67
MASSSPECTRA OF ISOPROPYLIDENEPENTOSES A N D -HEXOSES
Jan. 5 , 1964
much smaller in these cases than for the nitro, carbethoxy, or dimethylamino groups. The angles of twist of 37 and 49", respectively, seem reasonable, but it is difficult to discuss the behavior of these groups in more detail since the geometry of the groups and of the conjugating orbitals is open to question. A further significant feature of Table I1 is the demonstration that the resonance interaction, as reflected by U , of a functional group with a second substituent is a variable parameter which is very sensitive to the nature of the second substituent and the reaction process in question. For this reason it is impossible to assign a single U-value to a group which can be used successfully to correlate all reaction data through the Hammett equation, as W e p ~ t e rhas ~ ~ demonstrated.
[CONTRIBUTION FROM
THE
Since the real value of the Harnmett equation is not in correlating rate data but rather in illucidating reaction mechanisms, we feel that most applications of the Hammett equation should use only the a-values based on the ionization constants of benzoic acids15 and t h a t investigators should then concentrate their efforts on analyzing the correlation or lack of correlation observed rather than defining new U-values in an effort to obtain a straight line. Acknowledgment.-The authors wish to thank the California Research Corporation for partial support of this work. (24) H. von Bekkum, P. E. Verkade, and B M Wepster, Rec. frav. chim., 78,815 (1Y5Y).
DEPARTMENT OF CHEMISTRY, MASSACHUSETTS INSTITUTE
OF
TECHNOLOGY, CAMBRIDGE 39,
MASS.]
Mass Spectra of 0-Isopropylidene Derivatives of Pentoses and Hexoses1.2 BY DONC. DE JONGH
AND
K. BIEMANN
RECEIVEDA4UGUST 6, 1963 The mass spectra of 0-isopropylidene derivatives of D-glucose, D-galactose, D-mannose, D-fructose, L-sorbose, L-arabinose, L-fucose, D-xylose, D-ribose, and D-lyxose are interpreted and their relationships t o the stereochemistry of the parent monosaccharides are discussed. Both isotopic labeling and high resolution mass spectrometry are used t o corroborate the proposed fragmentation mechanisms. As an application of the technique, the determination of the structure of a new di-0-isopropylidene derivative of D-galactose is presented.
The mass spectra of polyacetates of pentoses and hexoses,3 of acetates of partially methylated derivatives t h e r e ~ f and , ~ of polymethyl ethers of monosaccharides5 have recently been reported and interpreted. I t was shown that it is possible t o deduce from these spectra molecular weight and ring size of the compound, and, in the case of the 0-methyl derivatives, also number and position of the methoxyl groups present in the m o l e c ~ l e s . The ~ ~ ~ spectra of these polyacetates. are, however, very insensitive with respect to the stereochemistry of the molecule. This is not surprising as the only difference, for example, among the various epimeric aldohexopyranose pentacetates is the spatial relationship between substituents attached via a single bond to the tetrahydropyran ring. The ensuing steric repulsions-or attractions- - are, however, much too weak to lead to appreciable differences in the electron-impact-induced fragmentation of the molecule and thus in the mass spectrum. The differences which can be observed are too small to permit interpretations in terms of the stereochemistry, beyond direct comparison with the spectrum of an authentic sample. Isopropylidene derivatives appeared t o be much more promising in this respect,6 as the formation of such a bi- or tricyclic ring system is greatly dependent on the availability of cis-1,Z- or cis-1,3-diol system^.^ Thus epimers may give isopropylidene derivatives which differ in actual bonding and are no longer merely stereoisomers but structural isomers; it is the latter to which mass spectrometry is very sensitive. As a well known (1) Paper X V I on t h e Application of Mass Spectrometry t o Structure Problems. ( 2 ) Part X V U Renner, D . A. Prins. A. L. Burlingame, and K Biemann, Helu. C h i m . A d a . 46, 2186 (1'363). (3) K . Biemann. D . C . De Jongh, and H. K . Schnoes, J. A m . Chem Soc : 86, 1763 (19G3). (4) D. C . De Jongh and K . Biemann, ibrd , 86, 2289 ( 1 9 R R ) . ( 5 ) N. K. Kochetkov, N. S. Vulfson, 0. S Chizhov, and B. M . Zolotarev, Dokl A k a d . Y a u k S S S R , 147, 1369 (lQ(i2i. (6) K . Biemann, H. K . Schnoes, and J. A. McCloskey. Chem. I n d . (Lond o n ) , 448 (19G3) (7) For a discussion of these derivatives and pertinent references, see M I,. Wolfrom and A. l'hampson in "The Carbohydrate-," W. W. Pigman, Ed.. Academic Press. Inc., New York. N . Y , 1957. pp. 236-240.
