Title of Invention

"A SINGLE POT PROCESS FOR THE PREPARATION OF ZINC AND/OR CHROMIUM NICOTINATES"

Abstract

The present invention relates to a single-pot process for the preparation of metal nicotinates useful as a dietary supplement from beta picoline as a source of starting material., said process comprising the steps hydrosulfonation of beta picoline with sulfuric acid, heating the reaction mixture thus obtained to a temperature of about 150° -210° C followed by oxidation with suitable oxidizing agent to obtain nicotinic acid sulfate and treating with a water soluble zinc and/or chromium salt to produce a solid metal nicotinate and separating it to thereby obtain the corresponding metal nicotinates of high purity,

Full Text

Field of Invention The present invention relates to a single-pot process for the preparation of zinc and/ or chromium nicotinates useful as a dietary supplement from beta picoline. Background of the Invention In 1996, according to WHO and the International Diabetes Federation there were 132 million diabetic patients worldwide and will increase to 240 millions in 2010. Diabetes is a serious disease that we need to cure. Trivalent chromium, element in a trace amount, is needed for the metabolism of sugar, protein and fat in the human body. The deficiency of this trace element causes diabetes. It is distributed in many tissues in human body, with liver and kidney containing the highest amount. According to a report published in the National Academy of Sciences, Page 160, 1980, only 0.5% of ingested inorganic chromium is assimilated into the body. Also, only 1-2% of most organic chromium compounds is assimilated into the body, whereas the synthetic coordination complex of picolinic acid with chromium is directly available for absorption without competition from other metals as reported in US Patent No. RE 33988 (Reissued on July 7, 1992). US published patent application no. 2002 098247 and published PCT application no. WO 02/36202 discloses that chromium nicotinate composition is used to improve insulin sensitivity, reduces hyperglycemia and reduces hypercholesterolemia. US Patent No. 6379693 and US Pat No. 6203819 reveals that chromium nicotinate can be supplemented to the patients for curing diabetes and according to US Pat No. 5194615 it can also be used as Glucose Tolerance Factor (GTF) material. Chromium nicotinate is also reported as a feed supplement to cattle to improve the milk production (US Pat No.6139881). Zinc, a trace element in the human body, is known to participate in the development of sexual organs, promotion of wound healing, activating the immune system and to be a component of metalloenzyme, an accelerator for dehydrogenase. Conventionally zinc oxide formulations have been topically used as medicines for treating skin diseases such as dermatitis, sunburn, neurodermatitis and eczema. These formulations have local astringent action and irritation and are not usually administered internally. US Pat No. 5582817 and US Pat No. 5696169 reported that zinc nicotinate can be used as cosmetics and as a drug for ameliorating sunburn and skin diseases, preventing sunburn, relieving irradiation disorders etc. In the prior art of preparation of chromium nicotinate US Pat No. 5194615 and US Pat No. 4923855 suggested the use of an alkali metal salt of nicotinic acid which is reacted with a trivalent chromium salt After the completion of reaction, the precipitated chromium complex is filtered and dried. Further, US Pat No. 5696169 and US Pat No. 5582817 discloses the preparation of zinc nicotinate complex by reacting nicotinic acid with zinc acetate dihydrate and adjusting the pH to 8.5. However these patents use nicotinic acid and chromium (III) chloride hexahydrate or zinc acetate dihydrate as the starting material for the manufacturer of chromium nicotinate or zinc nicotinate, respectively. Alkylpyridines can be oxidised by chemical agents such as KMnO4 but these reagents are expensive and can lead excessive oxidation and there by ring degradation [J. Org. Chem. 14, 14 (1949); J. Chem. Soc. 934 (1946)] and lot of MnO2 as solid waste is generated which has it's own problems in disposal. Other methodologies include nitric acid oxidation, which is reported as a more economical route, but it requires elevated temperature and pressure [Bengtsson, Acta. Chem. Scand.; 9, 832 (1955)]. These harsh conditions cause decarboxylation and thus resulting yield loss of pyridine carboxylic acid. US Pat. No. 2437938 reports catalytic air oxidation, but doesn't appear to have general application. US Patent No. 2522163 relates to preparation of pyridine carboxylic acids from sulfates of alkyl pyridine, quinoline, isoquinolines and alkyl quinolines. The invention is illustrated by an example wherein the preparation of nicotinic acid from beta