DESC:FIELD
The present disclosure relates to a process for preparing trifluoromethanesulfinyl chloride.
BACKGROUND
Fipronil is a 1-arylpyrazole based pesticide characterized by high efficiency, low toxicity and especially low residue. One of the commercial route for the preparation of fipronil involves oxidation of sulfenyl precursor (5-amino-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[trifluoromethylsulfenyl]-1H-pyrazole-3-carbonitrile). A disadvantage of this route is the formation of a sulfone compound, as an impurity due to the oxidation of fipronil. It is difficult to separate the sulfone impurity from fipronil. Therefore, this commercial route provides fipronil with low purity.
An alternate commercial route for the preparation of fipronil involves trifluoromethanesulfinylation of aryl-pyrazole intermediate (5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole) with trifluoromethanesulfinyl chloride [CAS No. 20621-29-8]. This route obviates the possibility of the formation of sulfone impurity. The advantage of this route is that high purity fipronil can be obtained.
However, hitherto known processes for preparing trifluoromethanesulfinyl chloride are complex, tedious and require purification step.
Thus, there is felt a need for developing a simple process for preparing trifluoromethanesulfinyl chloride of high purity.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is 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 trifluoromethanesulfinyl chloride.
Still another object of the present disclosure is to provide a process for the preparation of trifluoromethanesulfinyl chloride having 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 preparing trifluoromethanesulfinyl chloride. The process comprises oxidizing a compound of Formula-II using an oxidizing agent in the presence of at least one first fluid medium at a first pre-determined temperature to obtain a compound of Formula-III. The compound of Formula-III is chlorinated using a chlorinating agent in the presence of iodine and at least one second fluid medium at a second pre-determined temperature to obtain trifluoromethanesulfinyl chloride.
DETAILED DESCRIPTION
Conventional processes for the preparation of fipronil involving oxidation of sulfenyl precursor as the final step are associated with the formation of sulfone impurity, which is difficult to separate.
The present disclosure envisages a simple process for preparing trifluoromethanesulfinyl chloride of high purity and high yield. Trifluoromethanesulfinyl chloride prepared by the process of the present disclosure can be used for the synthesis of fipronil, without the formation of the sulfone impurity.
In an aspect of the present disclosure, there is provided a process for the preparation of trifluoromethanesulfinyl chloride (CF3SOCl) of Formula-I.

Formula-I
The process of the present disclosure for preparing trifluoromethanesulfinyl chloride involves the following steps:
- oxidizing a compound of Formula-II to obtain a compound of Formula-III; and
- chlorinating the compound of Formula-III to obtain trifluoromethanesulfinyl chloride (Formula-I).
The process is hereinafter described in detail.
In the first step, a compound of Formula-II is oxidized using an oxidizing agent in the presence of at least one first fluid medium at a first pre-determined temperature to obtain a compound of Formula-III.

Oxidation of compound of Formula-II
In an embodiment of the present disclosure, the compound of Formula-II is o-chlorobenzyltrifluoromethane sulfide. In another embodiment of the present disclosure, the compound of Formula-III is o-chlorobenzyltrifluoromethanesulfoxide.
The oxidizing agent can be hydrogen peroxide. In one embodiment the oxidizing agent is 30 % to 70 % aqueous hydrogen peroxide solution.
The molar ratio of the amount of oxidizing agent to the amount of compound of Formula-II can be in the range from 0.4:1 to 1:1.
The first fluid medium can be selected from the group consisting of acetic acid, trichloroacetic acid, dichloroacetic acid, trifluoroacetic acid, chloroform, methylene dichloride and ethylene dichloride.
The first pre-determined temperature can be in the range of 50 °C to 100 °C. Preferably, the first pre-determined temperature is in the range of 75 °C to 85 °C.
The oxidation step of the process of the present disclosure is carefully controlled so as to avoid the oxidation of compound of Formula- II to the corresponding sulfone. For this purpose, the molar amount of the oxidizing agent used in the oxidation step is lower than or equal to the amount of the compound of Formula-II. Further, the oxidizing agent is slowly added over a long period of time. The period of addition of the oxidizing agent can be in the range of 2 hours to 10 hours. For larger batches, longer period of time may be employed. Due to the controlled conditions, the formation of sulfone is minimized.
After the oxidation step, a mixture of the compound of Formula-II and compound of Formula-III is obtained. The compound of Formula-III can be separated using known techniques in the art, such as fractional distillation. The fraction containing the compound of Formula-III can be used directly for the next step.
