FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. Title of the Invention
A PROCESS FOR THE PREPARATION OF 2-AMINO-5-CHLORO-N,3-DIMETHYLBENZAMIDE
2. Applicant(s)
Name Nationality Address
GHARDA CHEMICALS LIMITED Indian R & D CENTER, B-27, MIDC PHASEI, DOMBIVILI (E), DIST.THANE421203, MAHARASHTRA, INDIA,
India
3. Preamble to the description
The following specification particularly describes the invention and the manner in which it is to be performed
2
FIELD
The present disclosure relates to a process for the preparation of 2-amino-5-
chloro-N,3-dimethylbenzamide.
BACKGROUND
5 The background information herein below relates to the present disclosure but is
not necessarily prior art.
2-amino-5-chloro-N,3-dimethylbenzamide (I) is an important intermediate used in
the production of chlorantraniliprole.
10 2-amino-5-chloro-N,3-dimethylbenzamide
(I)
Chlorantraniliprole is a broad-spectrum anthranilic diamide insecticide. When
consumed by insects chlorantraniliprole interrupts the normal muscle contraction,
resulting in death.
15 Various methods for the preparation of 2-amino-5-chloro-N,3-dimethylbenzamide
compounds are known in the art. However, the conventionally known methods
provide the product in comparatively low yield and with low purity.
Therefore, there is felt a need to provide a process for the preparation of 2-amino5-chloro-N,3-dimethylbenzamide that mitigates the aforestated drawbacks.
20 OBJECTS
Some of the objects of the present disclosure, which at least one embodiment
herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the
prior art or to at least provide a useful alternative.
3
Another object of the present disclosure is to provide a process for the preparation
of 2-amino-5-chloro-N,3-dimethylbenzamide.
Yet another object of the present disclosure is to provide a process for the
preparation of 2-amino-5-chloro-N,3-dimethylbenzamide with a comparatively
5 better yield.
Still another object of the present disclosure is to provide a simple and costefficient process for the preparation of 2-amino-5-chloro-N,3-dimethylbenzamide.
Another object of the present disclosure is to provide an environment friendly and
commercially scalable process for the preparation of 2-amino-5-chloro-N,3-
10 dimethylbenzamide.
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
15 The present disclosure relates to a process for preparing 2-amino-5-chloro-N,3-
dimethylbenzamide. The process comprises mixing a predetermined amount of 6-
chloro-8-methylisatoic anhydride in at least one fluid medium to obtain a mixture.
Aqueous methylamine is slowly added to the mixture and reacting with 6-chloro8-methylisatoic anhydride under stirring at a temperature in the range of 20 °C to
20 40 °C for a first predetermined time period to obtain a reaction mass. The so
obtained reaction mass is equilibrated at a temperature in the range of 20 °C to 40
°C for a second predetermined time period to obtain a slurry. Further, optionally
water is added to the slurry, followed by filtration to obtain a wet cake and a
filtrate. The wet cake is dried to obtain 2-amino-5-chloro-N,3-
25 dimethylbenzamide.
DETAILED DESCRIPTION
Embodiments, of the present disclosure, will now be described herein.
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,
4
relating to specific components, and methods, to provide a complete
understanding of embodiments of the present disclosure. It will be apparent to the
person skilled in the art that the details provided in the embodiments should not be
construed to limit the scope of the present disclosure. In some embodiments, well5 known processes, well-known apparatus structures, and well-known techniques
are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of
explaining a particular embodiment and such terminology shall not be considered
to limit the scope of the present disclosure. As used in the present disclosure, the
10 forms "a,” "an," and "the" may be intended to include the plural forms as well,
unless the context clearly suggests otherwise. The terms "comprises,"
"comprising," “including,” and “having,” are open ended transitional phrases and
therefore specify the presence of stated features, integers, steps, operations,
elements, modules, units and/or components, but do not forbid the presence or
15 addition of one or more other features, integers, steps, operations, elements,
components, and/or groups thereof. The particular order of steps disclosed in the
method and process of the present disclosure is not to be construed as necessarily
requiring their performance as described or illustrated. It is also to be understood
that additional or alternative steps may be employed.
