30 W. G. OVEREND AND M. STAGEY 



be converted quantitatively to the corresponding A'^-aryl-D-ribofuranosylamines 

 by heating in boiling alcoholic solution. Hydrogenation of both the pyranose and 

 furanose forms of the arylamine-A''-ribosides afforded the ribitylamine derivative.^'- 

 167, 168 Working with isomers of A^-phenyl-D-ribosylamine, Howard et aZ.'^' found that 

 the optical rotation of both isomers (i.e., pyranose and furanose isomers) is constant 

 in dry pyridine and that a trace of moisture is necessary for mutarotation. Under 

 these latter circumstances the two isomers do not come to the same end-value for 

 the specific rotation and it was considered likely that each is undergoing a,/3-isom- 

 erism. On the other hand, in solution in pyridine containing 10% acetic acid, the 

 isomers are claimed to mutarotate to the same end-point. It was thought that an 

 equilibrium involving change in ring size is established under these conditions and 

 acylation experiments supported this viewpoint. Acetylation of both A^-phenyl- 

 ribosylamines led to the same tri-0-acetyl-A^-phenyl-D-ribosylamine which upon 

 hydrolysis with methanolic ammonia afforded A^-phenyl-D-ribopyranosylamine. 

 Evidently the ribofuranosylamine had rearranged to the ribopyranosylamine during 

 acetylation. Acidic hydrolysis of tri-0-acetyl-A''-phenyl-D-ribopyranosylamine re- 

 moved the aniline residue, and upon further acetylation of the sugar moiety /3-d- 

 ribopyranose tetra-0-acetate was obtained. The mechanism of isomerization of amine 

 glycosides was discussed by Howard et al.^^^ Measurements of the changes in the 

 optical rotation of solutions of iV-phenyl-D-ribosylamines have also been reported 

 by Stacey and his colleagues.'*" In addition these workers also measured rates of 

 acidic hydrolysis of these compounds. Recent experiments by Barclay et al.^^^ sug- 

 gest that care must be exercised in attributing to true mutarotational phenomena 

 the changes in optical rotation that may occur in solutions of A^-glycosides without 

 prior ascertainment of the effect of water and pH alterations, since frequently the 

 changes in rotation are caused by hydrolysis rather than mutarotation. 



Very recently the reaction between D-ribose and aniline has been reexamined 

 critically by Ellis and Honeyman.'*' It was established that water has an influence 

 in determining which isomer is obtained. Contrary to the suggestions of previous 

 workers, temperature is not important in influencing the nature of the product. For 

 example, the isomer (A) thought to be iV-phenyl-D-ribopyranosylamine was produced 

 either at room temperature or at the boiling point when aqueous ethanol was used 

 as solvent. The presence of moisture in the condensation mixture always resulted in 

 the production of this isomer and the supposed A^-phenyl-D-ribofuranosylamine (B) 

 was obtained only in anhydrous ethanol. Similarly, even a small amount of water 

 prevents the conversion of isomer (A) into isomer (B) in boiling ethanol, and this 

 probably explains some of the inconsistencies reported by Howard et al.^^^ Contrary 

 to workers in other laboratories, Ellis and Tatchell found no mutarotation for these 

 isomers when in pyridine solution, even on addition of a drop of water. It will be 

 recalled that it was largely on the basis of the mutarotation that Berger and Lee 

 considered the isomers to have different lactol rings. 



A similar cycle of reactions was carried out with D-ribose and p-toluidine.'*' Until 

 the experiments of Ellis and Honeyman, the only known A'^-p-tolyl-D-ribosylamine 

 was that prepared and described by Berger and Lee.*' It was obtained by reaction at 

 room temperature, in a solvent of ethanol containing a trace of water. Ellis and 

 Honeyman obtained two isomers according to whether anhydrous or moist conditions 



1" L. Berger and J. Lee, J. Org. Chem. 11, 75 (1946). 



158 J. Lee, U. V. Solmssen, and L. Berger, U. S. Pat. 2,384,102 (Sept. 4, 1945). 



1" G. A. Howard, G. W. Kenner, B. Lythgoe, and A. R. Todd, /. Chem. Soc. 1946, 855. 



160 K. Butler, S. G. Laland, W. G. Overend, and M. Stacey, /. Chem. Soc. 1950, 1433. 



i«i G. P. Ellis and J. Honeyman, Nature 167, 239 (1951); J. Chem. Soc. 1952, 1490. 