Typically, the yield of the oxidation step is in the range of 80 % to 90 %.
In the second step, the compound of Formula-III obtained in the first step is chlorinated using a chlorinating agent in the presence of iodine and at least one second fluid medium at a second pre-determined temperature to obtain trifluoromethanesulfinyl chloride (Formula-I).

Chlorination of compound of Formula-III
Typically, the chlorinating agent can be chlorine gas.
The molar ratio of the amount of chlorinating agent to the amount of compound of Formula-III can be in the range from 0.5:1 to 2:1.
The second fluid medium can be selected from the group consisting of methylene chloride, ethylene dichloride, ethylene chloride, and chloroform.
The second pre-determined temperature can be in the range of 0 °C to 50 °C. Preferably, the second pre-determined temperature is in the range of 10 °C to 25 °C.
After the chlorination step, a mixture of the compound of Formula-I and compound of Formula-IV (o-chlorobenzyl chloride) is obtained. The compound of Formula-I can be separated using known techniques in the art, such as fractional distillation. The fraction containing trifluoromethanesulfinyl chloride can be used directly for the preparation of fipronil.
Typically, the yield of the chlorination step is in the range of 94 % to 98 %.
In one embodiment of the present disclosure, fipronil is prepared by the trifluoromethanesulfinylation of a pyrazole (compound of Formula-V) as illustrated below:

The present disclosure is further described in light of the following laboratory scale experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. These laboratory scale experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial/commercial scale.
Experimental Details
Experiment-1: Preparation of trifluoromethanesulfinyl chloride in accordance with the present disclosure
Step-1: Oxidation of compound of Formula-II (o-chlorobenzyltrifluoromethane sulfide)
226.5 g of compound of Formula-II (o-chlorobenzyltrifluoromethane sulfide, 1.0 M) and first fluid medium (acetic acid, 300 ml) were charged to a reactor and the resulting mixture was heated to 80 °C. 34 g of an oxidizing agent (50 % aqueous hydrogen peroxide solution) was slowly added through a dip tube over a period of 4 hours at 80 °C. After the addition of the oxidizing agent was complete, the reaction mass was stirred at 80 °C for 4 hours.
Acetic acid was distilled out from the reaction mass under reduced pressure at 75 °C to obtain a residual mass containing traces of acetic acid. 500 ml of water and 500 ml of ethylene dichloride (EDC) were added to the residual mass and the mixture was cooled to room temperature. The EDC layer was separated and the aqueous layer was extracted with 200 ml EDC at room temperature. The combined EDC layer was mixed with 250 ml of water and the pH was adjusted to 7.5 using 30 ml of 5 % sodium carbonate. The resultant mixture was stirred, allowed to stand for 40 minutes and the EDC layer was separated. The separated EDC layer was washed with 250 ml of 5 % sodium sulfite solution.
GLC analysis of the separated EDC layer showed the presence of the compound of Formula-III (52%), compound of Formula-II (42%), o-chlorobenzyl chloride (4%) and the sulfone of the compound of Formula-II (1%). The EDC layer was fractionated using a 4’ packed column. During fractional distillation, EDC distilled out initially, followed by fractions containing unconverted compound of Formula-II and compound of Formula-III. The amount of compound of Formula-III obtained was 105 g (Yield = 85 %). The amount of compound of Formula-II recovered was 115 g.
Step-2: Chlorination of the compound of Formula-III (o-chlorobenzyltrifluoromethane sulfoxide)
339.5 g of the compound of Formula-III (1.4 M) and 500 ml of second fluid medium (ethylene dichloride) were charged to a reactor and the mixture was stirred. 1 g of a catalyst (iodine) was added to the reactor followed by cooling the resultant mass to 20 °C. 95 g of a chlorinating agent (chlorine gas, 1.33 M) was passed into the resultant mass slowly over a period of 4 hours at 20 °C, followed by stirring at the same temperature for 2 hours.
The reaction mass was analyzed for the presence of the compound of Formula-III and o-chlorobenzyl chloride (OCBC). When the conversion was greater than 90 %, the reaction mass was distilled. The fraction containing trifluoromethanesulfinyl chloride was collected in 200 ml of pre-cooled mono chlorobenzene (MCB). GLC analysis of this fraction showed the presence of 96 % of trifluoromethanesulfinyl chloride and 2 % trifluoromethanesulfenyl chloride (CF3SCl) in MCB.
