Claims:WE CLAIM;
1. A process for the synthesis of fipronil, the process comprising the
following steps:
a) reacting trifluoromethane sulfinyl chloride with 5-amino-3-cyano-
1-(2,6-dichloro-4-5 trifluoromethylphenyl)-pyrazole and amine
hydrochloride in a halogenated fluid medium to obtain a reaction
mixture;
b) cooling said reaction mixture to a temperature in the range of
20 °C to 35 °C to obtain a cooled reaction mixture;
10 c) adding a mixture of said halogenated fluid medium and water to
said cooled reaction mixture obtain an admixture;
d) neutralizing said admixture with a neutralizing agent to obtain a
biphasic mixture containing an organic phase and an aqueous
phase;
15 e) separating said organic phase comprising fipronil followed by
cooling said separated organic phase to a temperature in the range
of 2 oC to 30 oC to obtain a precipitate of fipronil; and
f) filtering said precipitate to obtain a solid, washing said solid and
drying said washed solid to obtain fipronil with purity in the range
20 of 95 % to 97 %.
2. The process as claimed in claim 1, wherein fipronil is obtained with a
yield in the range of 75 % to 90 %.
23
3. The process as claimed in claim 1, wherein said step a) is carried out at a
temperature in the range of 40 °C to 80 °C.
4. The process as claimed in claim 1, wherein said step a) is carried out for a
time period in the range of 2 hours to 8 hours.
5. The process as 5 claimed in claim 1, wherein the halogenated fluid medium
is selected from the group consisting of dichloromethane, dichloroethane,
dibromoethane, chlorobromomethane, chloroform, carbon tetrachloride,
chlorobenzene, dichlorobenzene, and bromobenzene.
6. The process as claimed in claim 1, wherein the molar ratio of
10 trifluoromethane sulfinyl chloride to 5-amino-3-cyano-1-(2,6-dichloro-4-
trifluoromethylphenyl)-pyrazole is in the range of 1:1 to 2:1.
7. The process as claimed in claim 1, wherein the purity of said
trifluoromethane sulfinyl chloride is in the range of 95% to 99.9%.
8. The process as claimed in claim 1, wherein the molar ratio of amine
15 hydrochloride to 5-amino-3-cyano-1-(2,6-dichloro-4-
trifluoromethylphenyl)-pyrazole is in the range of 1:1 to 3: 1.
9. The process as claimed in claim 1, wherein the amount of 5-amino-1-(2,6-
dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulfonyl
pyrazole, in fipronil is in the range of 0% to 0.5%.
20 10. The process as claimed in claim 1, wherein said neutralizing agent is at
least one selected from the group consisting of water, aqueous ammonia
solution, aqueous NaOH solution, aqueous KOH solution, Na2CO3
solution, NaHCO3 solution and aqueous CaCl2 solution.
24
11. The process as claimed in claim 1, wherein amine hydrochloride, water,
and the halogenated fluid medium are recovered from said aqueous phase.
12. The process as claimed in claim 1, wherein said amine hydrochloride is
selected from the group consisting of diethylamine hydrochloride, N, N,
N’, N’-tetraethyl ethan-1,2-5 diamine dihydrochloride and amine sulphate
salt.
13. The process as claimed in claim 1, wherein Boric acid and CaCl2 are
added as a hydrofluoric acid binders prior to neutralization. , Description:FIELD
The present disclosure relates to a process for the synthesis of Fipronil.
BACKGROUND
The background information herein below relates to the present disclosure but is
5 not necessarily prior art.
Fipronil is a broad-spectrum insecticide and it belongs to 1-phenylpyrazole class
of insecticides. Fipronil is characterized by high efficiency, low toxicity, and
especially, low residue.
