FORM 2
THE PATENTS ACT 1970
(Act 39 of 1970)
&
THE PATENTS RULE, 2003
COMPLETE SPECIFICATION
(SECTION 10 and Rule 13)
TITLE OF THE INVENTION
"AN IMPROVED PROCESS FOR PREPARATION OF 2-
CARBOXYBENZALDEHYDE"
Emcure Pharmaceuticals Limited,
an Indian company, registered under the Indian Company's Act 1957
and having its registered office at
Emcure House, T-184, M.I.D.C., Bhosari, Pune-411026, India.
THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED

FIELD OF THE INVENTION
The present invention relates to a convenient and cost-effective process for the preparation of 3-chlorophthalide which is utilized for preparation of 2-carboxybenzaldehyde, an intermediate in the preparation of hydralazine
BACKGROUND OF THE INVENTION
2-Carboxybenzaldehyde of formula (I), chemically known as 3-hydroxy-[3H]-isobenzofuranone-1, is an important template for the introduction of the phthalidyl moiety in organic synthesis and which also happens to be an important intermediate in the synthesis of vasodilators such as hydralazine.

Various procedures are known in the literature for the synthesis of 2-carboxybenzaldehyde.
US 2,047,946 discloses a process in which gaseous chlorine is used as a chlorinating agent for preparation of a-chlorophthalide from phthalide, followed by aqueous hydrolysis of the resulting a-chlorophthalide to yield 2-carboxybenzaldehyde.
The process involves passing dry chlorine gas into stirred, hot phthalide at relatively high temperature of 130-140°C. Apart from the required logistic arrangements for introducing a gaseous reagent and the associated inconveniences, the chlorination process results in a mixture of products. When such mixture of chlorinated phthalide derivatives are subjected to hydrolysis without purification, the desired end product, phthalaldehydic acid is also obtained along with associated impurities, thus requiring successive purification steps prior to further conversion to hydralazine. Also, some of the undesired side products such as phthalyl chloride generated in the process are so reactive that they react with the starting material phthalide itself and generate further side products.

Further, the process demands strict control on the extent of chlorination since excessive chlorination leads to conversion of phthalide into phthalic acid, which interferes with the process for isolation of pure phthalaldehydic acid. All these factors ultimately result in increased input costs and lowered yields, rendering the process economically unviable.
US 4,446,327 discloses a process for preparation of 3-chlorophthalide in which pentachloro-ortho-xylene, which is synthesized by chlorination of ortho-xylene, is hydrolyzed with water at temperature 120-150 C in presence of Lewis acid catalysts such as zinc chloride, antimony chloride etc.
Although this process avoids using phthalide as a starting material and the associated side product formation, preparation of the starting material, pentachloro-ortho-xylene itself involves multiple chlorine substitution at the methyl groups of ortho-xylene. The process also involves use of metal salts such as zinc chloride which poses disposal problems, when used on commercial scales. Further, hydrogen chloride gas is evolved in the exothermic reaction at the time of water addition, hence, it necessitates careful control on the rate of addition and also requires elaborate arrangements for scrubbing of the toxic gas. Another process for preparation of 3-chlorophthalide reported in Journal of American Chemical Society (1954), vol.76, p. 5479-81 involves reaction of pentachloro-ortho-xylene and maleic acid in presence of zinc chloride. Elaborate isolation process is required for the separation of desired product from the acid chloride formed in the process, which is a major by product.
2-Carboxybenzaldehyde is also reported to be prepared by aqueous hydrolysis of 3-bromophthalide, the synthesis of which is disclosed in Organic Syntheses (1943), vol.23, p.74 and Organic Syntheses (1962), vol.42, p.26. In both these references, 3-bromophthalide is prepared by bromination of phthalide using either bromine or N-bromosuccinimide as a bromine source at a very high temperature. Although the possibility of polyhalogenated side products is reduced by use of bromine, synthesis of a potential allergen like 3-bromophthalide, in addition to the cost of bromine and the problems associated with handling of bromine make this process industrially unviable. Thus, there is a need to develop a convenient, economically viable process for preparation of 3-chlorophthalide which avoids substantially high temperatures, use of gaseous reactants, provides control on formation of side products and yields 3-chlorophthalide of

