Claims:WE CLAIM
1. A process for oxidative bromination of aromatic compounds, the process comprising:
• brominating the aromatic compounds using a brominating agent and an oxidizing agent at a temperature below 20°C to obtain a resultant comprising a crude brominated aromatic compound; and
• separating the crude brominated aromatic compound from the resultant to obtain the pure brominated aromatic compound with a yield of at least 92% and purity of at least 98%.
2. The process as claimed in claim 1, wherein the step of separating the crude brominated aromatic compound from the resultant comprises following steps:
• allowing the resultant to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer, separating the organic layer from the biphasic mixture to obtain the separated organic layer; and
• subjecting the separated organic layer to distillation to obtain the pure brominated aromatic compound.
3. The process as claimed in claim 1, wherein the brominating agent is at least one selected from the group consisting of hydrobromic acid, sodium bromide and combination thereof.
4. The process as claimed in claim 1, wherein the brominating agent is hydrobromic acid, wherein the concentration of hydrobromic acid is in the range of 40- 60%.
5. The process as claimed in claim 1, wherein the oxidizing agent is nitric acid (HNO3).
6. The process as claimed in claims 1 and 5, wherein the concentration of nitric acid is in the range of 30 to 80 wt%.
7. The process as claimed in claim 1, wherein the mole ratio of the aromatic compound to the brominating agent is in the range of 1: 0.5 to 1: 1.5.
8. The process as claimed in claim 1, wherein the mole ratio of the aromatic compound to the oxidizing agent is in the range of 1: 0.5 to 1: 2.0, preferably 1:0.9 to 1: 1.1.
9. The process as claimed in claim 1, wherein the aromatic compound is at least one selected from the group consisting of anisole, toluidine, nitro-aniline, derivatives of anisole, derivatives of toluidine, and derivatives of nitro-aniline.
10. The process as claimed in claim 1 comprising:
• brominating 3-methyl anisole using hydrobromic acid and nitric acid at a temperature below 20°C to obtain a resultant comprising a crude 4-bromo-3-methyl-anisole;
• allowing the resultant to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer, separating the organic layer from the biphasic mixture to obtain the separated organic layer comprising a crude 4-bromo-3-methyl-anisole; and
• subjecting the separated organic layer to distillation to obtain the pure comprising a crude 4-bromo-3-methyl-anisole with the yield of 92% and the purity of 98.8%.
, Description:FIELD
The present disclosure relates to a process for oxidative bromination of aromatic compounds.
BACKGROUND
Bromoaromatics form an important class of intermediates. Bromine is introduced into the aromatic ring to give desired properties to the final product, especially, to attain the required reactivity for further synthesis connected with exchange of bromine for various groups. Bromoaromatics can be converted efficiently into other functionality by simple chemical transformations, and therefore are widely used as intermediates in the manufacture of pharmaceuticals, agrochemicals and other specialty chemical products. Consequently varieties of methods for the bromination of aromatic compounds are reported.
Conventionally, bromination of aromatic compounds is typically carried out either in the vapor phase or in the liquid phase. The vapor phase bromination of aromatic compounds is a rapid reaction. However, it is observed that vapor phase reactions are highly exothermic and therefore need extreme care and control. In contrast, liquid phase bromination of aromatic compounds is safe but the rate of bromination is usually quite low, which further necessitates the use of catalysts. Further, conventional methods are also associated with drawbacks such as formation of undesired by-products, which are toxic and harmful to the environment.
There is, therefore, felt a need to provide a simple, economical and eco-friendly process for bromination of aromatic compounds.

