LASZL~ MESTERAND ADAMM.\JOR
3233 [CONTRIBUTION FROM
THE INSTITUTE O F
ITOl. 79
ORGANIC CHEMISTRY, TECHNICAL UNIVERSITY. BUDAPEST]
A New Interpretation of the Mutarotation of Sugar Osazones BY LASZL~ MESTERAND ADAMM A J O R RECEIVEDAUGUST6, 1956 Mutarotation of a sugar osazone was first observed by Levene and Jacobs,' but they did not attempt t o explain the plienomenun. Zerner and Waltuch2 suggested that it should be ascribed t o the tautomeric change of the bishj drazone form I into the azohydrazone form 11. Haworth3 favored the production of a n equilibrium with the cqclic forti) 111.
7
C=SNH-Cp,Hj
I
/*
HC-x=rU'-c&Ij
rHC-IYHNH-CsHa
I
C=Nh"-c6I-f&
1 (!k=XSH-c& 6 :
C=xNH-ce:lj
I
I1
Discarding all earlier views, Engel,4 in studying glucosazone, endeavored to show that rnutarotation is due to hydrolysis, with phenylhydrazine splitting off. Since evidence has lately been provided for the acyclic structure of sugar o s a z o n e ~ and ~ . ~ ~since ~ the previously postulated presence of a chelate ~ 'now ~ appears ring (Fig. 1) has been c ~ n f i r r n e d ,it necessary to revise current interpretations concerning their mutarotation.
I11 40 min.), -23.1' ( 7 hr., 10 min.), -20.1' (21 hr., 5 min.). The solutions were evaporated t o dryness, and mutarotation was repeated with the substances recovered without purifying them; the same mutarotations were observed. Ultraviolet spectra were determined with a Beckman DUtype spectrophotometer in samples taken from time t o time from the above solutions and diluted with ethanol to 0.0001 mole (Fig. 2 for D-glucose phenylosazone).
XH-CsHj
I
..
HC
/"\
HC
IS
I SH-Cp,Elj
IV'
1.' Fig. 1.
Experimental Mutarotation of D-glucose p h e n y l o s a z ~ n eand ~ D-glucose1-methylphenyl-2-phenylosazonelO u as measured ( c = 0.5) in a 1:l mixture of pyridine and ethanol a t 20 ?c 2'; for D-glucose phenylosazone: [cY]*~D -67.3' (10 min.), -45.5' (1 hr., 10 min.), -27.7' (5 hr., 10 min.), -23.8' (8 h r . ) , -23.8' (11 hr., 15 min.), -23.8" (24 hr.); for D-glucose-lmethylphenyl-2-phenylosazone: [ o ] * ~ D -52.2' (10 min.), -42.1' (1 hr., 15 min.), -36.1" (2 h r . ) , -26.1' (5 hr., (1) P. A. Levene and W. A. Jacobs, B e y . , 42, 3249 (1909). (2) E. Zerner and R. Waltuch, hfonatsh., 36, 1025 (1914). (3) W.pi. Haworth, "The Constitution of Sugars," Edward Arnold & Co., London, 1929, p. 7. (4) L. L. Engel, THISJ O U R N A L , 67, 2119 (1935). ( 5 ) L. Mester, i b i d . , 77, 4301 (1955). ( 6 ) L. Mester and A. Major, i b i d . , 77, 4305 ( 1 9 5 5 ) . (7) In t h e meantime V. C . Barry a n d co-workers8 have proved t h a t in dilute solution the osazones are present in the acyclic form only. (8) V. C. Barry, J. E. McCorrnick and P. W. D. Mitchell, J . Chent. Soc.. 222 11953). (9) E . Fischer. Rer., 17, 579 (1884); 20. 821 (1887). (10) S. Akija and S. Tejima, J. P h n r m . Soc J a f l a ~ 72, , 1574 (1452); C. A , , 47, 9275 (1953).
b
1
1
I
1
300 400 500 Fig. 2.--Ultraviolet spectrum of D-glucosazone: 1, immediately; 2, 1 hour; 3, 21 hours after solution.
