[Claes]

L.S.,

I have a question on the subject of amide hydrogenolysis (hydrogenation with bond cleavage) with molecular H2 towards amines.

Ketones undergo C-C cleavage, which makes sense to me as the C=O bond strength is 441 kJ/mol (for hydrogenation towards C-O) whereas the C-C bond strength is 346 (http://www.wiredchemist.com/chemistry/data/bond_energies_lengths.html). Esters cleave into two alcohols, but I've read this is preceeded by a hemi-acetal transition state. I'm already puzzled by this as the C-O bond strenght is only 358 kJ/mol, so purely on those facts the C-O cleavage should happen prior to C=O hydrogenation.

The weirdest thing though, is that amides simply lose water. The C-N bond strenght is only 305 kJ/mol and should therefore cleave long before the C=O is hydrogenated. Even when considering the resonance structure (60% O=C-N, 40% -O-C=N+) and the C=N bond strenght of 615 (thereby C=N to C-N hydrogenation should be 310 kJ/mol), this doesn't make sense. Not even a hemi-acetamide (would that be the correct term?) could explain this phenomena as C-O 358 kJ/mol versus C-N 305 kJ/mol would still favour C-N cleavage yielding an alcohol and an amine.

Is this anomaly merely caused by the fact that the bond strenghts I use are averages, or is something else going on here?

Thank you in advance.

Regards,
Claes

[renge ishyo]

I think you answered your own question...the resonance effect accounts for the differences in reactivity. Ketones lack resonance, so the reaction might proceed as you would expect taken from considerations of double bond and single bond strength energies. However, both esters and amides feature resonance stabilized carbonyl systems. These do not behave as you might expect from a simple consideration of bond energies, because in this case "single and double" bond energies are fundamentally innacurate (the actual bonding is neither). For instance, not only will the "C-O" bond energy be different in the resonating system, but the "C=O" bond energy will be different as well. It's just a different ballgame.

The amides are generally less reactive than esters because the nitrogens are able to donate their electrons into the resonating pi system more readily than the oxygens in esters, and thus the nitrogens "block" the partially positively charged carbonyl carbon that you are trying to react with more efficiently.