FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"PROCESS FOR PRODUCING 2-HYDROXY-3, 5-DIIODOBENZOIC ACID"
2. APPLICANT:
(a) NAME: Omkar Speciality Chemicals Limited
(b) NATIONALITY: Indian Company incorporated under the
Companies Act, 1956
(c) ADDRESS: B-34, MIDC, Badlapur (East), Dist-Thane-421503,
Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be formed.

FIELD OF INVENTION:
The present invention relates to a new process for producing 2-hydroxy-3, 5- diiodo benzoic acid, which serves as a useful source of drugs, source of iodine in chicken feed and a functional chemical. More particularly the invention relates to a process for producing 2-hydroxy-3, 5-diiodobenzoic acid with high yield and high purity.
BACKGROUND AND PRIOR ART:
It is known to substitute iodine into an aromatic compound by the action of iodine which can be added in solvent. It is also known to generate iodine insitu from hydro iodic acid or salt of acid by oxidants such as iodates, hydrogen peroxide, persulfates. Iodination is also carried by the action of iodine monochloride in acetic acid, elemental iodine in presence of mercuric oxide, alkali, iodic acid (G. Woolett, organic syntheses collective vol. 2, P.243 (1943)).
Organic Syntheses, Coll. Vol. 2, p. 343, 1943 Vol; 14, p.52 (1934) discloses preparation of diiodosalicylic acid by reacting salicylic acid with a solution of iodine monochloride in the presence of glacial acetic acid with continuous stirring. The reaction mixture gradually heated with stirring on a hot plate to 80°C and kept at approximately that temperature for twenty minutes till to obtain voluminous precipitate. After cooling to room temperature the precipitate is filtered on a Buchner funnel and washed with acetic acid and then with water.
In another method, diiodosalicylic acid has been prepared by heating salicylic acid with iodine in alcohol (Cofman, Gazz. chim. ital. 50 (II) 297 (1920).
In yet another method by Lautemann reported in Ann. 120, 300 (1861), wherein, the reaction is conducted with the same reagents, however, with the addition of mercuric oxide.

In yet another method reported by Weselsky, in ibid. 174, 103 (1874) and by Kekule, ibid. 131, 226 (1864), diiodosalicylic acid is prepared by treating salicylic acid with iodine in the presence of alkali.
In a further method, treatment of salicylic acid with iodine and iodic acid is reported by Liechti, ibid. Spl. 7, 133, 141 (1870).
An article titled Iodination of aromatic hydrocarbons and nuclear substituted phenols by L. Jurd (Australian Journal of Scientific Research 3(4) 587 - 592) discloses direct reaction of salicylic acid with iodine in alcohol inpresence of hydrogen peroxide. Since this reaction is slow, the rate of reaction is accelerated by the addition of concentrated mineral acid such as sulphuric, nitric, hydrochloric, or phosphoric acid, which results in diiodinated products with 85-90% yields. According to this article, use of hydrochloric acid results in smaller yields and less pure product.
However, the above mentioned methods neither yield good quality product nor in good yields.
JP03167153 provides a production method for an iodine compound in which iodine monochloride is added to the compound in presence of at least one compound selected from ferric chloride, aluminum chloride, zinc chloride, copper chloride, sulfuric acid and phosphoric acid. Iodine monochloride is added in anhydrous form or in solution along with sodium chloride or hydrochloric acid. However handling of iodine monochloride is difficult due to its corrosive and irritant nature. Preparation of iodine monochloride requires excess of iodine and the reported iodine monochloride yield is about 85-87% only. For iodination reaction, the required iodine monochloride should be of high purity or otherwise process suffers from low yield and purity. Secondly, while using iodine monochloride, towards the end of reaction, reaction volume becomes difficult to stir. In such case, operational problem will be encountered at large scale.
2-hydroxy-3, 5-diiodo benzoic acid has chemical formula C7H14I2O3 and can be produced in various ways. The original route starts with reaction of salicylic acid -with iodine compounds, but yields from this starting point are low. Numerous processes and process

