722
CHEMISTRY
that each of the four carbon atoms in the four CH(OH) groups is combined with four different radicles, so that there are four asymmetric carbon atoms in the formula. The number of modifications of an asymmetric compound— which is not itself symmetric—is 2W, where n is the number of such carbon atoms; it is therefore to be supposed that 16 isomeric aldohexoses of the formula C6H1206 can exist. At the time Fischer began to work at the group only one was known besides glucose—galactose, which is obtained together Math glucose on hydrolysing milk sugar. In 1894, when Fischer summarized the results of his work, he was able to speak of no fewer than eleven of the sixteen, and to define their structure precisely. The next chapter of discovery to be considered relates to the synthesis of fructose and glucose, one of the most memorable achievements in chemistry in view of the part these play in plant economy. Butlerow, a distinguished Russian chemist, as far back as 1861, by digesting trioxymethylene, the solid polymeride of formic aldehyde, H2CO, with lime, obtained a sugar-like substance, methylenitan, to which he assigned the formula C7H1406. Attention was specially directed to this research by Baeyer, in 1879, in the course of the celebrated paper in which he discussed the formation of sugar in the plant. Synthesis gaeyer maintained that formic aldehyde must of fructose - be regarded as the primary product formed by the reduction of carbon dioxide in the plant, and as that from which glucose and similar substances are gradually built up. Owing to the difficulty of preparing formic aldehyde, the subject was left untouched for a considerable time until Low, in 1886, greatly improved the method of producing the aldehyde—so much so, that it is now manufactured on a very large scale, and used in making certain aniline dyes and also as an antiseptic agent. Low carefully repeated Butlerow’s work, and obtained results which he regarded as confirmatory of Baeyer’s suggestion; he described the product as a sweet, unfermentable syrup, of the formula C6H1206, and termed tforrnose. Low, however, assigned the formula C18H22N40g to the osazone prepared from this formose, whereas that of glucosazone is C1SH22N404. To explain this discrepancy, E. Fischer repeated" Butlerow’s and Low’s experiments, and arrived at the conclusion that the main product was in reality a compound of the same composition as glucose, though resembling it only distantly in properties, for which formose was a very suitable name. At the same time he discovered in the product a relatively small proportion of an isomeric substance which was subsequently identified as the a-acrose to be referred to later. Meanwhile, Loav had continued his experiments, and by using magnesia in place of lime, had obtained a fermentable product which he named methose. In Fischer’s hand§ this also proved to be a-acrose. This substance was discovered by Fischer and Tafel in 1887, and was first obtained by cautiously adding baryta to a solution of acrolein dibromide, prepared by combining the aldehyde acrolein, CH2:CH.COH, with bromine. A better method of producing it, subsequently discovered, is to oxidize ordinary glycerol by means of bromine and alkali, and to subject the product to the action of very dilute alkali at 0 . Glycerol yields two compounds when oxidized the corresponding aldehyde and the corresponding ketone, and apparently a-acrose is formed from these by “ condensation in the manner indicated in the equation :— CH9(0H).CH(0H).C0H + CH2(OH).CO.CH2(OH) = CH2(OH).CH(OH).CH(OH).CH(OH).CO.CH2(OH).
resemble most closely that obtained from glucose and fructose, acrosazone differing only from glucosazone in being optically inactive. This observation showed that a most important step had been taken towards synthesizing the natural hexoses, as it justified the conclusion that a-acrose was merely the inactive form of either glucose or fructose—a view which was ultimately confirmed, but only after years of work. In the first place, it was necessary to reproduce the hexose from the osazone, the form in which alone it can be isolated from the crude synthetic product. Ultimately it was found that the action of phenylhydrazine on the hexoses could be reversed by means of muriatic acid, the group N.NHPh being thereby removed and displaced by oxygen, giving rise to an osone or onal—a compound combining in itself the properties of aldehyde and ketone, which on reduction by means of zinc dust and acetic acid is converted into a ketose ; thus— CH2(OH) CH2(OH) CH2(OH) CH(OH) CH(OH) CH(OH) CH(OH) CH(OH) CH(OH) CH(OH) CH(OH) CH(OH) C:N.NHPli C:0 C:0 CH:N.NHPh CH:0 CH2(OH) Glucosazone. Glucosone. Ketose.
The compound prepared from acrosazone was found to have the properties of fructose, to be fermentable by yeast, to give laevulinic acid when boiled with muriatic acid, and to be converted by the action of sodium amalgam into a-acritol, a substance indistinguishable from mannitol except by its inactivity toward polarized light. As illustrating the difficulties met with in the research, it may be mentioned that starting from a kilogram of glycerol, only 0'2 gram of a-acritol could be obtained, in consequence of the number of the operations and the bad yields afforded by some of them. The character of a-acritol was ultimately deciphered by a method of indirect approach. Prior to Fischer’s investigations, the attempt had often been made to reconvert mannitol and the isomeric alcohol dulcitol — which, besides being a natural product like mannitol, is formed on reducing galactose from milk sugar—into sugars by subjecting them to oxidation, but the results obtained were inconclusive owing to the difficulties met with in isolating the pro| ducts. It was here that phenylhydrazine again proved to be an invaluable agent. With its aid Fischer and Hirschberger were able to show in 1881 that when mannitol is oxidized by means of nitric acid, it yields, besides fructose, an isomeride of glucose, mannose, which is the true aldehyde of mannitol, glucose belonging to a stereoisomeric series. Mannose and glucose are, however, most intimately related, as both ultimately yield glucosazone when subjected to the action of phenylhydrazine; hence it follows that they differ only in respect of the first asymmetric carbon atom above the COH group. The investigation was assisted by the discovery made at this stage that mannose, the existence of which had so long lain hidden, was easily procurable from natural sources—Tollens and Gans obtaining it by hydrolysing salep mucilage, and Reis from so-called reserve cellulose, vegetable ivory turnings being a particularly suitable material from which to prepare it. On oxidation, mannose, like glucose, yields a monobasic acid—mannonic acid, which is a stereoisomeride of gluconic acid. M hen the aqueous solution of this acid is evaporated, the acid loses the elements of a molecule of water and is converted It should be mentioned, however, that it is only one of into a lactone, C6H10O6, which crystallizes well. Now it had been observed by Kiliani that when arabinose—a several products. The osazone prepared from a-acrose was found to sugar belonging to the pentose group, i.e., one containing