picoline(3-picoline) is described. US Pat. No. 2513099 discloses a process for oxidising N-heterocycle compounds containing a pyridine nucleus and an oxidizable organic group attached to the nitrogen containing aromatic nucleus by at least one carbon to carbon linkage. The process involves oxidation by reacting nitric acid with a solution containing the N-hetrocycle compound and a mixture of mercury and copper compounds dissolved in sulphuric acid. This process of oxidation may normally lead to the contamination of undesired metals with the nicotinic acid. While the prior art techniques for preparing chromium nicotinate and zinc nicotinate have been reasonably successful, the preparation is rather complex. These techniques involve multi-steps, which makes the product expensive. Therefore, it is an object of the present invention to produce chromium nicotinate and zinc nicotinate from a cheaper raw material (beta picoline) and using a single pot process. Object of the Invention The main object of the present invention is to provide a novel single pot process for the preparation of metal nicotinates using beta picoline as a source of starting material. Another objective of the present invention is to use metal nicotinates as a dietary supplement. Summary of the Invention Accordingly, the present invention provides a single pot process for the preparation of metal nicotinates as a dietary supplement, with high purity from beta picoline as a cheaper source of raw material. Statement of the invention Accordingly, the present invention relates to a single pot process for the preparation of zinc and / or chromium nicotinates useful as dietary supplements from beta picoline, said process comprising the steps of: ( a ) hydrosulfonation of beta picoline with sulfuric acid at a temperature in the range of 35 - 100°C to form a reaction mixture; ( b ) further heating the reaction mixture obtained in step (a) to a temperature of 150 to 210°C; ( c) oxidizing the reaction mixture of step (b) with an oxidizing agent such as herein described under proper ventilation to remove nitric oxide fumes for a time period in the range of 18 to 22 hours to obtain nicotinic acid sulfate at a temperature ranging from 35 to 90°C to form a solution; ( d ) maintaining the pH of the solution of step (c) of 7 to 8 as a basic solution using an alkali solution; ( e) treating the basic solution of step (d) with a water soluble zinc and / or chromium salt to produce a solid metal nicotinate in said water; and (f) filtering the resulting solid metal nicotinate of step (e) to remove such from said water and to thereby obtain the corresponding metal nicotinates. Detailed Description of the Invention The present invention relates to a single pot process for the preparation of metal nicotinates which are useful as dietary supplement, used as a drug or in the formulation of cosmetics, ointments etc., from beta picoline, the said process comprising steps of: (a) hydrosulfonation of beta picoline with sulphuric acid at a temperature of about 35- 100° C to form a reaction mixture; (b) further heating the reaction mixture thus obtained to a temperature of about 150° - 210° C; (c) oxidizing the reaction mixture of step (b) with an oxidizing agent to obtain nicotinic acid sulfate at a temperature of about 50-90° C, to form a solution; (d) maintaining the pH of the solution of step (c) at a pH of about 7 to 8 as a basic solution; (e) treating the basic solution of step (d) with a water soluble zinc and/or chromium salt to produce a solid metal nicotinate in said water, and (f) filtering the resulting solid nicotinate to remove such from said water and to thereby obtain the corresponding metal nicotinates of high purity. In another embodiment of the present invention, the reaction of beta picoline with sulphuric acid is carried out in the temperature range of 35° to 90° C. In still another embodiment of the present invention, the reaction of the beta picoline with sulphuric acid is carried out in the temperature range of 60-80° C. In yet another embodiment of the present invention, the reaction mass is heated upto a temperature of 150° - 210° C. In yet another embodiment of the present invention, the reaction mass is heated up to a temperature 190° - 205° C. In still another embodiment of the present invention, the oxidising agent used is 40-70% concentrated nitric acid. In still another embodiment of the present invention, proper ventilation is provided for removal of nitric oxide fumes produced during oxidation. In another embodiment of the present invention, oxidation is carried out for 18-22 hrs, more preferably for 20 hrs. In an embodiment of the present invention, the reaction mixture is cooled to an ambient temperature before dilution. In another embodiment of the present invention, the reaction mixture is diluted