Practically the same values and the same changes were observed for D-glucose-1-methylphenyl2-phenylosazone. The same results were obtained with recovered materials. Formazan Reaction During Mutarotation.-Froni D-glucose phenylosazone a 0.1-mole stock solution was prepared in a 1 : 1 mixture of pyridine and ethanol. From this 50ml. samples (1.8 g. of osazone) were taken a t times and on adding 50 ml. of 2 A' alcoholic potassium hydroxide were coupled t o formazan with diazo solution prepared from 0.7.5 g. of aniline.6 The crude foriiiaznns obtaiiiec! were twice recrystallized from a mixture of four times the volume of pyridine and ten times the volume of ethanol; m.p. 198". Simultaneously, samples taken from the stock solution were diluted with a 1 : 1 mixture of pyridine and ethanol ( c = 0.5), and the rotational changes observed. On completion of the mutarotation the stock solution was evaporated t o dryness in i n c m and the above experiment repeated with the substances obtained without purifying them (Fig. 3). Mutarotation of tetra-0-acetyl-D-galactose phenylosazone1] w t s measured in dioxane (c = 0.5): [alzo0,+*%" (10 min.), +60" (1 hr., 33 min.), $80' (38 hr., 40 niin.). T h e solution on concentration t o dryness, yielded the osazone unchanged ; dissolving the recovered material in dioxane gave the same rotatioixil values. ( 1 1 ) M . I,. Kolfrom, h l Kdnigsberg and S. Soltzherg, THISJ O I T R NAI.,
68, 490 (1936).
June 20, 1957
MUTAROTATION OF SUGAR OSAZONES
3233
The ultraviolet spectra were determined in samples taken from time t o time from the mutarotational solution and diluted with dioxane to 0.0001 mole. They showed the same changes for both the original and the recovered material, and these changes were identical with those for D-glucose phenylosazone.
4-Desoxy-~-glycerotetrosephenylosazone dissolved in pyridine was subjected to mutarotation and evaporated to dryness; the osazone recovered was again dissolved in pyridine, and once more the mutarotation as described by Fried, et nZ.,12 was observed.
40
-.
20 Result and Discussion Since mutarotation, spectral displacement and formazan formation 0 after distillation of the solvent in the 5 10 15 20 25 redissolved substance are reiterating Hours. Drocesses. Enpel's4 view that mutaro- Fig. 3.-Repeated mutarotation of D-glucosazone in a mixture of pyridine and alcohol. iation d e p e d s on the hydrolysis of osazones seems to be excluded. The reaction of the glucosazone with the diazo solution in samples taken from the mutarotating solution yields less and less osazone formazan (Fig. 2). This is due obviously to the same structural change which is optically perceivable during mutarotation. I . I A I Since Haworth's cyclic formula I11 is 0 unable to yield formazan, the transfor5 10 15 20 25 mation of the two anomers into each Hours. other cannot possibly be regarded as Fig. 4.-Yields of D-glucosazone formazan (twice recrystd). the cause of mutarotation. I t now remains to be ascertained whether the open-chain been suggested by Zerner and Waltuch.2 Nevercompound I changes into Haworth's cyclic form theless, on the evidence of our findings above it I11 during mutarotation. Were it so, owing to the would appear that the real cause of the mutarodisappearance of one chromophoric group, the tation is to be sought in the electron displacement maximum of the ultraviolet spectrum would have which takes place in the chelate structure of the to show a substantial alteration of the charac- osazones upon the action of the solvent,17-19 and which amongst others reveals itself in a displaceteristics.8 The observations of Weygand, et a l . , 1 3 on the ment of the ultraviolet spectra and in a decrease of mutarotation of 5,6-di-O-methyl-~-glucosep-bro- the ccsupling capacity. The two latter observations suggest the conclumophenylosazone, and those of Gorin, et a1.,14 on the mutarotation of L-glycerotetrulose phenylos- sion that in the course of mutarotation there is a azone and its derivatives, leave no room for a con- structural shift from somewhere near the IV state cept which holds that mutarotation might be caused toward the IV' state, since