improvements have been disclosed in prior art as detailed above. However, some of the methods involved earlier is evidently unsatisfactory, both economically and technically. Of the many methods proposed in the prior art, employing iodine monochloride is the most satisfactory. However, as mentioned above, preparation and handling of iodine monochloride is difficult due to its corrosive and irritant nature. Additionally, there is an operational problem like difficulty in stirring due to the viscous mass of the reaction.
On cursory review of prior art, it is evident that there is a need in the art to provide an improved process for preparation of 2-hydroxy-3, 5-diiodo benzoic acid which can be prepared on industrial scale without incurring any operational problems. Thus, it is an object of the present invention to substantially overcome or at least ameliorate one or more of the disadvantages of the prior art by providing a simpler and more economical method of preparation of 2-hydroxy-3, 5-diiodo benzoic acid, in view of the unsatisfactory process hitherto disclosed. This object is achieved by the process of the present invention by obtaining 2-hydroxy-3, 5-diiodo benzoic acid in high yield and high purity employing iodine monochloride prepared insitu in the reaction. Further, the process of the instant invention is simple and safe as the reaction advantageously utilizes low concentration of oxidizing agent to carry out in large scale.
STATEMENT OF INVENTION;
The inventors have invented a new process and composition for preparing 2-hydroxy-3, 5-diiodo benzoic acid.
DETAILED DESCRIPTION OF INVENTION:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
The present invention provides a process for producing 2-hydroxy-3, 5-diiodo benzoic acid with high yield and purity. The process of the present invention is characterized by iodination reaction of salicylic acid, separation and purification of the diiodo salicylic

acid that are simple in terms of operational procedure. Since the purification load is smaller it is very advantageous to carry out industrially.
The present invention successfully utilizes an alcoholic medium, a chlorinating agent and an oxidizing agent to carry out the preparation of 2-hydroxy-3, 5-diiodo benzoic acid with good yield and purity. The chlorinating agent as used in the present invention serves the purpose of maintaining the acidity as we/1 as the source of chlorine in the preparation of iodine monochloride. The oxidizing agent used according to the present invention is to render electrophilic iodine from elemental iodine and thus enable the production of iodine monochloride insitu in the reaction mass. The sequential addition of chlorinating agent followed by the addition of oxidizing agent generates iodine monochloride insitu and also favorable conditions to accelerate the reaction.
According to the preferred embodiment, the invention provides process for producing 2-hydroxy-3, 5-diiodo benzoic acid that involves a step of dissolution of 2-hydroxy benzoic acid in an alcohol. To this mixture, elemental iodine or salt of hydro iodic acid in solid form is charged at room temperature followed by addition of chlorinating agent at the same temperature. The temperature of the reaction mass is slowly increased and maintained at 45-50°C. The salt of hydro iodic acid may be selected from the group consisting of sodium iodide, potassium iodide, magnesium iodide or calcium iodide. To this mixture, an oxidizing agent is charged in 6-8hr at temperature of 40-45°C so as to form Iodine monochloride in situ and further maintained the reaction for 5h at the same temperature i.e., 40-45°C. After the completion of the reaction, DI water is charged and raised the temperature to 80-85°C and maintained at the same temperature for 2hrs. The reaction mass is cooled to 30-35°C and further to 25°C and filtered the product, 2-hydroxy-3, 5 benzoic acid. The product, 2-hydroxy-3, 5-benzoic acid thus obtained is washed with DI water followed by 20% sodium metabisulfite solution and finally with DI water. The wet cake, 2-hydroxy-3, 5-diiodo benzoic acid thus obtained is further purified by heating with a mixture of alcohol and hydrocarbon.
In another embodiment, the invention provides a process for purification of 2-hydroxy-3, 5-diiodo benzoic acid comprising the following steps:
a. charging mixture of alcohol and hydrocarbon in a ratio of 1:16 into a reactor.