with water before adjusting the pH. In an embodiment the pH of the reaction mixture is adjusted between 7.0 to 8.0 with an aqueous alkali solution In yet another embodiment the aqueous alkali solution used is aqueous ammonia solution. In still another embodiment the reaction mixture having pH 7.0 to 8.0 is heated to about 80 to 90 °C and treated with metal salts. In another embodiment of the present invention, the metal salt used for preparation of chromium nicotinate is selected from the group comprising of chromium (III) nitrate, chromium (III) chloride, chromium (III) acetate, chromium (III) formate and chromium (III) sulphate. In another embodiment of the present invention, chromium nicotinate having 8-14% chromium content is obtained. In yet another embodiment of the present invention, chromium nicotinate having 12.7 to 12.9% chromium content is obtained. In one more embodiment of the present invention, the metal salt used for the preparation of zinc nicotinate is selected from the group comprising of zinc sulphate, zinc chloride, zinc acetate and zinc carbonate. In another embodiment of the present invention, zinc nicotinate having 19-22% zinc content is obtained. In another embodiment of the present invention, zinc nicotinate having 21% zinc content is obtained. In another embodiment of the present invention, pure metal nicotinates is obtained by filtering, washing and drying the reaction product. In one more embodiment of the present invention, unreacted beta picoline is recovered from the filtrate. In another embodiment, the present invention provides a scope of utilising cheaper raw material and an economical single-pot preparation with high purity. Beta picoline is used in the preparation of metal nicotinates instead of nicotinic acid which has been used in the prior art for preparation and which is also a much costlier raw material in comparison to beta picoline. In still another embodiment of the present invention, beta picoline is reacted with sulphuric acid at a temperature ranging between 35-90° C and most preferably between 60-80° C. After the addition of beta picoline, the reaction mass temperature is raised to 150-210° C, preferably between 190-205° C nitric acid with 40-70% concentration is added, more preferably the concentration of nitric acid is 54-60%. The oxidation leads to evolution of nitric oxide fume, which is properly vented or scrubbed. Nitric acid is added within 18-22 hrs, and more preferably within 20 hrs. The reaction mass is then cooled to an ambient temperature, diluted with water, followed by adjusting the pH between 7.0 to 8.0 using aqueous ammonia. The reaction mass is again heated at 50-100° C, preferably at 70-100° C and most preferably at 80-90° C. To the above solution, the required hot metal salt solution is added to the reaction mass at 80-90° C. to get the desired metal nicotinate. The resulting mass is then cooled to an ambient temperature, filtered, washed and dried to get the pure metal nicotinate. In an another embodiment of the present invention chromium or zinc nicotinate is obtained by the reaction with metal salts selected from a group consisting of Chromium (III) nitrate, Chromium (III) chloride, Chromium (III) acetate, Chromium (III) formate, Chromium (III) sulphate etc., for chromium nicotinate. Zinc sulphate, Zinc chloride, Zinc acetate, Zinc carbonate, etc., for Zinc nicotinate An embodiment of the present invention provides an yield of about 77% zinc nicotinate . An embodiment of the present invention provides an yield of about 75% chromium nicotinate. The present invention is further described with the help of the following examples which are given by way of illustration and therefore should not be construed to limit the scope of the invention in any manner. EXAMPLES EXAMPLE 1 1.0 kg beta picoline is slowly added to concentrated sulphuric acid under agitation. After complete addition, the reaction mass temperature is raised to 180° C and 7.6 kg of 56% nitric acid is added and the temperature is maintained at 180-190° C for 20 hrs. After complete oxidation, the reaction mixture is cooled to an ambient temperature and diluted with 5.0 Kg water. After dilution, the pH of the reaction mixture is adjusted to pH 7.0 to 8.0 by the addition of aqueous ammonia solution. The resulted solution is heated to 80-90° C and a hot solution of 600 g chromium (III) chloride in 2.5 kg water added over a period of 2-6 hrs at 80-90° C. The whole mass is stirred at 80-90° C for further half an hour. The resulting mass is brought to an ambient temperature and the product is collected by filtration and washing. After drying 980 g of purple coloured chromium nicotinate, having 12.7% chromium content, is obtained and 335 g beta picoline is recovered from the filtrate. EXAMPLE-2 Example 1 was repeated by adopting the same