CLIAMS:1. An in-situ process for the sulfinylation of a heterocyclic compound using stoichiometric quantity of thionyl chloride under anhydrous conditions to produce Fipronil, comprising the following steps

a) Purification of sodium trifluoromethane sulfinate salt with a solvent.
b) Chlorination of the purified sulfinate salt with a chlorinating agent at -15 to +15°C for in-situ generation of sulfinyl chloride.
c) Sulfinylation of pyrazole derivative in the presence of moisture free acid amine complex at -10 to +25°C to get the final product, Fipronil.

2. The process according to claim 1, wherein the sulfinate salt is selected from the group comprising (CF3SO)2O, CF3SO2Na, CF3SO2K, CF3SO2Mg, CF3SO2Li and CF3SO2Ca.

3. The process according to claim 1, wherein the chlorinating agent is selected from the group comprising SOCl2, POCl3, COCl2 and PCl3.

4. The process according to claim 1, wherein the amine of the acid amine complex is selected from the group comprising HN(CH3)2, N(CH3)3, HN(C2H5)2, N(C2H5)3 and Pyridine.

5. The process according to claim 1, wherein the acid is selected from the group comprising Para toluene sulfonic acid, HF, HBr and HCl.

6. The process according to claim 1, wherein the organic solvent is selected from the group comprising EDC, Toluene, Benzene, Nitrobenzene, Cyclohexane, O-Xylene, M-Xylene and P-Xylene.

7. The process according to claim 1, wherein the heterocyclic compound used in the present invention is 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile.

8. The process according to claim 1, wherein the solvent used for purification is ethyl acetate.

9. The process according to claim 1, wherein the pyrazole derivative is used in liquid form.

10. The process according to claim 1, wherein the chlorinating agent is added in a stoichiometric ratio to the sodium trifluoromethane sulfinate salt to reduce the quantity of undesirable impurity of fipronil sulfide which would be difficult to get it separated from the end product.
,TagSPECI:
FIELD OF INVENTION:
The present invention relates to an improved process for the preparation of insecticidal and antiparasitic compound fipronil, involving sulfinylation of a pyrazole derivative which comes under the chemical technology.
BACKGROUND OF THE INVENTION:
Fipronil, an insecticidal and antiparasitic compound is characterized by high efficiency, low toxicity and especially low residue.
This compound is presently used commercially to control pests in, for example, agriculture, public health and animal health.
There are various routes to synthesize Fipronil by oxidation of thiopyrazole with various other oxidizing agents in suitable solvents. Oxidation of sulfides is a very useful route for the preparation of sulfoxides. Literature is replete with the conversion of sulfides to sulfoxides and/or sulfones. However, most of the existing methods use expensive, toxic or rare oxidizing reagents, which are difficult to prepare, are very expensive and cannot be used on commercial scale. Many of these processes suffer from poor selectivity.
To address the prior-art, the inventor has briefly described the available inventions as below;
US 7777052:
This invention relates to a process for the preparation of 5-amino-1-phenyl-3-cyano-4-trifluoromethyl sulphinyl pyrazoles as defined by Formula-I,

Wherein: R1=trifluoromethyl or trifluoromethoxy, and R2, R3=individually hydrogen, chlorine or bromine, the process comprising the step of oxidizing a compound of Formula-II,

wherein: R1=trifluoromethyl or trifluoromethoxy, and R2, R3=individually hydrogen, chlorine or bromine, in a medium comprising at least one oxidizing agent and trichloro acetic acid, and/or the reactions product (s) of the at least one oxidizing agent and trichloro acetic acid, and at least one melting point depressant. The preferred product is Fipronil, preferably prepared using hydrogen peroxide and dichloro acetic acid at room temperature.
US 5618945:
The invention relates to a process for the sulfinylation of heterocyclic compounds, which comprises reacting a compound of the formula RS(O)X, in which R is a linear or branched alkyl group having from 1 to 4 carbon atoms, which is substituted with one or more identical or different halogen atoms and X is a halogen atom, the hydroxyl group or one of the salts thereof, a group --NR.sub.2 R.sub.3, R.sub.2 and R.sub.3 being alkyl or haloalkyl groups of 1 to 4 carbon atoms, or an aryloxy or aralkoxy group, in which the aryl part preferably corresponds to a phenyl group, which is optionally substituted with one or more halogen atoms or alkyl or haloalkyl groups of 1 to 4 carbon atoms,with a heterocyclic compound chosen from the group consisting of pyrroles, pyrazoles, imidazoles, oxazoles, isoxazoles, thiazoles, isothiazoles and triazoles, all of these heterocycles (Het) optionally being substituted with one or more atoms or groups chosen from halogen, amine, alkylamine, dialkylamine, nitrile, aryl, and aryl substituted with one or more halogen atoms and/or one or more alkyl, haloalkyl or SF.sub.5 groups.
US 0190510:
The invention relates to a process for purifying trifluoromethanesulfinic acid by azeotropic distillation with an aromatic solvent, for preparing purified trifluoromethanesulfinic acid and to the use of the purified trifluoromethanesulfinic acid for preparing trifluoromethylsulfinylated pyrazole derivatives, especially fipronil.