10 IUPAC name: (R,S)-5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-
(trifluoromethylsulfinyl)pyrazole-3-carbonitrile
CAS number: 120068-37-3
A commercial process involves oxidation in the final step of the synthesis of
fipronil wherein, the sulfinyl precursor of Fipronil is oxidized using a suitable
15 oxidizing agent. However, during the oxidation process some amount of fipronil
(so obtained product) undergoes further oxidation, thereby resulting in the
3
formation of corresponding sulfone compound 5-amino-1-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-
carbonitrile, as an impurity. Therefore, the aforementioned commercial route
provides fipronil with a low purity. Further, the sulfone impurity is difficult to
5 separate from fipronil.
Another commercial process for the synthesis of fipronil involves
trifluoromethanesulfinylation of corresponding aryl-pyrazole intermediate using
trifluoromethanesulfinyl chloride [CAS no. 20621-29-8]. Unfortunately, hitherto
known processes for preparing trifluoromethanesulfinyl chloride are complex,
10 and provide trifluoromethanesulfinyl chloride with a low purity and with low
yield. Further, the trifluoromethanesulfinyl chloride may contain corresponding
sulfone impurity such as trifluoromethanesulfonyl chloride that can lead to the
formation of sulfone impurity (5-amino-1-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-
15 carbonitrile) during the synthesis of fipronil.
Thus, there is felt a need for developing a simple process for preparing Fipronil
which results in a high yield, with high purity.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment
20 herein satisfies, are as follows.
4
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
fipronil in a high yield, and with high purity.
Another object of the present 5 disclosure is to provide a simple and efficient
process for the synthesis of fipronil.
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.
10 SUMMARY
The present disclosure provides a process for the synthesis of fipronil. The
process comprises reacting 5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoro methyl
phenyl)-pyrazole with trifluoromethane sulfinyl chloride and amine
hydrochloride, in the halogenated organic fluid medium to obtain a reaction
15 mixture. The reaction mixture is cooled to a temperature in the range of 20 °C to
35 °C to obtain a cooled reaction mixture. A mixture of the halogenated organic
fluid medium and water is added to the cooled reaction mixture to obtain an
admixture. The so obtained admixture is neutralized with a neutralizing agent to
obtain a biphasic mixture containing an organic phase and an aqueous phase. The
20 organic phase comprising fipronil is separated and cooled to a temperature in the
range of 2 oC to 30 oC to obtain a precipitate of fipronil. The so obtained
5
precipitate is filtered, washed, and dried under vacuum to obtain fipronil with
purity in the range of 95 % to 97 %. The reaction of 5-Amino-3-cyano-1-(2,6-
dichloro-4-trifluoro methyl phenyl)-pyrazole with trifluoromethane sulfinyl
chloride and amine hydrochloride is carried out at a temperature in the range of
45 °C to 80 °C for a time period in the range 5 of 2 hours to 8 hours. In accordance
with the embodiments of the present disclosure, fipronil is obtained with a yield
in the range of 75% to 90%. In accordance with the present disclosure, amine
hydrochloride is selected from the group consisting of diethylamine
hydrochloride, N, N, N’, N’-tetraethyl ethan-1,2-diamine dihydrochloride and
10 their amine sulphate salt.
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
15 understanding of the 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 wellknown
techniques are not described in detail.
20 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
6
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 5 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
10 that additional or alternative steps may be employed.
As used herein, the term "and/or" includes any and all combinations of one or
more of the associated listed elements.
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
15 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.
Fipronil is a broad-spectrum insecticide. Conventional processes for the synthesis
20 of fipronil are complex, and provide fipronil of low purity. Further, the fipronil
obtained by the conventional processes may contain corresponding sulfone
compound 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoro
7
methyl)sulfonyl]-1H-pyrazole-3-carbonitrile, as an impurity, which is difficult to
separate from fipronil.
The present disclosure envisages a simple process for preparing fipronil in a high
yield and with high purity. Further, it is desired that the synthesized fipronil
contains less than 0.5%, more preferably 5 negligible amount of sulfone impurity
i.e.,5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)
sulfonyl]-1H pyrazole -3carbonitrile.
In one aspect, the present disclosure provides a process for synthesis of fipronil.
10 The process of the present disclosure is represented herein below as Scheme-1.
Scheme 1: Synthesis of fipronil
8
The process of the present disclosure is described in detail.
