United States Patent (19) 11 Patent Number: 4,464,530 Matsumura et al. 45) Date of Patent: Aug. 7, 1984

(54 PROCESS FOR PRODUCTION OF SUGAR KETALS OTHER PUBLICATIONS 75 Inventors: Koichi Matsumura, Ibaraki; Tetsuya Adkins et al. J. Amer. Chem. Soc., vol. 44, (1922) pp. Aono, Nagaokakyo, both of Japan 2749.2755. Migrichian, Organic Synthesis, vol. 1, (1957) pp. 43-46. 73 Assignee: Takeda Chemical Industries, Ltd., Journal of American Chemical Society, 45, 734-751 Osaka, Japan (1923), Harold Hibbert and Harold S. Hill. 21 Appl. No.: 478,201 The Journal of the American Chemical Society 37 1748 22 Filed: Mar. 23, 1983 (1915) ibid. 45,734 (1923). Primary Examiner-Johnnie R. Brown 30) Foreign Application Priority Data Assistant Examiner-Elli Peselev Mar. 29, 1982 (JP) Japan ...... 57-50574 Attorney, Agent, or Firm-Wegner & Bretschneider 51 Int. Cl...... C07H 1/00 (57) ABSTRACT 52 U.S. C...... 536/124; 536/120; 536/41; 568/394 A process is disclosed for production of a sugar ketal, 58) Field of Search ...... 536/120, 124; 568/594 which comprises reacting a sugar with a in the presence of hydrogen iodide. The formation of unfavor 56) References Cited able by-products can be reduced to a trace amount. The U.S. PATENT DOCUMENTS process offers the objective ketal in improved yields, 3,598,804 8/1971 Hindley et al...... 536/124 and an industrially advantageous process. 3,607,862 9/1971 Jaffe et al...... 536/124 3,622,560 1 1/1971 Hindley et al...... 536/124 12 Claims, No Drawings 4,464,530 1. 2 ing a sugar with ketone in the presence of hydrogen PROCESS FOR PRODUCTION OF SUGAR iodide. KETALS The sugar usable in the present invention is not spe cifically limited, and is exemplified by a pentose such as The present invention relates to a novel process for arabinose, xylose, ribose, lyxose, ribulose and xylulose, production of sugar ketals. More particularly, the pres a hexose such as glucose, galactose, talose, idose, gu ent invention provides a process for producing sugar lose, mannose, altrose, fructose, sorbose, tagatose and ketals in the presence of a catalyst. Production of sugar psicose, a deoxy-sugar such as rhamnose, fucose, 2 ketals is important for protection of hydroxyl groups of deoxyribose, and 2-deoxyglucose, and a sugar alcohol a sugar or for study of the structure of a sugar, and the 10 such as ribitol, arabitol, mannitol, sorbitol, dulcitol and sugar ketals are widely used as intermediates in various inositol. Among these sugars is valuable a pentose (e.g. syntheses, for example, an intermediate for production arabinose and xylose) or a hexose (e.g. glucose, man of vitamin C, thus being very important from the indus nose, Sorbose, galactose, fructose). trial point of view. The ketone usable in the present invention is not The dehydration-condensation reaction of a sugar 15 specifically limited, and the preferred examples include with a ketone is known as a ketal formation reaction, for an alkyl ketone such as acetone, methyl ethyl ketone, which various methods have been proposed so far. The diethyl ketone, di-n-propyl ketone and di-i-propyl ke conventionally known methods involve the use of acid tone, and a cyclic ketone such as cyclopentanone, cylo catalysts such as mineral acids exemplified by sulfuric hexanone and cycloheptanone. Among these is acid, hydrogen chloride, hydrogen bromide, phos 20 valuable acetone or cyclohexanone. The amount of phoric acid and perchloric acid; organic acids exempli these ketones to be used varies depending upon the fied by acetic acid, trifluoroacetic acid, methanesulfonic structure of the objective compounds. The ketone is acid, p-toluenesulfonic acid and acidic ion exchange normally used in about 1 to 10 times the theoretical resins; or Lewis acids exemplified by anhydrous alumi molar quantity; for example, it is preferable to use 1 num chloride, tin tetrachloride, boron trifluoride, anhy 25 mole or more of a ketone per mole of a sugar in the case drous zinc chloride and ferric chloride. The ketal for of the objective compound being a monoketal, to use 2 mation reaction is a dehydration-condensation reaction moles or more of a ketone per mole of a sugar in the and, in almost all cases, the acid catalyst is used in large case of the objective compound being a diketal, and to quantities