procedure but chromium (III) acetate is used in place of chromium (III) chloride. EXAMPLE-3 Example 1 is repeated by adopting the same procedure but chromium (III) oxalate is used in place of chromium (III) chloride. EXAMPLE-4 Example 1 is repeated up to the oxidation step by adopting the same procedure and the reaction mass is diluted with 5.0 kg water. After dilution the pH of the solution is adjusted to 7.0-8.0 by the addition of liquid ammonia solution. The temperature of the resulted solution is raised to 80-90° C and a hot solution of 975 g zinc sulphate heptahydrate in 2.0 kg water is added to the reaction mass slowly at 80-90° C and the mass is concentrated and chilled to 0-5° C. The white precipitate is filtered, washed and reprecipitated with water and again filtered, washed and dried to give 500 g pure zinc nicotinate having 21% zinc content. 330 g unreacted beta picoline is recovered from the filtrates. EXAMPLE-5 Example 4 is repeated following the same procedure but zinc chloride is used in place of zinc sulphate. WE CLAIM: 1. A single pot process for the preparation of zinc and / or chromium nicotinates useful as dietary supplements from beta picoline, said process comprising the steps of: (a) hydrosulfonation of beta picoline with sulfuric acid at a temperature in the range of 35 - 100°C to form a reaction mixture; ( b ) further heating the reaction mixture obtained in step (a) to a temperature of 150 to 210°C; (c) oxidizing the reaction mixture of step (b) with an oxidizing agent such as herein described under proper ventilation to remove nitric oxide fumes for a time period in the range of 18 to 22 hours to obtain nicotinic acid sulfate at a temperature ranging from 35 to 90°C to form a solution; (d ) maintaining the pH of the solution of step (c) of 7 to 8 as a basic solution using an alkali solution; ^, (e) treating the basic solution of step (d) with a water soluble zinc and / or chromium salt to produce a solid metal nicotinate in said water; and (f) filtering the resulting solid metal nicotinate of step (e) to remove such from said water and to thereby obtain the corresponding metal nicotinates. 2. The process as claimed in claim 1, wherein in step (c), the oxidising agent used is a 40-70 % concentrated nitric acid. 3. The process as claimed in claim 1, wherein the reaction of beta picoline and sulfuric acid is carried out preferably in a temperature ranging from 35 to 90°C. 4. The process as claimed in claim 1, wherein the reaction of beta picoline with sulfuric acid is carried out most preferably in a temperature ranging from 60 to 80°C. 5. The process as claimed in claim 1, wherein the heating of the reaction mixture of step (b) preferably at a temperature in the range of 190 to 205°C. 6. The process as claimed in claim 1, wherein said oxidation is carried out preferably for 20 hours. 7. The process as claimed in claim 1, wherein the alkali solution used is an aqueous ammonia solution. 8. The process as claimed in claim 1, wherein said zinc salt used for the preparation of said zinc nicotinate is selected from the group comprising of zinc sulphate, zinc chloride, zinc acetate and zinc carbonate. 9. The process as claimed in claim 1, wherein zinc nicotinate is recovered having zinc in the range of 19 to 22% by weight. 10. The process as claimed in claim 1, comprising recovering zinc nicotinate having 21% by weight of zinc. 11. The process as claimed in claim 1, wherein the metal salts used for the preparation of chromium nicotinates is selected from the group comprising of chromium nitrate, chromium chloride, chromium acetate, chromium formate, chromium carbonate and chromium sulphate. 12. The process as claimed in claim 1, wherein chromium nicotinate is recovered having chromium in the range of 8 to 14% by weight. 13. The process as claimed in claim 1, comprising recovering chromium nicotinate having chromium in the range of 12.7 to 12.9% by weight. 14. The process as claimed in claim 1, wherein the yield of zinc nicotinate is 77%. 15. The process as claimed in claim 1, wherein the yield of chromium nicotinate is 75%. 16. A single pot process for the preparation of zinc and / or chromium nicotinates useful as dietary supplements from beta picoline substantially as herein described with reference to the foregoing examples.

Documents:

1141-del-2002-abstract.pdf

1141-del-2002-claims.pdf

1141-DEL-2002-Correspondence-Others-(17-03-2011).pdf

1141-del-2002-correspondence-others.pdf

1141-del-2002-correspondence-po.pdf

1141-del-2002-description (complete).pdf

1141-del-2002-form-1.pdf

1141-del-2002-form-13.pdf

1141-del-2002-form-19.pdf

1141-del-2002-form-2.pdf

1141-del-2002-form-26.pdf

1141-DEL-2002-Form-27-(17-03-2011).pdf

1141-del-2002-form-3.pdf

1141-del-2002-form-5.pdf

1141-del-2002-petition-137.pdf

1141-del-2002-petition-138.pdf