In accordance with the process of the present disclosure, 5-Amino-3-cyano-1-
(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole is reacted with trifluoromethane
sulfinyl chloride and amine hydrochloride 5 in the halogenated organic fluid
medium to obtain a reaction mixture.
In accordance with the embodiments of the present disclosure, the halogenated
organic fluid medium is at least one selected from the group consisting of
dichloromethane, dichloroethane, dibromoethane,
10 chlorobromomethane,chloroform, carbon tetrachloride, chlorobenzene,
dichlorobenzene & bromobenzene .
In an embodiment, the amine hydrochloride is selected from the group consisting
of diethylamine hydrochloride, N, N, N’, N’-tetraethyl ethan-1,2-diamine
dihydrochloride and their amine sulphate salt.
9
The reaction of 5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoro methyl phenyl)-
pyrazole with trifluoromethane sulfinyl chloride and amine hydrochloride is
carried out at a temperature in the range of 40 °C to 80 °C. In an embodiment, the
reaction is carried out at a temperature in the range of 48-55 oC.
The reaction of 5-Amino-3-cyano-1-(2,6 5 -dichloro-4-trifluoro methyl phenyl)-
pyrazole with trifluoromethane sulfinyl chloride and amine hydrochloride is
carried out for a time period in the range of 2 hours to 8 hours. In an embodiment,
the reaction time period is 5 hours.
In accordance with the embodiments of the present disclosure, the molar ratio of
10 trifluoromethane sulfinyl chloride to 5-amino-3-cyano-1-(2,6-dichloro-4-
trifluoromethylphenyl)-pyrazole is in the range of 1:1 to 2:1. In an exemplary
embodiment, the molar ratio of trifluoromethyl sulfinyl chloride to 5-amino-3-
cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole is in the range of 1.1:1
to 1.2:1.
15 The purity of trifluoromethyl sulfinyl chloride used in the process of the present
disclosure can be in the range of 95% to 99.9%. Further, trifluoromethyl sulfinyl
chloride comprises sulfone impurity trifluoromethanesulfonyl chloride in the
range of 0 to 0.5%
The molar ratio of amine hydrochloride to 5-amino-3-cyano-1-(2,6-dichloro-4-
20 trifluoromethylphenyl)-pyrazole is in the range of 1:1 to 3:1. In an exemplary
embodiment of the present disclosure, the molar ratio of diethylamine
10
hydrochloride to 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-
pyrazole is in the range of 1.5 :1.0 to 2.5 :1
The reaction mixture is cooled at a temperature in the range of 20 °C to 35 °C to
obtain a cooled reaction mixture. A mixture of the halogenated organic fluid
medium and water is added to the cooled 5 reaction mixture to obtain an admixture.
The so obtained admixture is neutralized with a neutralizing agent to obtain a
biphasic mixture containing an organic phase and an aqueous phase. The organic
phase comprising fipronil is separated and cooled to a temperature in the range of
2 oC to 30 oC to obtain a precipitate of fipronil. The so obtained precipitate is
10 filtered, washed, and dried under vacuum to obtain fipronil with purity in the
range of 95 % to 97 %.
The neutralizing agent is at least one selected from the group consisting of an
aqueous ammonia solution, aqueous NaOH solution, aqueous KOH solution,
Na2CO3 solution, NaHCO3 solution and an aqueous CaCl2 solution.
15 In accordance with the embodiments of the present disclosure, fipronil is
obtained with a yield in the range of 75% to 90%.
In accordance with the embodiments of the present disclosure, the amount of
sulfone impurity 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-
trifluoromethylsulfonylpyrazole in fipronil obtained by the process of the present
20 disclosure is in the range of 0% to 0.5%.
11
In accordance with the embodiments of the present disclosure, amine
hydrochloride and the halogenated organic fluid medium are recovered from the
aqueous phase. The recovered amine hydrochloride can be reused in the process
of preparation of fipronil.
In accordance with one 5 embodiment of the present disclosure, fipronil is
recrystallized using the halogenated organic fluid medium.