desired purity, which upon hydrolysis provides 2-carboxybenzaldehyde which conforms to regulatory guidelines.
The present inventors have developed an efficient method for synthesis of 2-carboxybenzaldehyde of desired purity involving chlorination of phthalide with sulfuryl chloride in presence of a catalyst at moderate temperature, followed by aqueous hydrolysis of the resulting 3-chlorophthalide. The methods avoids use of gaseous chlorine, as well as elaborate separation procedures and provides 2-carboxybenzaldehyde in good yield
OBJECT OF THE INVENTION
An objective of the present invention is to provide 2-carboxybenzaldehyde (I) by a novel and convenient process which does not involve gaseous reagents and high temperature reactions.
Yet another object of the present invention is to provide an efficient process for preparation of 3-chlorophthalide (III), which is further hydrolyzed to yield 2-carboxybenzaldehyde (I) with good yield and having desired purity.
SUMMARY OF THE INVENTION
The present invention relates to a novel process for the preparation of 2-carboxybenzaldehyde (I) which overcomes the limitations faced in the prior art.
An aspect of the present invention relates to an improved and scalable process for the preparation of 2-carboxybenzaldehyde (I) comprising reaction of phthalide (II) with sulfuryl chloride in presence of a catalyst to give 3-chlorophthalide (III), which on aqueous hydrolysis yields 2-carboxybenzaldehyde (I).
Following detailed description will make the objectives of the present invention fully apparent.

DETAILED DESCRIPTION OF THE INVENTION
The present inventors have surprisingly found that 3-chlorophthalide of formula (III) can
be easily obtained by reaction of the phthalide (II) with sulfuryl chloride in presence of a
catalyst.
Further, 3-Chlorophthalide (III) on aqueous hydrolysis yields 2-carboxybenzaldehyde (I) as
disclosed in Scheme-1.

phthalide (II) 3-chlorophthalide (III) 2-carboxybenzaldehyde (I)
Scheme 1 Methods embodied in the present invention for preparation of 2-carboxy benzaldehyde (I)
In an embodiment, the phthalide of formula (II) was treated with sulfuryl chloride (SO2CI2)
in presence of a catalyst to give 3-chlorophthalide of formula (III). The reaction was carried
out at 65 to 85°C and completion of the reaction was monitored by TLC.
2, 2'-diamidinyl-2, 2'-azopropane dihydrochloride was used as a catalyst in the reaction.
After completion of the reaction, the reaction mixture was quenched with water at around
70 to 80°C and stirred at the same temperature.
After completion of the reaction as monitored by TLC, the reaction mixture was cooled to
50 to 60°C and basified by adding aqueous sodium hydroxide solution. The reaction mass
was filtered, cooled further and acidified to pH 3 to 4 by addition of hydrochloric acid.

After acidification, the reaction mass was cooled to 10 to 20oC, maintained at same temperature for one hour and the product separating out was filtered, dried to obtain 2-carboxy benzaldehyde of formula (I).
With the aforementioned process, 2-carboxy benzaldehyde of formula (I) was obtained in good yield, with purity conforming to regulatory specifications.

The following example is meant to be illustrative of the present invention. The example exemplifies the invention and is not to be construed as limiting the scope of the invention.
Example 1
Preparation of 2-carboxybenzaldehyde
Phthalide (300gms) was placed in a round bottom flask and heated to 70 to 80°C, followed by addition of 2,2'-diamidinyl-2,2'-azopropane dihydrochloride (3gms). Sulfuryl chloride (332gms) was gradually added to the mixture with stirring and the reaction mass was maintained at 70 to 80°C. Completion of the reaction was monitored by TLC. After completion of the reaction, water (300 ml) was gradually added to the reaction mass at 70 to 80°C and the reaction was continued till completion as monitored by TLC. After completion, the reaction mass was cooled to 50 to 60°C, made alkaline to pH 8 to 10 with aqueous sodium hydroxide and filtered. The filtrate was cooled, acidified to pH 3 to 4 using hydrochloric acid, further cooled to 10 to 20°C and stirred at the same temperature for one hour. The product which separated out was filtered, and dried to yield 2-carboxybenzaldehyde. Yield: 240 gms (72%) Purity: 99.0%

We claim,
1. A process for preparation of 2-carboxybenzaldehyde of formula (I) comprising reaction of phthalide of formula (II) with a chlorinating agent in presence of a catalyst to give 3-chlorophthalide of formula (III), which on aqueous hydrolysis yields 2-carboxybenzaldehyde (I).
2. A process according to claim 1, wherein the chlorinating agent is sulfuryl chloride.
3. A process according to claim 1, wherein the catalyst is 2,2'-diamidinyl-2,2'-azopropane dihydrochloride.
4. A process according to claim 1, wherein the reaction of phthalide of formula (II) is carried out at temperature 65-85 C