclave by maintaining a pressure in the range of 2 to 4.5 Kg/cm2 to obtain 4-methyl sulfonyl toluene.
In accordance with the present disclosure, the catalyst is selected from tetra n- butyl ammonium bromide (TBAB), tetra methyl ammonium chloride, triethylbenzyl ammonium chloride and triphenyl phosphonium bromide. In an exemplary embodiment of the present disclosure, the catalyst is tetra n- butyl ammonium bromide (TBAB).
In accordance with the present disclosure, the second predetermined temperature is 70°C to 130°C. In an exemplary embodiment of the present disclosure, the second predetermined temperature is 120 °C.
In accordance with the present disclosure, the second predetermined time period is in the range of 2 hours to 10 hours. In an exemplary embodiment of the present disclosure, the second predetermined time period is 8 hours.
In an exemplary embodiment of the present disclosure, the sodium salt of 4-toluene sulfinic acid obtained in step (a) is transferred to an autoclave and TBAB is added to obtain a second mixture. Methyl chloride is passed in the autoclave at 75 °C and further heated to 120 °C for 2 hours so as to keep the pressure of the autoclave less than 4.5 Kg/cm2 to obtain a third mixture.
The autoclave containing the third mixture is maintained at 120 °C and at the pressure of 4 Kg/cm2 for 8 hours to obtain a product mixture comprising 4-methyl sulfonyl toluene. The pressure of the autoclave is released and the product mixture is cooled to a temperature in the range of 30 °C followed by filtering and washing with water to obtain 4-methyl sulfonyl toluene.
In accordance with the present disclosure, a mole ratio of 4-toluene sulfonyl chloride to the catalyst is in the range of 1:0.01 to 1:0.05. In an exemplary embodiment of the present disclosure, the mole ratio of 4-toluene sulfonyl chloride to the catalyst is 1:0.015.
In accordance with the present disclosure, a mole ratio of 4-toluene sulfonyl chloride to the methyl chloride is in the range of 1:0.9 to 1:1.5. In an exemplary embodiment of the present disclosure, the mole ratio of 4-toluene sulfonyl chloride to the methyl chloride is 1:1.19.
In accordance with the present disclosure, a yield of 4-methyl sulfonyl toluene is greater than 85% with a purity more than 98%.
Conventionally, the process for synthesis of 4-methyl sulfonyl toluene is carried out at high pressure which is not industrially feasible. The present disclosure provides a process which is carried out at low pressure by using methyl chloride in the presence of a catalyst to obtain 4-methyl sulfonyl toluene with high yield and high purity. Thus, the process of the present disclosure is industrially feasible.
As the process of the present disclosure is carried out at a low pressure, continuous feeding of methyl chloride is possible instead of charging excess methyl chloride. Thus, the process of the present disclosure is cost effective as use of excess methyl chloride is avoided.
The process of the present disclosure doesn’t require any further purification step. Thus, the process of the present disclosure is simple.
The process of the present disclosure employs inexpensive and easily available reagents. Thus, the process of the present disclosure is economical.
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: Synthesis of 4-methyl sulfonyl toluene
Step (a): Preparation of sodium salt of 4-toluene sulfinic acid: 600 ml water was charged in a reactor followed by adding 163.8 g of Na2SO3 and 176.4 g of NaHCO¬3 in the reactor to obtain an aqueous solution. The reactor containing the aqueous solution was heated at 75°C followed by slowly adding 190.5 g of 4-toluene sulfonyl chloride in lots over a period of 5 hours and further maintaining the temperature at 75°C for 3 hours to obtain a sodium salt of 4-toluene sulfinic acid.
Step (b): Preparation of 4-methyl sulfonyl toluene: The sodium salt of 4-toluene sulfinic acid obtained in step (a) was transferred to a stainless steel (SS) high pressure autoclave followed by adding 9.66 g of tetra n-butyl ammonium bromide (3M%). 60 g of methyl chloride was continuously passed in the autoclave at 75°C and was heated to 120°C for 2 hours so as to keep the pressure less than 4.5 Kg/cm2. The temperature of the autoclave was maintained at 120 °C and pressure at 4 Kg/cm2 for 8 hours to obtain a product mixture comprising 4-methyl sufonyl toluene.
After completion of the reaction, the pressure of the autoclave was released and the product mixture was cooled to 30°C followed by filtering to obtain a cake of 4-methyl sufonyl toluene. The cake was washed with water and dried to obtain 4-methyl sufonyl toluene with 88% yield (150 g) and 99.54% purity.
Example 2:
Example 2 was carried out by using the similar experimental procedure as described in example-1, except that 1.5 M% of TBAB was used and the reaction temperature in step (b) was 110°C. Yield of 4-methyl sufonyl toluene was 88.8% and purity was 99.24%.
TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for the synthesis of 4-methyl sulfonyl toluene, which:
- is carried out at low pressure;
- is feasible for large scale manufacturing;
- is simple, economical and environment-friendly; and
- provides high yield and high purity 4-methyl sulfonyl toluene.
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 preparing 4-methyl sulfonyl toluene, said process comprising the following steps:
a) reacting 4-toluene sulfonyl chloride with an aqueous solution of sodium sulphite and a base at a first predetermined temperature for a first predetermined time period to obtain a sodium salt of 4-toluene sulfinic acid; and
b) methylating said sodium salt of 4-toluene sulfinic acid by using methyl chloride in the presence of a catalyst at a second predetermined temperature for a second predetermined time period in an autoclave by maintaining a pressure in the range of 2 to 4.5 Kg/cm2 to obtain 4-methyl sulfonyl toluene.
2. The process as claimed in claim 1, wherein said base is selected from the group consisting of sodium bicarbonate, sodium carbonate, potassium carbonate and potassium bicarbonate.
3. The process as claimed in claim 1, wherein said first predetermined temperature is in the range of 60°C to 80°C and wherein said first predetermined time period is in the range of 2 hours to 10 hours.
4. The process as claimed in claim 1, wherein said second predetermined temperature is in the range of 70°C to 130°C and wherein said second predetermined time period is in the range of 2 hours to10 hours
5. The process as claimed in claim 1, wherein said catalyst is selected from tetra n-butyl ammonium bromide (TBAB), tetra methyl ammonium chloride, triethylbenzyl ammonium chloride and triphenyl phosphonium bromide.
6. The process as claimed in claim 1, wherein the 4-toluene sulfonyl chloride is slowly added in said aqueous solution of sodium sulfite over a time period in the range of 3 hours to 7 hours.
7. The process as claimed in claim 1, wherein a mole ratio of 4-toluene sulfonyl chloride to said sodium sulphite is in the range of 1:1 to 1:1.5.
8. The process as claimed in claim 1, wherein a mole ratio of 4-toluene sulfonyl chloride to said base is in the range of 1:2 to 1:2.3.
9. The process as claimed in claim 1, wherein a mole ratio of 4-toluene sulfonyl chloride to said catalyst is in the range of 1:0.01 to 1:0.05.
10. The process as claimed in claim 1, wherein a mole ratio of 4-toluene sulfonyl chloride to said methyl chloride is in the range of 1:0.9 to 1:1.5.
Dated this 11 March 2021

MOHAN RAJKUMAR DEWAN
of R.K. DEWAN & COMPANY
IN/PA-25
APPLICANT’S PATENT ATTORNEY

TO,
THE CONTROLLER OF PATENTS
THE PATENT OFFICE, AT MUMBAI