Title of Invention

PROCESS FOR PRODUCING 5-IODO-2-METHYLBENZOIC ACID

Abstract

The present invention provides a process for producing 5-iodo-2-methylbenzoic acid through iodination of acetic acid solution, as essential steps, a reaction step of iodinating acetic acid in the presence of O-toluic acid, Potassium per sulphate, Iodine and Sulphuric acid, wherein the process comprises of ionization, mixing, stirring, heating, cooling, filtering, acid based purification and toluene based purification. According to the present invention, 5-iodo-2-methylbenzoic acid, which is useful for producing functional chemicals such as drugs, can be produced at high purity and high yield in a simple manner. Since the production process includes a simple reaction step and a simple separation/purification step, the load of purification is mitigated.

Full Text

PATENT ACT 1970 (39 OF 1970) COMPLETE SPECIFICATION (FORM-2) TITLE - PROCESS AND COMPOSITION FOR 5-IODO-2-METHYLBENZOIC ACID. NAME OF APPLICANT- OMKAR SPECIALITY CHEMICALS LTD. ADDRESS OF APPLICANT- B-34, M.I.D.C. Badlapur (E), Dist-Thane, Maharashtra, Pin Code : 421503, India PREAMBLE OF INVENTION- This invention in particular describes the nature of the invention and the manner in which it is to be performed. FIELD OF INVENTION - The present invention relates to a new process and composition for producing 5-IODO-2-METHYLBENZOIC ACID which serves as a useful source for drugs, agricultural chemicals, and functional chemicals. More particularly, the invention relates to a process for producing 5-IODO-2-METHYLBENZOIC possessing high purity in high yield. PRIOR ART- In the existing system as given in European Patent Application - EP1642881, wherein, the said invention provides a process for producing 5-iodo-2-methylbenzoic acid through iodination of 2-methylbenzoic acid, the process including, as essential steps, a reaction step of iodinating 2-methylbenzoic acid in the presence of a microporous compound, iodine, an oxidizing agent, and acetic anhydride, and a purification step including sublimation, distillation, crystallization, or a combination of two or more of these. According to the present invention, 5-iodo-2-methylbenzoic acid, which is useful for producing functional chemicals such as drugs, can be produced at high purity and high yield in a simple manner. Since the production process includes a simple reaction step and a simple separation/purification step, the load of purification is mitigated. In addition, the microporous compound such as a zeolite catalyst which has been separated and recovered from the reaction mixture can be repeatedly employed after performing of a simple treatment. Thus, the production process ensures a long service life of catalysts and high efficiency. In the existing system as given in United States Patent Application - 7750182, wherein, the said invention provides a production method for an iodine compound in which iodine is reacted with a substrate in the presence of a porous material having a pore diameter of 500 nm or less or in the presence of the above porous material and an oxidizing agent and a production process for high purity 5-iodo-2-methyIbenzoic acid comprising an iodination reaction step carried out by the above-mentioned, a crystal precipitation and separation step in which a product is precipitated by adding water or cooling and then separated and a purification step in which crystal separated is recrystallized using an organic solvent. According to the production method for an iodine compound described above, iodine can be introduced into various substrates at a high selectivity. Since expensive metals and specific reagents do not have to be used, it can readily be carried out in an industrially scale, and the product having a high purity can be obtained. Further, the process comprising the iodination reaction, separation and purification steps described above makes it possible to readily obtain at a high yield, 5-iodo-2-methylbenzoic acid having a high purity which is useful in uses for functional chemical products such as medicines. The process of the present invention comprising iodination reaction, separation and purification steps is characterized by that it is simple in terms of a procedure and that the purification load is smaller, and it is very advantageous in industrially carrying out. In the existing system as given in United States Patent Application - 20090209785, wherein, the said invention provides a process for production of 2,3,4-trifluoro-5-(iodo or bromo)benzoic acid, the process comprising a halogenation step in which direct iodination or bromination of 2,3,4-trifluorobenzoic acid is performed with an iodinating agent or brominating agent in a reaction solvent in the presence of an oxidizing agent. According to the invention, there is provided a process for convenient production of 2,3,4-trifluoro-5-(iodo or BRomo)benzoic acid in high yield and high purity in a highly regioselective manner. OBJECT OF THE INVENTION - 5-IODO-2-METHYLBENZOIC ACID has the chemical formula C8H7IO2 and it can be produced in various ways. The original route starts with reaction with iodine compound, but yields from this starting point are low. Numerous processes and process improvements have been disclosed in prior art. However, some of the method involved earlier is evidently unsatisfactory, both economically and technically. It is an object of the present invention to provide a simpler and more economical method of preparation of 5-IODO-2-METHYLBENZOIC ACID, in view of the unsatisfactory process hitherto disclosed. This object is achieved, and 5-IODO-2-METHYLBENZOIC ACID is obtained in high yield and high purity. STATEMENT OF INVENTION- The inventor has invented a new process and composition for preparing 5-IODO-2-METHYLBENZOIC ACID DETAILED DESCRIPTION OF INVENTION- Accordingly, the present invention provides a process for producing 5-iodo-2-methylbenzoic acid and high-purity 5-iodo-2-methylbenzoic acid, as described below. (1) A process for producing 5-iodo-2-methylbenzoic acid involves step of ionization of 4.135 kg of acetic acid with 0.36 litre of water. (2) A process for producing 5-iodo-2-methylbenzoic acid further involves step of stirring and charging 1.07 kg of O-toluic acid at Room Temperature; (3) A process for producing 5-iodo-2-methylbenzoic acid further involves step of charging 1.305 Kg of potassium persulphate at Room Temperature; (4) A process for producing 5-iodo-2-methylbenzoic acid further involves step of adding 1.0 Kg. Iodine in small lots in an hour time frame. (5) A process for producing 5-iodo-2-methylbenzoic acid further involves step of adding 0.36 kg of sulphuric acid slowly in 45-60 minutes at Room Temperature. (6) A process for producing 5-iodo-2-methylbenzoic acid further involves step of rising temperature to 80-85°C (7) A process for producing 5-iodo-2-methylbenzoic acid further involves step of rising heating temperature of reaction mixture slowly to 115-116°C. (8) A process for producing 5-iodo-2-methylbenzoic acid further involves refluxing the reaction mixture for 8 hours maintaining temperature at 118-120°C. (9) A process for producing 5-iodo-2-methylbenzoic acid further involves cooling reaction mixture naturally to 90°C and applies cooling. (10) A process for producing 5-iodo-2-methylbenzoic acid further involves cooling reaction mixture to 50-55°C and adding 10.75 litre of water. (11) A process for producing 5-iodo-2-methylbenzoic acid further involves cooling down the reaction mixture to 30-35°C and filtering the reaction mixture. (12) A process for producing 5-iodo-2-methylbenzoic acid further involves noting down the weight of wet cake. (13) A process for producing 5-iodo-2-methylbenzoic acid further involves acid base purification of wet cake, the process comprising of the following step - 1. Wet cake is charged with 5.5 liter water in a flask. 