(4) PREPARATION OF d-TALONIC ACID BY PYRIDINE REARRANGEMENT OF GALACTONIC ACID.

Method [25, 31].-Talonic acid is prepared from d-galactonic acid by epimerization with pyridine. Eighty grams of d-galactonic lactone monohydrate, 36 g of pyridine, and 500 ml of water are placed in a 1-liter flask and heated at 90° to 100° C for 115 hours. The solution is then evaporated to about 100 ml under reduced pressure. The residue in the flask is mixed with 25 g of cadmium carbonate and 1 liter of water. The resulting suspension is then boiled while the volume is kept constant until nearly all the carbonate is dissolved. The solution is then concentrated under reduced pressure to remove the pyridine. The resulting sirup is diluted to 1 liter with water and after treatment with a decolorizing carbon and boiling to dissolve all cadmium galactonate, the hot solution is filtered. Fifteen grams of cadmium hydroxide is added to the filtrate and the solution is boiled for some time, filtered hot, and evaporated to about 400 ml, after which it is allowed to stand overnight. The crystalline cadmium galactonate which separates is removed by filtration and the filtrate concentrated to about 100 ml and allowed to stand overnight. Cadmium galactonate which separates is removed again by filtration. The filtrate is then evaporated to dryness and taken up in 100 ml of The cadmium is removed by treating with hydrogen sulfide to precipitate the metal. An excess of hydrogen sulfide is avoided because it makes the filtration difficult. The precipitated cadmium sulfide is separated by filtration and the filtrate is concentrated almost to dryness under reduced pressure at a temperature of not more than 50° C. The residue in the flask is mixed with 500 ml of absolute alcohol and allowed to stand in the ice box overnight. About 20 g of crystalline talonic acid separates.

Recrystallization.-The crude talonic acid is dissolved in the least possible quantity of water at 40° C. The solution is cooled and poured into 5 volumes of absolute alcohol. After standing for several hours in the refrigerator, the resulting crystals are separated. Pure d-talonic acid melts at 138° C and gives [a]20=+19° (water, c=4).

(5) PREPARATION OF POTASSIUM d-ARABONATE FROM LEVULOSE BY OXIDATION IN ALKALINE SOLUTION.

Method [11].-A solution of 18 g (0.1 mole) of levulose in 150 ml of water is added to 150 ml of 2 N potassium hydroxide in a flask equipped with a mechanical stirrer and a tube for the introduction of oxygen. The air in the system is displaced by oxygen and oxidation is allowed to take place at about 20° C. Stirring is continued for about 1 day. Then the reaction mixture is concentrated to a thin sirup, which is diluted with 750 ml of methyl alcohol to precipitate the potassium salt of the sugar acid. The alcoholic solution containing the excess potassium hydroxide is decanted. The oily precipitate is dissolved in water, and the solution is clarified with a decolorizing carbon and evaporated. Crystals of potassium d-arabonate form during the evaporation and are separated by filtration. The yield is about 70 percent.

(b) PREPARATION OF DIBASIC ACIDS

(1) PREPARATION OF MUCIC ACID BY THE OXIDATION OF GALACTOSE WITH NITRIC ACID.

Method [32].-Five grams of galactose is treated with 60 ml of nitric acid of 1.15 specific gravity (about 25 percent) and heated on a steam

bath with occasional stirring until the volume has diminished to one-third. The following day the product is stirred with 10 ml of water, and after 24 hours the crystallized mucic acid is separated and washed with 25 ml of water. The product is recrystallized from hot water. The method can be used for the quantitative estimation of galactose or galactose-containing substances.

(c) PERIODIC ACID OXIDATION OF GLYCOSIDES

Periodic acid oxidation of the methyl glycosides according to the method of Jackson and Hudson [33] provides a convenient means for the determination of ring structure and the configuration of the glycosidic carbon. For an unknown substance it is merely necessary to follow the rotatory change during oxidation and determine the unused periodic acid by titration. In the oxidation, the alpha and beta methyl pentapyranosides form D'- or L'-methoxy-diglycolic aldehydes, giving [a]=approximately 124°. The alpha and beta methyl hexapyranosides and pentafuranosides of the d series form D'- or L'-methoxy-D-hydroxymethyl-diglycolic aldehydes which give [a]=about+120° and 150°, respectively. The specific rotation after oxidation indicates the configuration of the glycosidic carbon, while the amount of periodic acid used indicates the ring structure. Oxidation of a pentapyranoside or hexapyranoside requires 2 moles of periodic acid, while oxidation of a pentafuranoside requires 1 mole.

Method [33]. A known weight of the glycoside (approximately 2 g of the pentoside or 2.4 g of the hexoside) is dissolved in 98 ml of a standardized solution of periodic acid (about 0.3 M) in a 100-ml volumetric flask at 20°C. The rotatory change is followed at 20°C until the rotation becomes constant. The excess periodic acid is then determined as follows [34]: A sample of the solution of suitable size is treated with 5 to 10 ml of a saturated solution of sodium bicarbonate, 15 ml of 0.1 N carbonated arsenious acid, and 1 ml of 20-percent potassium iodide. After standing for 15 minutes at room temperature, the excess arsenious acid is titrated with 0.1 N iodine solution.

