a- and ,8-D-Glucose Pentaacetate
Wesley A. Pearson and Gary 0. Spessard St. Olaf College Northfield. Minnesota 55057
An experiment in structure assignment using nmr
-
The use of nmr soectrometrv as a teachine tool in the undergraduate organic chemistry laboratory is now common~lace.However. at the so~homorelevel the student is usuaily limited to studying rather simple molecules without eainine an a ~ ~ r e c i a t i oofn the fact that nmr can he a verv powerful toil-in the elucidation of the structure of rather complex compounds. We wish to report our results in utilizing what we feel is an unique example illustrating important principles of nmr spectrometry and the application of nmr to structure assignment. The synthesis of a- and (3-D-glucose pentaacetate is an experiment which is described in a number of organic chemistry laboratory manuals (1-3). The syntheses consist of treating D-(+)-glucose with acetic anhydride in the presence of anhydrous zinc chloride to prepare rr-D-glucose pentaacetate and in the presence of anhydrous sodium acetate to prepare 0-D-glucose pentaacetate.
Chemical Shifts and Coupling Constants for Pentaacstates at C-1.
ANOMER
6a (mm)
6~ (mrn)
a- and 0-D-Glucose J4
(Hz)
JL
(Hz)
Y S ~ e ~ t run r a on a JEOL-C6O-HL rpectrometer at 60 MHz as 10% lolutionl and With T M S as internal rtandard. bsee Reference ( 5 ) . The Lernieux spectra were run at 60 MHz and 100 M H r . A t 100 M H z the coupling constant far thep-anomer 16 6.9 t 2 while that for the a-anomer remained at 3.3 Hz.
814 / Journal of Chemical Education
"'As CH,OAc
OAc
OAc (Thermodynamically favored)
OAc (Kinetically favored)
These syntheses are illustrative in a theoretical sense since they demonstrate kinetic versus thermodynamic control of a reaction. The somewhat surprising result that the product favored under conditions of thermodynamic control is the a-isomer which has the large acetoxy group a t C-1 in the axial position emphasizes the importance of structure elucidation for the glucose pentaacetates or, in fact, for any system. Unfavorable dipole-dipole interactions between The differences in the enerev ".between the two chair eonformations of a- and of 0-D-glucose pentaacetate can be estimated to he approximately 8 and 11kcallmole, respectively.
the ring oxygen and the acetoxy group a t C-1 in the 6-isomer are believed to cause the decrease in stability even though all of the large groups are in equatorial positions. This is referred to as the anomeric effect. The two glucose pentaacetates can be obtained in high purity hy recrystallization. We have found that a 1:2 mixture of methanol-water is a better recrystallizing solvent for both isomers than either pure methanol or pure water as previously suggested. Solutions for nmr study can be prepared in deuteriochloroform. An analysis of the nmr spectra reveals how in cyclohexane type systems the difference in the chemical shift of a n axial versus a n eauatorial proton and the dependence of the coupling c o n s t k t on the dihedral angle between vicinal protons can be used t o distinguish between the diastereomeric glucose pentaacetates. The facts that each of the two isomers is essentially conformationally uniform and also that each is easily available make this an especially attractive system to illustrate these principles.' The complete interpretation of the nmr spectra of the glucose pentaacetates is difficult in that the chemical shifts for the protons of the five acetoxy groups are quite similar as are the chemical shifts of four of the five methine protons of the ring. However, the chemical shift for the methine proton a t C-1 is farther downfield than any of the others because the anomeric carbon atom is bonded to two oxygen atoms. Further. the anomeric Droton has onlv one vicinal proton so the absorption signai is a doublet as a result of simple first-order splitting. Lemieux showed that this farthest downfield absorption is due to the anomeric proton and used the chemical shift and coupline constant data for this absorption to unequivocally codfirm the structures for a- and 8-D-glucose pentaacetate (4, 5). There is some virtual coupling present especially in the 6-anomer but this does not change the size of the coupling constants measured appreciably and so does not affect the structure assignment. A comparison of our data to those of Lemieux appears in the table and reveals close agreement. The chemical shift for an axial proton has been observed to be different from that for an eouatorial nroton in substi= tuted cyclohexanes. The absorption for an equatorial proton is generally found 0.5 6 farther