FULL PAPER DOI: 10.1002/ejoc.200600968 The Effects of Ring Substituents and Leaving Groups on the Kinetics of S N Ar Reactions of 1-Halogeno- and 1-Phenoxy-nitrobenzenes with Aliphatic Amines in Acetonitrile Michael R. Crampton,* [a] Thomas A. Emokpae, [b] and Chukwuemeka Isanbor* [b] Keywords: Nucleophilic aromatic substitution / Reactivity–substituent effects / Amines Rate constants are reported for the reactions of a series of 1- chloro-, 1-fluoro- and 1-phenoxy-nitrobenzenes activated by CF 3 or CN groups or by ring-nitrogen with n-butylamine, pyrrolidine or piperidine in acetonitrile. The results are com- pared with results reported previously for more strongly ring- activated compounds. Decreasing ring activation leads to lower values of k 1 for nucleophilic attack although this may be mediated by reduced steric congestion around the reac- tion centre. Specific steric effects, leading to rate-retardation, Introduction Nucleophilic substitution in the reactions of activated aromatic compounds with amines usually involves the S N Ar mechanism [1,2] as shown in Scheme 1. When the second step is rate limiting then general base catalysis may be observed. Mechanisms and reactivity in these systems continue to attract attention [3–5] and we have recently made a compari- son of the displacement by aliphatic amines of chloride and phenoxide from strongly activated compounds 1 and 2 (X = Cl, OPh) carrying at least two nitro groups. [6] This study identified the following as major factors affecting values of k 1 for nucleophilic attack: (a) Ring activation – values increase with increasing elec- tron withdrawal by ring substituents but ortho substituents, notably the CF 3 group, can have serious steric effects. Scheme 1. [a] Chemistry Department, Durham University, Durham, DH1 3LE, UK [b] Chemistry Department, University of Lagos, Lagos, Nigeria Supporting information for this article is available on the WWW under http://www.eurjoc.org or from the author. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Eur. J. Org. Chem. 2007, 1378–1383 1378 is noted for the ortho-CF 3 group. The 1-phenoxy compounds are subject to base catalysis and values of k Am /k –1 are re- duced relative to more strongly activated compounds. This is likely to reflect increases in values of k –1 coupled with de- creases in values of k Am as the proton transfer from zwitter- ionic intermediates to catalysing amine becomes less thermo- dynamically favourable. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) (b) Steric effects at the reaction centre – values decrease with steric congestion at the reaction centre; steric effects increase in order Cl  OPh and n-butylamine  pyrrolidine ≈ piperidine. (c) Ground-state stabilisation – involving resonance inter- actions between the phenoxy group and the ring may de- crease reactivity. The observation of base catalysis, dependent on the value of the ratio k B /k –1 , was interpreted in line with previous evidence [7] in terms of rate limiting proton transfer from the zwitterionic intermediate, Z, to base. Here, we report rate data for the substitutions of a series of less activated compounds, 3–7, carrying only one nitro group, so that the reaction centre is less sterically crowded than in 1 and 2. The effects of changing the nature of the leaving group from chloride, to fluoride and to phenoxide and of the amine from n-butylamine to pyrrolidine and to piperidine are examined.