THE GEOMETRY OF N-HYDROXYMETHYL COMPOUNDS .5. STUDIES ON GROUND-STATEGEOMETRY AND REACTIONS OF N-(HYDROXYMETHYL)PENTAMETHYLMELAMINE AND RELATED-COMPOUNDS USING MNDO CALCULATIONS

MNDO and PM3 calculations of the most favoured conformations of antitu mour N-hydroxymethylmelamines including N-(hydroxymethyl)pentamethylme lamine (2) and trimelamol indicate that the O-H group is orientated to wards the closest ring nitrogen but is too distant far hydrogen bondin g. Modelling of decomposition pathways of 2 using MNDO predicts that c oncerted loss of formaldehyde is not favoured. Loss of [H2COH](+) from oxygen-protonated 2 is also a high energy process, but loss of formal dehyde from deprotonated 2 is exothermic with a low activation barrier ; this is the most likely decomposition mechanism under basic or neutr al conditions. Under acidic conditions loss of water from protonated 2 to give an iminium ion is exothermic from O-protonated 2, but the ini tial O-protonation is disfavoured over protonation on nitrogen, partic ularly ring nitrogens. Reaction of 2 with nucleophiles is difficult by S(N)2 routes but proceeds exothermically with low activation energies by the S(N)1 mechanism from protonated 2 to give products of similar thermodynamic stability to ring-protonated 2. Reaction of O-protonated 2 with amines gives aminals that may decompose with low activation en ergies to pentamethylmelamine and a methylene iminium ion.