20 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
distinguish one element, component, region, layer or section from another
25 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.
2-amino-5-chloro-N,3-dimethylbenzamide (I) is an important intermediate used in
the production of Chlorantraniliprole. Chlorantraniliprole is a broad-spectrum
5
anthranilic diamide insecticide, which when consumed by insects, interrupts the
normal muscle contraction, resulting in death.
2-amino-5-chloro-N,3-dimethylbenzamide
5 (I)
Various methods for the preparation of 2-amino-5-chloro-N,3-dimethylbenzamide
compounds are reported in the art. However, the conventionally known methods
provide the product in comparatively low yield and with low purity.
The present disclosure provides an improved process for the preparation of 2-
10 amino-5-chloro-N,3-dimethylbenzamide.
The process of the present disclosure is simple, environment friendly, economical,
resulting in improved yields and higher purity. The process of the present
disclosure discloses a process for the preparation of 2-amino-5-chloro-N,3-
dimethylbenzamide (I):
15
2-amino-5-chloro-N,3-dimethylbenzamide
(I)
the process comprising the following steps:
a) mixing a predetermined amount of 6-chloro-8-methylisatoic
20 anhydride in at least one fluid medium to obtain a mixture;
b) adding slowly an aqueous methylamine to the mixture and reacting
with 6-chloro-8-methylisatoic anhydride under stirring at a
6
temperature in the range of 20 °C to 40 °C for a first predetermined
time period to obtain a reaction mass;
c) equilibrating the reaction mass at a temperature in the range of 20
°C to 40 °C for a second predetermined time period to obtain a
5 slurry;
d) filtering the slurry by optionally adding water, followed by
filtration to obtain a wet cake and a filtrate;
e) drying the wet cake to obtain 2-amino-5-chloro-N,3-
dimethylbenzamide.
10 The process is described in detail.
In a first step, a predetermined amount 6-chloro-8-methylisatoic anhydride is
mixed in at least one fluid medium to obtain a mixture.
In accordance with one embodiment, the fluid medium is selected from the group
consisting of aliphatic alcohols and aliphatic nitriles.
15 In accordance with an embodiment of the present disclosure, the aliphatic alcohol
is selected from the group consisting of isopropanol, methanol, ethanol, and npropanol. In an exemplary embodiment, the aliphatic alcohol is isopropanol.
In accordance with an embodiment of the present disclosure, the aliphatic alcohol
is in aqueous form. In an exemplary embodiment, the aliphatic alcohol is the
20 aqueous isopropanol.
In accordance with an embodiment of the present disclosure, the aliphatic nitrile is
acetonitrile.
In accordance with an embodiment of the present disclosure, the aliphatic nitrile is
in aqueous form. In an exemplary embodiment, the aliphatic nitrile is the aqueous
25 acetonitrile.
In an embodiment, the ratio 6-chloro-8-methylisatoic anhydride to the fluid
medium is in the range of 1:2 to 1:6 (w/v). In an exemplary embodiment of the
present disclosure, the predetermined amount of 6-chloro-8-methylisatoic
7
anhydride to the fluid medium is 1:4.6 (w/v). In another exemplary embodiment
of the present disclosure, the predetermined amount of 6-chloro-8-methylisatoic
anhydride to the fluid medium is 1:4.46 (w/v). In yet another exemplary
embodiment of the present disclosure, the predetermined amount of 6-chloro-8-
5 methylisatoic anhydride to the fluid medium is 1:2.29 (w/v). In still another
exemplary embodiment of the present disclosure, the predetermined amount of 6-
chloro-8-methylisatoic anhydride to the fluid medium is 1:4.35 (w/v).
