FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL/COMPLETE SPECIFICATION
(See section 10 and rule 13)
AN IMPROVED PROCESS FOR THE PREPARATION OF
CARBAMAZEPINE
AMOLI ORGANICS PVT. LTD.,
A company incorporated under the companies' act, 1956, whose address is 407-DALAMAL HOUSE, J.B.ROAD, NARIMAN POINT, MUMBAI-400021,
INDIA.

AN IMPROVED PROCESS FOR THE PREPARATION OF
CARBAMAZEPINE
FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of 5H-dibenz(b,f)azepine-5-carboxamide, also known by the generic name carbamazepine. Further covers purification comprising the compound obtained by this process.
BACKGROUND OF THE INVENTION
Carbamazepine is chemically known as 5H-dibenz(b,f)azepine-5-carboxamide and represented by the following structural formula:

Carbamazepine is commercially available as Tegretol®, which was approved by the United States Food and Drug Administration for use as an anticonvulsant drug. It is a valuable agent for treating patients suffering from partial seizures,generalized tonic-clonic seizures orMixed seizure patterns.Tegretol® is indicated in the treatment of the pain associated with true trigeminal neuralgia.
Carbamazepine is commercially available in the US under the brand name Tegretol® as chewable tablets of 100 mg, tablets of 200 mg, XR tablets of 100, 200, and 400 mg, and as a suspension of 100 mg/5 mL(teaspoon), Carbamazepine is also approved by the USFDA as extended release capsules of strengths of 100, 200, 300 mg and is sold under the brand names of Carbatrol® and Equetro®.

Many processes for preparation of carbamazepine are known for example US Patent No.2948718, discloses reacting iminostilbene with phosgene to produce 5H-dibenz (b,f)azepine-5-carboxylic acid chloride, followed by the addition of ammonia.
GB1246606 discloses preparation of carbamazepine using 10, 11-dihydro-5H-dibenz(b,f)azepine with phosgene, l,3-dibromo-5,5-dimethylhydantoin,then potassium carbonate, and ammonia.
Another method for the production of carbamazepine is known from German published patent application DE2307174 by the reaction of iminostilbene with an acylisocyanate to produce 5H-dibenz(b,f)azepin-5-(N-acyl)-carboxamide followed by hydrolysis.
German published patent application DE2637666 discloses the reaction of 5-(methylisothiocarbamoyl)-5H-dibenzb.fazepine-hydroiodidewith a base.
The processes for the preparation of carbamazepine described in the prior art, discussed above suffer from various disadvantages, such as tedious and cumbersome work-up procedures, use of not so environment friendly solvents or reagents, reactions under pressure and high temperature, longer reaction times, column chromatographic purifications and thus resulting in low overall yields of the product.
The process of present application is simple, cost effective, environment friendlyand industrially viable which uses readily available reagents and solvents for the preparation of carbamazepine.
SUMMARY OF THE INVENTION

It is the principal aspect of the present invention is to provide an improved process for the preparation of carbamazepine wherein, compound of Formula-1 is reacted with ammoniain presence of solvent to give Carbamazepine with better yield and quality.

Wherein X is Cl, Br or I
In an embodiment, the present invention provides an improved process for the preparation of carbamazepine comprising
a) Reacting compound of Formula-1 with ammonia source in presence of a
suitable solvent.

Wherein X is Cl, Br or I
b) isolating carbamazepine
c) optionally slurring in a solvent and isolating the solid
d) optionally recrystallizing in a suitable solvent or solvent mixture.
In generalaspect, the present invention involves reacting 5H-dibenzo [b,f]azepine-5-carbonyl chloride with ammoniain presence of MIBK, followed by isolation, then addition of water that gives crude carbamazepine which is further purified and recrystallized usingactivated carbon in presence of acetone: watermixture and dried under vacuum.
In another general aspect, there is provided carbamazepine having a purity of at least about 99% by area percentage of HPLC.

DETAILED DESCRIPTIONOF THE INVENTION
The present invention is to provide an improved process for the preparation of Carbamazepine comprising:
a) reactingcompound of Formula-1 withammonia source in presence of a suitable
solvent

whereinX is Cl, Br or I
b) isolating carbamazepine
c) optionally slurring in a solvent and isolating the solid d)optionally recrystallizing and a suitable solvent or solvent mixture.
Suitable solvent that can be employed in step a) may be selected from ketones, alcohols, water or mixtures thereof, preferably ketones more preferably Methyl Iso Butyl Ketone or acetone.
Source of ammonia that can be employed in step a) may be selected from ammonia gas, ammonium chloride,ammonium carbonate,ammonium hydroxide,Liquid ammonia thereof, preferably liquid ammonia or ammonia gas.
The % of liquid ammonia can range from 15-50%, preferably 20-30%.
Suitable temperatures at which step a) can be employed isbetween 30-90°C, preferably between 50-70°C, more preferably 60-70°C.
Suitable temperatures at which step b) can be employed may be between 0-30°C, preferably between 5-15°C.
HPLC purity of isolated carbamazepine in step-b) is greater than 98.5%, preferably greater than 99.0%, more preferably greater than 99.5%.

