The present invention provides an industrially advantageous and an improved process for preparation of fluorinated aromatic compounds of formula I,
R1
X
*1
Formula I wherein R1 is hydrogen or Ci- C6a.lkyla.ndX1 andX2 are For Br, provided thatX1 andX2 are not same.
BACKGROUND OF THE INVENTION
Fluorinated aromatic compounds are used as important intermediates for synthesizing the agrochemical and pharmaceutical products.
Fluorinated aromatic compounds are produced from corresponding aromatic amines, by conversion into a diazonium tetrafluoroborate salt which is then decomposed thermally to produce the fluoro compound using anhydrous hydrofluoric acid with subsequent heating to produce the corresponding fluoro compound.
Journal of Fluorine Chemistry 116 (2002), pages 173-179 discloses the process for the preparation of compound of formula I from 3-amino-4-bromotoluene using sodium tetrafluoroborate in the presence of hydrochloric acid.
Jingxi Shiyou Huagong 24 (2007), pages 39-43 discloses a process for the preparation of compound of formula I comprising the step of diazotization using tetrafluoroboric acid.
The methods discussed above involve use of acids and isolation of hazardous tetrafluoroborate salt which limits the commercial viability of the processes.

There was therefore a need to tackle the deficiencies which have been described and to develop an industrially favorable process for the preparation of fluorinated aromatic compound of formula I.
SUMMARY OF THE INVENTION
A first aspect of the present invention provides a process for the preparation of a compound of formula I,
R1



X
X1

2

Formula I wherein R1 is hydrogen or Ci- C6a.lkyla.ndX1 andX2 are For Br, provided thatX1 andX2 are not same, the process comprises the step of diazotization of a compound of formula II,
R1


•R3
R2
Formula II wherein R1 is hydrogen or Ci- C 6 alky I andR2 andR3 are Br or NH2, provided that R2 andR3 are not same, in the presence of Olah's reagent.
A second aspect of the present invention provides a process for preparation of compound of formula II,

R


'R R~ Formula II wherein R1 is hydrogen or Ci- C 6 alky I, R2, andR3 are Br or NH2, provided thatR2 andR3 are not same, the process comprises the step of reducing a compound of formula III,
R1



X4

Xo
Formula III wherein R1 is hydrogen or Ci- C 6 alky I andXs andX4 are Br or NO 2, provided that X3 andX4 are not same.
A third aspect of the present invention provides a process for the preparation of a compound of formula I,
R



X,
X,

Formula I wherein R1 is hydrogen or Ci- CealkylandX1 andX2 are For Br, provided thatX1 andX2 are not same, the process comprises the steps of:
a) reducing a compound of formula III,

R


X4 X3 Formula III wherein R1 is hydrogen or Ci- C 6 alky I andXs andX4 are Br or NO 2, provided that X3 andX4 are not same, to obtain a compound of formula II
R1


'R R~ Formula II wherein R1 is hydrogen or Ci- C 6 alky I andR2 andR3 are Br or NH2, provided that R2 andR3 are not same, b) diazotizing the compound of formula II in the presence of Olah's reagent to obtain compound of formula I.
A fourth aspect of the present invention provides a process for preparation of 3-fluoro-4-bromotoluene comprising the step of diazotization of 3-amino-4-bromotoluene in the presence of Olah's reagent.
A fifth aspect of the present invention provides a process for preparation of 3-fluoro-4-bromotoluene comprising the steps of
a) reducing 3-nitro-4-bromotoluene to obtain 3-amino-4-bromotoluene;
b) diazotizing 3-amino-4-bromotoluene in the presence of Olah's reagent to obtain 3-fluoro-4-bromotoluene.