so that the catalyst may serve as a dehydrat use 3 moles or more of a ketone per mole of a sugar in 30 the case of the objective compound being a triketal. ing agent as well. When using a reduced amount of the Furthermore, the ketones may be used both as a reac acid catalyst it is necessary, furthermore, to use consid tant and a solvent, and in such case, a large excess of erable quantities of dehydrating agents such as phos them may be used, unless they give any adverse effect phorus pentoxide, calcium chloride, anhydrous sodium on the reaction. sulfate, anhydrous copper sulfate, pyrosulfates, meta 35 Hydrogen iodide as used in the method of this inven phosphoric acid esters, alum and molecular sieves. That tion may be hydrogen iodide as such or hydriodic acid is to say, the conventional methods demand large quan obtainable by dissolving hydrogen iodide in water. Or, tities of acid catalysts and dehydrating agents. There it may also be a compound or system that exists as hy fore, the step of isolating the objective ketal from the drogen iodide in the reaction system or one that liber reaction mixture is considerably troublesome. And a 40 ates hydrogen iodide in the reaction system. large amount of salts which are by-produced in the Examples of the compound or system that exists as neutralization step and the used dehydrating agent are hydrogen iodide or liberates the same therein include, unfavorable industrial wastes. Thus, any one of the for example, (1) a metal iodide and an acid, (2) an iodin above conventional methods includes a good deal of ation agent, and (3) an iodination agent and a reducing problematic points as an industrial production process 45 agent. Specific examples of said metal iodide are sodium from the standpoints of post-treatment problems and iodide, , magnesium iodide, calcium saving of natural resources. In addition, these conven iodide, ammonium iodide, lead iodide, etc., and those of tional methods entail a further disadvantage that side said acid include phosphoric acid, nitric acid, sulfuric reactions such as self-condensation of ketones are ready acid, hydrochloric acid, hydrobromic acid, trifluoro to take place, because the proposed catalysts are in 50 acetic acid, perchloric acid, etc. The said iodination every case strong acids. For example, U.S. Pat. Nos. agent is exemplified by iodine, iodine monochloride, 3,607,862 and 3,622,560 disclose the use of perchloric iodine monobromide, iodine trichloride, acid, ferric chloride and ferric bromide as a catalyst in iodide, diphosphorus tetraiodide, N-iodosuccinimide, the reaction of sugars and ketones. Though by use of etc. and said reducing agent by hydrogen sulfide, hypo these catalysts are much reduced production of unfa 55 phosphorous acid, sulfurous acid, , etc. vorable by-products such as a ketone dimer (e.g. ace The amount of hydrogen iodide used or that of hy tone dimer) as compared with said conventional cata drogen iodide made available in the reaction system lysts, these catalysts, however, still have a drawback to may be at least about 0.01 weight percent, preferably in produce by-product to some extent. the range of a catalyst amount (about 0.03 wt.%) to The present inventors conducted an extensive investi 60 about 20 wt.% and more desirably in the range of about gation in order to eliminate such disadvantages as 0.05 to 10 wt.%, all relative to the sugar. above, and have found that the reaction of a sugar with The reaction solvent may be any solvent that will not a ketone proceeds smoothly in the presence of hydro interfere with the reaction and is exemplified by aceto gen iodide, and the process is able to produce a sugar nitrile, propionitrile, nitromethane, nitroethane, nitro ketal in good yields and to decrease the formation of 65 benzene, dichloromethane, chloroform, carbon tetra by-products. chloride, 1,1-dichloroethane, 1,2-dichloroethane, ethyl Thus, the present invention is concerned with a pro bromide, pentane, cyclopentane, hexane, cyclohexane, cess for producing a sugar ketal, which comprises react heptane, benzene, toluene, xylene, etc. It is also possible 4,464,530 3 4. to employ said ketone as the reaction solvent. More was refluxed with stirring in a water bath at 65° C. for over, the reaction may also be conducted