2. Crude wet cake is charged and heated at 60-65°C. 3. 25 % caustic soda solution is added to it.(0.4 kg NaOH + 1.65 lit water) 4. Checking is done to ascertain complete dissolution. 5. Further it is added with 5% solution of H202 (0.1 kg. H202 + 1,0 lit. water) 6. Checking involves ascertaining that the colour of solution is colourless to light yellow, (pipette out sample add 5 % H2S04 solution if white ppt. forms proceed further If not then add little quantity of diluted H202.) 7. Adjust PH to 7.0 (0.3 kg. sulphuric acid +1.15 lit. water) 8. Filter solution and collect. 9. Then adjust PH to 5.2 10. Cool to Room temperature and filter. 11 .Note weight of wet cake. (14) A process for producing 5-iodo-2-methylbenzoic acid further involves toluene based purification of wet cake, the process comprising of the following step - 1, Charge 2.0 lit. of toluene 2, Add wet cake in toluene under stirring 3, Heat to 85-90 °C and maintain for 2 hours. 4, Cool to 20°C. 5, Dry at 100°C for 4 to 5 hours. 6, Expected dry weight = 1.1 to 1.2 kg. 7, MP=176-179°C. The process according to the invention can be carried out batchwise or by conventional continuous techniques. The continuous operation is technically particularly simple and also economical, compared to the 5-iodo-2-methyibenzoic acid syntheses of the prior art. Based on process employed, the resultant 5-iodo-2-methylbenzoic acid (which is in fact more than 99.5% pure) is obtained in yields of 90% or more. Next, the present invention shall more specifically be explained with reference to examples. However, the present invention shall by no means be restricted by the following examples. Example 1 - In the process of Ionization of acetic acid with water, acetic acid may be substituted with any other solvent like methanoh propionic acid, etc. or any other polar solvent containing at least one proton. Example 2 -The equipment used in step involving stirring and charging 1.07 kg of O-toluic acid at Room Temperature is an hmhdpe reactor with a agitator or a agitated poly propylene (PP) reactor or even a stainless steel reactor or a glass lined reactor at permissible pH ranges. Any other vessel which can resist corrosion of the aforesaid reaction mix may be used. Example 3 - The step involving charging 1.305 Kg of potassium per sulphate at room temperature can be substituted with any one of the following to give the same result:- a) Ammonium per sulphate b) Sodium per sulphate c) Any other compound containing per sulphate as an Anionic entity. d) Nitric acid of various concentrations. e) Oxidizing agents of class of Bromates as the anionic entity. Example 4 - The step involving addition of 0.36 kg sulphuric acid slowly in 45-60 minutes at Room Temperature may be substituted by adding any other strong acid, like Nitric acid, phosphoric acid. Example 5 - In the precipitation operation in purification process, NaOH may be substituted With any other Alkali metal, Hydroxide / carbonate or bicarbonate. Even liquor Ammonia may be used. Example 6 -In the purification process use of toluene may be substituted with Xylene's, cyclohexane or alcohols like butanol, ISO propanol or any other alcohol with 1-10 carbon atoms. According to the production method of the present invention for an iodine compound, iodine can be introduced into various substrates at a high selectivity. Since expensive metals and specific reagents do not have to be used, it can readily be carried out in an industrially scale, and the product having a high purity can be obtained. Further, the process of the present invention comprising iodination reaction, separation and purification steps makes it possible to readily obtain at a high yield, 5-iodo-2-methylbenzoic acid having a high purity which is useful in uses for functional chemical products such as medicines. The steps comprising iodination reaction, separation and purification are characterized by that they are simple in terms of a procedure and that the purification load is smaller, and it is very advantageous in industrially carrying out CLAIMS I claim, 1. A process for producing 5-iodo-2-methylbenzoic acid through iodination of acetic acid solution, as essential steps, a reaction step of iodinating acetic acid in the presence of O-toluic acid, Potassium persulphate, Iodine and Sulphuric acid, wherein the process comprises of ionization, mixing, steering, heating, cooling, filtering, acid based purification and toluene based purification. 2. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising of ionization of 4.135 kg of acetic acid with 0.36 litre of water. 3. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of stirring and charging 1.07 kg of O-toluic acid at Room Temperature; 4. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of charging 1.305 Kg of potassium per sulphate at Room Temperature; 5. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of adding 1.0 Kg. iodine in small lots in an hour time frame. 6. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of adding 0.36 kg of sulphuric acid slowly in 45-60 min. at Room Temperature. 10 7. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of rising temperature to 80-85°C. 8. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of rising heating temperature of reaction mixture slowly to 115-116°C. 9. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of refluxing the reaction mixture for 8 hours and maintaining temperature at 118-120°C. 10. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of cooling reaction mixture naturally to 90°C and applying further cooling. 11. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of cooling down reaction mixture to 50-55°C and adding 10.75 litre of water. 12. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of cooling down the reaction mixture to 30-35°C and filtering the reaction mixture. 13. A process for producing 5-iodo-2-methylbenzoic acid as per claim 1, comprising further of noting down the weight of wet cake. 14. A process for producing 5-iodo-2-methyIbenzoic acid as per claim 1, comprising further of acid based purification of wet cake by charging with 5.5 litre water in a flask; heating at 60-65°C; adding 25 % caustic soda solution (0.4 kg NaOH + 1.65 litre water); raising heating temperature to 70-75°C; checking the complete dissolution of mixture adding 5% solution of H202 (0.1 kg. H202 + 1.0 litre water); ascertaining that the colour of solution is colourless to light yellow; (pipette out sample add 5 % H2S04 solution if white ppt. forms proceed further If not then add little quantity of diluted H202; adjusting PH to 7.0 (0.3 kg. sulphuric acid +1.15 lit. water); filtering and collecting solution and adjusting PH to 5.2, cooling to room temperature and filtering the wet cake, noting down the net weight of the wet cake. 15. A process for producing 5-iodo-2~methylbenzoic acid comprising further of toluene based purification of wet cake by charge 2.0 litre of toluene; adding wet cake in toluene under stirring; heating it at 85-90 °C temperature for 2 hr; cooling it to 20°C, drying at 100°C for 4-5 hours, resultant expected dry weight equal to 1.1 to 1.2 kg and MP at 176-179°C.

