Nucleophilic aromatic substitution in heterocycles: alcoholysis and hydrolysis of 2-anilino-4,6-dichloro-1,3,5-triazines

Abstract

Kinetics are reported for the alkaline hydrolysis of 2-anilino-4,6-dichloro-1,3,5-triazines to yield the corresponding mono-hydroxy species. The pseudo-first-order rate constants are independent of general-base concentration and obey the rate law eqn. (i), where K₁=K_w/K_a, K_a is the ionisation k_obs=(k_H2O+k_OHK₁[OH])/([OH]+K₁)(i) constant for the aniline proton and k_OH is the bimolecular rate constant for attack of hydroxide ion on the neutral triazine molecule. The parameters k_OH and K_a obey Hammett equations with σ°[eqns. (ii) and (iii)]. The kinetically determined pK_a of the 4-chloroanilino-4,6-dichloro-1,3,5- log k_OH= 1.06 ± 0.15σ°– 0.064 ± 0.054 (r= 0.9709)(ii), pK_a=–2.13 ± 0.16 σ°+ 10.92 ± 0.06 (r= 0.9919)(iii) triazine is close to that measured by pH-titration.

The kinetics for hydrolysis and alcoholysis of 2-(N-methyanilino)-4,6-dichloro-1,3,5-triazine are independent of general-base concentration and are first order in oxyanion and triazine concentration; the derived second-order rate constants (k_RO^–)(excepting the hydroxide term) obey the extended Brønsted equation (iv).

log k_RO^–= 0.84 ± 0.06 pK_a^ROH– 10.89 ± 0.87 (r= 0.9886)(iv)

The hydroxide ion term is some three orders of magnitude less nucleophilic than an alkoxide of the same pK_a. The data exclude the conjugate base of the 2-anilino-4,6-dichloro-1,3,5-triazine as a major contributor to the reaction flux of the hydrolysis and are consistent with a mechanism involving addition of the hydroxide ion to the neutral triazine. The polar substituent effects on the hydroxide ion reactivity indicate that there is substantial charge accumulation in the triazine nucleus in the transition state of the addition step.