in a mixed 6 hours. During this reaction, the refluxing solvent was solvent consisting of two or more of such solvents. dried with 20 g of Molecular Sieves 3A (Wako Pure Moreover, a small quantity of water may be added at Chemical Industries, Ltd.) interposed between the reac the beginning of the reaction for the purpose of increas- 5 tion vessel and the cooling jacket. After completion of ing the solubility of the sugar and catalyst in the solvent. the reaction, a small amount of pyridine was added and Since this reaction is an equilibrium reaction and the the mixture was diluted with benzene, washed with yield is generally improved when the water produced is aqueous sodium bicarbonate and water and dried over removed, the reaction may be conducted with water anhydrous magnesium sulfate. The solvent and cyclo being constantly removed from the reaction system by 10 hexanone were distilled off under reduced pressure to the known procedure. An example of such known pro give 20.67 g (100%) of di-O-cyclohexylidene-D- cedure is distillative removal of water or the use of a arabinose (purity 2.98%). Melting point: 73.5'-75.5 C. drying agent. For distillative removal of water, azeo (recrystallized from petroleum ether) tropic removal of water with a solvent is a generally Elemental analysis: Calcd. for C17H26O5: C, 65.78; H, accepted practice and in such procedure, the water is 15 8.44. Found: C, 65.70; H, 8.50. removed from the vapor condensate and the recovered EXAMPLE 2 solvent is returned to the reaction system. As an alterna tive, the azeotrope vapor may be expelled from the To 200 ml of acetone were added 10.0 g of D-xylose system and, instead, the same quantity of the dry solvent and 175 mg of hydriodic acid (57%) and the mixture may be added to the reaction system. As an example of 20 was refluxed with stirring in a water bath at 60° C. for the technique using a drying agent, the azeotrope vapor 5 hours. During this reaction, the refluxing solvent was or the condensate thereof is dried with a drying agent dried with 20 g of Molecular Sieves 3A interposed such as anhydrous calcium sulfate, molecular sieves, between the reaction vessel and the cooling jacket. alumina, etc. and, then, returned to the reaction vessel. After completion of the reaction, a small amount of The reaction temperature is generally in the range of 25 pyridine was added and the acetone was distilled off about 0° C. to about 150° C., preferably about 20° C. to under reduced pressure. The residue was dissolved in 100° C. The reaction may be conducted under reduced benzene and the benzene solution was washed with pressure to adjust the azeotropic point of the solvent or aqueous sodium bicarbonate and water and dried over ketone and water. anhydrous magnesium sulfate. The benzene was dis While the reaction time depends on the kinds of sug- 30 tilled off under reduced pressure and the residue was ars and ketones, the amount of catalyst and reaction further distilled under reduced pressure, whereby 12.8g conditions, it generally ranges from about 30 minutes to (83.6%) of 1,2:3,5-di-O-isopropylidene-a-D- about 10 hours, preferably about 1 to 5 hours. xylofuranose was obtained as a fraction boiling at In order to isolate the sugar ketal thus produced from 94-97° C./3 mmHg. the reaction system, the reaction solvent may be dis- 35 Elemental analysis: Calcd. for C11H18O5: C, 57.58; H, tilled off as such, or after a small amount of alkalis (e.g., 7.88. Found: C, 57.33; H, 7.60. sodium hydrogencarbonate, potassium hydrogencar EXAMPLE 3 bonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, ammonia, pyridine, To a mixture of 150 ml of cyclohexanone and 120 ml etc.) or aqueous solutions of said alkalis are added to 40 of dichloromethane were added 10.0 g of D-xylose and adjust the pH of the reaction mixture to a weak alkalin 175 mg of hydriodic acid (57%) and the mixture was ity (a pH of about 7 to 9). The resultant residue, when refluxed with stirring in a water bath at 65° C. for 8 subjected to the known separatory means such as ex hours. During this reaction, the refluxing solvent was traction, distillation, column chromatography or re dried with 20 g of Molecular Sieves 3A interposed crystallization yields readily the objective sugar ketal. 