Documents:

2307-mum-2010-abstract.doc

2307-mum-2010-abstract.pdf

2307-MUM-2010-CLAIMS(AMENDED)-(17-10-2013).pdf

2307-MUM-2010-CLAIMS(AMENDED)-(2-5-2014).pdf

2307-MUM-2010-CLAIMS(AMENDED)-(23-1-2013).pdf

2307-mum-2010-claims.doc

2307-mum-2010-claims.pdf

2307-MUM-2010-CORRESPONDENCE(21-4-2014).pdf

2307-MUM-2010-CORRESPONDENCE(22-5-2014).pdf

2307-MUM-2010-CORRESPONDENCE(23-1-2013).pdf

2307-MUM-2010-CORRESPONDENCE(24-6-2014).pdf

2307-mum-2010-correspondence.pdf

2307-mum-2010-description(complete).pdf

2307-mum-2010-form 1.pdf

2307-MUM-2010-FORM 13(2-5-2014).pdf

2307-MUM-2010-FORM 13(23-1-2013).pdf

2307-MUM-2010-FORM 18.pdf

2307-mum-2010-form 2(title page).pdf

2307-mum-2010-form 2.doc

2307-mum-2010-form 2.pdf

2307-MUM-2010-FORM 26(17-10-2013).pdf

2307-MUM-2010-FORM 26(2-5-2014).pdf

2307-MUM-2010-FORM 26(23-1-2013).pdf

2307-mum-2010-form 3.pdf

2307-mum-2010-form 5.pdf

2307-MUM-2010-FORM 9.pdf

2307-MUM-2010-OTHER DOCUMENT(17-10-2013).pdf

2307-MUM-2010-REPLY TO EXAMINATION REPORT(17-10-2013).pdf

2307-MUM-2010-REPLY TO HEARING(2-5-2014).pdf

2307-MUM-2010-SPCIFICATION(AMENDED)-(23-1-2013).pdf