The fraction containing trifluoromethanesulfinyl chloride was stored at a temperature below 10 °C to avoid loss. This fraction was directly used for the condensation with an amino pyrazole to obtain fipronil.
Experiment-2: Synthesis of fipronil using trifluoromethanesulfinyl chloride prepared in accordance with the present disclosure
321 g of 5-amino-3- cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole (1.0 M) was added to a reactor followed by the addition of 500 ml of methylene dichloride (MDC) and 806 g of p-toluene sulfonic acid dimethyl amine salt in mono chlorobenzene (purity = 37 %, 1.3 M/M). The resultant mixture was cooled to 5 °C and the fraction containing trifluoromethanesulfinyl chloride obtained from Step-2 of experiment-1 was slowly added to the resultant mixture under stirring over a period of 4 hours at 6 °C. After complete addition, the reaction mass obtained was stirred at 8 °C for 2 hours. The temperature of the reaction mass was raised slowly at the rate of 5 °C/hour to 30 °C. After the reaction mass achieved 30 °C, it was stirred at 30 °C for 4 hours. Further, the temperature of the reaction mass was raised at the rate of 5 °C/hour to 45 °C and the reaction mass was stirred at 45 °C for 4 hours.
The reaction mass was analyzed by HPLC. Analysis showed less than 2 % of 5-amino-3- cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole. MDC was distilled out and 1 lit/M water was added to the residue. The reaction mass was cooled to 10 °C and the precipitated product was isolated by filtration. The product was washed with cold MCB followed by water. The washed precipitate was dispersed into water and steam distillation was performed to remove MCB from the cake. The resultant mixture was cooled to 50 °C, filtered, washed with water to obtain a wet cake. The wet cake was dried under reduced pressure at 140 °C for 6 hours to obtain fipronil (327 g, HPLC purity = 93 %, Yield = 70 %).
Experiment-3: Preparation of trifluoromethanesulfinyl chloride in accordance with the present disclosure
Step-1: Oxidation of compound of Formula-II (o-chlorobenzyltrifluoromethane sulfide)
226.5 g of compound of Formula-II (o-chlorobenzyltrifluoromethane sulfide, 1.0 M) and first fluid medium (acetic acid, 750 ml) were charged to a reactor and the resulting mixture was heated to 80 °C. 34 g of an oxidizing agent (50 % aqueous hydrogen peroxide solution) was slowly added through a dip tube over a period of 4 hours at 80 °C. After the addition of the oxidizing agent was complete, the reaction mass was stirred at 80 °C for 4 hours.
Acetic acid was distilled out from the reaction mass under reduced pressure at 75 °C to obtain a residual mass containing traces of acetic acid. 500 ml of water and 500 ml of ethylene dichloride (EDC) were added to the residual mass and the mixture was cooled to room temperature. The EDC layer was separated and the aqueous layer was extracted with 200 ml EDC at room temperature. The combined EDC layer was mixed with 250 ml of water and the pH was adjusted to 7.5 using sodium carbonate. The resultant mixture was stirred, allowed to stand and the EDC layer was separated. The separated EDC layer was washed with 250 ml of 5 % sodium sulfite solution.
GLC analysis of the separated EDC layer showed the presence of the compound of Formula-III (51 %), compound of Formula-II (44 %), o-chlorobenzyl chloride (3%) and the sulfone of the compound of Formula-II (1 %). The EDC layer was fractionated using a 4’ packed column. During fractional distillation, EDC distilled out initially, followed by fractions containing unconverted compound of Formula-II and compound of Formula-III. The amount of compound of Formula-III obtained was 105 g (Yield = 85 %). The amount of compound of Formula-II recovered was 115 g.
Step-2: Chlorination of the compound of Formula-III (o-chlorobenzyltrifluoromethane sulfoxide)
339.5 g of the compound of Formula-III (1.4 M) and 350 ml of second fluid medium (ethylene dichloride) were charged to a reactor and the mixture was stirred. 1 g of a catalyst (iodine) was added to the reactor followed by cooling the resultant mass to 20 °C. 95 g of a chlorinating agent (chlorine gas, 1.33 M) was passed into the resultant mass slowly over a period of 4 hours at 20 °C, followed by stirring at the same temperature for 2 hours.
The reaction mass was analyzed for the presence of the compound of Formula-III and o-chlorobenzyl chloride (OCBC). When the conversion was greater than 90 %, the reaction mass was distilled. The fraction containing trifluoromethane sulfinyl chloride was collected in 200 ml of pre-cooled mono chlorobenzene (MCB). GLC analysis of this fraction showed the presence of 96 % of trifluoromethane sulfinyl chloride and 2 % trifluoromethane sulfinyl chloride (CF3SCl) in MCB.