45 between the reaction vessel and the cooling jacket. The The present invention provides an industrially advan reaction mixture was diluted with benzene, washed tageous process for producing sugar ketals. with aqueous sodium bicarbonate and water and dried The advantageous features of the method according over anhydrous magnesium sulfate. The solvent and to this invention are as follows. The acetalization reac cyclohexanone were distilled off under reduced pres tion can be conducted at a sufficiently useful rate and 50 sure to give 19.8 g (96%) of 1,2:3,5-di-O-cyclohexyli selectively with the aid of a small amount of hydrogen dene-a-D-xylofuranose. After recrystallization from iodide which has not been known to be a catalyst for petroleum ether, it melted at 104.5-105.5° C. this type of reaction and as a consequence, the after Elemental analysis: Calcd. for C17H26Os: C, 65.78; H, treatment of the reaction product is facilitated. In addi 8.44. Found: C, 66.14; H, 8.47. tion, the desired sugar ketal is obtained in high yield. 55 EXAMPLE 4 Moreover, unlike the known methods, the method does To 200 ml of acetone were added 10.0 g of D-ribose not give industrial wastes. Since the amount of catalyst and 175 mg of hydriodic acid (57%) and the mixture required is small or very small, there occur only very was refluxed with stirring in a water bath at 60° C. for small amounts of by-products (e.g. ketone dimer). The 6 hours. During this reaction, the refluxing solvent was reaction time is curtailed and the used catalyst can be 60 dried with 20 g of Molecular Sieves 3A interposed easily recovered and reused. between the reaction vessel and the cooling jacket. The following examples illustrate the invention in After completion of the reaction, a small amount of more detail. aqueous sodium bicarbonate was added. The acetone EXAMPLE 1. 65 was then distilled off under reduced pressure, and the To a mixture of 100 ml of cyclohexanone and 100 ml residue was dissolved in benzene, washed with aqueous of dichloromethane were added 10.0 g of D-arabinose sodium bicarbonate and water and dried over anhy and 175 mg of hydriodic acid (57%) and the mixture drous sodium sulfate. The benzene was distilled off 4,464,530 5 6 under reduced pressure and the residue was further hours. During this reaction, the refluxing solvent was distilled under reduced pressure, whereby 3.84 g (30%) dried with 20 g of Molecular Sieves 3A interposed of 2,3-O-isopropylidene-D-ribofuranose was obtained between the reaction vessel and the cooling jacket. as a fraction boiling at 108-111° C./0.04 mmHg. After completion of the reaction, a small amount of Elemental analysis: Calcd. for C8H14O5: C, 50.52; H, pyridine was added. The acetone was then distilled off 7.42. Found: C, 50.49; H, 7.40. under reduced pressure and the residue was dissolved in benzene, washed with aqueous sodium bicarbonate and EXAMPLE 5 water and dried over anhydrous magnesium sulfate. To 200 ml of acetone were added 10.0 g of D-glucose The benzene was distilled off under reduced pressure to and 100 mg of hydrogen iodide and the mixture was 10 give 11.5 g (80%) of 2,3:5,6-di-O-isopropylidene-a-D- refluxed with stirring in a water bath at 60° C. for 8 mannofuranose. After recrystallization from petroleum hours. During this reaction, the refluxing solvent was ether, it melted at 122-123 C, dried with 20 g of Molecular Sieves 3A interposed Elemental analysis: Calcd. for C12H20O6: C, 55.37; H, between the reaction vessel and the cooling jacket. 7.75. Found: C, 55.41; H, 7.78. After completion of the reaction, a small amount of 15 pyridine was added. The acetone was then distilled off EXAMPLE 9 under reduced pressure and the residue was dissolved in To a mixture of 150 ml of cyclohexanone and 120 ml benzene, washed with aqueous sodium bicarbonate and of dichloromethane were added 10.0 g of D-mannose water and dried over anhydrous magnesium sulfate. and 175 mg of hydriodic acid (57%) and the mixture The benzene was distilled off under reduced pressure to 20 was refluxed with stirring in a water bath at 65 C. for give 11.5 g (80.0%) of 1,2:5,6-di-O-isopropylidene-a-D- 8 hours. During this reaction, the refluxing solvent was glucofuranose. After recrystallization from chloroform dried with 20 g of Molecular Sieves 3A interposed hexane (1:2), it melted at 107-109' C. between the reaction vessel and the cooling jacket. The Elemental analysis: Calcd. for C12H20O6: C, 55.37; H, reaction mixture was diluted with benzene, washed 7.75. Found: C, 55.74; H, 7.81. 