b. Charging the Crude wet cake, and slowly heating the reaction upto 75-80°C
and maintaining for lhr,
c. Cooling the reaction mass slowly to 30-35°C and chilling to 20°C.
d. Filtering the reaction mass and
e. drying the product in tray dryer at 100-110°C till LOD is less than 0.5%
The process according to the invention can be carried out batch wise or by conventional continuous techniques. The continuous operation of the instant process is technically simple and also economical, compared to the 2-hydroxy-3, 5-diiodo benzoic acid syntheses of prior art.
Based on a process employed, the resultant 2-hydroxy-3, 5-diiodo benzoic acid not less than 99.5% purity is obtained in yields of 90-94%.
The alcohol for dissolution of 2-hydroxy benzoic acid may be selected from the group consisting of alcohol ranging from carbon chain length of CI-CI 8 more preferably Cl-C10, straight or branched chain.
The equipment used in the process of the instant invention may be selected from the group consisting of an HMHDPE reactor, with agitator or agitated poly propylene reactor or stainless steel reactor or glass lined reactor or any other vessel which can resist corrosion of the aforesaid reaction mixture.
The chlorinating agent used in the preparation of iodine monochloride may be selected from the group consisting of 5-30% solution of hydrochloric acid; Dry hydrogen chloride gas and Chlorine gas.
The oxidizing agent used in the present invention may be selected from the group consisting of 30-60% hydrogen peroxide; Oxygen gas; Nitric acid of varying concentration; Compound containing persulfate as an anionic entity and Oxidizing agents of class bromates or iodates as the anionic entity.

The sodium metabisulfite solution as used for washing the product, 2-hydroxy-3, 5-diiodo benzoic acid can be substituted by any entity containing metabisulfite or thiosulfate anion.
In the purification process, the alcohol used may be selected from alcohol ranging from carbon chain length of C1-C18, more preferably, C1-C10 straight or branched chain.
In the purification process the hydrocarbon may be selected from the group consisting of aliphatic or aromatic including but not restricted to methylene dichloride, ethylene dichloride, n-Hexane, n-Pentane, n-heptane, n-decane, n-nonane, n-decane, mixed xylene, o-xylene, p-Xylene, cyclohexane, cumene, cymene.
According to the production method of the present invention for preparation of an iodine compound, elemental iodine can be introduced into various substrates at a high selectivity. Since expensive metals and special reagents do not have to be used, it can readily be carried out in an industrial scale and the product having a high purity can be obtained
Further a process of the present invention comprising iodination reaction separation and purification steps makes it possible to readily obtain at a high yield, 2-hydroxy-3, 5-diiodo benzoic acid having high purity which is useful for functional chemical products such as drugs. The steps comprising iodination reaction are simple in terms of procedure, no specially designed reactors or system are needed, purification load is smaller and it is very advantageous in carrying out industrially.
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

Examples Example 1
Preparation of 2-hydroxy-3, 5-diiodo benzoic acid
214Kg 2-hydroxy benzoic acid was charged in 317kg methanol. Charged 400kg elemental iodine in solid form at room temperature followed by the addition of 80kg hydrochloric acid of strength 30% at room temperature. The temperature of the reaction mass was slowly increased and maintained at 45-50°C. 140Kg 50% hydrogen peroxide was charged in 6-8hr at temperature 40-45°C and maintained the reaction for 5h at temperature of 40-45°C. Charged 2500kg DI water and raising temperature to 80-85°C and maintained reaction at 80-85oC for 2h. The reaction mass is cooled to 30-35°C and further to 25°C. The solid mass 2-hydroxy-3, 5 diiodo benzoic acid thus obtained was filtered and washed with 400kg DI water followed by 120kg of 20% sodium metabisulfite solution and finally by 50Kg of DI water and dried the wet cake.
Example 2
Purification of 2-hydroxy-3, 5-diiodo benzoic acid
The wet cake thus obtained was charged into a reactor containing mixture of 40kg of methanol and 550Kg of toluene. The reaction was slowly heated to 75-80°C and the reaction is maintained for lhr. The reaction mass was cooled slowly to 30-35°C and chilled to 20°C and filtered the reaction mass and noted the wet weight of the cake. The wet product is dried in tray dryer at 100-110°C till LOD was less than 0.5%. Yield: 575 gm (94.5% yield based on salicylic acid) Purity not less than 99.5%.
Example 3
Preparation of 2-hydroxy-3, 5-diiodo benzoic acid
214Kg 2-hydroxy benzoic acid was charged in 317kg methanol. Charged 400kg elemental iodine in solid form at room temperature followed by the addition of 80kg hydrochloric acid of strength 30% at room temperature. The temperature of the reaction mass was slowly increased and maintained at 45-50°C. 423Kg 30% nitric acid was charged in 6-8hr at temperature 40-45°C and maintained the reaction for 4h at temperature of 40-45°C. Charged 2500kg DI water and raising temperature to 80-85°C and maintained reaction at 80-85°C for 2h. The reaction mass is cooled to 30-35°C and

