to give additional product. The total yield from 100 g of melezitose is about 50 g. Recrystallization. One hundred grams of turanose is dissolved in 100 ml of hot water. After adding 5 g of a decolorizing carbon, the solution is filtered and then evaporated in vacuo to a sirup (n=1.490) containing about 80 percent of total solids. This sirup is dissolved in 100 ml of hot methyl alcohol. After the addition of 5 g of a decolorizing carbon, the hot solution is filtered. The filtrate, after cooling to room temperature, is seeded and preferably stirred while crystallization takes place. After several hours the crystals are collected on a filter and washed with methyl alcohol. The yield is about 75 g. The remaining sugar is reclaimed by concentrating the mother liquor, adding methyl alcohol, and separating the crystals which form. In 4-percent aqueous solution, turanose gives [a]+27.3° initially, changing in the course of an hour to an equilibrium value of +75.8°. NOTES The 3-glucosidofructose structure for turanose was first proposed by Isbell and Pigman [4]. 2 The method for obtaining melezitose is described on page 472. 3 The nutrient solution is prepared by dissolving 2.5 g of NH4NO3, 0.3 g of KH¿PO1, and 0.25 g of MgSỐ.7H2O in 100 ml of water. The seed crystals originally used at this Bureau were part of the product first discovered by Ď. H. Brauns. REFERENCES [1] C. S. Hudson and E. Pacsu, J. Am. Chem. Soc. 52, 2522 (1930). [2] G. Tanret, Compt. rend. 142, 1424 (1906). [3] M. Bridel and T. Aagaard, Bul. soc. chim. biol. 9, 884 (1927). [4] H. S. Isbell and W. W. Pigman, J. Research NBS 20, 787 (1938) RP1104. 24. d-XYLOSE Method. [1] One kilogram of shredded or broken corn cobs is boiled 2 for 3 hours with 6 liters of 7-percent sulfuric acid, after which the insoluble residue is separated on a filter and washed with water. The aqueous solution is neutralized with calcium carbonate, and after removal of the insoluble calcium sulfate, the liquor is treated with baker's yeast. When the ensuing fermentation is complete, about 100 g of decolorizing carbon is added and the solution is filtered.3 The filtrate is concentrated in vacuo to a sirup (n=1.442, 60 percent of total solids), which is then diluted with 3 volumes of methyl alcohol. After separation of the resulting precipitate, the alcoholic solution is evaporated in vacuo to a sirup (85 percent of total solids, n2=1.503), which is mixed with 250 ml of methyl alcohol and seeded with crystalline d-xylose. After standing for several days, the crystalline product is separated and washed with 75 percent by volume of aqueous methyl alcohol. The yield is about 12 percent.* Recrystallization.-One kilogram of xylose is dissolved with 400 ml of water containing a few drops of acetic acid. After the addition of 15 g of a decolorizing carbon, the hot solution is filtered and the filtrate is cooled and kept in gentle motion for several hours while crystallization takes place. The crystals which form are separated and washed with water or with aqueous alcohol. The yield is about 50 percent in the first crop. The sugar in the mother liquor crystallizes readily from sirups of about 75 percent of total solids. a-d-Xylose melts at 145° C and in 4-percent solution gives [a]=+93.6° initially, changing in several hours to +18.8°. NOTES The commercial production of xylose from cottonseed hulls is described by Schreiber, Geib, Wingfield, and Acree [2]. 2 The hydrolysis can be conducted in an Inchronel metal pot. 3 In the event that the solution at this point is dark colored, it should be clarified further by treatment with basic lead acetate followed by hydrogen sulfide [3]. 4 By using the basic lead acetate clarification mentioned in note 3, the method can be used for the preparation of xylose from cottonseed hulls. REFERENCES [1] C. S. Hudson and T. S. Harding, J. Am. Chem. Soc. 40, 1601 (1918). [2] W. T. Schreiber, N. V. Geib, B. Wingfield, and S. F. Acree, Ind. Eng. Chem. 22. 497 (1930). [3] H. S. Isbell, J. Research NBS 13, 515 (1934) RP723. XXXI. METHODS FOR THE PREPARATION OF CERTAIN SUGAR DERIVATIVES In this chapter characteristic methods for the production of acetal and ketal derivatives, esters, ethers, glycosides, mercaptals, and oxidation and reduction products are given. A résumé of the characteristic properties of each group is followed by typical directions for the synthesis of specific compounds and a list of pertinent references. The methods are selected from those found in the literature as being of general use. No attempt has been made to give a complete bibliography or to report original work. Many of the original methods have been modified and improved in various ways. The physical constants of the products are selected from data in the literature and are not always to be found in the articles describing the method. Additional literature references are cited in the table of sugar derivatives (p. 704). Whenever possible the examples were chosen from the work of the members of this Bureau's staff. For this reason a general method applicable to any sugar may have been illustrated by a specific example for a rare and relatively inaccessible sugar. 