example, the case of D-galactose and D-glucose may be cited. While the former, in the a-pyranoid form I , has two pairs of cis-1,2-diol groupings and therefore forms mainly a pyranoid 1,2 : 3,4-di-O.isopropylidene derivative (11),7 wglucopyranose has only one cisdiol group in the a-form 111 (none in the 6-form). The otherwise less favorable furanoid a-isomer I V , on the other hand, is capable of reacting with two moles of acetone to form 1,2 : 5,6-di-O-isopropylidene-D-glucofuranose (v).7 Similarly, D-mannose fornis aR isomeric di-0-isopropylidene-furanose (XXV).'
""eoH CHzOH
CHzOH
HOQ H -
HO-CHz
HO-CH 0
b k I
OH
I
1 &H~OH
Comparison of isomers I1 and V reveals that-in contrast to I and 111, or their peiitaacetates (-OCOCHp instead of -OH)--the covalent bonds are arranged in a very different way Of particular importance is the (2-4, C-5 bond in V, a single bond connecting two parts of the molecule. I t s cleavage, especially favorable because of the strong stabilization of the resulting positive charge on either C-3 or C-5 by the adjacent oxygen atom, is mainly responsible for the great difference in the mass spectra of V and 11 (Fig. 1 and 2 ) . While a situation similar to the one present in galactose (I) exists in P-L-arabinopyranose (VI), which also
68
DONC. DE JONGH
AND
K. BIEMANN
Vol. 86
-
HO
Ho@oH I
HoH*c@oH
1
OH VI
OH IX
OH VI11
I
VI1
CH2
C Ha
X
H O H ~ C 0 OH
9
HO OH
HOO H * HO OH
XI11 \
M+&~ Y.
x
E, 3: IC0
50
150
o
12I1lP241
1
HOHzC 0 OH
0 0 H ~ C ~ C H ~ XIV
1
A similar situation is found with ketohexoses which --I can, in principle, be considered as , hydroxymethyl200
Z50
,
substituted pentoses. D-Fructose in its pyranoid. forms XVI and XVII is able to form two isomeric di-0-isopropylidene derivatives XVIII and XIX.’ Fig. 2.--Mass spectrum of 1,2 :3,4-di-O-isopropylidene-~-galacto- The epimeric L-sorbopyranose (XX) cannot react with pyranose (11). two molecules of acetone but forms a di-0-isopropyliFig. 2a.-Mass spectrum of 1,2 : 3,4-di-O-isopropylidene-dl~-~-dene derivative X X I I via the furanoid form X X I . As in the similar case of 1,2:3,5-di-O-isopropylidene-~galactopyranose ( I I a ) . Fig. 3. -Mass spectrum of 1,2 : 3,4-di-O-isopropylidene-~-arabino- xylofuranose (X), XXIII’ contains a six-membered 1,3-dioxane ring. The 1,2 :4,6-isomer X X I I I is appyranose ( V I I ) . parently not formed; this may be due to steric inFig. 4.-Mass spectrum of 1,2 : 3,5-di-O-isopropylidene-~-xylo- terference between the 1,3-dioxolane and 1,3-dioxane furanose ( X ) . rings attached to a tetrahydrofuran. As expected on the basis of the earlier discussion, contains two 1,2-diol groupings and thus forms 1,2:the mass spectra of XVIII, X I X , and X X I I , shown 3,4-di-O-isopropylidene-L-arabinopyranose (VII),* the in Fig. 7 , 8, and 9, express these structural differences. epimeric a-D-xylopyranose VI11 like the glucose analog In addition, i t should be noted that the spectra of I11 has only one 1,2-diol group. Conversion of VI11 0-isopropylidene derivatives are most suitable for the to the furanose form I X still does not lead to two 1,2determination of the molecular weight of carbohydrates diols as in IV because pf the absence of C-6 with its as the loss of one of the methyl groups from the 