From intermolecular and intramolecular competition experiments, it has been established that, by comparison with an N-methyl substituent, an N-acetyl group deactivates glycine residues in piperazine-2,5-diones towards free-radical bromination. Combined with the ease of introduction and removal of N-acetyl substituents, the deactivating effect provides a method for regiocontrolled functionalization of these compounds.
Theoretical studies on free radical bromination by N-bromosuccinimide were carried out on a range of ethyl-3-methoxy-pyridazine derivatives. The investigations of these reactions performed, in order to develop a convenient and rapid theoretical means of predicting selectivity. The geometry optimizations of the total energies of the reactants and the products were calculated using Semi-empirical; AMI, MNDO, PM3 e Hartree Fock, HF3- 21 G computational methods. The calculation performed using PM3 Hamiltonian gave the best qualitative predictions, thus providing a rapid method for the selectivity of the reactions used in the synthesis of novel heterocyclic analogs of neurotransmitters.
Treatment of ethyl
(3-bromopropyl)phosphonochloridate with benzylmagnesium chloride gave ethyl (benzyl)(3-bromopropyl)phosphinate.
This underwent free-radical bromination to give ethyl
(a-bromobenzyl)(3-bromopropyl)phosphinate Cyclization with aqueous ammonia gave
3-ethoxy- 2-phenyl-1,3-azaphosphininane 3-oxide. Attempts to prepare the
2-(pyridin-3'-yl)-substituted 1,3-azaphosphininane are also discussed.