Suitable solvent that can be employed in step c) is water.
Suitable temperatures at which step c)can be employed may be between 35-65°C, preferably between 55-65°C, more preferablybetween 60-65°C.
HPLC purity of isolated carbamazepine in step c) is greater than 99.0%, preferably greater than 99.5%, more preferably greater than 99.8%.
Suitable solvent that can be employed in step d) may be selected from ketones, alcohols, water or mixtures thereof, preferably ketones water mixture, more preferably acetone:water mixture.
Suitable temperatures at which step d) can be employed may be between 35-60°C, preferably between 45-60°C, more preferably between 55-60°C.
Suitable temperatures at which pure solid carbamazepine is isolated in step d) may be between 0-30°C, preferably between 0-10°C, more preferably between 0-5°C.
HPLC purity of isolated carbamazepine in step d) is greater than 99.90%, preferably greater than 99.9%.
The present invention is commercially viable, cost effective, easy solvent recovery and easy to scale up at large scales.
The following non-limiting examples illustrate specific embodiments of the present invention, whichshould not be construed as limiting the scope of present invention in any way.
EXAMPLES Example. 1: Preparation of crude Carbamazepine:
To a reaction flask with 5H-dibenzo[b,f]azepine-5-carbonyl chloride(100gms),acetone (200 ml) was added and stirred at 15-20°C. To this mixture slowly ammonia gas was purgedby maintaining temperature 18°C for 2.5 hours. After completion of the reaction the reaction mixture was subjected to atmospheric distillation to remove acetone completely below 60°C.Water-lot-

1(500ml) was added and stirred for 1 hour at 55°C.The solid was filtered and washedwith 100 ml of preheated water and suck dried. The solid was again charged into round bottom flask and added 500 ml of water and heated to 55°C and stirred for 1 hour at the same temperature.The solid was filtered and washed with 100 ml of preheated water and suck driedto obtain 125gms of wet crude carbamazepine.
HPLC Purity: 99.76%.
Example. 2: Preparation of crude Carbamazepine:
To a reaction flask withliquid ammonia (97ml),MIBK (400ml) were added and stirred at 25-35°C. To this mixture slowly 5H-dibenzo[b5f]azepine-5-carbonyl chloride (100gms) was addedand the temperature of the reaction mixture maintained temperature at60-70°C for 4 hours. After completion of the reaction the reaction mixture then cooled to 5-15°C.The solid was filtered and washed with water-Lot-1 (200ml).The solid was again charged in to round bottom flask and added water-Lot-2(500ml)and heated and stirred for 1 hour at 60-65°C.The solid was filtered and washed with water-Lot-3 (200ml)to obtain 120gm of wet crude carbamazepine.
HPLC Purity: 99.5%.
Example.3: Purification of crude Carbamazepine using acetone/water mixture:
To a reaction flask with a mixture of acetone (400 ml) and water (45ml),added wet crude carbamazepine (120gms) at room temperature. The temperature was then raised to 55-60°Cand stirred for complete dissolution. After complete dissolutionactivated carbon (2gms) was added and maintained for 30 minutes. The reaction mass was then filtered through hyflow and washed with acetone: water mixture (56ml: 6ml). The obtained filterate was then cooled to 25-30°C, further cooled to 0-5°C and stirred for 2 hrs. The separated solid was filtered and washed

with chilled acetone (25ml). The solid was dried under vacuum to obtain 78gm Carbamazepine.
HPLC Purity: 99.9%.

We Claim,
1. A process for preparation of Carbamazepine,

comprising the steps of:
a) reacting compound of Formula-1 with an ammonia source in presence of
suitable solvent.

wherein, X is Cl, Br or I
b) isolating carbamazepine
c) optionally slurring in a solvent and isolating the solid
d) optionally recrystallizing in a suitable solvent or solvent mixture.

2. A process as claimed in claim 1, wherein solvent in step a) is selected from Alcohols, ketones or a mixture there of.
3. Solvent as claimed in claim 1 wherein the solvent is methyl isobutyl ketone or acetone or mixture thereof.

4. A process as claimed in claim 1, wherein ammonia source is selected from . group comprising of Liquid Ammonia or Ammonia gas.
5. A process as claimed in claim 1, wherein ammonia source is liquid Ammonia.

6. A process as claimed in claim 1, wherein step b) is carried out at a temperature in the range of from about 5°C to about 15°C.
7. A process according to claim 1, wherein said solvent in step c) is water.
8. A process according to claim 1, wherein step d) wherein said solvent mixture is Acetone: water.
9. A process for preparation of Carbamazepine,


comprisingthe steps of
a) reacting 5H-dibenzo[b,f]azepine-5-carbonyl chloride with liquid ammonia in
presence of Methyl isobutyl ketone.

b) isolating carbamazepine.
c) optionally slurring in a water and isolating the solid.
d) optionally recrystallizing using activated carbon and Acetone: water mixture.