2,2hydroxyl group. A di-0-isopropylidene derivative dimethyl- 1,3-dioxolane or 1,3-dioxane ring gives rise is still formed on reaction of I X with acetone, but the to an abundant fragment of mass 11 - 15, because of the product (X) now contains a 1,3-dioxane ring (involving exceptional stabilization of the tertiary carbonium ion C-3, C-4, and C-5) in addition to the 1,3-dioxolane ring by two neighboring ether oxygens (see discussion (involving C-1 and C-2). of fragment A, below). Finally, D-ribose (XI), while possessing two pairs of The presence of the many ether oxygens leads to a cis hydroxyl groups, does not form the di-0-isopronoticeable “1.11 1” peak due to ion-molecule colpylidene derivative XI1 apparently because of the steric lisions, if the spectrum is determined with a sufficiently interference of the bulky gem-dimethyl groups. It high sample pressure. As in simple ethers,12 this peak rather forms, via the furanose X I I I , a mono-0-isoprocan be taken as an indication of the molecular weight, pylidene derivative XIV’O and an anhydro derivative which is one mass unit less. While too small to be thereof, XV. I o shown on the scale of Fig. 1-9, the “11 I ” peak is Thus, depending on their stereochemistry. pentoses easily recognized on the original record. form either pyranoid di-0-isopropylidene derivatives I t now remains to discuss and interpret the spectra (e.g., VII), furanoid derivatives containing one 1,3of di-0-isopropylidenealdopyranoses(e.g., TI and VII), dioxolane and one 1,3-dioxane ring (e.g., X ) , or monodi-0-isopropylidenealdofuranoses (e.g., V and X) , di-00-isopropylidene derivatives (e.g,, XIV or possibly isopropylideneketopyranoses (e.g., XVIII and X I X ) . XV) , All these compounds are easily distinguished di-0-isopropylideneketofuranoses (e.g., X X I I ) , arid mass spectrometrically as illustrated in Fig. 3-6. mono-0-isopropylidenefuranoses (e.g., XIV and XV) Fig. 1.-Mass
spectrum of 1,2 :5,6-di-O-isopropylidene-~-glucofuranose (V).
+
+
(8) P . A , Levene and J . Compton. J Bioi. C h e m . . 116, 189 (193F). (9) W. N. Haworth a n d C. R. Porter, J . Chnm. Soc.. 611 (1928) (10) P. A. Levene nnd E T Stiller, J . B i d . Chem , 102, 187 (1933).
(11) T. Reichstein and A. Grdssner, Helw. Chim. Acta 17, 311 (1934) (12) F. W. McLafferty, Anal. Chem.. 29, 1783 (1957’.
X4ss SPECTRA OF ISOPROPYLIDENEPENTOSES AND -HEXOSES
69
H3C
HO
H3C
XVI (C-1 up) XVII (C-1 down)
I
1
-
I
1
H3 C
c
1
XVIII
OH,CH20H
xx
II
CH3
\ OH
30
40
'
'
CHs
C H3 XIX
xCH3 XXII
in greater detail to support the general statements made above. For a confirmation of the proposed fragmentation processes, the spectra of some of the key compounds (11, V, XVIII, and XIX) have been determined not only with a conventional mass spectrometer (CEC 2 1-1O3C) but, in addition, with a double-focusing inswument (CEC 21-110) of very high resolving power, permitting determination of the mass of an ion with r;n accuracy of 1 part in 10j or better.13 The elemental compositions of fragments mentioned below are derived from the accurate mass found (the value is given in parentheses, along with the deviation, in mil% mass units, from the theoretical mass of a particle of that elemental composition). Particularly in the lower mass range (
