Cyclic Forms of Glucose

Internal Nucleophilic and Electrophilic Sites

Glucose includes an aldehyde group with an electrophilic carbon. Call this carbon C-1. It is also a poly-alcohol. Each of the other carbon atoms is an alcohol carbon and bears an OH group. These are nucleophiles. When a nucleophile and an electrophile are in the same molecule, they react together much more quickly than separate nucleophilic and electrophilic molecules do.

Take a look at the linear form of glucose below. If the OH group on C-4 adds to the aldehyde carbon it will make a 5-membered ring, and if the OH group on C-5 adds to C-1 it will make a 6-membered ring.

Rings smaller than 5 atoms or larger than 6 atoms are not very stable so the OH groups on C-2, C-3, and C-6 don't react with the aldehyde carbon.

Glucose is a pretty complicated molecule with all of its functional groups. To see the reaction more clearly, The scheme below shows only the reactive OH group on C-5 and the aldehyde group.

All the carbon atoms are free to rotate around the C-C bonds in the linear molecule and they do this rapidly. In one of the conformations that places the oxygen near the C-1 carbon, a O-C bond can form. Both of the electrons are donated from the nucleophilic oxygen atom. Because carbon can have a maximum of 8 electrons, when the OH group donates a pair of electrons, electron density must shift to the carbonyl oxygen. This oxygen is then very basic and it can abstract the acidic proton from the former alcohol oxygen atom.

Adding to the Two Sides of the Carbonyl Group

In the scheme above, the new OH group formed from the aldehyde is on the same side as the R group (CH2OH). Another isomer results from addition of the C-5 OH group to the other side of the flat CHO group.

Forming the 5-Membered Ring Isomers

To form the 5-membered ring isomer of glucose, the nucleophilic OH group on C-4 is the one that adds to the electrophilic carbon at C-1. After the oxygen donates its electron pair to form the new bond, there is a proton transfer between an acidic site and a basic site.

When the OH group attached to C-4 adds to the other side of the carbonyl (CO) group, another isomer is formed.

Professor Patricia Shapley, University of Illinois, 2012