Controlling ring-chain tautomerism through steric hindrance

Abstract

We have explored the use of steric hindrance for favouring/hindering the tautomerisation of Schiff bases (SB) into tetrahydroquinazolines (TQ) in two systems that derive from the condensation of 2-tosylaminobenzylamine with two different aldehydes: 2,3-dihydroxybenzaldehyde (H₂L¹_SB/H₂L¹_TQ) and N-(3-formylpyridin-2-yl)pivalamide (H₂L²_SB/H₂L²_TQ). The four possible ring-chain tautomers were unequivocally characterised by a combination of ¹H NMR spectroscopy, infrared spectroscopy, mass spectrometry and elemental analysis. Furthermore, two of the tautomers, H₂L¹_SB and H₂L²_TQ, have been characterised by X-ray crystallography. Crystal data of E-H₂L¹_SB have revealed the existence of a prototropic ketoenamine–enolimine equilibrium at room temperature that is the cause of the thermochromism of H₂L¹_SB. A firm intramolecular interaction O_hydroxyl–H⋯N_imine hinders the conversion of the chain tautomer H₂L¹_SB into the ring tautomer H₂L¹_TQ. Crystals of H₂L²_TQ and H₂L²_TQ·HCCl₃ consist of racemic mixtures of their enantiomers, C(R),N(R)-H₂L²_TQ and C(S),N(S)-H₂L²_TQ. A terminal pivalamide group prevents the existence of the intramolecular interaction N_pivalamide–H⋯N_imine in the chain tautomer H₂L²_SB, favouring its conversion into the ring tautomer H₂L²_TQ.