US 0004307:
The invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile is reacted with a sulfinylating agent S in the presence of at least one amine acid complex wherein the amine(s) are selected from secondary and/or tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent, wherein S is [CF3S(O)]2O; or CF3S(O)X wherein X means fluoro, chloro, bromo, iodo, a hydroxy group, or an alkaline or alkaline earth metal salt of the hydroxy group; or mixtures thereof, wherein the temperature of the reaction mixture at no time exceeds 39° C.
US 0030211:
This invention relates to a process for the preparation of 5-amino-1-phenyl-3-cyano-4-trifluoromethyl sulphinyl pyrazoles as defined by Formula-I,wherein: R1=trifluoromethyl or trifluoromethoxy, and R2, R3=individually hydrogen, chlorine or bromine, the process comprising the step of oxidizing a compound of Formula-II,wherein: R1=trifluoromethyl or trifluoromethoxy, and R2, R3=individually hydrogen, chlorine or bromine, in a medium comprising at least one oxidizing agent and trichloro acetic acid, and/or the reactions product (s) of at least one oxidizing agent and trichloro acetic acid, and at least one melting point depressant. The preferred product is Fipronil, preferably prepared using hydrogen peroxide and dichloro acetic acid at room temperature.
US 5232940:
N-Phenylpyrazole derivatives of the formula: ##STR1## wherein R.sup.1 represents cyano, nitro, halogen, acetyl or formyl;
R.sup.2 represents R.sup.5 SO.sub.2, R.sup.5 SO or R.sup.5 S in which R.sup.5 is optionally halogen substituted alkyl, alkenyl or alkynyl;
R.sup.3 represents a hydrogen atom or a group NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 each represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R.sup.6 and R.sup.7 together form a cyclic imide and R.sup.4 represents a substituted phenyl group possess arthropodicidal, plant nematocidal, anthelmintic and anti-protozoal properties; their preparation, compositions containing them and their use are described.

WO 077853:
The invention relates to a process for preparing 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(trifluoromethylthio)-IH-pyrazole-3-carbonitrile (hereinafter referred to as compound of formula II), which is useful as an intermediate for the antiparasitic agent fipronil, and a process for preparing 5-amino-3-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethyl sulfinylpyrazole (hereinafter referred to as compound of formula I or fipronil). In one aspect, there is provided a process for preparing fipronil comprising: a) a step of reacting CF3S(=O)ONa with the compound of a pyrazole derivative in the presence of a reducing/halogenating agent; and b) a step of oxidizing the compound of formula II in the presence of a selective oxidizing agent, under suitable conditions, wherein the selective oxidizing agent selectively effects oxidation of II to the corresponding sulfoxide, Fipronil. In certain exemplary embodiments, the selective oxidizing agent is MHSO5, wherein M is an alkaline metal cation.
WO 055877:
The invention relates to a process for purifying trifluoromethanesulfinic acid by azeotropic distillation with an aromatic solvent, for preparing purified trifluoromethanesulfinic acid and to the use of the purified trifluoronnethanesulfinic acid for preparing trifluoromethylsulfinylated pyrazole derivatives, especially fipronil.
WO 122440:
This invention relates to a process for the preparation of 5-amino-1-phenyl-3-cyano-4-trifluoromethyl sulphinyl pyrazoles as defined by Formula- I, wherein: Rl = trif luoromethyl or trif luoromethoxy, and R2, R3 = individually hydrogen, chlorine or bromine , the process comprising the step of oxidizing a compound of Formula- II, wherein: Rl = trifluoromethyl or trif luoromethoxy, and R2, R3 = individually hydrogen, chlorine or bromine , in a medium comprising at least one oxidizing agent and trichloro acetic acid, and/or the reactions product (s) of the at least one oxidizing agent and trichloro acetic acid, and at least one melting point depressant. The preferred product is Fipronil, preferably prepared using hydrogen peroxide and dichloro acetic acid at room temperature.
WO 089616:
A process for the preparation of 5-amino- 1 -(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4- trifluoromethyl sulphinyl pyrazole (1). The said process comprises oxidizing a compound of formula (II) in a medium comprising at least one oxidizing agent, a solvent system and a corrosion inhibiting compound.

