Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-02-12
2002-11-05
Dentz, Bernard (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06476239
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a process for the preparation of ascorbic acid. More particularly, this invention pertains to a process wherein 2-keto-L-gulonic acid (KLG) or a KLG derivative is converted to ascorbic acid in simulated moving bed reactor (SMB).
BACKGROUND OF THE INVENTION
The commercial importance of ascorbic acid has resulted in numerous processes for its manufacture. Known commercial processes for the production of ascorbic acid generally involve four major steps: (1) a fermentation section where a sugar such as glucose or sorbose is subjected to fermentation to produce 2-keto-L-gulonic acid (KLG); (2) the purification and isolation of anhydrous KLG; (3) the conversion of the isolated KLG to an alkyl KLG ester (AKLG) by esterification with an alcohol, typically methanol; and (4) cyclization of the AKLG to produce L-ascorbic acid using stoichiometric amounts of a base. These processes have evolved from the original Reichstein Process (T. Reichstein, A. Grussner,
Helv. Chim. Acta
17, p. 311, 1934).
The traditional Reichstein processes described above, in particular the last 3 steps, suffer from a number of disadvantages. For example, the esterification of KLG to an alkyl ester (Step 3) typically requires isolation of KLG as a solid from the aqueous fermentation broth by crystallization and drying. During crystallization of KLG, a significant amount of KLG present in the mother liquor stream may not be recovered. The isolated KLG normally must be free of water to obtain an acceptable yield of the ester of KLG in the subsequent esterification step. Drying KLG is normally accomplished by evaporation which requires large amounts of energy and costly equipment. This esterification is frequently carried out in anhydrous methanol using sulfuric acid or other strong acid catalysts which requires subsequent removal of the acid and its salts. For example, U.S. Pat. No. 5,391,770 describes a series of steps consisting of esterification of KLG with methanol in the presence of a strong soluble acid followed by a cyclization with an inorganic base and protonation with sulfuric acid. This is a lengthy process and requires crystalline KLG monohydrate and nearly anhydrous conditions to effect esterification and cyclization. U.S. Pat. No. 5,744,634 (European Patent Application EP 0 671 405 A) discloses a process for the production of the methyl or ethyl ester of KLG by esterification of KLG with methanol or ethanol in the presence of an ion exchange resin. The esterification process takes place in a tubular reactor containing an ion exchange resin using a residence time of from 10 to 120 minutes. The process disclosed in the '634 patent requires the monohydrate or, preferably, the anhydrous form to esterify KLG with methanol or ethanol.
The water formed during the esterification of KLG limits the equilibrium conversion and results in lost yield. As noted above, this problem is worsened if KLG monohydrate is utilized instead of anhydrous KLG and requires additional steps during the esterification to remove the water of hydration. An example of such a process is described in PCT Patent Application WO 99/03853.