while the former is suitable, the latter is definitely unsuited for coupling by cyclization departing from the second carbon. Finally, the mutarotation in tetra-O-acety1-D- and for the change in the ultraviolet spectra, the glucose phenylosazone, l1 in tetra-0-acetyl-D-galac- above structural shift seem to be r e s p o n ~ i b l e . ~ ~ ~ * ~ tose phenylosazone and in 4-desoxy-~-glycero-~- (17) Reference is made t o Burawoy, et a1.,'8 concerning l-phenylazo-2-naphthol and 1,2-naphthoquinon-2-phenylhydrazone,the chetetrose phenylosazone,l*can in no way be explained late structure of which can be influenced by t h e solvent. by cyclization, since in these cases there is defi(18) A. Burawoy, A. G. Salem and A. R. Thompson, J. Chcm. SOC., nitely no possibility for ring formation to take 4793 (1452). (19) There are several references in the literature pointing o u t t h a t place. l5 a,@-unsaturated azo-structure forms in the P-nitroyhenylhydraI t also seeins impossible that a stable conjugated an zones of unsaturated ketoneszo-22 and t h a t the rearrangement of hysystem I of double bonds should change into an un- drazone of the compound of azo-structure takes place upon the action stable compound TI of isolated double bonds, as has of a solvent, finally t h a t this is a somewhat slow process causing changes
I
(12) J. Fried, S. E. Walz and 0. Wintersteiner, THIS JOURNAL, 68, 2746 (1946). (13) F. Weygand, H. Grisebach, K. Kirchner and M. Haselhorst, Bcr., 88, 487 (1955). (14) P. A. J. Gorin, L. Hough and J. K. N. Jones, J. Chem. Sac., 2699 (1955). (15) Some objections expressed by E. E. Percival and E. G. V. Percival16 t o the acyclic structure of the osazone acetates proposed by M. L. Wolfrom, et al.," are contradictory t o our findings concerning t h e structure of tetra-0-acetyl-D-glucose phenylosazone formazan.5 (16) E. E. Percival and E. G. V. Percival, J . Chcm. Soc., 1320 (1937).
in the optical rotation.2s (20) F. Ramirez and A. F. Kirby, THIS J O U R N A L , 76, GO26 (1953). (21) J. van Alphen, Rec. Iran. chim., 64, 305 (1945). (22) R. J . W. Le FPvre, M . F. O'Dwyer and R. L. Werner, Chcmirt r y & I n d u s t r y , 378 (1953). (23) W. F. McGuckin and E. C. Kendall, T H I S J O U R N A L , 74, 5812 (1952). (24) As regards D-glucose 1-methylphenyl-2-phenylosazone,of t h e chelate structures proposed by Fieser and Fieseru the V and V' structures must be discarded because of t h e presence of t h e methyl group, and only the I V and I V ' structures can be taken into consideration. I n our view, t h e extraordinary resemblance of the mutarotation, t h e ultraviolet spectrum and t h e polarographic behavior of glucosazone
Experiments t u disclose the mechanism of this structural displacement are in progress. t o those of glucose-1-methylphtnyl-2-phenylosazonejustifies discarding t h e V and V' formulas of glucosazone as well. All the more SD. a s t h e methylation of glucosazone, as has already been pointed oiit.5 invariably leads t o o-glucose-1-methylphenyl ?-phenylosazone derivable from t h e I V and IV' forms, and so, so f a r , it has proved i n possible to prepare methylated o-glucosazone from t h e chelate structures V and V' neither by direct methylation nor in some roundabout way. T h e so-called mixed osazone B, which could be supposed t o possess this structure, has been proved t o be ~-glucosa7onecontarnininated with mixed osazone A.5
Acknowledgment.-iVe wish to express our indebtedness to Professor G. ZempKn for valuable advice given and to thank Dr. W. Cieleszky for the determination of the ultraviolet spectra, finally, Miss Ilona Batta for the microanalyses. ( 2 2 ) L. I>. Fieser and .\I. Fieser, "Organic Chemistry," D. C. Heath CY Co., Boston, Mass., 1944, p. 351. (26) F. Ramircz and R . J. Bellet. TaIs J O U X N A I . , 7 6 , 4!11 (IL(S4).
I~UDAPEW HUNGARY ,
[CONTRIBUTION FROX THE NATIONAL INSTITUTE O!3 L~RTHRITIS A S D METABOLIC DISEASES, NATIONAL INSTITUTES O F HEALTIT]
1-0-Benzoyl-a-D-talopyranose BY HARRYB. WOOD,JR.,
AND
HEWITTG. FLETCHER, JR.
RECEIVED JANUARY 26, I957 Osidatioii of u-gulactal rvitli perbenzoic acid has givcn a ncw D-tdOSe moiiobenzoate.