WO 030760:
The present invention relates to a method for the preparation of the 5-amino, 1-phenyl, 3-cyano, 4- trifluoromethyl sulfinyl pyrazole having the described general formula (I), particularly preferred for the synthesis of Fipronil, through oxidation of a compound having the general formula (II) as follows: (II) wherein R1 and R2 are independently hydrogen or halogen, and wherein the oxidising agent is dichloroperacetic acid.
WO 107998:
A process for preparation of a trifluoromethylsulfinyl pyrazole compound of formula (I) from a pyrazole derivative is provided, wherein R, R1 and R2 represent a group containing halogen respectively and R3 represents a perhaloalkyl.
WO 007938:
An improved oxidation process for preparing 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulphinyl-pyrazole, of formula (I) is described. The process includes admixing 5-amino-3-cyano-l- (2, 6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole of formula (II) with dichloroacetic acid and hydrogen peroxide in the presence of a strong acid.
WO 090314:
The invention relates to 1-(2,4,6-trisubstituted-phenyl)-5-amino-4-substituted-pyrazole derivatives of formula (I) or salts thereof wherein the various symbols are as defined in the description, to processes for their preparation, to compositions thereof, and to their use for the control of pests (including arthropods and helminths).
EP 295117:
This invention relates to an N-phenylpyrazole derivative, to compositions containing it and to its use against arthropod, plant nematode, helminth and protozoan pests.
CN 1176078 C:
The invention relates to a CF3 SO2 K or CF3 SO2 K and CF3 SO2 Na mixed salt with pyrazole compounds sulfenylated way, it is the CF 3 SO2K or CF3SO2K and CF 3 SO2Na mixed salt and pyrazole compounds, the reaction when the first enable CF 3 SO 2 K or CF 3SO 2 K and CF3 SO2Na mixed salt of the reaction with the reagent A, and then adding the reaction pyrazole compound or added to the pyrazole compounds for reaction, wherein A is selected from phosgene, TCF, POCl 3, PCl 3 or SOCl2, that is obtained with trifluoro-methylsulfinyl pyrazole compounds. The present invention found a new sulfinyl reagent, it’s easy preparation, high reactivity, easy to use, so as to maintain the easiness of the reaction and improve the yield of the reaction.
CN 101250158 A:
The invention discloses a 5 - amino-3 - cyano-1 - (2,6 - dichloro-4 - trifluoromethyl-phenyl)-4 - trifluoromethylthiopyrazole as a raw material in a solvent, and sulfuric acid medium catalyzed oxidation of fipronil approach. The chemical reaction of the above formula, the present invention is oxidized to sulfuric acid medium fipronil, dilute sulfuric acid is added after the release of water, can be recovered layered. The invention process is simple, environmentally friendly, mild reaction conditions, low production cost, etc., with good prospects for industrial applications.