Various processes to improve the esterification of KLG by increasing the efficiency of water removal have been described. U.S. Pat. Nos. 6,146,534 and 6,153,791 describe similar processes to dewater KLG solids using a solvent exchange process aided by ion exchange resins. Both processes accomplish separation only and an additional step to esterify KLG is required. The extent of esterification can be increased by simultaneously removing water or the ester as the reaction proceeds. WO 99/03853 discloses that the esterification of KLG may be carried out in a 2-stage process in which the reaction can be driven to completion by crystallization of methyl 2-keto-L-gulonate coupled with efficient removal of water. This process requires multiple crystallization stages and solid liquid separation equipment. German Patent Application DE 199 38 980 Al discloses a method for producing C
1
-C
10
alkyl KLG esters by the esterification of KLG with a C
1
-C
10
alcohol in the presence of an acid catalyst wherein the esterification is carried out in a liquid film on a hot surface with simultaneous removal of water. This process is simple to operate but requires significant energy and large volumes of alcohol solvent to act as a carrier for water removal. This process does not provide a means to remove impurities. Other known means to enhance the extent of esterification include membrane reactors for the selective removal of water during esterifications. These methods are well known and described in many publications, for example, by Feng. and Huang, Studies of a Membrane Reactor: Esterification Facilitated By Pervaporation, Chemical Engineering Science, Vol 51, No. 20, pp4673-4679, 1996; Jennings et al. U.S. Pat. No. 2,956,070; Okomoto et al., Pervaporation-aided Esterification of Oleic Acid, Journal of Chemical Engineering of Japan, Vol 26, No 5, pages 475-481, 1993; Kwon, et al, Removal of Water Produced from Lipase-Catalyzed Esterification in Organic Solvent by Pervaporation, Biotechnology and Bioengineering, Vol 46, pp 393-395, 1995; Keurentjes, The Esterification of Tartaric Acid with Ethanol: Kinetics and Shifting the Equilibrium by Means of Pervaporation, Chemical Engineering Science, Vol 49, No. 24A, pages 4681-4689, 1994; and Xiuyuam, et al., Modified Aromatic Polyimide Membrane Preparation and Pervaporation Results for Esterification System, Water Treatment, 10, pages 115-120, 1995. Simulated moving bed reactors have been proposed as another alternative to enhance the extent of esterifications. See, for example, Kawase et al., Increased Esterification Conversion By Application Of The Simulated Moving-Bed Reactor, Chemical Engineering Science, Vol 51, No 11, pages 2971-2976, 1996; Mazzotti et al., Dynamics Of A Chromatographic Reactor: Esterification Catalyzed By Acidic Resins, Ind. Eng. Chem. Res. 1997, 36,3163-3172; and U.S. Pat. No. 5,405,992. These publications describe processes that remove water formed during esterification of a carboxylic acid.
An improvement to the above processes is described by Arumugam et a/. in U.S. patent application Ser. No. 09/975,872, filed Oct. 12, 2001. This process utilizes a SMB reactor to dewater, esterify KLG, and remove the water formed during esterification by the selective adsorption of water using an acidic ion-exchange resin. The process described in Arumugam et. al. does not, however, convert the KLG ester product into ascorbic acid.
Numerous processes for the preparation of ascorbic acid from KLG and esters of KLG have been published. Good reviews of the prior art are found in Crawford et. al.
Adv. Carbohydrate Chemistry
. 37, (1980), 79 and in
Ullman's Encyclopedia of Industrial Chemistry
, Vol. A27 (1996), 551-557. The conversion of KLG to L-ascorbic acid may be carried out by the original Reichstein process, or variants thereof, involving esterification with methanol followed by cyclization using stoichiometric amounts of a base. Alternatively, a diacetone-2-keto-L-gulonic acid intermediate may be cyclized directly, with loss of acetone followed by consecutive lactonization and enolization, to form ascorbic acid. Direct cyclization, however, requires extensive equipment for recovery of the acetone and other byproducts generated. Alternative methods involve the lactonization of KLG esters or KLG directly using acids. For example, U.S. Pat. No. 2,185,383 describes the reaction of KLG and its readily hydrolysable derivatives with concentrated hydrochloric acid in acetic acid solvent. A variant of this process is disclosed in U.S. Pat. No. 2,462,251 where 2-keto-L-gulonic acid is converted to ascorbic acid in an inert organic solvent under acidic conditions. Modifications to improve the process such as the use of surfactants (see e.g. U.S. Pat. No. 5,744,618; WO 98/00839; and JP-B 48-15931) or conducting the reaction in the melt phase (EP 1 048 663 A1) have been described. Generally, because of the decompos
Arumugam Bhaskar Krishna
Blair Larry Wayne
Mackenzie Elaine Beatrice
Perri Steven Thomas
Zoeller Joseph Robert
Dentz Bernard
Eastman Chemical Company
Graves, Jr. Bernard J.
Tubach Cheryl J.
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