| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | May 11, 1999 |
| PATENT TITLE |
Production of L-ascorbic acid |
| PATENT ABSTRACT | L-ascorbic acid is produced by allowing an acid to act on 2-keto-L-gulonic acid in a mixture solvent of an inert organic solvent and an aliphatic ketone in the presence of water and a surfactant. The method produces L-ascorbic acid in a high yield 90% or more and is an industrially advantageous method |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | January 8, 1993 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
We claim: 1. A method of preparing L-ascorbic acid, which comprises allowing an acid to act on 2-keto-L-gulonic acid in a mixed solvent consisting essentially of an inert organic solvent and an aliphatic ketone in the presence of water and a surfactant wherein the volume of the aliphatic ketone in the mixed solvent is in a range of 0.02 to 0.3 relative to the volume of the inert organic solvent, and wherein the amount of water is 1.5 to 3.5 times as much in molar ratio relative to 2-keto-L-gulonic acids and the amount of the acid is 0.5 to 2 times as much in molar ratio relative to 2-keto-L-gulonic acid. 2. The method claimed in claim 1, wherein the inert organic solvent is an aromatic hydrocarbon. 3. A method claimed in claim 1, wherein the aliphatic ketone is a ketone having an alkyl whose carbon number is 1 to 6 or a cyclic ketone having a cycloalkyl whose carbon number is 5 to 6. 4. A method claimed in claim 1, wherein the acid is hydrochloric acid. 5. The method claimed in claim 1, wherein the surfactant is a quarternary ammonium salt. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
This invention relates to a method of preparing L-ascorbic acid, in which 2-keto-L-gulonic acid is employed as the starting material. As one of the methods of preparing L-ascorbic acid, there has been known a method which comprises employing 2-keto-L-gulonic acid as the starting material and allowing an acid to act thereon to prepare L-ascorbic acid in one step. The known methods include, for example, 1 a method which comprises allowing concentrated hydrochloric acid to act on 2-keto-L-gulonic acid using acetic acid as the solvent ›U.S. Pat. No. 2,185,383 Specification (1940)!, 2 a method which comprises adding ethanol and acetone to sodium salt of 2-keto-L-gulonic acid, neutralizing with hydrochloric acid, separating precipitating sodium chloride by filtration, then maintaining the reaction mixture at temperatures ranging from 25.degree. C. to 75.degree. C. to thereby obtain L-ascorbic acid Japanese Unexamined Pat. Pub. No. 58-177986, 3 a method which comprises allowing a mineral acid to act on 2-keto-L-gulonic acid in an inert solvent in the presence of a surfactant (Japanese Examined Pat. Pub. No. 48-15931) and 4 a method which comprises causing slurry of substantially anhydrous 2-keto-L-gulonic acid to be produced in an inert organic solvent containing a surfactant, then allowing a substantially anhydrous acid catalyst to act on this slurry to give L-ascorbic acid ›PCT,WO87/00839 (1987)!. On the other hand, fermentative methods of preparing 2-keto-L-gulonic acid in a large amount from L-sorbose have been proposed (e.g. U.S. Pat. No. 4,543,331, EP 132,308), and thus a method of industrial production of L-ascorbic acid at one stroke by using this starting material has been desired to be established as early as possible. However, the known methods mentioned above have still some drawbacks, while, some improvement is observed in e.g. yield, including still insufficient yield from the viewpoint of industrial production, a large content of colored substances in the reaction mixture as impurities, which inevitably imposes a burden on the purification process, thus preventing them from being employed as methods in an industrial scale. The present inventors have conducted study on methods of preparing L-ascorbic acid employing 2-keto-L-gulonic acid as the starting material, and have established an industrially advantageous method affording a high yield of about 90% or more of the desired product with little production of impurities More specifically, the present inventors have found that the reaction proceeds advantageously by conducting lactonization of 2-keto-L-gulonic acid in a mixture solvent of an inert organic solvent e.g. toluene, benzene, etc. and an aliphatic ketone e.g. acetone, methyl ethyl ketone, etc. And, the present inventors have also found that the reaction proceeds more advantageously by suitably controlling the amounts of water and an acid catalyst. Namely, the present invention relates to a method of preparing L-ascorbic acid, which comprises allowing an acid to act on 2-keto-L-gulonic acid in a mixture solvent of an inert organic solvent and an aliphatic ketone in the presence of water and a surfactant. The reaction of this invention is conducted in a mixture solvent prepared by adding a given amount of an aliphatic ketone to an inert organic solvent. The inert organic solvent means an organic solvent with which 2-keto-L-gulonic acid and L-ascorbic acid are not reactive and in which 2-keto-L-gulonic acid and L-ascorbic acid are insoluble. Inert organic solvents usable for the present invention include aromatic hydrocarbons which may be substituted with halogen or alkyl, such as benzene, toluene, xylene and chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform and ethylene chloride; aliphatic hydrocarbons such as hexane, heptane and octane; and ethers such as tetrahydrofuran, dioxane and isopropyl ether; or a mixture of them. Preferable ones are aromatic hydrocarbons such as benzene or toluene. Aliphatic ketones usable for the present invention include ketones containing alkyl having 1 to 6 carbon atoms, and cyclic ketones containing cycloalkyl having 5 to 6 carbon atoms. The alkyl may be straight-chain or branched one, preferably a one having 1 to 4 carbon atoms. These two alkyls bonding to carbonyl may be the same as or different from