JOURNALS:
Bull.chem.soc.jpn. 46 (1973) 3615: EP 0668269 B1:
The invention relates to a process of sulfinylation of heterocyclic compounds. The sulfinylation of heterocyclic compounds, i.e. the incorporation of a group RS (O) -, is conventionally carried out by the action of a product of formula RSX (R and X being as defined below) on the heterocyclic compound bearing a hydrogen atom on the carbon to be substituted. This reaction therefore consists sulfenyl heterocycle that must oxidize to give sulfinyl compound desired. However, it is found that this oxidation step is often difficult. In addition, the compound RSX has in some cases been found to be highly toxic. This is the case for example of the compound CF 3 SCl which makes handling very difficult.Another conventional method is via a disulfide compound intermediate cut at the SS bond by a compound RX to give the sulphenyl compound, which compound is then oxidized to sulfinyl. This method avoids the use of the compound RSX but does not prevent the subsequent oxidation step.
Tetrahedron 55 (1999) p 7243-7250: WO 2008055879 A1:
The invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile is reacted with a sulfinylating agent S in the presence of at least one amine acid complex wherein the amine(s) are selected from cyclic secondary amines and the acid(s) are selected from sulfonic acid derivatives, and with the addition of a halogenating agent, wherein S is [CF3S(O)]2O; or CF3S(O)X wherein X means fluoro, chloro, bromo, iodo, a hydroxy group, or an alkaline or alkaline earth metal salt of the hydroxy group; or mixtures thereof.

Syn.lett. 2001, p 550-552: WO 2008055879 A1
The invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile is reacted with a sulfinylating agent S in the presence of at least one amine acid complex wherein the amine(s) are selected from cyclic secondary amines and the acid(s) are selected from sulfonic acid derivatives, and with the addition of a halogenating agent, wherein S is [CF3S(O)]2O; or CF3S(O)X wherein X means fluoro, chloro, bromo, iodo, a hydroxy group, or an alkaline or alkaline earth metal salt of the hydroxy group; or mixtures thereof.
J. Hebei University of Science & Technology, Vol. 25(2), sum 69(2004), serial no: 1008-1542(2004) 02-0018-03. US 20120309806 A1
The invention relates to a process for the preparation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile is reacted with a sulfinylating agent selected from trifluoromethylsulfinic acid, trifluoromethylsulfinic acid anhydride, and a trifluoromethylsulfinate alkaline or alkaline earth metal salt and mixtures of the acid and/or the salt(s), in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent.
The focus of the search is to identify and locate processes deal with in-situ generation of sulfinyl chloride which is then reacted with pyrazole derivative to produce Fipronil.
US 5618945 (Rhone-Poulenc)
The invention relates to a novel process for the sulfinylation of heterocyclic compounds, which comprises reacting:
a compound of the formula RS(O)X, in which R is a linear or branched alkyl group having from 1 to 4 carbon atoms, which is substituted with one or more identical or different halogen atoms and X is a halogen atom, the hydroxyl group or one of the salts thereof, a group --NR.sub.2 R.sub.3, R.sub.2 and R.sub.3 being alkyl or haloalkyl groups of 1 to 4 carbon atoms, or an aryloxy or aralkoxy group, in which the aryl part preferably corresponds to a phenyl group, which is optionally substituted with one or more halogen atoms or alkyl or haloalkyl groups of 1 to 4 carbon atoms,with a heterocyclic compound Het chosen from the group consisting of pyrroles, pyrazoles, imidazoles, oxazoles, isoxazoles, thiazoles, isothiazoles and triazoles, all of these heterocycles Het optionally being substituted with one or more atoms or groups chosen from halogen, amine, alkylamine, dialkylamine, nitrile, aryl, and aryl substituted with one or more halogen atoms and/or one or more alkyl, haloalkyl or SF.sub.5 groups

The above US patent cover in-situ process but it differ with the present invention from the following aspects:
(a) The reaction temperature involved is 0 to 50 °C as against -15 to +25 °C.
(b) The above US invention does not include purification of sodium trifluoromethane sulfinate.
(c) Pyrazole derivative is used as a solid instead of solution.