DETAILED DESCRIPTION OF THE INVENTION
The present invention provides an improved and an industrially advantageous process for the preparation of compound of formula I.
Olah’s reagent is a nucleophilic fluorinating agent and it is a mixture of pyridine present in the range of 70% to 90% and hydrogen fluoride present in the range of 10% to 30%.
Diazotization refer to the nitrosation of compound of formula II with nitrous acid leads to formation of diazonium salts.
A first aspect of the present invention provides a process for the preparation of a compound of formula I,
R1
X
X1
Formula I wherein R1 is hydrogen or C1- C6 alkyl and X1 and X2 are F or Br, provided that X1 and X2 are not same, the process comprises the step of diazotization of a compound of formula II:
R1
X
\^R3
R2 Formula II wherein R1 is hydrogen or C1- C6 alkyl, R2, and R3 are Br or NH2, provided that R2 and R3 are not same,
in the presence of Olah’s reagent and a diazotization agent selected from the group consisting of sodium nitrite, potassium nitrite, nitrous anhydride, nitrous acid, a
6

nitrosyl halide to produce a corresponding diazoniumfluoride and decomposing said diazoniumfluuoride.
Diazotization reaction may be carried out in the absence of solvent.
In preferred embodiment, the compound of formula II is reacted with Olah’s reagent to obtain a reaction mixture and followed by reaction of the resulting mixture with diazotization agent to obtain corresponding diazoniumfluoride.
The diazotization reaction is carried out a temperature in the range of -10ºC to 10ºC and preferably -5ºC to 5 ºC.
After completion of the reaction, the resulting diazoniumfluoride is decomposed to obtain compound of formula I. The compound of formula I thus obtained is isolated from the reaction mixture.
The decomposition reaction is carried out at a temperature in the range of 20ºC to 130ºC.
The compound of formula I can be isolated by the techniques know in the art such as extraction, filtration and evaporation of solvent.
In general, the isolation of compound of formula I is done with extraction comprises the steps separation of organic layer followed by distillation or concentration of organic layer to obtain compound of formula I.
A second aspect of the present invention provides a process for preparation of compound of formula II,
R1
X
\^R3
R2 Formula II wherein R1 is hydrogen or C1- C6 alkyl and R2 and R3 are Br or NH2, provided that R2 and R3 are not same, the process comprises the step of reducing a compound of formula III,
7

R1
X
X3
Formula III wherein R1 is hydrogen or C1- C6 alkyl and X3 and X4 are Br or NO2, provided that X3 and X4 are not same.
The reduction of compound of formula III may be carried out using catalytic hydrogenation or in the presence of a reducing agent to give compound of formula II. The catalytic hydrogenation may be carried out using hydrogen in the presence of Palladium-on-carbon, Raney nickel, Rhodium on carbon, Ruthenium on carbon, Nickel on carbon and platinum on carbon or the like.
The concentration of the catalyst may vary from 1% to 10% loading on carbon.
The reducing agent may be selected from lithium aluminum hydride, zinc in aqueous ammonium chloride and iron in ammonium chloride or the like.
It is advantageous to use low concentration of the catalyst. Eventually, the use of low concentration of catalyst reduce the cost, make the process more economical thereof. The use of low concentration of catalyst increase the recovery of the catalyst by many folds.
Particularly, when 5% of Pd/C is used as a catalyst, then it is recycled for four folds as compare to 10% Pd/C.
Although, the concentration of the catalyst do not impact on the purity of the compound of formula II.
Optionally, water may be added in the reactor along with the metal catalyst.
In a preferred embodiment of this aspect of the invention the reduction is carried out using a mixture of iron and aqueous ammonium chloride.
8

The reduction reaction is carried out at a temperature in the range of 40ºC to 90ºC. The reduction reaction is carried out in the presence of solvent can be selected from hydrocarbon solvent, cyclic ethers, esters, alcohols and alike or mixture thereof.
The hydrocarbon solvent can be selected from aliphatic and aromatic hydrocarbons having carbon chain between C5-C12, such as toluene, hexane, heptane and alike or mixture thereof.
The cyclic ether solvent can be selected from tetrahydrofuran, 1,4 dioxane and alike or mixture thereof.
The ester solvent can be selected from ethyl acetate, methyl acetate and alike or mixture thereof.
The alcohol solvent can be selected from methanol, ethanol, isopropanol and alike or mixture thereof.
After completion of the reaction, the compound of formula II may be isolated from the reaction mixture by the techniques know in the art such as filtration, evaporation of solvent and solvent extraction.
A third aspect of the present invention provides a process for the preparation of a compound of formula I,
R1
X
X1
Formula I wherein R1 is hydrogen or C1- C6 alkyl and X1 and X2 are F or Br, provided that X1 and X2 are not same, the process comprises the step of:
a) reducing a compound of formula III,
9

