Nitriles of the Aldonic Acids

The work which Wohl reported in his earliest paper on sugar degradation had been planned with the expectation that the nitriles of the aldonic acids would react as cyanohydrins. When he carried out his first degradation with pentaacetyl-D-glucononitrile (XXIX) he used ammonia 

Ammonia with dissolved silver oxide was employed as the only degradation reagent until Maquenne showed that ammonia alone could be employed with the same success this method has been developed further by Hockett.  

Propionylated aldononitriles, prepared by Gim nez, have been degraded in a similar way and the dipropionamide derivatives of the lower sugars obtained without difficulty. 

Restelli de Labriola and Deulofeu have degraded benzoylated nitriles of the hexose series and tetrabenzoyl-L-rhamnononitrile, with ethanolic ammonia. The dibenzamide compounds of the lower sugars were obtained, but in the case of compounds with a benzoylated primary hydroxyl group, such as pentabenzoyl-D-glucono-, D-mannono- and D-galactononitriles (XXXI) the benzoyl group that esterifies the terminal hydroxyl was not removed (XXXII). 

With tetrabenzoyl-L-rhamnononitrile (XXXIII), a normal 5-desoxy-L-arabinose dibenzamide (XXXIV) was obtained. 

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Wohl prepared the acylated nitriles of the aldonic acids by heating the aldose oximes with a mixture of sodium acetate and acetic anhydride. With careful control of the reaction, this method may be used for preparative work with fairly good results. 

Acetylated nitriles of the aldonic acids are crystalline solids that are very soluble in most nonpolar organic solvents (chloroform, ether, benzene), less soluble in the alcohols usually employed for recrystallization, and almost insoluble in cold water some compounds have a remarkably high solubility in water at elevated temperatures. 

The nitrile group is very sensitive to alkalis and the elimination of it by the action of potassium hydroxide on acetaldehyde cyanohydrin was described by Simpson and Gauthier as one of the reactions of the acetaldehyde cyanohydrin, a substance that they prepared for the first time. That the nitriles of the aldonic acids yield cyanides under the action of alkali, is described by Wohl as one of the properties of penta-acetyl-D-glucononitrile. 

With the exception of V-acetyl-D-glucofuranosylamine studied by Hockett and Chandler, all the acetylated nitriles of the aldonic acids (60) G. Zempl4n, Ber., 69, 2402 (1926). 

The first step in the degradation is the preparation, starting from an aldose, of the acylated nitrile of an aldonic acid. The nitrile and the acyl groups may be removed by various methods to yield a new aldose,... 

The first benzoylated nitrile of an aldonic acid was prepared by Brigl, Muhlschlegel and Schinle by benzoylation of the n-manno-n- oZa-heptononitrile the hexabenzoyl derivative was obtained. A series of benzoylated nitriles has recently been prepared by Restelli de Labriola and Deulofeu by treatment of the oximes of L-rhamnose, D-glucose, D-galactose and D-mannose with benzoyl chloride and pyridine. They were the sole products and were obtained in high yields. 

III. Degradation of the Nitriles op the Aldonic Acids 1. The Wohl Degradation... 

Removal of the acetyl and nitrile groups by acid hydrolysis was also achieved by Wohl, who isolated a pentosazone from the products from heating pentaacetyl-D-glucononitrile with 2 N hydrochloric acid. Fischer also isolated what is now known to have been a 5-desoxy-L-arabinosazone from the products obtained by treatment of tetraacetyl-L-rhamnononitrile with 5% hydrochloric acid. At the same time partial transformation of the nitrile into the aldonic acid takes place as shown by Maquenne, who obtained D-xylonic acid by treating tetraacetyl-D-xylononitrile with concentrated hydrochloric acid. 

The cyanohydrin synthesis is particularly important in the carbohydrate series Fischer thus converted, e.g., pentoses into hexoses by way of the lactones of the aldonic acids which he later reduced. Admittedly, the nitriles produced as intermediates (best obtained in other cases by dehydration of the corresponding oximes) are generally not isolated. On the other hand, the corresponding amides can often be separated in a pure state, as shown, e.g., by Kiliani166 for heptonamide ... 