US 2010 / 0004307 (BASF) & WO 2008 / 055877
US 2010 / 0004307 -The invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile is reacted with a sulfinylating agent S in the presence of at least one amine acid complex wherein the amine(s) are selected from secondary and/or tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent, wherein S is [CF3S(O)]2O; or CF3S(O)X wherein X means fluoro, chloro, bromo, iodo, a hydroxy group, or an alkaline or alkaline earth metal salt of the hydroxy group; or mixtures thereof, wherein the temperature of the reaction mixture at no time exceeds 39° C.
WO/ 2008 / 055877 -The invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3- carbonitrile is reacted with a sulfinylating agent selected from trifluoromethylsulfinic acid, trifluoromethylsulfinic acid anhydride, and a rifluoromethylsulfinate alkaline or alkaline earth metal salt and mixtures of the acid and/or the salt(s), in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent.
(a) The above patents include the use of triethyl amine hydrochloride (TEA. HCl) as acid amine complex instead of Para toluene sulfonic acid – dimethyl amine (PTSA.DMA) complex which is used in our invention.
(b) The purification of trifluoromethane sodium sulfinate is not covered.
(c) The use of toluene as solvent is mentioned in these patents instead of ethylene dichloride (EDC) used in our invention.
US 2010 / 0004307: US 20100004307 A1:
The invention relates to a process for the sulfinylation of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile is reacted with a sulfinylating agent S in the presence of at least one amine acid complex wherein the amine(s) are selected from secondary and/or tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent, wherein S is [CF3S(O)]2O; or CF3S(O)X wherein X means fluoro, chloro, bromo, iodo, a hydroxy group, or an alkaline or alkaline earth metal salt of the hydroxy group; or mixtures thereof, wherein the temperature of the reaction mixture at no time exceeds 39° C.
WO 2008 / 055877: EP 2349987 A1:
The invention relates to a method for purifying trifluoromethanesulfinic acid by azeotropic distillation using an aromatic solvent, for producing purified trifluoromethanesulfinic acid, and to the use of the purified trifluoromethanesulfinic acid for the production of trifluoromethylsulfinylated pyrazole derivatives, in particular fipronil.
DRAWBACKS OF THE PRIOR ART:
The preparation of Fipronil is in general involve a two step process and the following difficulties were encountered in earlier published work.
(1) The reaction between RSX (trifluoromethane sulfenyl chloride) with a pyrazole derivative to give the sulfide derivative of Fipronil, which has to be further oxidized to give the final product of Fipronil in a two step process.
(2) Trifluoromethane sulfinyl chloride (RSOX) is generated by reacting trifluoromethane sodium sulfinate (RSO2Na) with SOCl2 followed by fractionation of trifluoromethane sulfinyl chloride (RSOX) and is a cumbersome process.
(3) RSX is a volatile gas and hazardous to operate and toxic in nature.
(4) RSOX being toxic and unstable cannot be stored for longer period.
(5) The previous inventions make use of pyrazole derivative directly as a solid which is difficult to handle.

OBJECTIVE OF THE INVENTION:
In order to avoid the above stated drawbacks encountered in earlier published work, the objective of the present invention is thus aimed to generate sulfinyl chloride in-situ during the reaction and then react with pyrazole derivative to form Fipronil. The mass is quenched in sodium carbonate solution and then isolated.
The objective of the present invention is also to use [5-amino-1-(2,6-dichloro-4-trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile derivative in the form of a solution and not as solid.
The objective of the present invention is also to minimize the concomitant reduction at the sulfur atom which leads to the major impurity of Fipronil sulfide, and it is difficult to separate it from the end product.

DETAILED DESCRIPTION OF THE INVENTION:
SUMMARY OF THE INVENTION:
The invention relates to an in-situ process involving sulfinylation of a heterocyclic compound ([5-amino-1-(2,6-dichloro-4-trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile) using Sulfinyl chloride which is a product of the reaction between trifluoromethane sodium sulfinate and stoichiometric quantity of thionyl chloride to produce Fipronil which effectively minimizes the undesirable production of the major impurity i.e. Fipronil sulfide which would be difficult to get separated from the end product.
ADVANTAGES OVER THE PRIOR TECHNOLOGIES:
1. It is a single pot reaction.
2. The quantity of SOCl2 used is less as compared to other inventions.
3. It avoids handling of hazardous sulfinyl chloride which is generated in-situ in the present invention.
4. Ease of operation
5. Ease of handling the materials.

DESCRIPTION OF FIGURE:
Figure 1 specifies a flow chart which explains the various steps involved in the production of Fipronil by sulfinylation of a pyrazole derivative.