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 is 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 oxidative bromination of aromatic compounds.
Another object of the present disclosure is to provide a simple and economical process for oxidative bromination of aromatic compounds.
Still another object of the present disclosure is to provide an eco-friendly process for oxidative bromination of aromatic compounds.
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
The present disclosure relates to a process for oxidative bromination of aromatic compounds.
The process of the present disclosure involves brominating the aromatic compounds using a brominating agent and an oxidizing at a temperature below 20 °C to obtain a resultant comprising a crude brominated aromatic compound, and separating the crude brominated aromatic compound from the resultant to obtain the pure brominated aromatic compound with a yield of at least 92% and a purity of at least 98%.
DETAILED DESCRIPTION
Brominated aromatic compounds are widely used as the building blocks for pharmaceuticals, and agrochemicals. However, conventional methods for bromination of the aromatic compounds are associated with drawbacks such as polybromination, disposal of toxic and corrosive by-products, multi-step reactions.
The present disclosure provides a simple, economical and eco-friendly process for bromination of aromatic compounds.
The aromatic compounds are brominated using a brominating agent and an oxidizing agent at a temperature below 20°C to obtain a resultant comprising a crude brominated aromatic compound.
In accordance with the process of the present disclosure, the bromination reaction is carried out at a temperature below 20°C. Further, the oxidizing agent is added to the mixture comprising aromatic compound and brominating agent in drop-wise manner, so as to maintain the temperature of the mixture below 20°C. It is observed that controlling the temperature below 20°C during this addition provides the brominated aromatic compound of high purity by limiting the formation of impurities.
After completion of the reaction (monitored by TLC), the resultant is allowed to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer is separated from the biphasic mixture. The separated organic layer is subjected to distillation to obtain a pure brominated compound.
In accordance with the process of the present disclosure, the separated organic layer is washed with aqueous caustic solution having pH in the range of 7 to 8, and dried over solid sodium sulphate to obtain a separated organic layer.
In accordance with the embodiments of the present disclosure, the aromatic compound is at least one selected from the group consisting of anisole, toluidine, nitro-aniline, derivatives of anisole, derivatives of toluidine, and derivatives of nitro-aniline.
In accordance with the embodiments of the present disclosure, the brominating agent is at least one selected from hydrobromic acid, sodium bromide and combinations thereof.
In accordance with an exemplary embodiment of the present disclosure, the brominating agent is hydrobromic acid having concentration in the range of 40- 60%.
In accordance with another exemplary embodiment of the present disclosure, the brominating agent is a combination of hydrobromic acid and sodium bromide.
In accordance with the embodiments of the present disclosure, the oxidizing agent is nitric acid (HNO3). The oxidizing agent can also be hydrogen peroxide (H2O2) or other oxygen containing compounds.
In accordance with the exemplary embodiments of the present disclosure, the oxidizing agent is dilute nitric acid, and the concentration of nitric acid is in the range of 30 to 80%, preferably 70 to 75%.
In accordance with the embodiments of the present disclosure, the mole ratio of the aromatic compound to the brominating agent is in the range of 1: 0.5 to 1: 1.5.
In accordance with the embodiments of the present disclosure, the mole ratio of the aromatic compound to oxidizing agent is in the range of 1: 0.5 to 1: 1.5, preferably 1: 0.9 to 1: 1.1.
The process of the present disclosure is characterized in that the brominated aromatic compounds are obtained with a yield of at least 92% and a purity of at least 98%.
In accordance with the exemplary embodiment of the present disclosure, the process comprises brominating 3-methyl anisole using hydrobromic acid and nitric acid at a temperature below 20°C to obtain a resultant comprising a crude 4-bromo-3-methyl-anisole. The resultant is allowed to settle to obtain a biphasic mixture comprising an organic layer and an aqueous layer. The organic layer is separated from the biphasic mixture to obtain the separated organic layer comprising a crude 4-bromo-3-methyl-anisole. The separated organic layer is subjected to distillation to obtain the pure comprising a crude 4-bromo-3-methyl-anisole with the yield of 92% and the purity of 98.8%.
The present disclosure provides simple single step process for bromination of the aromatic compounds. In accordance with the embodiments of the present disclosure, the organic layer comprising crude brominated product is washed with alkaline solution and the subjected to distillation to obtain pure brominated aromatic compound. No further step of purification is required as the brominated aromatic compound obtained has a greater than 98%. Further, the process of the present disclosure uses commonly available and inexpensive reagents. Furthermore, the process of the present disclosure is region-selective, thereby obviating polybromination of aromatic compounds. Overall, the present process has short reaction cycle and reduces production costs. Still further, the formation of toxic and hazardous by-products is substantially reduced, and therefore process is eco-friendly.
The present disclosure is further described in light of the following laboratory experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following laboratory scale examples can be scaled up to industrial/commercial scale.
Experimental details
General procedure: Bromination of aromatic compounds.
The reactor is charged with an aromatic compound and a brominating agent to obtain the mixture, followed by cooling the mixture to at a temperature below 20 °C. An oxidizing agent is added to the cooled mixture in a drop wise manner under stirring, so as to maintain the temperature of the mixture below 20 °C. The stirring is continued for a time period in the range of 2 hours to 8 hours to obtain a resultant containing a biphasic mixture comprising an organic layer and an aqueous layer.
The organic layer is separated from the biphasic mixture and washed with aqueous caustic solution having pH of 7, followed by drying over solid sodium sulphate. The dried organic layer is subjected to distillation to obtain pure brominated compound.
Experiment 1 to 3: Bromination of the different aromatic compounds
Experiments 1-3 were carried out following the general experimental procedure described herein above using different aromatic compounds. The aromatic compounds used were 3-methyl anisole, p-toluidine and p-nitro aniline.
The reactor was charged with an aromatic compound (1.0 mmol) and 48% aqueous hydrobromic acid (1.1 mmol) to obtain the mixture. The mixture was cooled to 15 °C and dilute HNO3 (0.98 mmol) was added under stirring in a drop wise manner. The stirring was continued for 3 hours to obtain a resultant containing a biphasic mixture comprising an organic layer and an aqueous layer.
The organic layer was separated from the biphasic mixture and washed with aqueous caustic solution having pH of 7, followed by drying over solid sodium sulphate. The dried organic layer was subjected to distillation to obtain pure brominated compound.
The results of bromination are given below in Table 1.
Table 1: Bromination of the different aromatic compounds
Sr. No. Aromatic compound used Yield
% Purity
% Impurity
%
1 3-methyl anisole 94 98.8 0.627
2 p-toluidine 95 98 0.5
3 p-nitro aniline 92 98 0.5