In a second step, aqueous methylamine is slowly added to the mixture and reacted
with 6-chloro-8-methylisatoic anhydride present in the fluid medium under
10 stirring at a temperature in the range of 20 °C to 40 °C for a first predetermined
time period to obtain a reaction mass.
In accordance with an embodiment of the present disclosure, the first
predetermined time period is in the range of 10 minutes to 90 minutes. In an
exemplary embodiment of the present disclosure, the first predetermined time
15 period is 60 minutes. In another exemplary embodiment of the present disclosure,
the first predetermined time period is 45 minutes. In yet another exemplary
embodiment of the present disclosure, the first predetermined time period is 15
minutes.
In accordance with an embodiment of the present disclosure, a weight ratio of 6-
20 chloro-8-methylisatoic anhydride to aqueous methylamine is in the range of 1:0.3
to 1:0.6. In an exemplary embodiment of the present disclosure, the weight ratio
of 6-chloro-8-methylisatoic anhydride to aqueous methylamine is 1: 0.43. In an
exemplary embodiment of the present disclosure, the weight ratio of 6-chloro-8-
methylisatoic anhydride to aqueous methylamine is 1: 0.4.
25 In a third step, the reaction mass is equilibrated at a temperature in the range of 20
°C to 40 °C for a second predetermined time period to obtain a slurry.
In accordance with an embodiment of the present disclosure, the second
predetermined time period is in the range of 2 hrs to 5 hrs. In an exemplary
embodiment of the present disclosure, the second predetermined time period is 3.5
8
hrs. In another exemplary embodiment of the present disclosure, the second
predetermined time period is 3 hrs. In yet another exemplary embodiment of the
present disclosure, the second predetermined time period is 4 hrs.
In a fourth step, water is optionally added to the slurry, followed by filtration to
5 obtain a wet cake and a filtrate.
The wet cake is subjected to drying to obtain 2-amino-5-chloro-N,3-
dimethylbenzamide.
In an embodiment of the present disclosure, the filtrate is concentrated until the
water started distilling out to obtain a slurry. The slurry is filtered to obtain 2-
10 amino-5-chloro-N,3-dimethylbenzamide.
The process of the present disclosure uses aliphatic alcohol, preferably
isopropanol which is less expensive, thus making the process economic.
The aqueous isopropanol being a constant boiling azeotrope can be easily
separated, recovered, and recycled from the reaction process. Hence, the process
15 of the present disclosure is economic and environment friendly.
A schematic representation of the process for the preparation of 2-amino-5-
chloro-N,3-dimethylbenzamide is given as scheme A.
20
SCHEME A
The foregoing description of the embodiments has been provided for purposes of
illustration and not intended to limit the scope of the present disclosure. Individual
components of a particular embodiment are generally not limited to that particular
6-chloro-8-methylisatoic
anhydride
2-amino-5-chloro-N,3-
dimethylbenzamide
9
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
5 which are set forth for illustration purpose only and not to be construed for
limiting the scope of the disclosure. The following experiments are scalable to
industrial/commercial process.
EXPERIMENTAL DETAILS
Example 1:
10 76 gm of 6-chloro-8-methylisatoic anhydride was charged into a reactor
containing 350 ml of isopropanol to obtain a mixture in orange brown colour. To
the mixture, 33 gm of 40% aqueous methylamine was slowly added under stirring
over a period of 60 min by maintaining the reaction temperature at 28 °C to 30°C
to obtain a yellow coloured reaction mass. The reaction mass was equilibrated at
15 28 °C to 30°C for a period of 3.5 hrs to obtain a slurry.
The so obtained slurry was concentrated under vacuum, then diluted the
concentrated mass with 200 ml of water and equilibrated at 30°C for 30 min to
obtain a resultant mixture. The resultant mixture was filtered and washed with
water to obtain a wet cake. The so obtained wet cake was dried to obtain 2-amino20 5-chloro-N,3-dimethylbenzamide (65gms). The purity was 96% by HPLC and the
yield on purity was 89%.
