Field of the invention
The present invention provides a process for the preparation of 1-bromo-2,4,5-trifluoro benzene of Formula I.
Background of the invention
The 1-bromo-2,4,5-trifluoro benzene is an important intermediate used in organic synthesis, and in the field of pharmaceuticals and agrochemicals. Particularly, it is a useful intermediate for the preparation of broad-spectrum antimicrobial quinolones.
The Chinese Patent No.101168495 discloses a process for preparation of 1-bromine-2, 4, 5-trifluoro benzene which comprises reacting 1, 2, 4-trifluoro-benzene with iron powder in presence of an organic solvent such as chloroform or carbon tetrachloride followed by addition of bromine at a temperature 43℃ to 48℃ for 4 h and azobisisobutyronitrile at a temperature 62°C to 68°C. The reaction mixture is heated to 82°C to 102°C. The disclosed process is impractically tedious involving numerous steps and thus has a low yield of 70%. The disclosed process additionally involves chlorinated solvents, thus, making it unsuitable for large scale industrial productions.
The present invention provides a process for the preparation of 1-bromo-2,4,5-trifluoro benzene which is environmental friendly and solvent free and is carried out without the use of chlorinated solvents. Further, the process of the present invention is carried out in the absence of radical initiator such as azobisisobutyronitrile. The current invention is simple, economically viable and industrially doable.
Summary of the invention
The present invention provides a process for the preparation of 1-bromo-2,4,5-trifluoro benzene of Formula I comprising; 2
a) reacting source of bromine with 1,2,4-trifluorobenzene of Formula II in the
presence of iron catalyst,
b) contacting step a) reaction mixture with sodium bisulphite to obtain 1-bromo-
2,4,5-trifluoro benzene of Formula I, and
c) isolating 1-bromo-2,4,5-trifluoro benzene of Formula I from step b) reaction
mixture; wherein step a) is carried out in the absence of radical initiator.
F
F
Br
F
Formula I
F
F
F
Formula II
Detailed description of the invention
In an aspect, the present invention provides a process for the preparation of 1-bromo-2,4,5-
trifluoro benzene of Formula I comprising;
a) reacting source of bromine with 1,2,4-trifluorobenzene of Formula II in the
presence of iron catalyst,
b) contacting step a) reaction mixture with sodium bisulphite to obtain 1-bromo-
2,4,5-trifluoro benzene of Formula I, and
c) isolating 1-bromo-2,4,5-trifluorobenzene of Formula I from step b) reaction
mixture; wherein step a) is carried out in the absence of radical initiator.
3
F
F
Br
F
Formula I
F
F
F
Formula II
The 1,2,4-trifluorobenzene of Formula II may be prepared by methods disclosed in the prior
art or may be obtained from commercial source e.g. Oakwood Chemicals.
The catalyst is selected from iron powder and ferric chloride. The source of bromine may be
in gaseous form or liquid form.
The reaction of source of bromine with 1,2,4-trifluorobenzene of Formula II in the presence
of iron catalyst may be carried out at a temperature in the range of about 5oC to about 100oC,
preferably, about 35oC to about 60oC.
The reaction mixture in step a) may be stirred to aid the reaction. The reaction in step a) may
take place for about 5 minutes to about 6 h, preferably, about 1 h to about 4 h.
The isolation of 1-bromo-2,4,5-trifluoro benzene from step b) is carried out by crystallization,
re-crystallization, distillation, evaporation and decantation or mixture thereof.
The term ‘about’ refers to variation of 10% on the higher and lower side of specified
parameter.
4
The following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.
Examples
Example 1: Preparation of 1-bromo-2,4,5-trifluoro benzene
1,2,4-trifluorobenzene (80g, 0.6 mol) was added to iron catalyst (0.06mol) at room temperature into a 250ml round bottom flask. The reaction mixture was heated to 45°C and bromine (150g, 0.93 mol) was added using an addition funnel for 2 h. The reaction progress was monitored after 30 minutes of complete bromine addition. The reaction mixture was poured while stirring into 40% aqueous sodium bisulphite solution. The organic layer and the aqueous layer were separated. The aqueous layer was washed with dichloromethane. The organic layer and the aqueous layer were again separated. The organic layer was concentrated and dried to obtain the title compound.

We Claim:
1. A process for the preparation of 1-bromo-2,4,5-trifluoro benzene of Formula I
comprising;
a) reacting source of bromine with 1,2,4-trifluorobenzene of Formula II in the
presence of iron catalyst,
b) contacting step a) reaction mixture with sodium bisulphite to obtain 1-bromo-
2,4,5-trifluoro benzene of Formula I, and
c) isolating 1-bromo-2,4,5-trifluorobenzene of Formula I from step b) reaction
mixture; wherein step a) is carried out in the absence of radical initiator.
F
F
Br
F
Formula I
F
F
F
Formula II
2. The process of claim 1, wherein the iron catalyst in step a) is selected from iron
powder and ferric chloride.
3. The process of claim 1, wherein the source of bromine may be in gaseous form or
liquid form.
4. The process of claim 1, wherein step a) is carried out at a temperature in the range of
35oC to 60oC.
5. The process of claim 1, wherein step c) is carried out by crystallization, recrystallization,
distillation, evaporation and decantation or mixture thereof.