downfield than that due to an axial proton. This difference in chemical shift has been attributed to the diamaenetic anisotro~veffect of the a bond electrons. An equatorial proton lies-&thin the deshielding cone of a carbon-carbon bond a, b to the carbon hearing the hydrogen in question, while the axial proton is in the shieldine- cone. An alternate exnlanation for this chemical shift difference is that paramagnetic ring current effects exist in the cvclohexane rine svstem. The eauatorial proton falls in the ;egion in whicb the magnetic-lines of force set up by the ring current more distinctly align with the applied magnetic field and so appears deshielded in a manner analogous to aromatic protons. Both explanations are found in the current literature (6, 7). The fact that the difference in chemical shift here is a t the upper limit for that observed in cyclohexane can he attributed to the presence of the oxygen atom in the ring. The well-known Karplus equation can be used to calculate coupling constants between vicinal protons as a function of dihedral anele (8). Values of 9 Hz for diaxial ~ r o tons and 1.8 Hz foraxia1:equatorial protons in cyclohe&me rines are obtained usine this eauation. In ~ractice.values of 8-14 Hz and 1-7 HZ-have heen reported. The observed c o u.~ l i-n econstants for the anomeric Droton in a- and B-Dglucose pentaacetate lie a t the lower end of these rangis. I t has been observed that the presence of electronegative groups on the carbon atoms holding the hydrogens which are coupled decreases the size of the coudine constant (9). In the-glucose pentaacetates, C-2 contai& an acetoxy group and C-1 is bonded to an acetoxy moup and the alvcoiidi; oxygen. The observed coupling cons&ts can there-
7
6
5
4 porn
3
2
1
1
The nrnr spectra of aD-glucose pentaacetate (above) and 8-D-glucosepentaacetate (below).In both spectra the G 1 rnelhina hydrogen appears in the upper left corner with e scale expansion of five.
fore be rationalized in light of the substitution observed a t the carbon atoms of the absorbing system. Historically, the assignment of configuration to the aand @-anomerspresented a real problem. Hudson in the early 1900's suggested that the anomer in the D-family of sugars which has the greater positive rotation he designated the a-anomer (10). Proof of configuration by synthetic means was carried out as well. I t appears, however, that judicious use of nmr spectroscopy is the most convenient method for structure assignment of anomers today. This experiment utilizes a readily interpreted example from this area and gives students a feel for the elegance and power of the nmr method. Experimental u-and 8-D-Glucose pentaacetate were prepared according to the procedures described by Mohrig and Neckers ( I ) . The aqueous mixture resultins from the addition of the reaction mixture to ice water was stirre; for 1 hr instead of 30 min. This completely hydrolyzed the excess acetic anhydride yielding a more granular, less sticky product, especially in the case of the a-isomer. The crude products were purified by recrystallization from a 12 methanol-water mixture. Ten milliliters of this solvent mixture per gram of product was required for each isomer. Both isomers dissolve in less solvent than this but better purification results were obtained with the larger volume of solvent with little sacrifice in product recovery (about 80% recovery). Two recrystallizations of each gave a-D-glucose pentaacetate, mp 108-109T (lit. ( I ) mp IlO'C) and 8-D-glucosepentaacetate, mp 130-131'C (lit. ( I ) mp 131°C).
Literature Cited (11 Mohrig, J. R.,and Neckerr. D. C.,%ahorstory Experimonta in organic Chemistry." 2nd. Ed.,D. Van Noatrand &,New Y o r t L973. (2) Adamr, R.. Jahnson, J. R.. and Wileox, C. F., JI., "Laboratory Experiments in Organic Chemiruy,"6fh.Ed.,Maemillsn, New York, 1970. (31 Yogel. A. I.. "A Terthmk of Practical Organie Chemistry Induding Qualitdive Organic Anslysis," 3rd Ed., Longmans, London, 1956. (0 Lcmieux. R. U., Kullnig. R. K., Bermtoin. H.J.. and Schneider. W. G., J Amer. Chem. S o c ,
80.EQ98i1958).
(5) Lemieux, R. U., and Stovena, J. D., Can. J Chsm.. 43.2059 (19651. (61 Silverstoin, R. M.. Bssrler, C. G..and Morrill. T. C., "SprctmmeVie Identification of Organic Compounds."3rd. Ed.. John Wiley & Sons. New York. 1971. (7) Pople. J. A,, Schneider, W. G. and Bernstein. H. J., "High Resolution Nudear Magnetic Reaonanee,"McGrew.Hiil,NewYork, 1959. (6) Karplua, M . . J Chem. Phys., 30.11 (19591. (91 Williams,K.L.,J. Amar. Chem Soc, 85.516 11963). (10) Hudson.C.S., J Amer Cham. Soc., 31.66 (1900).
Volume 52, Number 12, December 1975 / 815
