Aminonitrogen and carbonyl oxygen in competitive situations: which is the best hydrogen-bond acceptor site?

Abstract

The relative hydrogen-bond acceptor abilities of amino nitrogen and carbonyl oxygen in various chemical environments have been investigated using data retrieved from the Cambridge Structural Database (CSD) and viaab initio molecular orbital calculations. Surveys of the CSD for hydrogen bonds between HX (X = N, O) donors and push–pull or saturated aminoketone and aminoester molecular fragments show that the hydrogen bonds are much more frequent on the oxygen than on the amino nitrogen. In the push–pull families, the hydrogen-bonding (HB) ability of the carbonyl oxygen is increased by conjugation between the lone pair of the amino substituent and the CO group, a behaviour similar to resonance-assisted hydrogen bonding. The unexpected behaviour of twisted amides, in which only the amino nitrogen is involved in hydrogen bonding, is pointed out. This unusual feature is explained by the disruption of conjugation between the amino lone pair and the carbonyl owing to the cyclisation involving the amino moiety. In aliphatic systems, the amino nitrogen retains its HB ability but is still involved in a rather low number of contacts. This behaviour reflects the sensitivity of the amino nitrogen to steric hindrance. The relative strengths of the hydrogen bonds on the carbonyl oxygen in ketones and esters follow the experimental order of hydrogen-bond basicity as observed in solution through the pK_HB scale. Ab initio molecular orbital calculations (B3LYP/6-31+G** level) of electrostatic and charge transfer descriptors also confirm the experimental observations.