Aminocyclodextrins to facilitate the deprotonation of 4-tert-butyl-α-nitrotoluene

Abstract

6^A-Amino-6^A-deoxy-β-cyclodextrin enhances the rate of the deprotonation of 4-tert-butyl-α-nitrotoluene. The rate constants for reaction of the cyclodextrin-bound species, k_inc = 4 × 10⁻³, 9 × 10⁻³ and 19 × 10⁻³ s⁻¹, at pH 6.0, 6.5 and 7.0, respectively, in 0.1 mol dm⁻³ aqueous phosphate buffer containing 1% methanol at 298 K. These rate constants correspond to a rate acceleration (k_inc/k_un) of ca. 10 times at each pH. Under the same conditions, 6^A-dimethylamino-6^A-deoxy-β-cyclodextrin and 6^A-(2-aminoethylamino)-6^A-deoxy-β-cyclodextrin are more effective; at pH 6.0, 6.5 and 7.0, for the former, k_inc = 3 × 10⁻², 7 × 10⁻² and 12 × 10⁻² s⁻¹, whilst for the latter, k_inc = 4 × 10⁻², 5 × 10⁻² and 9 × 10⁻² s⁻¹, respectively. Each cyclodextrin also decreases the pK_a of the nitrotoluene, from 6.8 in free solution, to 6.2 when bound. The accelerated deprotonation by 6^A-amino-6^A-deoxy-β-cyclodextrin is reflected in the enhanced rates of hydrogen–deuterium exchange of the nitrotoluene in deuterium oxide, and in the conjugate addition of the nitrotoluene to methyl vinyl ketone in aqueous solution.