Kinetics and thermodynamics of the structural transformation of thiamine and its analogues in aqueous media. Part 4. The case of sulphamoylthiamine

Abstract

In Sulphamoylthiamine (ST) one of the two amino-group protons at the pyrimidine ring of thiamine is replaced by a sulphamoyl group, which should prevent the formation of a yellow form analogous to that of thiamine. Nevertheless, in basic media, ST changes into a yellow form with the loss of two protons (average pK 11.59). The rate-limiting step of this transformation is the intramolecular nucleophilic attack at the 2-site by the 7′-amine to yield σ-adduct (D′) with a second-order rate constant k₁₄= 66 dm³ mol^–1 s^–1. Adduct (D′) is in turn transformed into (J′)^– with a second-order rate constant k₄₅= 7.90 × 10⁶ dm³ mol^–1 s^–1. Species (J′)^– yields ST thiolate (C′)^–via intramolecular σ-adduct (D′), cation (A′)⁺ and pseudo-base (B′), the formation of which is the rate-limiting step of the structural transformation of ST in basic media (second order rate constant k₃₄= 10.80 dm³ mol^–1 s^–1). Although different from those values measured for thiamine, these rates and equilibrium constants show that the reactions involved in the structural transformations of ST and thiamine occur essentially in the same way. However, the secondary amine in (D) is replaced by a tertiary amine in (D′) which can be deprotonated at the 2-position to yield anion (D′)^– which, by ring-opening, can produce a resonance-stabilized carbene species resembling Breslow's biocatalyst (A)_–H. The ¹³C NMR spectra of (J)^– and (J′)^– seem to confirm this hypothesis which is consistent with the involvement of species (D)^– in the structural transformations of thiamine in basic media.