How to Determine Acidity of Compounds From Structure

Estimation of Acidity

1). Examine the molecular structure of the compound. Determine if the compound is capable of resonance stabilization of the anion resulting from loss of a proton, that is, whether the negative charge can move around to different locations on the anion. If resonance stabilization is possible, the compound is typically a relatively strong acid, or at least more acidic than a similar molecule without resonance. An example is the very acidic compound nitric acid, where the anion can share its negative charge among three oxygen atoms. An increase in relative acidity due to resonance can be demonstrated by comparing phenol, where the benzene ring can provide resonance stabilization after loss of the proton on the hydroxyl group, to the structurally similar compound cyclohexanol. Unable to use resonance to stabilize its anion, cyclohexanol is a million times less acidic.
2). Determine from the molecular structure the atom that will take the negative charge if a proton leaves and locate that element on the periodic table. The closer an element is to the bottom of the table, the larger its atomic radius will be. Since a larger atom is more stable with a negative charge, a compound where the negatively charged atom is closer to the bottom of the periodic table will be more highly acidic. For example, HBr will be more acidic than HCl since Br is below Cl in the table.
3). Determine the relative electronegativity of the atom that will take the negative charge if a proton leaves. This can be done by finding the relative position of that element on the periodic table. The closer an element is to the top right of the table, the more electronegative it is. An electronegative atom is more likely to acquire a negative charge, so a compound where a highly electronegative atom will take the negative charge will be acidic. For example, water is more acidic than ammonia since oxygen is more electronegative than nitrogen.
4). Examine the atoms attached to the atom that will hold the negative charge if a proton is lost. If these elements are electronegative, they can increase the acidity of the compound through the inductive effect. A compound that has an electronegative chlorine atom next to a carbon holding a hydrogen will be more likely to lose a proton and thus be acidic.