R1
X
X3
Formula III wherein R1 is hydrogen or C1- C6 alkyl and X3 and X4 are Br or NO2, provided that X3 and X4 are not same, to obtain a compound of formula II
R1
X
\^R3
R2 Formula II wherein R1 is Hydrogen or C1- C6 alkyl and R2 and R3 are Br or NH2, provided that R2 and R3 are not same, b) diazotizing of the compound of formula II in the presence of Olah’s reagent.
A fourth aspect of the present invention provides a process for preparation of 3-fluoro-4-bromotoluene comprising the step of diazotization of 3-amino-4-bromotoluene in the presence of Olah’s reagent.
A fifth aspect of the present invention provides a process for preparation of 3-fluoro-4-bromotoluene comprising the step of
a) reducing 3-nitro-4-bromotoluene to obtain 3-amino-4-bromotoluene;
b) diazotization of 3-amino-4-bromotoluene in the presence of Olah’s reagent to obtain 3-fluoro-4-bromotoluene.
10

The compound of formula III may be prepared on an industrial scale by any methods known in the art or particularly prepared by acylating para-toluidine followed by the steps nitration, acid or base hydrolysis and bromination. The intermediates used in the preparation of compound of formula III can be carried forward in-situ or can be isolated.
The compound of formula III is converted into compound of formula I by the method as described above; comprises reduction of compound of formula III to give compound of formula II and followed by diazotization in the presence of Olah’s reagent to obtain compound of formula I.
The completion of the reaction can be monitored by any one of chromatographic techniques such as thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), Gas chromatography (GC) and alike.
Purity of the final compound and intermediates may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, extraction, distillation, slurry wash, acid or base treatment, solvent-anti solvent system, crystallization, recrystallization or combination of these procedures.
The compound of formula I, prepared by the process of the present invention, may be used as a key intermediate for preparing agrochemical and pharmaceutical products.
It is against this and other backgrounds, which shall be filed in a detailed manner in complete specifications, in due course, the present invention is brought out and explained in following non-limiting examples.
Examples Example 1: Process for the preparation of 3-fluoro-4-bromotoluene Step 1: Process for preparation of 4-methylacetanilide
Acetyl chloride (190.4g) was slowly added to a mixture of p-toluidine (200g) and aqueous sodium hydroxide (20%) in dichloromethane (925 ml) at 30°C in 90 minutes. The reaction mixture was allowed to warm to 35ºC and stirred at the same
11

temperature for 60 minutes. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). After the completion of the reaction, the reaction mixture was cooled to 5°C and filtered to obtain a solid mass. The solid mass was washed with water, filtered and suck dried to obtain 257g of 4-methylacetanilide. Yield: 92.5%; Purity: 99.98%
Step 2: Process for preparation of 3-nitro-4-aminotoluene
An aqueous solution of sulfuric acid (95 ml; 98%) and nitric acid (125 ml; 50%) was added to a solution of 4-methylacetanilide (149.19 g) in dichloromethane (710 ml) at 10°C. The reaction mixture was at a temperature of 30°C for 45 minutes. The progress of the reaction was monitored by HPLC. After completion of the reaction, the reaction mixture was quenched with water (270 ml). The layers were separated and the aqueous layer was extracted with dichloromethane (210.ml). The organic layers were combined and washed with aqueous solution of sodium bicarbonate (938 ml; 6%). The organic layer was concentrated to obtain a reaction mass. Toluene (857 ml) was added to the reaction mass to obtain a reaction mixture. An aqueous solution of sodium hydroxide (265 ml; 20%) was slowly added to the reaction mixture. The progress of the reaction was monitored by HPLC After completion of the reaction, the reaction mixture was cooled to 10°C to obtain a reaction mass. The reaction mass was filtered, washed with water and dried to obtain 65g of 3-nitro-4-aminotoluene. Yield: 73.5%; and Purity: 99.98%
Step 2 (Alternate process): Process for preparation of 3-nitro-4-bromotoluene An aqueous solution of sulfuric acid (32 ml; 98%) and nitric acid (42 ml; 50%) was added to a solution of 4-methylacetanilide (50g) in dichloromethane (235 ml) at 10°C. The reaction mixture was stirred at a temperature of 30°C for 45 minutes. The progress of the reaction was monitored by HPLC. After completion of the reaction, the reaction mixture was quenched with water. The layers were separated and the organic layer was washed with 6% bicarbonate solution. To the resulting
12