25 with aqueous sodium bicarbonate and water and dried over anhydrous magnesium sulfate. The solvent and EXAMPLE 6 cyclohexanone were distilled off under reduced pres To a mixture of 150 ml of cyclohexanone and 120 ml sure to give 11.9 g (82.6%) of 2,3:5,6-di-O-cyclohexyli of dichloromethane were added 10.0 g of D-glucose and dene-a-D-mannofuranose. After recrystallization from 175 mg of hydriodic acid (57%) and the mixture was 30 cyclohexane, it melted at 122-124 C. refluxed with stirring in a water bath at 65 C. for 8 Elemental analysis: Calcd. for C18H28O6: C, 63.51; H, hours. During this reaction, the refluxing solvent was 8.29. Found: C, 63.17; H, 8.32. dried with 20 g of Molecular Sieves 3A interposed between the reaction vessel and the cooling jacket. The EXAMPLE 10 reaction mixture was diluted with chloroform, washed 35 To 200 ml of acetone were added 10.0 g of D-fructose with aqueous sodium bicarbonate and water and dried and 175 mg of hydriodic acid (57%) and the mixture over anhydrous magnesium sulfate. The solvent and was refluxed with stirring in a water bath at 60° C. for cyclohexanone were distilled off under reduced pres 6 hours. During this reaction, the refluxing solvent was sure and the residue was recrystallized from ligroin to dried with 20 g of Molecular Sieves 3A interposed give 11.2 g (77.8%) of 1,2:5,6-di-O-cyclohexylidene-a- 40 between the reaction vessel and the cooling jacket. D-glucofuranose, melting at 133-136 C. After completion of the reaction, a small amount of Elemental analysis: Calcd. for C18H28O6: C, 63.51; H, pyridine was added. The acetone was then distilled off 8.29. Found: C, 63.27; H, 8.34. under reduced pressure, and the residue was dissolved in benzene. The benzene solution was washed with EXAMPLE 7 45 aqueous sodium bicarbonate and water and dried over To 200 ml of acetone were added 10.0 g of D-galac anhydrous magnesium sulfate. The benzene was dis tose and 175 mg of hydriodic acid (57%) and the mix tilled off under reduced pressure to give 10.7 g (74.3%) ture was refluxed with stirring in a water bath at 60° C. Of 2,3:4,5-di-O-isopropylidene-a-D-fructopyranose. for 8 hours. During this reaction, the refluxing solvent After recrystallization from n-hexane, it melted at was dried with 20 g of Molecular Sieves 3A interposed 50 96-98 C. between the reaction vessel and the cooling jacket. Elemental analysis: Calcd. for C12H20O6: C, 55,37; H, After completion of the reaction, a small amount of 7.75. Found: C, 55.61; H, 7.77. pyridine was added. The acetone was then distilled off under reduced pressure and the residue was dissolved in EXAMPLE 11 benzene, washed with aqueous sodium bicarbonate and 55 To 200 ml of acetone were added 10.0 g of L-sorbose water and dried over anhydrous magnesium sulfate. and 223 mg of hydriodic acid (57%) and the mixture The benzene was distilled off and the residue was fur was refluxed with stirring in a water bath at 60° C. for ther distilled under reduced pressure, whereby 8.5 g 6 hours. During this reaction, the refluxing solvent was (59%) of 1,2:3,4-di-O-isopropylidene-a-D-galac dried with 20 g of Molecular Sieves 3A interposed topyranose was obtained as a fraction boiling at 60 between the reaction vessel and the cooling jacket. 129-133° C./0.2 mmHg. After completion of the reaction, a small amount of Elemental analysis: Calcd. for C12H2OO6: C, 55.37; H, pyridine was added. The acetone was then distilled off 7.75. Found: C, 55.01; H, 7.80. under reduced pressure and the residue was dissolved in benzene. The benzene solution was washed with aque EXAMPLE 8 65 ous sodium bicarbonate and water and dried over anhy To 200 ml of acetone were added 10.0 g of D-man drous magnesium sulfate. The benzene was distilled off nose and 100 mg of hydrogen iodide and the mixture under reduced pressure to give 12.13 g (84.0%) of was refluxed with stirring in a water bath at 60° C. for 5 2,3:4,6-di-O-isopropylidene-L-sorbofuranose (purity 4,464,530 7 8 2.98%). Melting point: 77-78° C. (recrystallized from refluxed with stirring in a water bath at 