Nucleophilic heteroaromatic substitution: Kinetics of the reactions of nitropyridines with aliphatic amines in dipolar aprotic solvents

Abstract Rate data are reported for the reactions of 2‐chloro‐5‐nitropyridine 2a , 2‐chloro‐3‐nitropyridine 2b , and the corresponding 2‐phenoxy derivatives 2c with n ‐butylamine, pyrrolidine and piperidine and 2d with n ‐butylamine and pyrrolidine in dimethyl sulfoxide (DMSO) as solvent. The same reactions in acetonitrile had been reported earlier (Crampton et al., Eur J Org Chem 2007, 1378–1383). Values in these solvents are compared with those of 2,4‐dinitrochlorobenzene 3a , 2,6‐dinitrochlorobenzene 3b , and the corresponding nitroactivated diphenyl ethers 3c and 3d . Reactions with n ‐butylamine in both solvents gave values of k obs , which increase linearly with amine concentration indicating that nucleophilic attack is rate limiting. The only exception is the reactions in acetonitrile with 2c where base catalysis was observed. Values of k 1 , the rate constant for the nucleophilic attack, decrease in the order pyrrolidine > piperidine > n ‐butylamine. In acetonitrile, kinetic data show that k / k ratios are more than unity while the inverse is the case in DMSO. With the phenoxy derivatives, substitution was the only process observed. Base catalysis detected in the reactions of the 1‐phenoxy derivatives is attributed to rate‐limiting deprotonation of the initially formed zwitterionic intermediate. Our results shed more light on fundamental aspects of activation, hydrogen bonding, and steric effects associated with an aza or a nitro group in the molecules investigated as it affects the nucleophilic aromatic substitution (S N Ar) reaction pathways. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 125–135, 2008