NOTE

1 For the subsequent oxidation to the diglycolic acids, isolation of the strontium or barium salts and hydrolysis, see Jackson and Hudson [33].

(d) REFERENCES

[1] O. E. May and H. T. Herrick, Circular No. 216, 1 (1932). U. S. Dept. Agric. [2] H. Kiliani, Liebigs Ann. Chem. 205, 183 (1880).

[3] R. Willstätter and G. Schudel, Ber. deut. chem. Ges. 51, 780 (1918).

[4] A. Heffter, Ber. deut. chem. Ges. 22, 1049 (1889).

[5] A. Stoll and W. Kussmaul, U. S. Patent 1,703,755 (1925).

[6] H. S. Isbell and H. L. Frush, BS J. Research 6, 1145 (1931) RP328.

[7] H. S. Isbell, U. S. Patent 1,976,731 (1934).

[8] H. S. Isbell and W. W. Pigman, BS J. Research 10, 337 (1933) RP534.

[9] H. S. Isbell, BS J. Research 8, 615 (1932) RP 441.

[10] C. S. Hudson and H. S. Isbell, BS J. Research 3, 57 (1929) RP82.

[11] O. Spengler and A. Pfannenstiel, Z. Wirtschaftsgruppe Zuckerind. 85, 546 (1935).

[12] N. K. Richtmyer, R. M. Hann, and C. S. Hudson, J. Am. Chem. Soc. 61,

340 (1939).

[13] H. Kiliani, Ber. deut. chem. Ges. 18, 3066 (1885).

[14] C. S. Hudson, O. Hartley, and C. B. Purves, J. Am. Chem. Soc. 56, 1248

(1934).

[15] H. S. Isbell and H. L. Frush, BS J. Research 11, 649 (1933) RP613.

[16] R. M. Hann, A. T. Merrill, and C. S. Hudson, J. Am. Chem. Soc. 57, 2100

(1935).

[17] E. Fischer and R. Stahel, Ber. deut. chem. Ges. 24, 528 (1891).

[18] F. B. LaForge, U. S. Patent 1,285,248 (Nov. 19, 1918).

[19] G. Bertrand, Bull. soc. chim. 5, 554 (1891).

[20] H. S. Isbell, J. Research NBS 17, 331 (1936) RP914.

[21] W. A. Van Ekenstein and C. A. Lobry de Bruyn, Rec. trav. chim. 18, 305 (1899).

[22] H. S. Isbell, J. Research NBS 14, 305 (1935) RP770; 19, 639 (1937) RP1052. [23] H. Kiliani, Ber. deut. chem. Ges. 59, 2462 (1926).

[24] H. S. Isbell and H. L. Frush, J. Research NBS 14, 359 (1935) RP773.

[25] O. F. Hedenburg and L. H. Cretcher, J. Am. Chem. Soc. 49, 478 (1927)

[26] E. Fischer and J. Hertz, Ber. deut. chem. Ges. 25, 1256 (1892).

[27] E. Fischer, Liebigs Ann. Chem. 270, 84 (1892).

[28] H. S. Isbell, H. L. Frush, and F. J. Bates, BS J. Research 8, 571 (1932) RP436; also Ind. Eng. Chem. 24, 375 (1932).

[29] F. P. Phelps and F. J. Bates, J. Am. Chem. Soc. 56, 1250, (1934).

[30] P. A. Levene and W. A. Jacobs, Ber. deut. chem. Ges. 43, 3141 (1910). [31] L. H. Cretcher and A. G. Renfrew, J. Am. Chem. Soc. 54, 1590 (1932). [32] Methods of Analysis, Assn. Official Agr. Chem. (Washington, D. C., 4th ed. 1935), p. 345.

[33] E.. L. Jackson and C. S. Hudson, J. Am. Chem. Soc. 59, 994 (1937). [34] P. Fleury and J. Lange, J. pharm. chim. (8) 17, 107 (1933).

12. REDUCTION PRODUCTS

(a) ALCOHOLS

General characteristics.-The sugar alcohols may be prepared by reduction of the sugars and sugar acids with sodium amalgam, by catalytic reduction of the sugars with hydrogen, or by electrolytic reduction of the sugars. Electrolytic reduction of sugars has been developed commercially under the patents of Creighton [1, 2]. The reaction is carried out by cathodic reduction of the sugar, using lead electrodes and sodium sulfate as electrolyte. Sorbitol and mannitol are obtained from dextrose by this process. The catalytic reduction of the sugars to polyhydric alcohols with hydrogen was reported by Ipatieff in 1912 [3]. Glucose was reduced to sorbitol, fructose to mannitol (and presumably sorbitol), while lactose was split and reduced to dulcitol (and presumably sorbitol). Senderens [4] studied the high-pressure hydrogenation of lactose further, and obtained a crystalline lactositol hydrate from the sirupy mother liquor after removal of the dulcitol. Böeseken and Leefers [5] used a nickel and cobalt catalyst and hydrogenated glucose in 95-percent alcohol. Nickel catalysts, such as Raney nickel [6] are generally used in sugar hydrogenation [7, 8, 9].

