FORM2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. Title of the invention. - PROCESS FOR PREPARATION OF 4-CHLORO-4'-HYDROXY-
BENZOPHENONE
2. Applicant(s)
(a) NAME: VIHITA CHEM PVT. LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS : 305, GIDC, ANKLESHWAR, 393002, GUJARAT, INDIA
3. PREAMBLE TO THE DESCRIPTION:
. The following specification particularly describes the invention and the manner in which it is to be
performed:'

Field of the invention:
The present invention relates to an improved process for the preparation of 4-chloro-4'-hydrbxy benzophenone of formula (I). 4-chloro-4,-hydroxy benzophenone, which is an intermediate for the preparation of many pharmaceutical compounds like fibrates such as fehofibrate and polymers.

Background of the invention:
4-chloro-4'-hydroxy benzophenone of formula (I) is a key intermediate for the preparation of many pharmaceutical compounds like fenofibrate and polymers including poly ether ketone (PEK)
The synthesis of 4-chloro-4'-hydroxy benzophenone of formula (I) is reported in GB 2446397, which involves reaction of 4-chlorobenzoyl chloride with phenol in presence of AlCl3 in orthodichlbrobenzene. However, the process generates impurities, which is difficult to remove and requires purification by distillation under high vacuum.
U.S. Patent No. 4,179,515 discloses the process for preparation of 4-chloro-4'-hydroxy benzophenone. The reported process involves, reaction of anisole with 4- chlorobenzoylchloride in presence of aluminium chloride in methylene dichloride followed by hydrolysis and demethylation to provide 4-chloro-4'-hydroxy benzophenone
However, the process is tedious and requires more usage of aluminum chloride, which is difficult to remove and generates tremendous amount of effluent.

Therefore, there is need to have a simple, commercially advantageous process for preparation of 4-chIoro-4'-hydroxy benzophenone. Inventors of the present invention has found an. improved process for the preparation of 4-chloro-4'-hydroxy benzophenone.

Object of the Invention:
The object of the present invention is to provide a novel process for the preparation of 4-chloro-4'-hydroxy berizophenone of formula (I).
Another object of the present invention is to provide a process for purification of 4-chloro-4'-hydroxy berizophenone formula (I).
Another object of the, present invention is to provide a novel process for the preparation of 4-ehloro-4'-hydroxy benzophenone of formula (I), which is a key intermediate for the preparation of fibrate.
Another object of the present invention is to use 4-chloro-4' -hydroxy benzophenone of formula (1) for the preparation of fenofibrate prepared in accordance with invention.

Detailed Description of the invention:
The present invention provides an improved process for the preparation of 4-chloro-4-hydroxy benzophenone of formula (I),

which comprises reacting a 4-chloro-benzotrichloride of formula (II) with phenol (III) in presence of a lewis acid in a suitable solvent to provide 4-chloro-4'-hydroxy benzophenone.

According to the present invention, there is provided an improved process for the preparation of 4-chloro-4'-hydroxy benzophenone of formula (I)

which comprise;
(a) reacting a 4-chIoro-benzotrichloride of formula (II) with phenol (III) in presence of a lewis acid in a suitable solvent;

(b) treating with hydrochloric acid to provide 4-chloro-4'-hydroxy benzophenone; and
(c) isolating 4-chloro-4,-hydroxy benzophenone.
Another object of the invention to provide a process for the purification of 4-chloro-4'-hydroxy benzophenone, which comprise,
(a) reacting 4-chloro-4'-hydroxy benzophenone with alkali metal hydroxide to provide alkali metal 4-chloro-4'-hydroxy benzophenoalate in a suitable solvent; and
(b) treating alkali metal 4-chloro-4'-hydroxy benzophenoalate with mineral acid to provide pure 4'-chloro,4'-hydroxy benzophenone.
According to the present invention, the process for the preparation of 4-chloro-4'-hydroxy benzophenone involves reaction of 4-chloro benzotrichloride of formula (II) with phenol (III) . in presence of lewis acid in'a suitable solvent. The reaction mass is further treated with hydrochloric acid to provide 4-chloro-4'-hydroxy benzophenone
-.-' The lewis acid can be selected from the group comprising of aluminium chloride, zinc . chloride. The preferred lewis acid is aluminium chloride.
The suitable solvent comprises one, or more solvent selected from halogented solvent, hydrocarbon solvent. Preferably, the suitable solvent can be selected from the group . comprises of methylene dichloride, chlorobenzene, chloroform, carbon tetrachloride, toluene, xylene or mixtures thereof. The preferred solvent is methylene dichloride.
The reaction of 4-chloro-benzotrichloride with phenol can be carried out at about 5°C to 50°C; preferably the reaction is carried out at 15° to 35°C.