65° C. for 8 petroleum ether). hours. During this reaction, the refluxing solvent was Elemental analysis: Calcd. for C12H20O6: C, 55.37; H, dried with 20 g of Molecular Sieves 3A interposed 7.75. Found: C, 55.40; H, 7.80. between the reaction vessel and the cooling jacket. The reaction mixture was diluted with benzene, washed EXAMPLE 12 with aqueous sodium bicarbonate and water and dried To 200 ml of acetone were added 10.0 g of L-sorbose over anhydrous magnesium sulfate. The solvent and and 127 mg of iodine and the mixture was refluxed with cyclohexanone were distilled off under reduced pres stirring in a water bath at 60° C. for 6 hours. During this sure to give 8.4 g (44.4%) of 2,3:4,6-di-O-cyclohexyli reaction, the refluxing solvent was dried with 20 g of 10 dene-L-sorbofuranose. After recrystallization from pe Molecular Sieves 3A interposed between the reaction troleum ether, it melted at 118-119 C. vessel and the cooling jacket. The reaction mixture was Elemental analysis: Calcd. for C18H28O6: C, 63.51; H, then subjected to an after-treatment similar to that de 8.29. Found: C, 63.72; H, 8.24. scribed in Example 11 to give 11.15 g (77.2%) of 2,3:4,6- di-O-isopropylidene-L-sorbofuranose (purity 298.5%). 15 EXAMPLE 18 To a mixture of 150 ml of cyclohexanone and 120 ml EXAMPLE 13 of dichloromethane were added 10.0 g of L-sorbose and To 200 ml of acetone were added 10.0 g of L-sorbose 254 mg of iodine and the mixture was refluxed with and 81.5 mg of iodine monochloride and the mixture stirring in a water bath at 65° C. for 8 hours. During this was refluxed with stirring in a water bath at 60° C. for 20 reaction, the refluxing solvent was dried with 20 g of 6 hours. During this reaction, the refluxing solvent was Molecular Sieves 3A interposed between the reaction dried with 20 g of Molecular Sieves 3A interposed vessel and the cooling jacket. The reaction mixture was between the reaction vessel and the cooling jacket. The diluted with benzene, washed with aqueous sodium reaction mixture was then subjected to an after-treat bicarbonate and water and dried over anhydrous mag ment similar to that described in Example 11 to give 25 nesium sulfate. The solvent and cyclohexanone were 10.9 g (75.8%) of 2,3:4,6-di-O-isopropylidene-L-sor distilled off under reduced pressure to give 12.3 g (65%) of 2,3:4,6-di-O-cyclohexylidene-L-sorbofuranose. After bofuranose (purity 297%). recrystallization from petroleum ether, it melted at EXAMPLE 14 18-119 C. To 200 ml of acetone were added 10.0 g of L-sorbose 30 Elemental analysis: Calcd. for C18H28O6: C, 63.51; H, and 234 mg of iodine trichloride and the mixture was 8.29. Found: C, 63.76; H, 8.38. refluxed with stirring in a water bath at 60° C. for 4 hours. During this reaction, the refluxing solvent was EXAMPLE 19 dried with 20 g of Molecular Sieves 3A interposed To 200 ml of acetone were added 10.0 g of D-man between the reaction vessel and the cooling jacket. The 35 nitol and 175 mg of hydriodic acid (57%) and the mix reaction mixture was then subjected to an after-treat ture was refluxed with stirring in a water bath at 60° C. ment similar to that described in Example 11 to give for 5 hours. During this reaction, the refluxing solvent 9.85 g (68.2%) of 2,3:4,6-di-O-isopropylidene-L-sor was dried with 20 g of Molecular Sieves 3A interposed bofuranose (purity 2.98%). between the reaction vessel and the cooling jacket. After completion of the reaction, a small amount of EXAMPLE 15 pyridine was added. The acetone was then distilled off To 200 ml of acetone were added 10.0 g of L-sorbose under reduced pressure and the residue was dissolved in and 225 mg of N-iodosuccinimide and the mixture was chloroform. The solution was washed with aqueous refluxed with stirring in a water bath at 60° C. for 6 sodium bicarbonate and water and dried over anhy hours. During this reaction, the refluxing solvent was 45 drous magnesium sulfate. The chloroform was distilled dried with 20 g of Molecular Sieves 3A interposed off under reduced pressure to give 15.0 g (90%) of between the reaction vessel and the cooling jacket. The 1,2:3,4:5,6-tri-O-isopropylidene-D-mannitol. After re reaction mixture was then subjected to an after-treat crystallization from 70% ethanol, it melted at ment similar to that described in Example 11 to give 68.5-70.5 C. 8.43 g (58.4%) of 2,3:4,6-di-O-isopropylidene-L-sor 50 Elemental analysis: Calcd. for C15H26O6: C, 59.58; H, bofuranose (purity 297%). 