(1) REDUCTION OF d-a-GLUCOHEPTOSE WITH SODIUM AMALGAM TO GIVE d-a-GLUCOHEPTITOL.

Method [10].-Ten grams of d-a-glucoheptose is dissolved in 100 ml of water at room temperature, and after addition of 4 ml of 20-percent sulfuric acid, 300 g of pure 2.5-percent sodium amalgam is introduced. The mixture must be continuously shaken and the reaction of the solution must be held slightly acid or neutral by the frequent addition of dilute sulfuric acid. When the sodium amalgam is spent, the mercury is separated and if the solution gives a positive test for reducing sugar, 200 g of sodium amalgam is added and the process is repeated while the reaction is held neutral to slightly alkaline. When the reduction is complete, as shown by a negative test for reducing sugars with Fehling solution, the aqueous liquid is decanted from the

mercury, neutralized with sulfuric acid, treated with a small quantity of a decolorizing carbon, and filtered. The filtrate is diluted five-fold with warm alcohol, filtered after cooling, and evaporated in vacuo to a sirup. After cooling and standing, the sirup yields crystalline d-a-glucoheptitol almost quantitatively. The crystalline mixture is triturated with alcohol, filtered, and recrystallized from ethyl or methyl alcohol. Pure d-a-glucoheptitol melts at 127° to 128° C and is optically inactive.

(b) GLYCALS

General characteristics.-The glycals are unsaturated derivatives containing two hydroxyls less than the parent sugars. Usually they are prepared by the reactions represented by the following equations:

The glycals are of importance because they can be used for the preparation of new sugars and sugar derivatives. Oxidation of glycals with perbenzoic acid followed by treatment with water gives a mixture of the two epimeric sugars [11]; hence, by conversion of a sugar into its glycal and subsequent oxidation, the epimeric sugar may be prepared. Strangely, substitution of the hydroxyls greatly alters the proportions of the epimeric sugars produced. Thus the oxidation of triacetylglucal gives almost exclusively glucose derivatives, whereas the oxidation of glucal gives glucose and mannose, with mannose in predominating quantity [11, 12]. By treating glycals with perbenzoic acid in the absence of water, followed by the addition of methyl alcohol, methyl glycosides are obtained [11]. The products obtained by the perbenzoic acid oxidation usually contain small quantities of monobenzoyl derivatives [13].

Treatment of the glycals with cold aqueous sulfuric acid gives sulfuric esters which on hydrolysis yield desoxy sugars. Chlorine adds to the double bond to give a mixture of epimeric 1,2-dichloro derivatives, while hydrobromic acid appears to give 2-bromo derivatives [14]. Oxidation of the glycals with ozone splits the molecule at the double bond. Reduction with hydrogen in the presence of a catalyst yields hydroglycals [14]. The behavior of the glycals towards hydrogen chloride provides a convenient qualitative test: A pine splinter moistened with a glycal solution and exposed to hydrogen chloride gas turns green.

The tendency of the glycals to undergo intramolecular change is particularly noteworthy and should be kept in mind when working with these products. Boiling triacetylglucal with water results in the migration of the double bond to the 2,3 position and the hydrolysis of one acetyl group [15]. The product, diacetylpseudoglucal, on treatment with barium hydroxide, undergoes further rearrangement to give isoglucal and protoglucal [16].

(1) TRIACETYLGALACTAL AND GALACTAL.

Method [13]. To a 12-liter flask surrounded by an ice-salt bath there is added 1,000 ml of water, 500 ml of acetic acid, and 100 g of zinc dust which is kept in suspension by the aid of a mechanical stirrer. During a period of 3 hours, ten 75-g portions of finely powdered bromotetraacetylgalactose, each dissolved in 300 ml of warm glacial acetic acid, are added. Water is added in quantities to keep the composition at approximately 50-percent acid, and 600 g of zinc dust is added in portions at intervals during this period. The temperature is allowed to rise slowly to room temperature over a period of 18 hours. Then the mixture is filtered,' and the filtrate is extracted four times with a total of about 11 liters of benzene. The washed extracts are evaporated at a pressure of 14 mm to a thick sirup. The weight of the sirup, obtained by the combination of two such preparations from a total of 1,370 g of the bromo-tetraacetylgalactose, is about 685 g. This sirup is then purified by distillation at 140° to 155° C at a pressure of approximately 0.05 mm. The distillate (500 g) is deacetylated by dissolving it in 4 liters of dry methyl alcohol containing 0.1 mole of barium methylate. After standing for 18 hours in the refrigerator, the solution is saturated with carbon dioxide and the barium carbonate is separated and discarded. The alcoholic solution is evaporated in vacuo to a thick sirup, which is dissolved in 200 ml of absolute alcohol and evaporated again. The resulting sirup is extracted with absolute ethyl alcohol. The insoluble residue is discarded and the extracts are concentrated to a sirup containing about 60 percent of solids. The galactal crystallizes readily from this solution. It is separated by filtration and recrystallized from hot ethyl acetate. About 200 g of the recrystallized product is obtained from 500 g of the acetate. The pure substance melts at 100° C.