From table 1, it is evident that the process of the present disclosure works efficiently for activated aromatic compounds as well as deactivated aromatic compounds.
Experiment 4 to 6: Effect of the different brominating agent on the oxidative bromination reaction
Experiments 4-6 were carried out following the general experimental procedure described herein above using different brominating agents. The brominating agents used were liquid bromine, hydrobromic acid and combination of hydrobromic acid and sodium bromide.
The reactor was charged with 3-methyl anisole (1.0 mmol) and a brominating agent (1.1 eq) to obtain the mixture. The mixture was cooled to 15 °C and dilute HNO3 (0.98 eq) was added under stirring in a drop wise manner. The stirring was continued for 3 hours to obtain a resultant containing a biphasic mixture comprising an organic layer and an aqueous layer.
The organic layer was separated from the biphasic mixture and washed with aqueous caustic solution having pH of 7, followed by drying over solid sodium sulphate. The dried organic layer was subjected to distillation to obtain pure brominated compound.
The results of bromination are given below in Table 2.
Table 2: Effect of the different brominating agent on the oxidative bromination reaction

Sr. No. Brominating agent Yield
% Purity
% Impurity
%
1 Liq. bromine 76.4 12 88
2 Hydrobromic acid + sodium bromide 92 98.8 0.6
3 Hydrobromic acid 91.9 98.7 0.627

