DESC:Field of the Disclosure
The present disclosure relates to an oxidation of sulfenyl compounds to sulfinyl compound.

Background
Sulfinyl pyrazoles (alkyl sulfinyl pyrazoles) such as fipronil, ethiprole and the like are widely used for the purposes of crop protection, control of pests, termites and ticks in pets.

Oxidation of the sulfenyl group to the sulfinyl group has traditionally been carried out by using an oxidizing agent. Oxidizing agents such as hydrogen peroxide, substituted perbenzoic acid, sodium perborate and per acids (per acetic acid, per monochloro acetic acid, per dichloroacetic acid, per trichloroacetic acid, per trifluoro acetic acid) have been used for this purpose.

During the oxidation process, however, the actual process may continue even after the formation of the sulfinyl groups, giving rise to the formation of the sulfone groups, which contaminates the sulfinyl product. This necessitates steps like repeated purification and isolation, which decreases the product yield. With this background, it is evident that the reaction conditions and the oxidizing agent should be chosen prudently in order to avoid extended oxidation.

Oxidizing agents such as meta chloro per benzoic acid and per trifluoro acetic acid have been used for oxidation of sulfenyl compounds. Most of the oxidizing agents used for the conversion of the sulfenyl group to sulfinyl group are, however, expensive and unstable which limits their commercial exploitation.

Therefore, the inventors of the present disclosure provide a process for oxidation of sulfenyl compounds that obviate the problems associated with the prior art processes.

Objects
Some of the objects of the present disclosure which at least one embodiment is adapted to provide, are described herein below:

It is an object of the present disclosure to provide a process for the oxidation of a sulfenyl compound to a sulfinyl compound.

Particularly, it is an object of the present disclosure to provide a process for the oxidation of alkyl thiopyrazoles to alkyl sulfinyl pyrazoles.

It is another object of the present disclosure to provide a process for the oxidation of sulfenyl compound, which is economical and can be easily exploited on a commercial scale.

It is still another object of the present disclosure to provide a process for the oxidation of sulfenyl compounds which uses readily available chemicals.

It is yet another object of the present disclosure to provide a simple and stable process for the oxidation of a sulfenyl compound.

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 of the invention
The present invention relates to a process for oxidation of sulfenyl compound to sulfinyl compound. The process of oxidation of sulfenyl compound involves the steps of reacting at least one sulfenyl compound with at least one acid, in the presence of at least one phase transfer catalyst and in a solvent in the temperature range of 25-35oC for 30-40 minutes to obtain a solution. The so obtained solution is then reacted with at least one oxidizing agent, which is added drop wise into the solution in the temperature range of 25-30oC for 1-3 hours to obtain the sulfinyl compound.

Detailed Description
In accordance with the present disclosure, there is provided a process for the oxidation of sulfenyl compound (aryl thiopyrazole) to sulfinyl compound (alkyl sulfinyl pyrazole). The process of the present disclosure is economical, avoids extended oxidation and can be easily prepared on a commercial scale.

The process of oxidation of sulfenyl compound to a sulfinyl compound of the present disclosure involves the following steps:

In the first step of the process, a predetermined amount of a sulfenyl compound is dissolved in a solvent by stirring followed by the addition of at least one acid in the presence of at least one phase transfer catalyst in the temperature range of 25-30oC for 20-40 minutes to obtain a solution.

The sulfenyl compound (aryl thiopyrazole) used in the process of the present disclosure can be 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazole.

The acid is selected from the group consisting of acetic acid, monochloroacetic acid, dichloroacetic acid, trichloroacetic acid & sulfuric acid. The solvent used in the present disclosure is selected from the group consisting of ethylene dichloride, methylene dichloride and combination thereof. The phase transfer catalyst of the present disclosure is selected from the group consisting of triethyl benzyl ammonium chloride and tetrabutyl ammonium bromide.

In the second step of the process, an oxidizing agent is added slowly, to said solution (obtained in the first step) under stirring to obtain a reaction mass comprising sulfinyl compound. The reaction is carried out in the temperature range of 25-30 oC and the oxidizing agent are introduced during a period of 1 to 3 hours into said solution.

The oxidizing agent used in the process of the present disclosure is hydrogen peroxide.

The molar ratio of sulfenyl compound to the oxidizing agent used in the present disclosure ranges from 1:1 to 1:1.5.

During this process, the formation of the sulfinyl compound is checked by HPLC method, known in the art. A typical sulfinyl compound formed by this process is ethiprole.

In accordance with one aspect of the present disclosure, the oxidation of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazole is carried out and forms 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulfinylpyrazole as the oxidized product.

In accordance with an exemplary embodiment of the present disclosure, oxidation is carried out by reacting 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazole with acetic acid in the presence of triethyl benzyl ammonium chloride and ethylene dichloride to obtain a solution. Hydrogen peroxide is added drop wise in said solution at a temperature below 30oC for 2 hours to obtain 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulfinylpyrazole (ethiprole).

