USOO6320061B1 (12) United States Patent (10) Patent No.: US 6,320,061 B1 Collins et al. (45) Date of Patent: Nov. 20, 2001 (54) SOLVENT EXCHANGE PROCESS 5,712,131 1/1998 Felman et al. ....................... 435/136 5,741,681 4/1998 Kato et al. ........................... 435/109 (75) Inventors: Nick Allen Collins, Fall Branch; 5,827,700 10/1998 Felman et al. ....................... 435/144 Steven Thomas Perri, Kingsport, both 5,852,211 12/1998 Dimpelmann et al. ............. 562/580 of TN (US) FOREIGN PATENT DOCUMENTS (73) Assignee: Eastman Chemical Company, 922,949 * 6/1947 (FR). Kiingsport, t TN (US)(US OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this Chemical Abstracts, vol. 82, 65021 Zh. Prikl. Khim, (Len patent is extended or adjusted under 35 ingrad), 47(11), p. 2530–2532 (1974), 1975.* U.S.C. 154(b) by 0 days. Anderson, et al., “Production of 2-Keto-L-Gulonate, an Intermediate in 1-AScorbate Synthesis, by a Genetically (21) Appl. No.: 09/587,752 Modified Erwinia herbicola,” Science, vol. 230, pp. (22) Filed: Jun. 5, 2000 Reichstein,144-149 (1985). et al., “Eine Ergiebige- 0 Synthesis der L-AScorb (51) Int. Cl." ............................................... C07D 307/62 ins?ure (C-Vitamin)).” Helv. Chim. Acta, vol. 17:311-328 (52) U.S. Cl. .............................................................. 549/315 (1934). (58) Field of Search ............................................... 549/315 Saito, et al., “Cloning of Genes for L-Sorbose and L-Sor bOSone Dehydrogenases from Gluconobacter Oxydans and (56) References Cited Microbial Production of 2-Keto-L-Gulonate, A Precursor of L-AScorbic Acid, in a Recombinant G. Oxydans Strain.” U.S. PATENT DOCUMENTS Applied & Environmental Microbiol., 63(2):454-460 2,421,611 6/1947 Gray ....................................... 195/47 (1997). 2,421,612 6/1947 Gray ....................................... 195/47 2,462,251 2/1949 Bassford, Jr. et al. ... 549/315 cited by examiner 4,113,771 9/1978 Lawrence, Jr. et al. ............. 562/568 4,191,841 3/1980 Soreau et al. ........................ so.247s Primary Examiner-Bernard Dentz 4,202,828 5/1980 Matsuura et al. ... 562/408 (74) Attorney, Agent, or Firm-Cheryl J. Tubach; Bernard 4,334,074 6/1982 Peterson ............ ... 546/327 J. Graves, Jr. 4,699.999 10/1987 EI-Chahawi et al 562/450 4,771,001 9/1988 Bailey et al. ..... ... 435/139 (57) ABSTRACT 4,990,441 2/1991 Barthole et al. ... ... 435/138 5,128,487 7/1992 Tomislav et al. ... ... 549/315 A process for recovering an organic acid O metal salt 5,159,110 10/1992 Thunberg ....... ... 562/554 thereof includes contacting an alcoholic phase containing 5,168,055 12/1992 Datta et al. ... ... 435/145 one or more organic acid(s) or metal salt(s) thereof with 5,202,475 4/1993 Cook et al. .... ... 562/509 water under conditions effective to provide an aqueous 5,202,476 4/1993 Tsuda et al. ... ... 562/513 phase containing a portion of the organic acid(s) or metal 5,210.296 5/1993 Cockrem et al. ... 562/589 salt(s) thereof. The aqueous phase does not contain Substan 5,349,074 9/1994 Bonaldi ............. ... 552/551 tial amounts of the alcohol(s). This process can also include 5,391,770 2/1995 Le Fur et al. ... 549/315 recovery of the organic acid(s) or metal salt(s) thereof from 5,410,076 4/1995 Coope et al. ...... ... 562/450 the aqueous phase. 5,426.219 6/1995 Lehnhardt et al. ... 562/580 5,449,824 9/1995 Feman et al. ..... ... 562/580 5,522,995 6/1996 Cockrem .............................. 210/637 38 Claims, 4 Drawing Sheets U.S. Patent Nov. 20, 2001 Sheet 1 of 4 US 6,320,061 B1 v. C Process in Methanol Solids 1st Crystallization 2nd Crystallization Purge or Partial Recycle Water Recrystallization Product ASCOrbic Acid F.G. 1 U.S. Patent Nov. 20, 2001 Sheet 2 of 4 US 6,320,061 B1 Water it. C Process in Alcohol Alcohol Solvent Exchanger Product ASCorbic Acid or Aq. Vit C Crystallization Alkali ASCOrbate Purge or Partial Recycle FG. 2 U.S. Patent Nov. 20, 2001 Sheet 3 of 4 US 6,320,061 B1 Water Vit. C PrOCeSS in Alcohol Alcohol Optional Carbon Aq. Vit C Treatment Optional CX/AX Crystallization ) Product ASCOrbic Acid Purge or Partial Recycle FIG. 3 U.S. Patent Nov. 20, 2001 Sheet 4 of 4 US 6,320,061 B1 Water Wit. C Process in Alcohol Alcohol Optional Carbon Treatment Crystallization -) Product Alkali ASCOrbate Purge or Partial Recycle FIG. 4 US 6,320,061 B1 1 2 SOLVENT EXCHANGE PROCESS alcohol Solvent. This allows for a process to recover an acid ACKNOWLEDGMENT or Salt thereof from an alcohol Solvent without transitioning through the isolation of Solids. Because of this, a process that This invention was made with United States Government is capable of providing a more economical operation and a Support under Cooperative Research Agreement No. more integrated continuous operation can be provided. 