From table 2, it is evident that bromination using hydrobromic acid and combination of hydrobromic acid and sodium bromide is more effective as compared to bromination using liquid bromine.
Experiment 7 to 8: Effect of the different oxidizing agent on the oxidative bromination reaction
Experiments 7-8 were carried out following the general experimental procedure described herein above using different oxidizing agents. The oxidizing agents used were dilute nitric acid (HNO3) and hydrogen peroxide (H2O2).
The reactor was charged with 3-methyl anisole (1.0 mmol) and 48% hydrobromic acid (1.1 eq) to obtain the mixture. The mixture was cooled to 15 °C and an oxidizing agent (0.98 eq) was added under stirring in a drop wise manner. The stirring was continued for 3 hours to obtain a resultant containing a biphasic mixture comprising an organic layer and an aqueous layer.
The organic layer was separated from the biphasic mixture and washed with aqueous caustic solution having pH of 7, followed by drying over solid sodium sulphate. The dried organic layer was subjected to distillation to obtain pure brominated compound.
The results of bromination are given below in Table 3.
Table 3: Effect of the different oxidizing agent on the oxidative bromination reaction
Sr. No. Oxidizing agent Yield
% Purity
% Impurity
%
1 30% H2O2 76.4 12 88
2 dil. HNO3 91.9 98.7 0.627

From table 3, it is evident that the dilute nitric acid enhances the yield and purity of the brominated compound. Dilute nitric acid offers a dual function of oxidant as well as proton donor which is essential for oxidative bromination reaction.
Experiment 9 to 10: Effect of the ratio of oxidizing agent on the bromination reaction
Experiments 9-10 were carried out following the general experimental procedure described herein above varying the molar ratio of aromatic compound to oxidizing agent.
The reactor was charged with 3-methyl anisole (1.0 mmol) and 48% hydrobromic acid (1.1 eq) to obtain the mixture. The mixture was cooled to 15 °C and dil. HNO3 was added under stirring in a drop wise manner. The stirring was continued for 3 hours to obtain a resultant containing a biphasic mixture comprising an organic layer and an aqueous layer.
The organic layer was separated from the biphasic mixture and washed with aqueous caustic solution having pH of 7, followed by drying over solid sodium sulphate. The dried organic layer was subjected to distillation to obtain pure brominated compound.
The results of bromination are given below in Table 4.
Table 4: Effect of the ratio of oxidizing agent on the bromination reaction
Sr. No. Molar ratio of aromatic compound to dil. HNO3 Yield
% Purity
% Impurity
%
1 1.64 87.8 96 3.6
2 0.984 91.9 98.7 0.627

From table 4, it is evident that the optimum quantity of the dilute nitric acid enhances the yield and purity of the brominated compound.
Experiment 11 to 13: Effect of temperature on the bromination reaction
Experiments 11-13 were carried out following the general experimental procedure described herein above varying the temperature.
The reactor was charged with 3-methyl anisole (1.0 mmol) and 48% hydrobromic acid (1.1 eq) to obtain the mixture. Dil. HNO3 (0.98 eq) was added under stirring in a drop wise manner. The stirring was continued for 3 hours to obtain a resultant containing a biphasic mixture comprising an organic layer and an aqueous layer.
The organic layer was separated from the biphasic mixture and washed with aqueous caustic solution having pH of 7, followed by drying over solid sodium sulphate. The dried organic layer was subjected to distillation to obtain pure brominated compound.
The results of bromination are given below in Table 5.
Table 5: Effect of temperature on the bromination reaction
Sr. No. Temperature
°C Yield
% Purity
% Impurity
%
1 50 - 55 90.3 88.75 9.9
2 30 - 35 87.8 96 3.6
3 15 - 20 91.9 98.7 0.627

From table 5, it is evident that with decreasing temperature, the yield and the purity of the brominated product increase. Further, the step of cooling the mixture to a temperature in the range of 10 - 20 °C before addition of an oxidizing agent is essential for the process of the present disclosure, as it helps in limiting the formation of impurities.
TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of the process for bromination of aromatic compounds, that is:
- simple;
- eco-friendly;
- economical; and
- capable of providing the brominated aromatic compound with high yield and high purity.
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 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 embodiment of the invention to achieve one or more of the desired objects or results. While 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 within the spirit of this invention.
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 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 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.