reaction mixture, 60.5 ml of sulfuric acid was added and was heated to 70ºC for 2 hours. The reaction mixture was then cooled to 5º C. A solution of sodium nitrite (108 ml, 20%) was added to the reaction mixture and stirred at the same temperature for 30 minutes. The reaction mixture was added to a solution of copper bromide (1.88 g) and hydrogen bromide (36 ml; 47 %) and heated at 50°C. After completion of the addition, the reaction mixture was cooled to 30ºC. The reaction mixture was allowed to settle and layers were separated. The organic layer was washed subsequently with a solution of sodium bisulfite (160 ml 15%) and a solution of sodium bicarbonate (120 ml 5%). The organic layers were combined and concentrated completely to obtain 51g of 3-nitro-4-bromotoluene containing about 13% 3-nitro-4-bromo benzyl bromide and taken as such to the next step without purification.
Step 3: Process for preparation of 3-amino-4-bromotoluene
Palladium on carbon (5g; 5%) was added to a solution of 3-nitro-4-bromotoluene (50g) in toluene (608 ml). The hydrogen gas was pressurized to 16Kg/Cm2 and the reaction mixture was heated to 50°C for 12 hours till the pressure come down to 4 Kg/cm2. The progress of the reaction was monitored by HPLC. After completion of the reaction, the reaction mixture was cooled to 30°C and vented off excess hydrogen.. The reaction mixture was filtered to recover the catalyst. The filtrate was concentrated to give 38g of 3-amino-4-bromotoluene and the product is taken as such to the next step without purification. Yield: 80.5%; Purity: 91.8%
Step 3 (Alternate process): Process for preparation of 3-amino-4-bromotoluene An aqueous solution of ammonium chloride (133.ml; 20 %) was added to a mixture of 3-nitro-4-bromotoluene (50g) and iron (77.5g) in ethanol (427 ml) at 80°C and progress of the reaction was monitored by HPLC. After, completion of the reaction, the reaction mixture was cooled to a temperature of 30°C. The reaction mixture was filtered and the filtrate was concentrated to give biphasic reaction mixture. Dichloromethane (83.3 ml) was added to the biphasic reaction mixture and layers
13

were separated. Aqueous layer was extracted with dichloromethane and layers were
separated. The organic layers were combined and concentrated to obtain 38.0g
(88%) of crude 3-amino-4-bromotoluene
HPLC Purity: 90.8%; Meta-toluidine: 2.1% and Impurity at 23.3 RT: 3.5%
GC Purity: 94.5% and Meta-toluidine: 2.0%
The crude 3-amino-4-bromotoluene was purified by steam distillation to give 34.0g
of 3-amino-4-bromotoluene.
Yield: 76%; HPLC Purity: 98.5%; Meta-toluidine: 1.1%
GC Purity: 98.6% and Meta-toluidine: 1.2%
Step 4: Process for preparation of Olah’s reagent
Pyridine (215g) was taken in the reactor. To this anhydrous hydrogen fluoride (460ml) was added at a temperature of -50ºC under inert atmosphere. Once the addition was over, the reaction mixture was allowed to warm to a temperature of 30ºC. The reagent was kept under inert atmosphere and analyzed for hydrogen fluoride content. Process for preparation of 3-fluoro-4-bromotoluene
3-Amino-4-bromotoluene (120g) was slowly added to Olah’s reagent (396g, 12.9 mole as hydrogen fluoride) at a temperature of -2°C for 45 minutes and stirred at 0°C to 5°C for an hour .To this 53 g of sodium nitrite was added over a period of 2 hours in about 15 to 20 lots to control exothermicity and once this addition was completed, the reaction mass was stirred for further one hour to obtain a homogenous clear solution. The solution was transferred to autoclave and stirred at 30°C. The reaction mixture was stirred at a temperature of 105°C for 30 minutes, pressure reaches 10Kg and then cooled the reaction mass to 50°C and slowly vented off the nitrogen. After completing nitrogen venting, the biphasic mixture was separated and the upper pyridine-hydrogen fluoride layer was extracted with pentane (2 x 200g). The organic layers were combined and neutralized with an
14

