PROCESS FOR THE PREPARATION OF 5-HALO BENZONITRILES
Field of the invention
The present invention provides a process for the preparation of 5-halo
benzonitriles.
Background of the invention
Halo benzonitrile compounds of Formula I are employed as intermediates in the
synthesis of pesticides, pharmaceuticals and dyes. Thus, these intermediates have
great commercial value.
CN
X
Y
Formula I
where X and Y are independently selected from fluorine, chlorine,
bromine and iodine.
The recent CN Patent Application No. 101898976 describes a process for the
preparation of 2-fluoro-5-bromo benzonitrile by treating o-fluoro benzonitrile
with N-bromosuccinimide in the presence of sulphuric acid. The 2-fluoro-5-
bromo benzonitrile, so obtained, is further purified by re-crystallization with
absolute ethanol. The art is silent about the purity of re-crystallized product.
The present inventors, while working on present invention, observed that reaction
of o-fluoro benzonitrile with N-bromosuccinimide in the presence of sulphuric
acid did not complete even after 12 hours. Further, it was observed by the present
inventors that bromination as per the process disclosed in ‘976 yielded both 2-
fluoro-5-bromo benzonitrile and 2-fluoro-3-bromo benzonitrile. Such synthesis,
with respect to what is known in the prior art, is apparently advantageous in that
it requires few steps and reagents. However, the conversion rates and selectivity
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towards the preparation of 2-fluoro-5-bromo benzonitrile in CN Patent
Application No. 101898976 is not reproducible.
Such non-reproducible results and yield is unsatisfactory in terms of industrial
application, and it is essentially due to these reasons, there still arises the need for
providing an efficient as well as economic methods that can be used at industrial
scale for the synthesis of compound of Formula I.
Object of the invention
An object of the invention is to provide a process for the preparation of 5-halo
benzonitriles compound of Formula I
CN
X
Y
Formula I
where X and Y are independently selected from fluorine, chlorine,
bromine and iodine.
Summary of the invention
The present invention provides a process for the preparation of compound of
Formula I comprising;
CN
X
Y
Formula I
where X and Y are independently selected from fluorine, chlorine,
bromine and iodine.
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a) treating compound of Formula II with compound of Formula III in the
presence of catalyst, and
CN
X
Formula II
N
O
O
Y
Formula III
where X and Y are independently selected from fluorine, chlorine, bromine
and iodine.
b) isolating the compound of Formula I.
Detailed description of the invention
In an aspect, the present invention provides a process for the preparation of
compound of Formula I comprising;
CN
X
Y
Formula I
where X and Y are independently selected from fluorine, chlorine,
bromine and iodine.
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a) treating compound of Formula II with compound of Formula III in the
presence of catalyst,and
CN
X
Formula II
N
O
O
Y
Formula III
where X and Y are independently selected from fluorine, chlorine, bromine
and iodine.
b) isolating the compound of Formula I.
The compounds of Formula II and Formula III are obtainable by known
processes or commercially available. The reaction of compound of Formula II
and compound of Formula III takes place in the presence of catalyst. The catalyst
is selected from alkali metal halide, iodine and alkaline metal halide or mixture
thereof. The alkali metal halide may be selected from lithium iodide, sodium
iodide, potassium iodide and caesium iodide or mixture thereof. The alkaline
metal halide may be cuprous iodide. The reaction of compound of Formula II and
compound of Formula III may take place at a temperature of about -10oC to about
100oC, for example, about 0oC to about 40oC for about 10 minutes to about 4
hours, for example, for about 1 hour to about 3 hours. The reaction of compound
of Formula II and compound of Formula III may take place in the presence of
organic solvent. The reaction may be facilitated by stirring the reaction mixture.
The compound of Formula I is isolated from the reaction mixture by layer
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separation, distillation, filtration, evaporation, crystallization and decantation or mixture thereof. The compound of Formula I, obtained by present invention, has the purity greater than about 95%, preferably greater than 96% by High Performance Liquid Chromatography.
The present invention process for the preparation of compound of Formula I has regioselectivity of greater than 97% by HPLC.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Examples
Preparation of 2-fluoro-5-bromobenzonitrile
Sulphuric acid (31 g), 2-fluorobenzonitrile (5 g) and potassium iodide (5 mg) were taken in a reaction vessel. The temperature was maintained at 0oC-5oC. TheN-bromosuccinimidewas added in a lot wise addition over a period of 1 hour. The reaction mixture was stirred for 2 hours to 3 hours. The solid obtained was filtered and washed with water to obtain title compound.
Yield (%): 90.9
Purity (%): 97.2
Comparative example
Preparation of 2-fluoro-5-bromobenzonitrile
Sulphuric acid (31 g) and 2-fluorobenzonitrile (5 g) were taken in a reaction vessel. The temperature was maintained at 0oC-5oC. The N-bromosuccinimidewas added in a lot wise addition over a period of 1 hour. The reaction mixture was stirred for 12 hours. The reaction was found to be incomplete.
The 2-fluorobenzonitrile (34%) was present even after 12 hours.

We claim:
1. A process for the preparation of compound of Formula I comprising;
CN
X
Y
Formula I
where X and Y are independently selected from fluorine, chlorine,
bromine and iodine.
a) treating compound of Formula II with compound of Formula III in the
presence of catalyst, and
CN
X
Formula II
N
O
O
Y
Formula III
where X and Y are independently selected from fluorine, chlorine, bromine
and iodine.
b) isolating the compound of Formula I.
2. The process of claim 1, whereinthe catalyst is selected from alkali metal
halide, iodine and alkaline metal halide or mixture thereof.
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3. The process of claim 2, wherein the alkali metal halide is selected from lithium iodide, sodium iodide, potassium iodide and caesium iodide or mixture thereof.
4. The process of claim 2, wherein the alkaline metal halide may be cuprous iodide.
5. The process of claim 1, wherein step a) takes place at a temperature in the range of -10oC to 100oC.
6. The process of claim 1, wherein the compound of Formula I is isolated from step a) reaction mixture by layer separation, distillation, filtration, evaporation, crystallization and decantation or mixture thereof.
7. The process of claim 1, wherein the compound of Formula I, obtained by present invention, has the purity greater than about 97%.