further to 25°C. The solid mass 2-hydroxy-3, 5 diiodo benzoic acid thus obtained was filtered and washed with 400kg DI water followed by 120kg of 20% sodium metabisulfite solution and finally by 50Kg of DI water and dried the wet cake. Purification of product was carried as mentioned in example 2. 92.78% yield based on salicylic acid with purity not less than 99.5% was obtained.
Example 4
214Kg 2-hydroxy benzoic acid was charged in 317kg methanol. Charged 400kg elemental iodine in solid form at room temperature followed by the addition of 80kg hydrochloric acid of strength 30% at room temperature. The temperature of the reaction mass was slowly increased and maintained at 45-50°C. 250kg potassium persulfate in 115kg cone. Sulfuric acid was added for 7hr at 40-45°C and maintained the reaction for 6-8h at temperature of 40-45°C. Charged 2500kg DI water and raising temperature to 80-85oC and maintained reaction at 80-85°C for 2h. The reaction mass is cooled to 30-35°C and further to 25°C. The solid mass 2-hydroxy-3, 5 diiodo benzoic acid thus obtained was filtered and washed with 400kg DI water followed by 120kg of 20% sodium metabisulfite solution and finally by 50Kg of DI water and dried the wet cake. Purification of product was carried as mentioned in example 2. 93.6% yield based on salicylic acid with purity not less than 99.5% was obtained.
Example 5
Preparation of 2-hydroxy-3, 5-diiodo benzoic acid
214Kg 2-hydroxy benzoic acid was charged in 317kg methanol. Charged 400kg elemental iodine in solid form at room temperature followed by the addition of 60kg water and dry hydrogen chloride gas is purged. The temperature of the reaction mass was slowly increased and maintained at 45-50°C. 140Kg 50% hydrogen peroxide was charged in 6-8hr at temperature 40-45°C and maintained the reaction for 5h at temperature of 40-45°C. Charged 2500kg DI water and raising temperature to 80-85oC and maintained reaction at 80-85°C for 2h. The reaction mass is cooled to 30-35°C and further to 25°C. The solid mass 2-hydroxy-3, 5 diiodo benzoic acid thus obtained was filtered and washed with 400kg DI water followed by 120kg of 20% sodium metabisulfite solution and finally by 50Kg of DI water and dried the wet cake. Purification of product was carried as