The halogenated organic fluid medium used for recrystallization of fipronil can
be further recovered and reused.
The process of the present application further comprises addition of Boric acid
10 and CaCl2 as hydrofluoric acid binders prior to neutralization. The addition of
Boric acid and CaCl2 protects hydrofluoric acid attack on glass reactor.
The process of the present is disclosure is simple, and efficient, and provides
fipronil in a high yield, and with a high purity. The process of the present
disclosure is carried out using a low amount of the halogenated fluid medium.
15 The halogenated fluid medium used in the process step is carried forward in the
distillation step. The used halogenated organic fluid medium is recovered and the
recovered halogenated organic fluid medium is reused. Therefore, the process of
the present disclosure is environment friendly.
The foregoing description of the embodiments has been provided for purposes of
20 illustration and not intended to limit the scope of the present disclosure.
Individual components of a particular embodiment are generally not limited to
12
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 5 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
10 Preparation of fipronil in accordance with the process of the present
disclosure:
Example-I: -
500 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
15 [2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 197.1 gm of diethyl amine hydrochloride (dry
powder) was added in the ethylene dichloride with stirring and heated to 50 °C
under stirring to obtain a mixture. 175.3 gm of trifluoro methyl sulfinyl chloride
was added to the mixture with stirring at 50 °C for 5 hours to obtain a reaction
mixture. The so obtained reaction mixture was cooled to 25 o20 C to obtain a cooled
reaction mixture. 3000 ml of ethylene dichloride and 400 ml of water (H2O) was
added in the cooled reaction mixture to obtain an admixture. The admixture was
13
neutralized by using an aqueous ammonia solution (8-10N) till pH 7 to obtain a
neutralized admixture. After neutralization, the neutralized admixture was heated
to 65 °C to obtain a biphasic mixture containing bottom organic layer and top
aqueous layer. The bottom organic layer was separated and cooled to 5 °C to
obtain precipitate. The so 5 obtained precipitated was filtered, washed twice with
the ethylene dichloride to minimize impurities in Fipronil mass. The Fipronil
mass was dried under vacuum and then dried at 100 °C to get 335 gm (Yield=
76.66%) of fipronil having purity of 96%.
Example-II: -
10 600 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 219 gm of diethyl amine hydrochloride (dry
powder) was added in the ethylene dichloride with stirring and then heated to 45
15 °C with stirring to obtain a mixture. 175.3 gm of trifluoro methyl sulfinyl
chloride was added to the mixture at 45 oC with stirring for 5 hours to obtain a
reaction mixture. The so obtained reaction mixture was cooled to 25 oC to obtain
a cooled reaction mixture. 2900 ml of ethylene dichloride and 400 ml of water
(H2O) was added to the cooled reaction mixture to obtain an admixture. The
20 admixture was neutralized by using an aqueous ammonia solution (8-10N) till pH
7 to obtain a neutralized admixture. After neutralization, the neutralized
admixture was heated to 70 °C to obtain a biphasic mixture containing bottom
organic layer and top aqueous layer. The bottom organic layer was separated and
14
cooled to 5 °C to obtain precipitate. The so obtained precipitate was filtered,
washed twice with the ethylene dichloride. The filtered fipronil mass was dried
under vacuum and then dried at 100 °C to get 338 gm (Yield= 77.34%) of
fipronil with purity= 96.4%.
5 Example-III: -
500 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 164.25 gm of diethyl amine hydrochloride (dry
10 powder) was added in ethylene dichloride with stirring and heated to 60 °C with
stirring to obtain a mixture. 175.3 gm of trifluoro methyl sulfinyl chloride was
added in the mixture with stirring and stirred for 5 hours at 60 °C to obtain a
reaction mixture. The so obtained reaction mixture was cooled to 20 oC to obtain
a cooled reaction mixture. 3000 ml of ethylene dichloride and 400 ml of water
15 (H2O) was added to the cooled reaction mixture to obtain admixture. The
admixture is neutralized by using an aqueous ammonia solution (8-10N) till pH 7
to obtain a neutralized admixture. The neutralized admixture was heated to 65 °C
to obtain a biphasic mixture containing bottom organic layer and top aqueous
layer. The bottom organic layer was separated and cooled to 3 °C to obtain
20 precipitate. The so obtained precipitate was filtered, washed twice with the
ethylene dichloride. The filtered Fipronil mass was dried under vacuum and then
dried at 110 °C to get 330 gm (Yield= 75.51%) of fipronil with purity= 95.8%.
