Chemoselectivities in acetalization, thioacetalization, oxathioacetalization and azathioacetalization

Abstract

In the present article (experimental as well theoretical) the relative yields of cyclic (O,O), (S,S), (S,O) and (S,N) acetals, formed from p-(NO₂)C₆H₄CHO and p-(OH)C₆H₄CHO, are compared. Atomic charges, global electrophilicity descriptor (w) [as proposed by Parr et al., J. Am. Chem. Soc. 1999, 121, 1922] and hard−soft acid−base concept of Pearson (J. Am. Chem. Soc. 1963, 85, 3533) are used to explain the experimental observations. Although the w values can explain the yields, charge and local softness values of the interacting sites explain the plausible reaction mechanism. The bisnucleophiles chosen for acetalization are CH₂(OH)−CH₂(OH) (glycol), CH₂(SH)−CH₂(SH) (dithiol), CH₂(OH)−CH₂(SH) (oxathiol) and CH₂(SH)−CH₂(NH₂) (azathiol). For p-(NO₂)C₆H₄CHO, the experimental yield of cyclic acetals were found to follow the trend as (S,N) > (S,O) > (O,O) > (S,S), which is also supported by theoretical explanation based on the w values and applying the concept of hard−hard (i.e., charge-controlled) and soft−soft (i.e., orbital-controlled) interaction between the interacting sites of the substrates (i.e., aldehydes) and the reactants (bisnucleophiles). Similarly, for p-(OH)C₆H₄CHO the relative yields of cyclic acetals follow the trend (S,N) ≈ (S,S) > (S,O) > (O,O). It is argued that the attack on C_CHO (i.e., C-atom of the CHO group) in p-(NO₂)C₆H₄CHO by O_OH (i.e., O-atom of OH group) or N_NH2 (i.e., N-atom of NH₂ group) is mainly charge-controlled but the attack on C_CHO in p-(OH)C₆H₄CHO) by S_SH (i.e., S-atom of SH group) is orbital-controlled.