Example 2:
56 gm of 6-chloro-8-methylisatoic anhydride was charged into a reactor
containing 250 ml of aqueous isopropanol (88:12 vol/vol) under stirring to obtain
25 a mixture in orange brown colour. To the mixture 24 gm of 40% aqueous
methylamine was slowly added under stirring over a period of 60 min by
maintaining the reaction temperature at 28 °C to 30 °C to obtain a yellow coloured
reaction mass. The reaction mass was equilibrated at 28 °C to 30°C for a time
period of 3 hrs to obtain a slurry.
10
The slurry was filtered and washed with water to obtain a filtrate and a wet cake.
The so obtained wet cake was dried to obtain 2-amino-5-chloro-N,3-
dimethylbenzamide.
The filtrate was concentrated and to the concentrated mass water was added to
5 get resultant mixture. The resultant mixture was filtered, washed with water and
suck dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. The combined
yield of 2-amino-5-chloro-N,3-dimethylbenzamide was 49 gm. The purity was
87% by HPLC and the yield on purity was 89%.
Example 3:
10 109 gms of 6-chloro-8-methylisatoic anhydride was charged into a reactor
containing 250 ml of aqueous acetonitrile (88:12 vol/vol) to obtain a mixture in
orange colour. To the mixture 47 gms of 40% aqueous methylamine was slowly
added under stirring over a period of 45 min by maintaining the reaction
temperature at 20 °C to 25 °C to obtain a yellow coloured reaction mass. The
15 reaction mass was equilibrated at 20 °C to 25°C for a time period of 4 hours to
obtain a slurry.
The slurry was filtered and washed with water to obtain a filtrate and a wet cake.
The so obtained wet cake was dried to obtain 2-amino-5-chloro-N,3-
dimethylbenzamide.
20 The filtrate was concentrated and to the concentrated mass water was added to
obtain resultant mixture. The resultant mixture was filtered, washed with water &
suck dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. The combined
yield of 2-amino-5-chloro-N,3-dimethylbenzamide was 91 gm. The purity was
87% by HPLC with yield on purity was 78%.
25 Example-4:
168 gms of 6-chloro-8-methylisatoic anhydride was charged into a reactor
containing 730 ml of isopropanol to obtain a mixture. To the mixture, 68 gms of
40% aqueous methylamine was slowly added under stirring over a period of 15
min by maintaining the reaction temperature at 25°C to 32°C to obtain a yellow
11
coloured reaction mass. The reaction mass was equilibrated at 25°C to 32°C for a
period of 3.5 hrs to obtain a slurry.
The slurry was filtered and washed with isopropanol to obtain a filtrate and a wet
cake. The so obtained wet cake was suck dried to obtain 2-amino-5-chloro-N,3-
5 dimethylbenzamide.
The filtrate was concentrated and to the concentrated mass water was added to
obtain resultant mixture. The resultant mixture was filtered, washed with water,
and suck dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. The
combined yield of 2-amino-5-chloro-N,3-dimethylbenzamide was 135 gm. The
10 purity was 92% by HPLC and the yield on purity was 79%.
Purification of 2-Amino-5-chloro-N,3-dimethylbenzamide:
250 ml of 0.5N NaOH solution was charged into a reactor and 135 gms of 2-
amino-5-chloro-N,3-dimethylbenzamide cake obtained from example-4 was
added to obtain stirrable slurry. The stirrable slurry was equilibrated at 25°C to
15 32°C for a period of 1 hr and filtered to obtain wet cake. The so obtained wet cake
was washed with water and dried to obtain 2-amino-5-chloro-N,3-
dimethylbenzamide (123 gms). The HPLC purity was 98%.