The fraction containing trifluoromethane sulfinyl chloride was stored at a temperature below 10 °C to avoid loss. This fraction was directly used for the condensation with an amino pyrazole to obtain fipronil.
Experiment-4: Synthesis of Fipronil using trifluoromethane sulfinyl chloride prepared in accordance with the present disclosure
1200 ml. of EDC added into reactor and charged 321 g of 5-amino-3- cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole (1.0 M) to a reactor. Added 806 g of p-toluene sulfonic acid dimethyl amine salt in EDC (purity = 37 %, 1.3 M/M). The resultant mixture was heated to 40 °C and the fraction containing trifluoromethane sulfinyl chloride obtained from above experiments was slowly added to the resultant mixture under stirring over a period of 2 hours at 40°C. After complete addition, the reaction mass obtained was stirred at 40°C for 10 hours.
The reaction mass was analyzed by HPLC. Analysis showed less than 2 % of 5-amino-3- cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole. The reaction mass was cooled to 10 °C and added 800 ml of water at 10 °C and stirred mass for 1 hour at 10 °C. The precipitated product was isolated by filtration. The product was washed with cold EDC followed by water. The washed precipitate was dispersed into water and adjusted pH to 6.5-7 with sodium bicarbonate. The resultant mixture was filtered, washed with water to obtain a wet cake. The wet cake was dried under reduced pressure at 140 °C for 6 hours to obtain fipronil (334 g, HPLC purity = 98 %, Yield = 75 %).
The present disclosure provides a simple process for the preparation of trifluoromethanesulfinyl chloride, which can be directly used for the preparation of fipronil without the formation of sulfone impurity.
TECHNICAL ADVANCES AND ECONOMICAL SIGNIFICANCE
The present disclosure described herein above has several technical advantages including but not limited to, the realization of a process for preparation of trifluoromethanesulfinyl chloride that:
- is simple; and
- is capable of providing trifluoromethanesulfinyl chloride of high purity and high yield.
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 objects or results. While certain embodiments of the inventions have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Variations or modifications to the formulation of this invention, within the scope of the invention, may occur to those skilled in the art upon reviewing the disclosure herein. Such variations or modifications are well within the spirit of this invention.
The numerical values given for various physical parameters, dimensions and quantities are only approximate values and it is envisaged that the values higher than the numerical value assigned to the physical parameters, dimensions and quantities fall within the scope of the invention unless there is a statement in the specification to the contrary.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment 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:1. A process for preparing trifluoromethanesulfinyl chloride of Formula-I, said process comprising the following steps:

Formula-I
- oxidizing a compound of Formula-II using an oxidizing agent in the presence of at least one first fluid medium at a first pre-determined temperature to obtain a compound of Formula-III; and

Formula-II Formula-III
- chlorinating said compound of Formula-III using a chlorinating agent in the presence of iodine and at least one second fluid medium at a second pre-determined temperature to obtain trifluoromethanesulfinyl chloride of Formula-I.
2. The process as claimed in claim 1, wherein said oxidizing agent is hydrogen peroxide.
3. The process as claimed in claim 2, wherein said oxidizing agent is 30 % to 70 % aqueous hydrogen peroxide solution.
4. The process as claimed in claim 1, wherein the molar ratio of the amount of said oxidizing agent to the amount of said compound of Formula-II is in the range of 0.4:1 to 1:1.
5. The process as claimed in claim 1, wherein said at least one first fluid medium is selected from the group consisting of acetic acid, trichloroacetic acid, dichloroacetic acid, trifluoroacetic acid, chloroform, methylene dichloride and ethylene dichloride.
6. The process as claimed in claim 1, wherein said first pre-determined temperature is in the range of 50 °C to 100 °C.
7. The process as claimed in claim 1, wherein said chlorinating agent is chlorine gas.
8. The process as claimed in claim 1, wherein the molar ratio of the amount of said chlorinating agent to the amount of said compound of Formula-III is in the range of 0.5:1 to 2:1.
9. The process as claimed in claim 1, wherein said at least one second fluid medium is selected from the group consisting of methylene chloride, ethylene dichloride, ethylene chloride, and chloroform.
10. The process as claimed in claim 1, wherein said second pre-determined temperature is in the range of 0 °C to 50 °C.