Kinetic and equilibrium studies of sigma-adduct formation and nucleophilic substitution in the reactions of 2-phenoxy-3,5-dinitropyridine and 2-ethoxy-3,5-dinitropyridine with aliphatic amines in dipolar aprotic solvents

The reactions of aliphatic amines with 2-phenoxy-3,5-dinitropyridine, 4, and 2-ethoxy-3,5-dinitropyridine, 5, in DMSO result in the rapid reversible formation of anionic sigma-adducts at the 6-position. Kinetic studies show that proton transfer from the initially formed zwitterions to base may be rate-limiting. Slower reactions result, except in the case of 5 and piperidine, in displacement of the 2-substitutent via intermediates which have lower thermodynamic stabilities than their 6-isomers. Base catalysis of the substitution process is attributed in the case of 4 to rate-limiting proton transfer from zwitterionic intermediates, but in 5 to acid catalysis of ethoxide departure (SB-GA mechanism). X-Ray crystallography of 5 shows a planar non-strained structure although the structure of 2-piperidino-3,5-dinitropyridine, 10c, shows distortion resulting from steric interactions of the 2- and 3-substituents. Kinetic and equilibrium results are compared with those for related reactions of the more sterically strained 2,4,6-trinitrobenzene derivatives. Results for the reactions of 4 and 5 with pyrrolidine in three dipolar aprotic solvents are compared. Values of equilibrium constants for sigma-adduct formation decrease in the order DMSO > DMF > Acetonitrile, while values of rate constants for proton transfer are in the reverse order.     

Computational studies of the effects of ortho‐ring and para‐ring activation on the kinetics of SNAr reactions of 1‐chloro‐2‐nitrobenzene and 1‐phenoxy‐2‐nitrobenzene with aniline

Computational studies are reported for reactions of 4‐substituted‐1‐chloro‐2,6‐dinitrobenzenes 1 , 6‐substituted‐1‐chloro‐2,4‐dinitrobenzenes 2 and some of the corresponding 1‐phenoxy derivatives 3 and 4 with aniline in the gas phase. The effects of substituent groups in the calculated energy values for reactants 1–4 , transition states structures, intermediates and products formed in the reactions between the compounds and anilines have been compared. Calculated bonds length and angles from optimized structures of the reactants were comparable with values reported for some of compounds 1–4 obtained by X‐ray crystal structures analysis. Generally, the decomposition of the Meisenheimer intermediate to the products requires more energy compared with the reactants except for when R = H. The order of stabilization of the intermediate was found to reflect the relative order of activation by substituents in the substrates. The 4‐substituted‐1‐chloro‐2,6‐dinitrobenzenes 1 and the phenoxy derivatives 3 were found to be more stable than their corresponding 6‐substituted analogues. This is an indication that the rate of nucleophilic attack at 1‐position will increase with increasing ring activation but may be reduced by steric repulsion at the reaction centre that increases in the order Cl < OPh. However, the steric hindrance to the steps involved in nucleophilic substitution by aniline is significantly increased when the substrates contain two ortho‐substituents. In most cases, the rate determining step is the decomposition of the σ‐adduct intermediate except with 1‐chloro‐2,6‐dinitrobenzenes 1 and 6‐substituted‐1‐chloro‐2,4‐dinitrobenzenes 2 , either because of reduction in ring activation or the presence of bulky ortho‐substituents in the chloro compounds 1 and 2 . Copyright © 2014 John Wiley & Sons, Ltd.