15
Example-IV: -
500 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 219 gm 5 of diethyl amine hydrochloride (dry
powder) was added in ethylene dichloride with stirring and heated to 50 °C with
stirring to obtain a mixture. 175.3 gm of trifluoro methyl sulfinyl chloride was
added to the mixture under stirring and heated for 5 hours at 50 °C to obtain a
reaction mixture. The so obtained reaction mixture was cooled to 25 oC to obtain
10 cooled reaction mixture. 3000 ml of ethylene dichloride and 400 ml of water
(H2O) was added to the cooled reaction mixture to obtain an admixture. The
admixture is neutralized by using an aqueous ammonia solution (8-10N) till pH 7
to obtain a neutralized admixture. The so obtained neutralized admixture was
heated to 70°C to obtain a biphasic mixture containing bottom organic layer and
15 top aqueous layer. The bottom organic layer was separated and concentrated to
adjust the level of ethylene dichloride to 800 ml by recovering 2700 ml ethylene
dichloride at 85 °C followed by cooling to 20 °C to obtain precipitate. The so
obtained precipitated was filtered, washed twice with the dichloroethane. The
solid mass was dried under vacuum and then dried at 110 °C to get 360 gm
20 (Yield= 82.38%) of fipronil with purity= 96.5%.
Example-V: -
600 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
16
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 273.75 gm of diethyl amine hydrochloride (dry
powder) was added in ethylene dichloride with stirring and heated to 50 °C to
obtain a mixture. To the mixture 183 gm of trifluoro methyl sulfinyl chloride was
added under stirring and heated at 50 oC for 5 5 hours to obtain a reaction mixture.
The so obtained reaction mixture was cooled to 25 oC to obtain a cooled reaction
mixture. To the reaction mixture, 2900 ml of ethylene dichloride and 400 ml of
water (H2O) was added to obtain an admixture. The admixture was neutralized by
using an aqueous ammonia solution (8-10N) till pH get 7 to obtain a neutralized
10 admixture. The neutralized admixture was heated to 70 °C to obtain a biphasic
mixture containing bottom organic layer and top aqueous layer. The bottom
organic layer was separated and concentrated to adjust the level of ethylene
dichloride to 800 ml by recovering 2700 ml ethylene dichloride at 85 °C followed
by cooling to 20 °C to obtain precipitate. The so obtained precipitated was
15 filtered, washed twice with the chlorinated solvent to obtain a cake. The cake was
dried under vacuum and then dried at 100 °C to get 375 gm (Yield= 85.81%) of
fipronil with purity of 96.3%.
Example-VI: -
600 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
20 stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 490 gm of N, N, N’, N’-tetraethyl ethan-1,2-
diamine dihydrochloride (dry powder) , was added in ethylene dichloride with
17
stirring and heated at 50 °C with stirring to obtain a mixture. 183 gm of trifluoro
methyl sulfinyl chloride was added to the mixture under stirring for 5 hours at
50 °C to obtain a reaction mixture. The so obtained reaction mixture was cooled
to 25 oC to obtain a cooled reaction mixture. To the reaction mixture, 2900 ml of
ethylene dichloride and 400 ml of water (5 H2O) was added to obtain an admixture.
The admixture was neutralized by using an aqueous ammonia solution (8-10N)
till get the pH 7 to obtain a neutralized admixture. The neutralized admixture was
heated to 70 °C to obtain a biphasic mixture containing bottom organic layer and
top aqueous layer. The bottom organic layer was separated and concentrated to
10 adjust the level of ethylene dichloride to 800 ml by recovering 2700 ml ethylene
dichloride at 85 °C followed by cooling to 20 °C to obtain precipitate. The so
obtained precipitated was filtered, washed twice with the dichloroethane solvent
to obtain a Fipronil solid mass. The Fipronil solid mass was dried under vacuum
and then dried at 90 °C to get 345 gm (Yield= 78.95%) of fipronil with purity=
15 95.5%.