Certain exceptions to this general scheme have been noted in which the normal hydrogenation of the nitrile group has not taken place. In these cases, a hydrolytic reaction has occurred, with the formation of an aldonic acid instead of the expected aldose.12 The anomalous reaction occurs when the nitrile exists in the (isomeric) iminolactone form for example, compound I is hydrolyzed directly, before hydrogenation can take place. This isomerism of the aldononitriles was established by Papadakis and Cohen,16 and the cyclic structure I was postulated by Wolfrom and coworkers.108... 

Cyanohydrin Synthesis from Osones (14 )- For this method, 3-keto aldonic acids are formed as intermediates which are not isolated. The first product, the nitrile, immediately enolizes with simultaneous ring formation to an imino analog (XI) of the ascorbic acid, and the latter is formed by... 

It already has been mentioned (Chapter 2) that the cyanohydrin reaction of adding hydrogen cyanide to carbohydrates played an important role in the elucidation of the configurational structures of the carbohydrates. The reaction increases the length of the carbohydrate chain by one carbon but, unfortunately, forms two epimeric products that must be separated. Sometimes one of the two products is produced in much larger amounts than the other, facilitating the separation, but sometimes also providing the unwanted product. The nitrile products can be converted into the aldonic acids by hydrolysis with sodium hydroxide. The aldonic acid can be converted into the lactone by treatment with sulfuric acid. The lactone can then be reduced by sodium borohydride to the hemiacetal (reaction 4.41). 

Deulofeu, Venancio, The Acylated Nitriles of Aldonic Acids and Their Degradation, IV, 119-151... 

Afterward, Behrend found that the nitrile is also produced when o-glucose oxime is treated with pyridine and acetic anhydride, and this method has been extended to the preparation of other nitriles of aldonic acids. ... 

Free aldonic acid nitriles have been prepared in a few cases. Kiliani obtained the cyanohydrin of D-fructose by adding hydrocyanic acid to the ketose and Miksic obtained the nitriles already mentioned in a similar way. 

Apart from the general procedures that have been described, nitriles of aldonic acids are capable of other reactions that also lead to degradations. 

For a long time, this reaction was conducted exclusively with acety-lated nitriles of aldonic acids, and the products obtained were known in general as "aldose-amides. Fischer2 used this reaction to transform tetra-O-acetyl-L-rhamnononitrile into l,l-bis(acetamido)-l,5-dideoxy-L-arabinitol, whose subsequent hydrolysis and oxidation allowed him to determine the configuration of dextro-tartaric acid (L-threaric acid). 

Brigl and coworkers9 discovered the first example showing that the formation of aldose amides is not restricted to the degradation of acylated nitriles of aldonic acids. By ammonolysis of 2,3,4,5,6-penta-O-benzoyl-aldehydo-n-glucose (16), they obtained l,l-bis(benz-amido)-l-deoxy-D-glucitol (17). 

H. Kiliani, as Fischer always emphatically acknowledged, discovered and developed the method of building up the aldose series by the cyanohydrin reaction to give nitriles from the nitrile, the next higher aldonic acid could then be prepared. In 1890, A. Wohl, working in Fischer s Berlin laboratory, elaborated the dehydration of an aldose oxime to the nitrile, from which the next lower aldose could be prepared by loss of hydrocyanic acid. Fischer exploited the possibilities of sugar extension and degradation afforded by the use of these two important methods. 

Derivatives of 2-deoxyglycuronic acids have been obtained by catalytic oxidation193 of suitably protected alcohols, and by hydroformylation194 of terminal epoxide groups in aldonic acids. 6-Deoxyhepturonic acids or derivatives thereof have been obtained by cyanide displacement of a 6-sulfonyloxy group from derivatives of hexoses and hydrolysis of the resulting nitriles.195... 

Deulofeu, Venancio, The Acylated Nitriles of Aldonic Acids and Their Degradation, 4, 119-151 Dimler, R. J., 1,6-Anhydrohexofuranoses, A New Class of Hexosans, 7, 37-52 Doudoroff, M. See Hassid, W. Z. Dubach, P. See Mehta, N. C. 

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