Oxidation of Aldoses With Bromine

Rates of oxidation of aldoses with bromine have bee n reappraised and inte rpreted in th e light of present concepts of conformation and reaction mechanism. It is suggested that differences in t he rates of ox idation of the a and /3 anomers are largely determin ed by differences in the free energy req uired by the reactants for passing from the ground state to the com plex in the transition state. Structures for t he a ldoses in th e ground states and in the transition states are postulated, a nd factors affecting the energy required for reaching the transition states from t he ground states are di scussed. The relative ra tes of ox idation are in accordance with the hypothesis t hat cac h of th e a ldoses in the ground state has the conformation predicted by Reeves, and, in the transit ion state, has a conformation in which the oxygen atom of the C1-hydroxyl group lies in the plall e formed by t he r ing oxygen atom, C1, C2, and C5. Presumably, this conformation is stabilized by resonance in volving the oxygen atom of th e r ing. For a ldoses hav in g high stability in on e cha ir conformation, th e rates of ox idat ion of the anomers d iffer widely; in each in stance, t he anomer in which the Cl-hydroxyl group is axial is ox idized more slowly t han th e anomer in whi ch this group is equatorial. For aldoses having less stabil ity in a cha ir co nformation, the rates of oxidatio n of t he a nomers difrer lcss widely, but, n evertheless, show a defin ite corrclat ion with the angular pos it ion of the Cl-hydroxyl group relative to the p lane of t he rin g. For aldoses for which the stab ili ty in both chair confo rmations is so low that they probably exist in a vari et y of conformations, the rates of ox idat ion of th e anomers show littl e difference and no pa rt icular correlat ion with the angular position of the Cl-h ydroxyl group. The presence 0 " absence of an oxygen atom in the rin g is used to account for the large d iff erences between the rates of bromine ox idat ion of t he aldoses a nd those of deri vat i ves of eycloh exanol. Diffe rences in conformation in the t ra nsiti on s tatp, associated with t he prese nce o r absence of th is oxygen atom, likewi se acco un t for t he fact that t he relative rates of oxidation of t he axial and equatorial isomers in the two classes of compound a re reversed . Because of un certa in ty as to th e anomeri c configurations co mmonl.v ass igned to so n1(' of t Ile a ldoses, the co nfigurations of 22 aldoses were reapp ra ised. Advantage was taken of t he principle that th e anomer p reponderat in g in th e equ ili brium solu t ion has l1'ans hydroxy l groups at Cl and C2. Except for crystalline D-gl yceTo-D-ido-heptose , the ass ignments of con fi gurat ion based on this p ri ncip le agree with t he configurations genera ll y accepted. Classifi ciation of cr ys tallin e D-glyceTo-D-ido-heptose as an a-D-pyranose necessitates co rrection of ea dier reco rds in which t his suga r was co ns ide red to be a /3-D-py ranose. In accorda nce wit h th e author's earli er formulation, oxidation of th e ax ial a nomer is beli eved to take p lace by two co urses : (1 ) di rect ox idation and (2) conversion to the eq uatori al a nomer by the anomerizat ion r eaction and the subsequent ox idation of thi s ano mer. The relative importa nce of the two courses is not cons idered in thi paper . It is poin ted out, however, that th e actual difference in t he ra tes for t he direct ox idation of the two anomers must be at least as great as that obser ved For the overall rates of ox idation.