The kinetics and mechanism of the cyclisation of some 2′-hydroxychalcones to flavanones in basic aqueous solution

Abstract

Rate coefficients for the chalcone–flavanone equilibration reaction have been established for some 2′-hydroxychalcones over the pH range (ca. 8–11) in which their 2′-hydroxy-groups undergo ionisation. The chalcones studied were the parent 2′-hydroxychalcone (I) and its following derivatives : 4′-OMe (II), 6′-OMe (III), 4′-OH (IV), 4′,6′-Me₂(V), and 5′,6′-benzo (VI). Pseudo-first-order rate coefficients (k_obs) which, for the reversible reactions concerned, are the sum of the forward and reverse rate coefficients, were fitted to the kinetic form K_obs=kf_A+k′f_B+k″a_OH^– in which k and k′ are the rate coefficients for the unimolecular cyclisation of neutral and of ionised chalcones respectively (f_A and f_B are the fractions of total chalcone present in the neutral and ionised forms at the pH concerned) and where k″ is the second-order rate coefficient for the reverse reaction of flavanone which involves hydroxide ion (activity a_OH^–). Data analysis gave rate coefficients and pK_a values for all but chalcone (IV) which has a different kinetic form. A conjugate addition–elimination mechanism is proposed to account for the pH–rate profiles, one of which [chalcone (I)] differs from that previously reported. Possible effects on rate coefficients of non-bonded interactions between 6′-substituents and carbonyl oxygen are briefly considered but the differences between chalcones with and without 6′-substituents are sufficiently small to deter prolonged discussion. There seems to be little serious hindrance of cyclisation for any of the 6′-substituted chalcone anions.