aqueous solution of sodium bicarbonate (600ml; 5%) followed by washing with sodium hydroxide (10%) solution. The organic layer was fractionated under reduced pressure. Purity: 99.01% by GC Yield: 70%
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention and specific examples provided herein without departing from the spirit and scope of the invention. Thus, it is intended that the present invention covers the modifications and variations of this invention that come within the scope of any claims and their equivalents.

We Claim:

A process for the preparation of a compound of formula I,
.1
R



X2
X1

Formula I wherein R1 is hydrogen or Ci- C6a.lkyla.ndX1 andX2 are F or Br, provided thatX1 andX2 are not same, the process comprises the step of diazotization of a compound of formula II:
R1


•R3
R2
Formula II wherein R1 is hydrogen or Ci- C 6 alky I, R2, andR3 are Br or NH2, provided that R2 andR3 are not same,
in the presence of Olah's reagent and a diazotization agent selected from the group consisting of sodium nitrite, potassium nitrite, nitrous anhydride, nitrous acid and nitrosyl halide to produce a corresponding diazoniumfluoride and decomposing said diazoniumfluoride.
2. The process as claimed in claim 1, wherein, Olah's reagent is a mixture of pyridine present in the range of 70% to 90% and hydrogen fluoride present in the range of 10% to 30%.
3. The process as claimed in claim 1, wherein, diazotization reaction is carried out in absence of a solvent.

4. The process as claimed in claim 1, wherein, diazotization reaction is carried out at a temperature selected in the range of -10°C to 10°C.
5. The process as claimed in claim 1, wherein, diazoniumfluoride is decomposed at a temperature selected in the range of 20°C to 130°C.
6. A process for preparation of a compound of formula II,
R1


■R3
R2
Formula II wherein R1 is hydrogen or Ci- C6 alky I andR2 andR3 are Br or NH2, provided that R2andR3 are not same, the process comprises the step of reducing a compound of formula III,
R1


X4 X3 Formula III wherein R1 is hydrogen or Ci- C 6 alky I andXs andX4 are Br or NO 2, provided that X3 andX4 are not same.
7. The process as claimed in claim 6, wherein, reduction is carried out using catalytic hydrogenation or reducing agent at a temperature in the range of 40°C to 90°C.
8. The process as claimed in claim 7, wherein, catalytic hydrogenation is carried out using hydrogen in the presence of Palladium-on-carbon, Raney nickel, Rhodium on carbon, Ruthenium on carbon, Nickel on carbon and platinum on carbon.

9. The process as claimed in claim 7, wherein, reducing agent is selected from
lithium aluminum hydride, zinc in aqueous ammonium chloride and iron in
ammonium chloride or a mixture thereof.
10. A process for the preparation of a compound of formula I,
R1



X2

*1
Formula I wherein R1 is hydrogen or Ci- C6a.lkyla.ndX1 andX2 are For Br, provided thatX1 andX2 are not same, the process comprises the step of:
a) reducing a compound of formula III,
R1



X4

X3
Formula III wherein R1 is hydrogen or Ci- C 6 alky I andXs andX4 are Br or NO 2, provided that X3 andX4 are not same,
to obtain a compound of formula II
j
R


■R3
R2 Formula II

wherein R is Hydrogen or Ci- C 6 alky I andR andR are Br or NH2, provided that R2 andR3 are not same,
b) diazotizing of the compound of formula II in the presence of Olah's reagent to obtain compound of formula I, and
c) isolating the compound of formula I.