70NANB5H1138 awarded by the Advanced Technology One example of a process according to the invention Program of the National Institute of Standards and Technol includes contacting an alcoholic phase containing one or ogy. The United States Government has certain rights in the more organic acid(s) or metal salt(s) thereof with water invention. under conditions effective to provide an aqueous phase BACKGROUND OF THE INVENTION containing a portion of the organic acid(s) or metal Salt(s) 1. Field of the Invention thereof. The aqueous phase does not contain Substantial The present invention relates to a Solvent eXchange amounts of the alcohol(s). This process can also include process, and in one embodiment, a process that is capable of recovery of the organic acid(s) or metal salt(s) thereof from Separating an organic acid Such as ascorbic acid from an the aqueous phase. alcoholic phase. 15 One specific embodiment of the invention relates to the 2. Background Art use of this process in recovering ascorbic acid. Attempts to efficiently and effectively Separate an organic BRIEF DESCRIPTION OF THE DRAWINGS acid from an alcoholic phase in which the acid resides have proven to be quite inefficient. In particular, one environment FIG. 1 illustrates a prior art System for removing an acid which these inefficiencies have been particularly apparent from an alcoholic phase. relates to the production of ascorbic acid. FIGS. 2-4 illustrate system according to the present L-ascorbic acid (vitamin C) has been produced commer invention for exchanging the alcoholic phase with an aque cially by way of chemical fermentation processes Starting ouS phase. from glucose or Sorbose. A common intermediate generated 25 PREFERRED EMBODIMENTS OF THE during the fermation process is 2-keto-L-gulonic acid or its INVENTION protected form of diacetone-2-keto-L-gulonic acid. In the case of 2-keto-L-gulonic acid, a process involves esterifi The present invention relates, in one embodiment, to a cation of the Sugar with methanol followed by cyclization process for recovering organic acids or metal Salts thereof using Stoichiometric amounts of base. This process has from an alcoholic phase. The processes can include contact ing the alcoholic phase with water under conditions effective evolved from the original Reichstein process (T. Reichstein, to provide an aqueous phase containing at least a portion of A. Grussner, Helv. Chim. Acta 17, p. 311, 1934). the organic acid(s) or metal salt(s) thereof and which acque Recent modifications to the Reichstein process have ous phase does not contain Substantial amounts of the become more prevalent as alternative fermentation pro alcohol. ceSSes for producing 2-keto-L-gulonic acid directly from 35 glucose or Sorbose have been reported. These processes have This embodiment of the invention is capable of being eliminated or removed Some of the chemical processing employed in connection with any combination of organic StepS prior to production of 2-keto-L-gulonic acid in the acid(s) or metal salt(s) thereof with any alcohol So long as Reichstein process. However, these processes have neces the organic acid/metal Salt is at least partially Soluble within sitated the Separation and purification of ascorbic acid from 40 the alcohol(s). its alcoholic or aqueous alcoholic Solution, all initiated from Specific examples of Suitable organic acids include an alkali metal ascorbate. ascorbic, Succinic, tartaric, gluconic, glyconic, citric, lactic, The esterification and cyclization processes employed in malic, maleic, acetic, formic, pyVuric, propionic, butyric, the art utilized an organic Solvent with the cyclization Step itaconic, gulonic and mixtures thereof. Moreover, the metal and therefore eventually include an isolation of either solid 45 Salts of these acids include any metal Salts recognized the art alkaliascorbate or Solid ascorbic acid by dissolving the Solid Such as alkali metal Salts and alkaline earth metal Salts with in water with Subsequent crystallization from water. A alkali metal Salts being preferred. Specific examples of typical arrangement is illustrated by FIG. 1 in which the feed preferred metal Salt include Sodium Salts. involves ascorbic acid in an alcoholic phase. The Solids are AS discussed above, any Suitable alcoholic phase can be removed by a Series of crystallization Steps and then dis 50 employed as long as the organic acid(s) or metal Salt(s) Solved in, and recrystallized from, water to provide the thereof are at least partial soluble in the alcohol. The desired final product. preferred alcoholic phase is depended on the particular acid AS can be seen, this Series of processing Steps necessitates being recovered. a complex Separation System. Solid-liquid handling equip One aspect of the inventive proceSS involves contacting ment Such as crystallizers are needed for Switching from the 55 the alcoholic phase with water under conditions effective to organic Solvent to an aqueous-based Solvent System as well provide an aqueous phase containing at least a portion of the as Similar Solid-liquid handling equipment as required from organic acid(s) or metal salt(s) thereof.