The invention providesa process for the purification of 4-chloro-4'-hydroxy benzophenone, which comprise reacting 4-chloro-4'-hydroxy benzophenone with alkali metal hydroxide to provide alkali metal 4-chloro-4'-hydroxy benzophenoalate in a suitable solvent and treating alkali metal 4-ehloro-4'-hydroxy benzophenoalate with mineral acid to provide pure 4-chloro-. 4:-hydroxy benzophenone.
The alkali metal hydroxide can be selected from sodium hydroxide or potassium hydroxide.
The suitable solvent may be selected from water, alcohol, ester or a polar solvent. The
. . preferred solvent is water or alcohol selected from methanol, ethanol and isopropanol. The
most preferred solvent is water..
The mineral acid can be selected from hydrochloric acid, sulfuric acid, phosphoric acid. The preferred acid is hydrochloric acid.
In the preferred embodiment of the present invention, 4-chloro benzotrichloride is reacted with phenol in methylene chloride in presence of anhydrous aluminium chloride at about 10 to 25°C about 20 to 40°C. Aqueous hydrochloric acid is added to the reaction mass and isolated 4-chloro-4'-hydroxy benzophenone. The wet cake was washed water and purified.
The invention further provides purification of 4-chloro-4'-hydroxy benzophenone, which is simple and easy to isolate purified 4-chioro-4'-hydroxy benzophenone. In the preferred embodiment, the 4-chloro-4'-hydroxy benzophenone is treated with aquous sodium hydroxide to provide solution of sodium salt of 4-chloro-4'-hydroxy benzophenolate. The solution was filtered and treated with aquous hydrochloric acid. The precipitated 4-chloro-4'-hydroxy, benzophenone was isolated by Alteration and dried.

The process for the preparation of 4-chloro-4 '-hydroxy benzophenone (I) may be illustrated by following scheme-1.

Having described the invention with reference to certain preferred embodiments, other embodiments will become apparent to one skilled in the art from consideration of the specification.
The process for the preparation of 4-chloro-4'-hydroxy benzophenone and its purification
described in the present invention is demonstrated in examples illustrated below. This
example is provided as illustration only and therefore should not be construed as limitation of
the scope of invention.

Example: Preparation of 4-chIoro-4'-hytlroxy benzophenone
14.0gm anhydrous Aluminum chloride was charged in 500 ml dichloromethane at about30°C. A solution of 94 gm phenol in 100 ml dichloromethane was slowly at about 25 to 30°C. The 4-Chloro Benzo trichloride (230gm) added to the reaction mass at about 25 to 30°C and maintained at 25 to .30° C for about 6 hours. The reaction mass was dumped in aqueous .-. hydrochloric acid and stirred for about 2 hours at about 25 to 30° C. The reaction mass was filtered and washed with water to isolate 4-chloro-4'-hydroxy benzophenone.
Purification:
The crude 4-chloro-4,-hydroxy benzophenone dissolved in aqueous solution of sodium. hydrocide and filted. The filteate was treated with aqueous hydrochloric acid and precipitated pure 4-chloro-4'-hydroxy benzophenone. The reaction mass was stirred for about 30 minutes at about 25-30°C and filtered, dried and obtained pure 4-chloro-4'-hydroxy benzophenone. Yield: 85%.

We claim:
1. An improved process for the preparation of 4-chloro-4'-hydroxy benzophenone of formula (I),

which comprises reacting a 4-chloro-benzotrichloride of formula (II) with phenol (III) in presence of a lewis acid in a suitable solvent to provide 4-chloro-4'-hydroxy benzophenone.

2. An improved process for the preparation of 4-chloro-4'-hydroxy benzophenone of formula
(0.


which comprise;
(a) reacting a 4-chloro-benzotrichloride of formula (II) with phenol (III) in presence of a lewis acid in a suitable solvent;
(b) treating'with hydrochloric acid to provide 4-chloro-4'-hydroxy benzophenone; and
(c) isolating 4-chloro-4,-hydroxy benzophenone.

3. The process as claimed claim 1 or 2, wherein the lewis acid is selected from aluminum chloride, zinc chloride.
4. The process as claimed in claim 3., wherein the lewis acid is anhydrous aluminum chloride.
5. The process as claimed in claim 1 or 2, where in the suitable solvent.is selected from the group comprising of methylene dichloride, chlorobenzene, chloroform, carbon tetrachloride, toluene, xylene or mixtures thereof.
6. The process as claimed in claim 5, wherein the suitable solvent is methylene dichloride.
7. A process for the purification of 4-chloro-4'-hydroxy benzophenone, which comprises,
(a) reacting 4-chloro-4'-hydroxy benzophenone with alkali metal hydroxide to provide alkali metal 4-chloro-4'-hydroxy benzophenoalate in a suitable solvent; and
(b) treating alkali metal 4-chloro-4'-hydroxy benzophenoalate with mineral acid to provide pure 4-chloro-4'-hydroxy benzophenone.

8. The process as claimed in claim 7, wherein the alkali metal hydroxide is.selected from sodium hydroxide or potassium hydroxide.
9. The process as claimed in claim 7, wherein the suitable solvent is selected from water, alcohol, ester or a polar solvent. The preferred solvent is water or alcohol selected from methanol, ethanol and is isopropanol.
10. The process as claimed in claim 7, wherein the mineral acid is selected from hydrochloric
acid, sulfuric acid, phosphoric acid.