mentioned in example 2. 93.2 % yield based on salicylic acid with purity not less than 99.5% was obtained.
Example 6
214Kg 2-hydroxy benzoic acid was charged in 317kg methanol. Charged 400kg elemental iodine in solid form at room temperature followed by the addition of 55kg diluted sulphuric acid and chlorine gas is purged. The temperature of the reaction mass was slowly increased and maintained at 45-50°C. 140Kg 50% hydrogen peroxide was charged in 6-8hr at temperature 40-45°C and maintained the reaction for 5h at temperature of 40-45°C. Charged 2500kg DI water and raising temperature to 80-85oC and maintained reaction at 80-85oC for 2h. The reaction mass is cooled to 30-35°C and further to 25°C. The solid mass 2-hydroxy-3, 5 diiodo benzoic acid thus obtained was filtered and washed with 400kg DI water followed by 120kg of 20% sodium metabisulfite solution and finally by 50Kg of DI water and dried the wet cake. Purification of product was carried as mentioned in example 2. 93.45 % yield based on salicylic acid with purity not less than 99.5% was obtained.
Example 7
Preparation of 2-hydroxy-3, 5-diiodo benzoic acid
214Kg 2-hydroxy benzoic acid was charged in 317kg methanol. Charged 1045kg potassium iodide at room temperature followed by the addition of 80kg hydrochloric acid of strength 30% at room temperature. The temperature of the reaction mass was slowly increased and maintained at 45-50°C. 140Kg 50% hydrogen peroxide was charged in 6-8hr at temperature 40-45°C and maintained the reaction for 5h at temperature of 40-45oC. Charged 2500kg DI water and raising temperature to 80-85°C and maintained reaction at 80-85°C for 2h. The reaction mass is cooled to 30-35°C and further to 25°C. The solid mass 2-hydroxy-3, 5 diiodo benzoic acid thus obtained was filtered and washed with 400kg DI water followed by 120kg of 20% sodium metabisulfite solution and finally by 50Kg of DI water and dried the wet cake. Purification of product was carried as mentioned in example 2. 91.23 % yield based on salicylic acid with purity not less than 99.5% was obtained.

WE CLAIM,
1. A process for preparation of 2-hydroxy-3, 5-diiodo benzoic acid with high yield and purity comprising reacting salicylic acid in an alcohol with iodine monochloride by generating iodine monochloride insitu from the mixture of elemental iodine or salt of hydro iodic acid and chlorinating agent in presence of an oxidizing agent.
2. The process for preparation of 2-hydroxy-3, 5-diiodo benzoic acid according to claim 1, wherein the reaction of salicylic acid in an-alcohol with iodine monochloride characterized by the sequential process steps consisting of
a. dissolving salicylic acid in an alcohol followed by adding elemental iodine or
salt of hydro iodic acid;
b. adding chlorinating agent at room temperature followed by adding oxidizing
agent at a temperature range of 40-45oC and maintained up to 10-15 hrs;
c. adding demineralized water to the reaction mass followed by heating the
reaction mass upto a temperature range of 80-85oC and maintaining upto 2hrs
followed by cooling the reaction mass up to 25°C to obtain solid cake;
d. filtering the wet cake followed by washing the cake with a solution containing
sulfite anion; and
e. Purifying the 2-hydroxy-3, 5-diiodo benzoic acid from mixture of alcohol and
hydrocarbon.
3. The process according to claims 1 and 2, wherein said alcohol is selected from the group consisting of carbon chain length of CI-CI 8 straight or branched chain.
4. The process according to claim 3, wherein the alcohol is of carbon chain length of C1-C10.
5. The process according to claim 1, wherein said chlorinating agent is selected from hydrochloric acid, chlorine gas or salt containing chloride anion.
6. The process according to claim 1, wherein said hydrochloric acid is either in gaseous form or in liquid-form.

7. The process according to claim 6, wherein said hydrochloric acid is liquid form.
8. The process according to claim 7, wherein the strength of hydrochloric acid is 5-30% added in carrier solvent.
9. The process according to claim 1, wherein, the oxidizing agent is selected from,
hydrogen peroxide, oxygen gas, nitric acid of varying strength, compounds
containing anionic moiety selected from the group consisting of persulfates,
bromates and iodates.
10. The process according to claim 9, wherein, the strength of hydrogen peroxide ranges from 30-60%.
11. The process according to claim 2, wherein, the sulfite anion is selected from the group consisting of metabisulfite, bisulfite or thiosulfate anion.
12. The process according to claim 2, wherein the washing of wet cake is done with 20% sodium metabisulfite.
13. The process according to claim 2, the hydrocarbon is selected from the group consisting of methylene dichloride, ethylene dichloride, n-Hexane, n-Pentane, n-heptane, n-decane, n-nonane, n-decane, mixed xylene, o-xylene, p-Xylene, cyclohexane, cumene, cymene.
14. The process according to claim 1, wherein the salt of hydro iodic acid is selected from the group consisting of sodium iodide, potassium iodide, magnesium iodide or calcium iodide.
15. The process according to any one of the preceding claims, wherein the process can be conducted in batch or in continuous mode.