Question

a) Why does the ketone (1-indanone) react with the base, but the aldehyde (3,4- dimethoxybenzaldehyde) does not?

b) Why is the α-proton so acidic? (You must support your argument with appropriate drawings).

Answer 1

Dear Student,

Aldehydes are usually more reactive toward nucleophilic substitutions than ketones because of both steric and electronic effects. In aldehydes, the relatively small hydrogen atom is attached to one side of the carbonyl group, while a larger R group is affixed to the other side. In ketones, however, R groups are attached to both sides of the carbonyl group. Thus, steric hindrance is less in aldehydes than in ketones.

A hydrogen on an alkane is not at all acidic – its pKa is somewhere on the order of 50, about as non-acidic as it gets in the organic chemistry world. The reason for this is that if the hydrogen were to be abstracted, the electrons from the broken bond would be localized on a single carbon atom.

Because carbon is not electronegative and is terrible at holding a negative charge, such carbanion species are extremely unstable.

How, then, can a proton bonded to a carbon be acidic? Remember that an acid becomes stronger if the conjugate base is stabilized, an in particular if the negative charge on the conjugate base can be delocalized to an electronegative atom such as an oxygen. This is possible when a carbon is located adjacent to a carbonyl group. Consider, for example, the conjugate base of acetone.

One resonance contributor puts the negative charge on the carbon #1. Due to the presence of the adjacent carbonyl group, however, a second resonance contributor can be drawn in which the negative charge is located on the carbonyl oxygen, where it is much more stable. This type of stabilized carbanion species is specifically referred to as an enolate. Acetone is in fact weakly acidic, with a pKa of about 19. The importance of the position of the carbonyl group is evident when we consider 2-butanone: here, the protons on carbons #1 and #3 are somewhat acidic (in the neighborhood of pKa = 20), but the protons on carbon #4 are not acidic at all, because carbon #4 is not adjacent to the carbonyl.

A carbon that is located next to a carbonyl group is referred to as an alpha (α) carbon, and any proton bound to it is an alpha-proton. In 2-butanone, carbons #1 and #3 arealpha carbons, and their five protons are alpha protons.   Carbon #4 is a beta (β) carbon, as it is two positions removed from the carbonyl carbon

An active methylene is a carbon in the alpha position relative to two carbonyl groups rather than just one. Protons on active methylene carbons are more acidic than other alphaprotons, because the charge on the conjugate base can be localized to two different oxygen atoms, not just one. This keto-ester compound, for example, has a pKa of approximately 11, close to that of phenol.

Electronically, aldehydes have only one R group to supply electrons toward the partially positive carbonyl carbon, while ketones have two electron‐supplying groups attached to the carbonyl carbon. The greater amount of electrons being supplied to the carbonyl carbon, the less the partial positive charge on this atom and the weaker it will become as a nucleus.