TECHNICAL ADVANCEMENT
20 The present disclosure described hereinabove has several technical advantages
including, but not limited to, the realization of a process for the preparation of 2-
amino-5-chloro-N,3-dimethylbenzamide, wherein:
 a simple and economical process for the preparation of 2-amino-5-chloroN,3-dimethylbenzamide;
25  the aqueous isopropanol (88:12 vol/vol) being a constant boiling
azeotrope, can be recycled thus reducing effluent load;
 the solvent recycling reduces the cost, also environment friendly;
 the cost of isopropanol is relatively less; and
12
 provides 2-amino-5-chloro-N,3-dimethylbenzamide having comparatively
high purity and in high yield.
The embodiments herein and the various features and advantageous details thereof
are explained with reference to the non-limiting embodiments in the following
5 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
10 should not be construed as limiting the scope of the embodiments herein.
The foregoing description of the specific embodiments so fully reveal the general
nature of the embodiments herein that others can, by applying current knowledge,
readily modify and/or adapt for various applications such specific embodiments
without departing from the generic concept, and, therefore, such adaptations and
15 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
20 recognize that the embodiments herein can be practiced with modification within
the spirit and scope of the embodiments as described herein.
The use of the expression “at least” or “at least one” suggests the use of one or
more elements or ingredients or quantities, as the use may be in the embodiment
of the invention to achieve one or more of the desired objects or results. While
25 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
30 within the spirit of this invention.
13
Any discussion of documents, acts, materials, devices, articles or the like that has
been included in this specification is solely for the purpose of providing a context
for the disclosure. It is not to be taken as an admission that any or all of these
matters form a part of the prior art base or were common general knowledge in the
5 field relevant to the disclosure as it existed anywhere before the priority date of
this application.
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
10 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
15 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.
14
WE CLAIM:
1. A process for preparing 2-amino-5-chloro-N,3-dimethylbenzamide
represented by formula (I):
5 2-amino-5-chloro-N,3-dimethylbenzamide
(I)
wherein said process comprising the following steps:
f) mixing a predetermined amount of 6-chloro-8-methylisatoic
anhydride in at least one fluid medium to obtain a mixture;
10 g) adding slowly an aqueous methylamine to said mixture and
reacting with 6-chloro-8-methylisatoic anhydride under stirring at a
temperature in the range of 20 °C to 40 °C for a first predetermined
time period to obtain a reaction mass;
h) equilibrating said reaction mass at a temperature in the range of 20
15 °C to 40 °C for a second predetermined time period to obtain a
slurry;
i) filtering said slurry by optionally adding water, followed by
filtration to obtain a wet cake and a filtrate;
j) drying said wet cake to obtain 2-amino-5-chloro-N,3-
20 dimethylbenzamide.
2. The process as claimed in claim 1, wherein said filtrate is subjected to
distillation to obtain 2-amino-5-chloro-N,3-dimethylbenzamide.
3. The process as claimed in claim 1, wherein said fluid medium is selected
from the group consisting of aliphatic alcohols and aliphatic nitrile.
15
4. The process as claimed in claim 3, wherein said aliphatic alcohol is
selected from the group consisting of isopropanol, methanol, ethanol, and
n-propanol.
5. The process as claimed in claim 3, wherein said aliphatic nitrile is
5 acetonitrile.
6. The process as claimed in claim 3, wherein said aliphatic alcohol is
aqueous aliphatic alcohol and said aliphatic nitrile is aqueous acetonitrile.
7. The process as claimed in claim 1, wherein said first predetermined time
period is in the range of 10 minutes to 90 minutes.
10 8. The process as claimed in claim 1, wherein said second predetermined
time period is in the range of 2 to 5 hrs.
9. The process as claimed in claim 1, wherein a weight ratio of said 6-chloro8-methylisatoic anhydride to said aqueous methylamine is in the range of
1:0.3 to 1:0.6.
15 10. The process as claimed in claim 1, wherein a ratio of said 6-chloro-8-
methylisatoic anhydride to said fluid medium is in the range of 1:2 to 1:6
(w/v).