Xcetylution of this ester al'fortlctl
im aniorphous ester which is identical with 2,3,4,B-tetra-0-acet~-l-l-~-beiizoyl-ol-losesynthesized from 2,3,4,6-tetraO-acetyl-ol-D-talopyranos)T1bromide. The new substance is, therefore, 1-0-benzoyl-cu-D-talopyranose. ture of another D-talose monobenzoate, described carlier in the literature, is discussed.
I n 1937, Pigman and Isbell' described a mono-0benzoyl-D-talose which they had obtained as a byproduct in the preparation of D-talose via the oxidation of n-galactal (11) with perbenzoic acid. Owing to the fact that the substance was stable in dilute acid solution but mutarotated in water, methanol, dilute alkali and pyridine, a cyclic orthoacid structure (I) was assigned to it.
The possible struc-
normal ester as shown by its characteristic ester carbonyl absorption in the infrared. FH,OH
Ch,Oh
CH,OH Ac,O CH,OAc
CH,OAc
I
3
The lability of this substance compared with the stability of the well-characterized l-O-benzoyl-/.j'D-glucopyranose prepared somewhat earlier by Zervas2 and the widespread currency of the cyclic orthoacid concept which had first been suggested by Ernil F i ~ c h e rcombined ,~ to make such a tentative assignment of structure a reasonable one a t that peri~d.~ However, subsequent advances in the chemistry of the sugar esters have shown (a) that acyl groups are very prone to migrate from C1 to Cz of an aldose when the hydroxyl a t Cz is free and spatially accessible to C15*6 and (b) that cyclic orthoacid structures such as I are not likely to be sufficiently stable for isolation.6 Furthermore, Isbell and his co-workers7 have shown recently that the sample of D-talose inoiiobenzoate prepared in 1037 had undergone no change in physical properties during the intervening years and was indeed a (1) 1%'. 1%'. Pigman and H. S Isbell. J . Reseavch .\-ail. Buy. Slanduvds, 19, 189 (1937). ( 2 ) L . Zervas, B e ( , 64, 2289 (1931). C3) E. Fischer, $bid , 63, l(j1'4 (1920) (1) Cf.E . Pncsu, A d u ~ i i r v .iri ~ Coi.boiiyi!r.irfr. C / r ~ i ? i1, . , 7 8 (194.5) l'letcher, J r . , 'I'HIS J C ) l i R N A l . , 78, 28,L!l f.5) 13.H.\ V o i d , J r , a n d H. ( 1 9.56). (I;) R. E(.&-cas arid H G . Fletcher, J r . , ibid., 7 8 , 4710 (195Iii ( 7 ) H . S. Isbell, J . E Sterrart, €I I , , Frush, .I. D . Xloyer and 1'. ;\ S m i t h , J . Kesriwch S u t l . B w . S t a m i t i i d ~ 6, 7 , 179 c l i l i a ) .
0 AgOBz
AcO \L-€3' OAc
+ CH, N,
1
-
ALO
Y,?Ac
A$oB2
.I__-
IV
V
In all known additions to the double bond of glycals8 the anionic portion of the adding molecule has been found attached to C1 of the sugar and i t seems reasonably certain, therefore, that the substance reported by Pigman and Isbell is a 1-0-benzoyl-Dtalopyranose. Its failure to mutarotate in acid solution1 and to give a phenylhydrazonei appear to support this assumption. The mutarotations in water, methanol, dilute alkali and pyridine reported by Pigman and Isbell' i may then represent acyl migration from CI to C2or some other position. Indeed these mutarotations, which start in a leoo direction and then turn in the dextro direction, suggest that an initial acyl migration frees a d-hydroxyl a t C1 and that normal equilibration of the anomeric forms then ensues. If the instability of the ester is due to a C1-+ Czmigration we must espect it to be the p- rather than the a-1-0-benmylD-ta~OpyranOSe,for such a cis isomer would resemble the easily rearranged 1-0-inesitoyl-a u-gluu s e 5 and 1,3,5-tri-O-benzoyl-ru-~-ribosc~ while tlic (8) bee for Inbtance R Hclferich, 7 , 11u ( I S % )
il i A i i i E \
l i
L i i t i d i ~1 1
ite
Chi
ill
,