8.67. Found: C, 59.77; H, 8.58. EXAMPLE 16 EXAMPLE 20 To 200 ml of acetone were added 10.0 g of L-sorbose, To 200 ml of acetone were added 10.0 g of L-sorbose 166 mg of potassium iodide and 152 mg of conc. sulfuric 55 and 57 mg of diphosphorus tetraiodide and the mixture acid and the mixture was refluxed with stirring in a was refluxed with stirring in a water bath at 60° C. for water bath at 60° C. for 4 hours. During this reaction, 4 hours. During this reaction, the refluxing solvent was the refluxing solvent was dried with 20 g of Molecular dried with 20 g of Molecular Sieves 3A interposed Sieves 3A interposed between the reaction vessel and between the reaction vessel and the cooling jacket. The the cooling jacket. The reaction mixture was then sub 60 reaction mixture was then subjected to an after-treat jected to an after-treatment similar to that described in ment similar to that described in Example 11 to give Example 11 to give 6.79 g (47.0%) of 2,3:4,6-di-O-iso 8.60 g (59.5%) of 2,3:4,6-di-O-isopropylidene-L-sor propylidene-L-sorbofuranose (purity 2.96%). bofuranose (purity 290%). EXAMPLE 17 65 EXAMPLE 21 To a mixture of 150 ml of cyclohexanone and 120 ml To 200 ml of acetone were added 10.0 g of L-sorbose, of dichloromethane were added 10.0 g of L-sorbose and 90 mg of hydriodic acid (57%) and 50.8 mg of iodine 175 mg of hydriodic acid (57%) and the mixture was and the mixture was refluxed with stirring in a water 4,464,530 9 10 bath at 60° C. for 8 hours. During this reaction, the 2. A process according to claim 1, wherein the sugar refluxing solvent was dried with 20 g of Molecular is a pentose or a hexose. Sieves 3A interposed between the reaction vessel and 3. A process according to claim 2, wherein the hexose the cooling jacket. The reaction mixture was then sub is sorbose or glucose. jected to an after-treatment similar to that described in 4. A process according to claim 1, wherein the ketone is acetone. Example 11 to give 12.07 g (83.6%) of 2,3:4,6-di-O-iso 5. A process according to claim 1, wherein the hydro propylidene-L-sorbofuranose (purity 2.98%). gen iodide is reacted in the form of hydriodic acid ob EXAMPLE 22 tained by dissolving hydrogen iodide in water. 10 6. A process according to claim 1, wherein the hydro To 200 ml of acetone were added 10.0 g of L-sorbose, gen iodide is reacted in the form of a compound or 127 mg of iodine and 110 mg of aqueous hypophospho system that exists as hydrogen iodide in the reaction rous acid solution (about 30%) and the mixture was system or one that liberates hydrogen iodide in the refluxed with stirring in a water bath at 60° C. for 6 reaction system. hours. During this reaction, the refluxing solvent was 15 7. A process according to claim 6, wherein the com dried with 20 g of Molecular Sieves 3A interposed pound is an iodination agent. between the reaction vessel and the cooling jacket. The 8. A process according to claim 7, wherein the iodin reaction mixture was then subjected to an after-treat ation agent is iodine, iodine monochloride, iodine tri ment similar to that described in Example 11 to give chloride, N-iodosuccinimide, phosphorus iodide or di 11.56 g (80.0%) of 2,3:4,6-di-O-isopropylidene-L-sor 20 phosphorus tetraiodide. 9. A process according to claim 6, wherein the system bofuranose (purity 2.98%). is a metal iodide and an acid. What we claimed is: 10. A process according to claim 9, wherein the metal i. A process for producing a sugar ketal which com iodide is sodium iodide, and the acid is sulfuric acid. prises reacting a sugar of the class consisting of the 25 11. A process according to claim 9, wherein the sys pentoses, hexoses, rhamnose, fucose, deoxyribose, deox tem is an iodination agent and a reducing agent. yglucose, ribitol, arabitol, mannitol, sorbitol and inosi 12. A process according to claim 11, wherein the tol with a ketone of the group consisting of di-(Cl-3- iodination agent is iodine, and the reducing agent is alkyl)ketones and C-7-cycloalkanones in the presence hypophosphorous acid. of hydrogen iodide. 30 sk 2k k - k

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