each other. Practical examples of such ketones include acetone, methyl ethyl ketone, diethyl ketone, methyl isobutyl ketone and cyclohexanone, preferably acetone and methyl ethyl ketone. Such a ketone as exemplified above is required to be present in a specified amount in an inert organic solvent. The amount of a ketone to be mixed is about 0.02 to 0.3 volume part, preferably 0.05 to 0.2 volume part, relative to 1 volume part of an inert organic solvent. By maintaining the ketone concentration within this range throughout the reaction, the reaction can be allowed to proceed more smoothly. And, the ketone may be supplemented in the course of the reaction, so long as the amount of ketone does not deviate the above-mentioned range. When the amount of a ketone to be mixed is out of the range specified as above, the amount of degradation products increases to cause more strong coloration of the reaction mixutre, thus complicating the purification procedure, which is far from an industrially advantageous method. When the amount of a ketone exceeds the above-mentioned range, the amount of unreacted materials tends to become more, thus lowering the yield of the object compound. In this invention, the lactonization of 2-keto-L-gulonic acid is carried out in the above-mentioned mixutre solvent. The concentration of 2-keto-L-gulonic acid relative to the mixtrue solvent is not limitative, but is usually 5 to 40 weight %, preferably 10 to 30 weight % from the economical viewpoint. In the present invention, the reaction is allowed to proceed by adding an acid in the presence of water and a surfactant. In this case, the amounts of water and an acid are preferably restricted as follows, respectively. The amount of water is 1.5 to 3.5 times as much in molar ratio, preferably 1.8 to 3 times as much in molar ratio relative to 2-keto-L-gulonic acid. Water is allowed to be present within the mentioned range in the solvent when the reaction is carried out. When the starting material 2-keto-L-gulonic acid is, for example, hydrated or contains water, such water is taken into account for calculation of the amount of water. And, the amount of water contained in an acid catalyst used for promoting the reaction or in a mixture solvent then employed is also taken into account for calculation of the amount of water. When the amount of water deviates from the above-mentioned range, the amount of decomposed materials increases to cause lowering of the yield. Surfactants that can be used in this invention include nonionic surfactants such as polyoxyethylene alkylaryl ether, polyoxyethylene alkyl ether, etc, cationic surfactants such as quarternary ammonium salts, pyridinium salts, etc., and anionic surfactants such as higher aliphatic alkylaryl sulfonates, etc.; each surfactant may be used alone or in combination with one or more of them Desirable surfactants for this invention are cationic ones, especially quaternary ammonium salts such as trimethyl tetradecyl ammonium chloride, trimethyl dodecyl ammonium chloride, trimethylcetyl ammonium chloride, trimethyloctyl ammonium chloride, diiethylethylcetyl ammonium chloride, trimethylstearyl ammonium chloride, dimethyl butylcetyl ammonium bromide and trimethyldodecyl ammonium bromide. The amount of the surfactant to be added ranges from 0.01 to 10 w/w %, preferably from 0.05 to 3.0 w/w % relative to 2-keto-L-gulonic acid. Acids employable as the catalyst are exemplified by mineral acids including, for example, hydrochloric acid, phosphoric acid, etc., and hdyrochloric acid is espacially preferable The amount of an acid to be added for allowing the reaction to proceed advantageously, in the presence of water of an amount within the above-mentioned range, is 0.5 to 2 times as much in molar ratio, preferably 0.5 to 1.5 times as much in molar ratio relative to 2-keto-L-gulonic acid. As water is required for the reaction, it is preferable to employ hydrochloric acid of 20 to 45% concentration, usually a one having 35% concentration. The ketone solution containing hydrogen chloride is employable for adjusting the amount of an acid. Addition of an acid may be conducted in two installments within the above-mentioned range. Under the above-mentioned conditions, the starting material 2-keto-L-gulonic acid is lactonized by the action of an acid to give L-ascorbic acid. The reaction proceeds in a heterogenous system. As the reaction proceeds, 2-keto-L-gulonic acid becomes gruel-like to oily (usually in 30 minutes to one hour after initiating the reaction). At this point of time, it is preferable to adjust the amounts of water and acid to the given ones. It is also possible to adjust the volume of water remaining in the reaction mixture by eliminating water in the reaction mixture by means of a conventional dehydrating procedure such as azeotropic distillation. This dehydration process is preferable to complete within a period as short as possible. When an aliphatic ketone or an acid catalyst is distilled off together with water, for example, by azeotropic dehydration, they may be suitably supplemented. Reaction temperatures range from about 40.degree. C. to about 80.degree. C., preferably from 50.degree. C. to 70.degree. C. The recation completes usually in 3 to 8 hours. For separating the object compound from the reaction mixture, a per se conventional process, for example, filtration, concentration, extraction, etc is employable. Further, if necessary, the object compound may be led to a highly purified one through, for example, recrystallization. According to the method of this invention, L-ascorbic acid can be prepared in a high yield of 90% or more. In addition, due to a little amount of impurities (e.g decomposition products) which may cause coloring occurs, no troublesome purification process is required, which is of a very industrial advantage |
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| PATENT PHOTOCOPY | Available on request |
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