1. ACETAL AND KETAL DERIVATIVES General characteristics of the acetal and ketal derivatives.-The sugars and many of their derivatives condense with aldehydes and ketones to give compounds which are useful for the preparation of partially substituted sugars, and for the preparation and purification of derivatives and products of diverse types. The configurational relationships of the hydroxyls determine in large measure whether or not a condensation will take place. The effect of configuration in relation to the particular ketone or aldehyde used has been reviewed [1, 2]. The condensation of acetone with a sugar is carried out by mixing the sugar with acetone and a dehydrating agent. Some of the dehydrating agents which have been used are hydrogen chloride [3], anhydrous copper sulfate [4], sulfuric acid [5, 6], zinc chloride [7], and phosphorus pentoxide [8]. The use of anhydrous copper sulfate rather than an acid is often desirable when glycosides are condensed with acetone, as otherwise ring shifts and other structural changes may occur. Most sugars give diacetone derivatives. The monoacetone sugars are most easily prepared from the diacetone derivatives by carefully regulated acid hydrolysis. Usually the acetone groups are split off at different rates; for example, the acetone group in the 5,6 position of 1,2-5,6-diacetone-d-glucose is hydrolyzed 40 times as fast as that in the 1,2 position. Examples of the condensation of sugars with aldehydes are the benzylidine sugars, which are prepared by the action of benzaldehyde on the sugars in the presence of a dehydrating agent, such as phosphorus pentoxide [9], anhydrous sodium sulfate [9], zinc chloride [10], or hydrogen chloride [11]. The benzylidine groups are removed by treatment with acid in water solution or by hydrogenation with a palladium catalyst in alcoholic solution [12]. The di-o-nitrobenzylidine derivatives of a number of sugars have been prepared and are interesting in that they resist acylation, and isomerize to o-nitrosobenzoates in the presence of light, sometimes with a simultaneous Walden inversion [13]. The preparation of 4,6-benzylidine-a-dglucose is described later in this section. Condensation products of sugars and derivatives with acetaldehyde (ethylidine sugars) [14,15], furfuraldehyde [16], and formaldehyde [17] have also been prepared. (a) SULFURIC ACID METHOD FOR THE PREPARATION OF ACETONE DERIVATIVES (1) 1,2-5,6-DIACETONE-d-GLUCOSE. Method [6]. One hundred grams of anhydrous dextrose is shaken with 2 liters of dry acetone containing 80 ml of concentrated sulfuric acid. After 5 hours, when most of the sugar has dissolved, an excess of anhydrous sodium carbonate is added, the solution is filtered, and the filtrate is evaporated to a heavy sirup which is taken up with cold water. A small amount of amorphous material which separates is discarded. The solution is extracted three times with benzene and the extracts are washed with water. The combined aqueous solution and washings of the benzene extracts are treated with a decolorizing carbon and are then extracted a number of times with one-fifth of their volume of chloroform. The chloroform extract, upon drying and evaporation in vacuo, yields 102 to 106 g of crystalline diacetoneglucose. The mother liquor, after concentration in vacuo to a heavy sirup which is taken up with alcohol, gives about 20 g of monoacetoneglucose. The pure 1,2-5,6-diacetone-d-glucose melts at 110° to 111° C and gives [a]=-18.5° (water, c=5). The 1,2-monoacetone-d-glucose melts at 161° C and gives [a]=-11.8° (water, c=8). (2) 1,2-4,5-DIACETONE-d-FRUCTOSE. Method [4]. Seventy-five grams of dry powdered levulose is shaken with 11⁄2 liters of acetone and 7% ml of sulfuric acid for 20 hours. The reaction product is neutralized with ammonia gas, filtered, and concentrated in vacuo. The partially crystallized sirup is extracted with ether. The undissolved sirup is mainly 2,3-monoacetonefructose which can be extracted by shaking with 100 ml of 5 N sodium hydroxide. The ether solution containing 1,2-4,5-diacetonefructose is purified by washing, first with dilute (1: 10) sulfuric acid and then with dilute sodium hydroxide solution. The ether solution, dried with sodium sulfate, is evaporated in vacuo and the residue recrystallized from petroleum ether. The yield is 32 g of pure 1,2-4,5-diacetone-d-fructose, which has a melting point of 118° to 119° C and gives [a]=-146.6° (chloroform, c=2.5) [18]. (b) COPPER SULFATE METHOD FOR THE PREPARATION OF ACETONE DERIVATIVES (1) MONOACETONE AND DIACETONE DERIVATIVES OF METHYL a-d-MANNOPYRANOSIDE. Method [19].