In a typical process, according to this disclosure, the yield of ethiprole is in the range of 82 to 87% and the sulfone content by weight of the total mass is in the range of 1 to 2%. In the process in accordance with the present disclosure, the selectivity of the sulfinyl compound is in the range of 85 to 90%.

The oxidation of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazole forms 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulfinylpyrazole (ethiprole) which is widely used in crop protection as well as in the veterinary industry.

The present disclosure is further illustrated herein below with the help of the following examples. 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 embodiments herein.

Example 1:
Procedure: 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethyl thiopyrazole (Et-TPR- 382 gms; 1 mole) was stirred with 1.5 liters of ethylene dichloride (EDC) followed by addition of acetic acid (AcOH -120 gms; 2 mole/mole) and triethyl benzyl ammonium chloride (TEBACl- 3.42 gms; 1.5 m%) to obtain a solution. The solution was then equilibrated at 28-30°C for 30 mins.

50.5% aqueous H2O2 (75 g; 1.10 mole/mole) was added drop by drop to the solution obtained from above step at 28-30°C in 2 hours under stirring to obtain reaction mass. The reaction mass comprises the oxidized product (ethiprole). The formation of the oxidized product was checked by HPLC method.

The reaction mass was stirred further for 12 hours at 28-30°C & after 12 hours of maintenance at 28-30°C, the conversion of the sulfenyl compound to sulfinyl compound was found to be 89% and the ratio of ethiprole to sulfone was 97:3.

Example 2-7
Example 1 was repeated by varying the concentration of reactant, catalyst, acid and varying the reaction conditions (temperature and time). The results which were measured by HPLC are given in table 1 below.
Table 1:
Ex-No Et-TPR
gms EDC
lts/m Acid
gms/m TEBACl
g/m H2O2
M/m Temp. and
duration HPLC analysis (%) of reaction mass
Ethiprole Et-TPR Sulfone
2 382 1.5 Acetic acid
195 gms 3.4 1.3 28°C for 12 hours 96% 1.10 2.11
3
97 1.5 MCA*
47 gms 3.4 1.10 28°C for 12 hours 92.02 1.32 5.47
4
97 1.5 DCA*
65 gms 3.4 1.10 28°C for 12 hours 93.54 1.10 3.63
5
266 3 85% H2SO4 1000gms/m 3.4 1.00 0°C for 6 hours 89.6 0.44 2.83
6
58.6 3 98% H2SO4 1000gms /m 3.4 1.00 0°C for 1 hour 82.43 0.64 3.19
7 749 1.5 AcOH
390gms 3.4 1.30 30°C for 12 hours 85.22 11 1.11
*MCA: Monochloro acetic acid
*DCA: Dichloroacetic acid
*AcOH: Acetic acid

From the table1, it is observed that, the process of oxidation of Et-TPR forms ethiprole with better yield and selectivity. The amount of sulfones formation is comparatively less (~1-5%).
TECHNICAL ADVANTAGES AND ECONOMIC SIGNIFICANCE
• The process of oxidation of sulfenyl compound is stable and avoids amide & acid formation of sulfenyl compound (alkyl thiopyrazole).
• The process of oxidation of sulfenyl compound results in comparatively lesser sulfone formation (byproduct of oxidation of sulfenyl compound).
• A simple and cost-effective process for preparing Ethiprole.

Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

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 invention to achieve one or more of the desired object or results.

The exemplary embodiments herein quantify the benefits arising out of this disclosure and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the 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 will 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.

Any discussion of documents, acts, materials, devices, articles and 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.

While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications 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 modifications in the nature of the disclosure or the preferred embodiments 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:1. A process for oxidizing a sulfenyl compound to a sulfinyl compound, said process comprising the steps:
a. reacting the sulfenyl compound with at least one acid, in the presence of at least one phase transfer catalyst and in a solvent in the temperature range of 25-35oC to obtain a solution; and
b. adding at least one oxidizing agent dropwise to said solution with stirring in the temperature range of 25-35oC for 1-3 hours to obtain the sulfinyl compound.

2. The process as claimed in claim 1, wherein said sulfenyl compound is 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4- ethylthiopyrazole.

3. The process as claimed in claim 1, wherein said acid is selected from the group consisting of sulfuric acid, acetic acid, monochloroacetic acid, dichloroacetic acid and trichloroacetic acid.

4. The process as claimed in claim 1, wherein said solvent is selected from the group consisting of ethylene dichloride and methylene dichloride.

5. The process as claimed in claim 1, wherein said phase transfer catalyst is selected from the group consisting of triethyl benzyl ammonium chloride and tetrabutyl ammonium bromide.

6. The process as claimed in claim 1, wherein said oxidizing agent is hydrogen peroxide.

7. The process as claimed in claim 1, wherein the molar ratio of sulfenyl compound to the oxidizing agent ranges from 1:1 to 1:1.5.

8. The process as claimed in claim 1, wherein said sulfinyl compound is 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulfinylpyrazole (ethiprole).