Example-VII: -
600 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
20 Boric acid, 2.0 gm CaCl2 and 273.75 gm of diethyl amine hydrochloride (dry
powder), was added in ethylene dichloride with stirring and heated to 50 °C with
stirring to obtain a mixture. 183 gm of trifluoro methyl sulfinyl chloride was
added the mixture with stirring and stirred for 5 hours at 50 °C to obtain a
18
reaction mixture. The so obtained reaction mixture was cooled to 25 oC to obtain
a cooled reaction mixture. To the reaction mixture, 2900 ml of ethylene
dichloride and 400 ml of water (H2O) was added to obtain an admixture. The
admixture was neutralized by using an aqueous ammonia solution (8-10N) till
pH 7 to obtain a neutralized admixture. The neutralized 5 admixture was heated to
70 °C to obtain a biphasic mixture containing bottom organic layer and top
aqueous layer. The bottom organic layer was separated and concentrated to
recover 3500 ml ethylene dichloride at 85-90 °C and then to the concentrated
mass added 1000 ml of monochlorobenzene followed by cooling to 20 °C to
10 obtain precipitate. The so obtained precipitated was filtered, washed twice with
monochlorobenzene the to obtain a Fipronil solid mass. The Fipronil solid mass
was dried under vacuum and then dried at 115 °C to get 375 gm (Yield= 85.81%)
of fipronil with purity= 97%.
Example-VIII: -
15 500 ml dry ethylene dichloride was charged in 1-lit vertical reactor equipped with
stirrer, thermometer pocket, and condenser with scrubber. 321 gm of 5-amino-1-
[2,6-dichloro-4- (trifluoro methyl) phenyl]-1H- pyrazole-3-carbonitrile, 1.0 gm
Boric acid, 2.0 gm CaCl2 and 219 gm of diethyl amine hydrochloride (dry
powder) was added in ethylene dichloride with stirring and heated to 50 °C with
20 stirring to obtain a mixture. 175.3 gm of trifluoro methyl sulfinyl chloride was
added to the mixture under stirring and heated for 5 hours at 50°C to obtain a
reaction mixture. The reaction mixture was drowned into 3000 ml of ethylene
dichloride and 1000 ml of 10.0% W/V CaCl2 solution at 30 oC to obtain an
19
admixture. The so obtained neutralized admixture was heated to 70°C to obtain a
biphasic mixture containing bottom organic layer and top aqueous layer. The
bottom organic layer was separated and neutralized by using an aqueous
ammonia solution (0.5-1.0N) till pH 7 to obtain a neutralized admixture. The so
obtained neutralized admixture 5 was heated to 70°C to obtain a biphasic mixture
containing bottom organic layer and top aqueous layer. The bottom organic layer
was separated and concentrated to adjust the level of ethylene dichloride to 800
ml by recovering 2700 ml ethylene dichloride at 85 °C followed by cooling to 20
°C to obtain precipitate. The so obtained precipitated was filtered, washed twice
10 with the dichloroethane. The solid mass was dried under vacuum and then dried
at 110 °C to get 380 gm (Yield= 87.00%) of fipronil with purity= 96.5%.
To achieve the yield of Fipronil greater than 85 %, the catalyst (diethylamine
hydrochloride) quantity should be minimum 219 grams per mole of batch size
and drowning of the reaction mass in CaCl2 solution gives better yield in
15 comparison to other examples. Diethyl amine hydrochloride is preferably better
catalyst than the other amine hydrochloride.
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 that:
20 ? is simple and efficient;
? provides fipronil in high yield with high purity; and
20
? is environmentally friendly.
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 5 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
10 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
15 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
20 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.
21
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 5 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
10
15