-Ten grams of methyl a-d-mannopyranoside is shaken at room temperature with 400 ml of dry acetone for 10 days in the presence of anhydrous copper sulfate.' The filtered solution is concentrated in vacuo to a sirup from which some unchanged methyl a-d-mannoside is eliminated by taking up the sirup in cold acetone. The resulting sirup is separated into two fractions by a vacuum distillation at 0.03 mm pressure. One fraction (1.6 g), which distills at a bath temperature of 125° to 130° C, crystallizes slowly when kept in a desiccator. This product, methyl 2, 3-4, 6-diacetone-a-d-mannoside, after recrystallization from aqueous alcohol, melts at 76° to 77° C and gives [a] = +3° (methyl alcohol, c=2.4). A second portion (0.8 g) distills at a bath temperature of 165° to 170° C and crystallizes when seed of methyl 2,3-monoacetone-a-d-mannopyranoside is added. This substance melts at 105° C and gives [a] = +24.3° (water, c=4). [20] NOTES 1 In order to prevent ring changes during the reaction, it is necessary that the acetone be free of methyl alcohol. Better yields may be obtained by carrying out the reaction at 50° C. Certain glycosides, such as methyl B-d-mannoside, require a longer reaction time, in some cases several months. (c) HYDROLYSIS OF THE DIACETONE DERIVATIVE TO GIVE A MONOACETONE DERIVATIVE (1) 1,2-MONOACETONE-d-GLUCOSE. Method [21].-Fifty grams of 1,2-5,6-diacetone-d-glucose (see p. 483) is dissolved in 400 ml of ethyl acetate containing 4 ml of concentrated nitric acid. The solution is heated to boiling and cooled. The 1,2-monoacetone-d-glucose which separates at once is purified by recrystallization from water or neutral ethyl acetate. (d) ZINC CHLORIDE METHOD FOR PREPARING BENZYLIDINE DERIVATIVES (1) 4,6-BENZYLIDINE-a-d-GLUCOSE. Method [12].-One hundred and thirty grams of anhydrous dextrose and 100 g of finely powdered fused zinc chloride are shaken with 300 ml of freshly distilled benzaldehyde for 24 hours on the shaking machine. The thick liquid is then mixed with 400 ml of ice-cold water, whereupon crystallization takes place. The mixture is filtered and the crystals are washed, first with cold water and then with petroleum ether. Between 60 and 70 g of material is obtained. The crystals are recrystallized several times from 10 times their weight of hot water to which enough ammonia is added to make the solution alkaline. About 20 to 25 g of pure material is obtained which melts at 188° C. 4,6-Benzylidine-a-d-glucose is dextrorotatory in methyl alcoholic solution and mutarotates to a value of about -4°. (e) REFERENCES [1] W. N. Haworth and E. L. Hirst, Ann. Rev. Biochem. 5, 82 (1936). [5] J. Böeseken and P. H. Hermans, Ber. deut. chem. Ges. 55, 3758 (1922). [6] D. J. Bell, J. Chem. Soc. 1935, 1874. [7] H. O. L. Fischer and C. Taube, Ber. deut. chem. Ges. 60, 488 (1927). [8] L. Smith and J. Lindberg, Ber. deut. chem. Ges. 64, 505 (1931). [9] W. A. Van Ekenstein and J. J. Blanksma, Rec. trav. chim. 25, 153 (1906). [10] K. Freudenberg, H. Toepffer, and C. C. Andersen, Ber. deut. chem. Ges. 61, 1750 (1928). [11] W. A. Van Ekenstein and C. A. Lobry de Bruyn, Rec. trav. chim. 18, 305 (1899). [12] L. Zervas, Ber. deut. chem. Ges. 64, 2289 (1931). [13] I. Tanasescu and E. Craciunescu, Bul. soc. chim. 3, 581, 1517 (1936). [14] B. Helferich and H. Appel, Ber. deut. chem. Ges. 64,, 1841 (1931). [15] H. Appel, J. Chem. Soc. 1935 425. 16 H. Brederick, Ber. deut. chem. Ges. 68, 777 (1935). [17] C. A. Lobry de Bruyn and W. A. Van Ekenstein, Rec. trav. chim. 22, 159 (1903). [18] D. H. Brauns and H. L. Frush, BS J. Research 6, 454 (1931) RP287. [19] R. G. Ault, W. N. Haworth, and E. L. Hirst, J. Chem. Soc. 1935, 1012. [20] R. G. Ault, W. N. Haworth, and E. L. Hirst, J. Chem. Soc. 1935, 517. [21] H. W. Coles, L. D. Goodhue, and R. M. Hixon, J. Am. Chem. Soc. 51, 523 (1929). 2. ACETYL DERIVATIVES General characteristics of the acetylation reactions. The acetylation of the nonreducing sugars and other derivatives which consist of a single modification can be carried out by almost any method which does not affect the rest of the molecule, but the acetylation of the reducing sugars is complicated by the existence of several ring modifications. For this reason it is necessary to select a method which will give the desired crystalline product. The isomer obtained depends upon the catalyst used in the acetylation and upon the temperature. The following general scheme [1] illustrates the effect of these factors on the acetylation of glucose. At low temperatures (0°C) the equilibria represented by reactions I and II are only slowly established and the acetylation reactions III or IV take place without isomerization. By using pyridine (or zinc chloride) and a low temperature, the alpha aldohexose yields the alpha pentaacetate and the beta aldohexose yields the beta pentaacetate. At higher temperatures, in the presence of acid catalysts, isomerization between the acetates takes place and the products obtained depend upon the position of the equilibrium represented by the reaction II. For glucose the equilibrium mixture of pentaacetates consists of 90 percent of the alpha and 10 percent of the beta pentaacetylglucose [2]. For most sugars the alpha acetate predominates in the equilibrium mixture |