DESCRIPTION OF THE PREFERRED EMBODIMENT:
The invention relates to in-situ process involving sulfinylation of a heterocyclic compound (pyrazole derivative) to produce Fipronil an insecticide and antiparasitic agent.
The commercially available trifluoromethane sodium sulfinate is employed in the current invention. The sulfinate salt is initially purified with ethyl acetate solvent to get pure salt, which is then reacted with optimum quantity of SOCl2 (Thionyl chloride) for in-situ generation of sulfinyl chloride at -15 o C to +15 °C which is further reacted with a purified solution of [5-amino-1-(2,6-dichloro-4-trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile (pyrazole derivative) to give the final product Fipronil.
By in-situ generation of sulfinyl chloride (RSOX), the major impurity i.e Fipronil sulfide can be reduced to below 2% (HPLC analysis) without increasing the mole ratio of SOCl2 and trifluoromethane sodium sulfinate.
It was observed that when SOCl2 is used in excess, the percentage formation of Fipronil sulfide is high.
Hence, it was aimed to use stoichiometric quantity of SOCl2 in the reaction.
The above synthesized Fipronil is used as antiparasitic agent for agriculture / horticulture and in animal health protection.
Permissible Ranges of Parameters used during the Process:
1. Temperature maintenance during sulfinyl chloride addition -15 °C to +15 °C.
2. Main reaction temperature is at -10 °C to + 25 °C.
3. SOCl2 addition time is in 20 to 30 min.
4. Pyrazole derivative addition time is 10 to 15 min.
5. Reaction maintenance time is 5 to 10hrs.
EXAMPLES:
Example – 1
50g (208mmol) of CF3SO2Na and ethyl acetate (100g) were placed in 500ml RB flask at room temperature, stir for 10min. and filter through hyflow bed.The filtrate is taken in the flask and distilled azeotropically to remove moisture. To the residue charge PTSA.DMA complex in EDC solution (218g) and then cool to room temperature under inert atmosphere. It is further cooled to -15 oC and SOCl2 (26.3g) was added over a period of 20 to 30min. while maintaining the reaction temperature below 25 oC. Stir the reaction mass for further 30 min. and pyrazole derivative (50g 148mmol) dissolved in 150g of EDC is added as a solution to the reaction mass at +25 oC over a period of 10 to 15 min. The reaction mixture is kept at +25 oC for 90 min. and maintained for 5 to 10hrs at this temperature. The sample is checked for unreacted pyrazole derivative content and it should be preferably below 0.5%. The reaction is then terminated and then quench the mass into sodium carbonate (25g, 236 mmol) in 350ml water solution at 25 oC and stir for 20 to 30min. and filter the mass. The wet cake is washed with water to get the final wet product of Fipronil and is dried. The yield is 78% and the purity obtained is 94 to 95%.
Example – 2
The procedure followed is same as in example – 1 but with 1.5 mole of SOCl2 instead of 1 mole.
Example – 3
The procedure followed is same as in example – 1 but with COCl2 addition is done after the pyrazole derivative is charged.
Example – 4
The procedure followed is same as in example – 1 but with POCl3 instead of SOCl2.
Table-1:
List Of Various Ingredients Which Can Be Used In The Preparation Of Fipronil
S.No Type of Salts Type of Amine Type of Acid Chlorinating Agent Solvent
1 (CF3SO)2O N(CH3)3 HF SOCl2 EDC
2 CF3SO2Na N(CH3)3 HCl POCl3 Toluene
3 CF3SO2K N(CH3)3 PTSA COCl2 Benzene
4 CF3SO2Mg N(C2H5)3 AlCl3 PCl3 Nitrobenzene
5 CF3SO2Li Pyridine HCl SOCl2 Cyclohexane
6 CF3SO2Ca N(C2H5)3 HCl SOCl2 O,M,P-Xylene
7 CF3SO2Na HN(CH3)2 PTSA SOCl2 EDC

Table-2
Quantities of Various Ingredients:
S.No CF3SO2Na
(g) Pyrazole
Derivative(g) POCl3 / COCl2/SOCl2 (g) Ethyl acetate(g) PTSA.DMA
In EDC (g) Output
(g) Purity(%)
By HPLC
1 50 50 26.3(SOCl2) 100 218 48.0 95.0
2 50 50 37.2(SOCl2) 100 218 45.0 93.0
3 50 50 26.3(COCl2) 100 218 38.0 91.0
4 50 50 32.0(POCl3) 100 218 41.5 84.5