Question

Although tryptophan contains a heterocyclic amine, it is considered a neutral amino acid. Explain why the indole nitrogen of trytophan is more weakly basic than one of the imidazole nitrogens of histidine.

Short answer

In tryptophan, the nitrogen’s electron pair is part of aromatic pi-system which enables system to become aromatic. If this electron pair bonds with the proton, then the system would not be aromatic. In the imidazole ring of histidine, out of two nitrogen atoms present, one is basic and is available for bonding. Thus, indole nitrogen of tryptophan is weakly basic than one of the imidazole nitrogen of histidine.

Step-by-step solution

Step-1. Basicity of tryptophan:

The basicity of nitrogen in any system depends on its lone pair availability for bonding with the proton. In tryptophan, the nitrogen’s electron pair is part of aromatic pi-system which enables system to become aromatic. If this electron pair bonds with the proton, then the system would not be aromatic.

Tryptophan

Step-2.Explain the reasoning

In the imidazole ring of histidine, the lone pair of one nitrogen atom is also a part of aromatic pi-system and is unavailable for bonding, that is, this nitrogen is not basic. Lone pair on other nitrogen is basic and is in sp² orbital, thus is available for bonding.

Histidine