Solvent effects in aromatic nucleophilic substitution reactions in non‐polar aprotic solvents. Inhibition by electron‐donor–acceptor (EDA) complexation of the substrate by aromatic solvents

Abstract

The reactions of n‐butylamine and piperidine with 1‐chloro‐2, 4‐dinitrobenzene and 4‐chloro‐3‐nitrotrifluoromethylbenzene were studied in n‐hexane, benzene and mesitylene. The reactions seem to follow a bimolecular SNAr mechanism for both substrates and amines. However, whereas in n‐hexane they are base catalysed, in the aromatic solvents only mild acceleration is observed. The different behaviour of these reactions in the aromatic solvents in comparison with hexane is explained by the specific solvent effect exerted by the aromatic compounds, which solvates the aromatic reactant preferentially in view of its electron‐donor properties. These conclusions were confirmed by kinetic studies in hexane‐aromatic solvent binary mixtures. It can be concluded that the presence of electron‐donor solvents may inhibit SNAr reactions when association constant of the solvent with the substrate is greater than the EDA constants between the reactants. These specific solvent effects could also explain why only mild acceleration is observed in aromatic solvents.

Kinetics of the Reaction of 2‐Chloro‐3,5‐dinitrobenzotriflouride with Aniline in Toluene and Methanol‐Toluene Mixed Solvents

“…[35] The second order rate constants, k A for the reaction in presence of fixed concentration of pyridine and different aniline concentrations (Table 2), showed linear behaviour for k A , similar to that observed for k A values for the reaction of 1 with different pyridine concentrations at fixed aniline concentration. Accordingly a dimer mechanism is suggested involving the formation of homo and hetero aggregate between aniline-aniline and aniline-pyridine, respectively (Scheme 1, pathway d).…”

“…For example, the reaction of 1 with aniline (present study) showed a rate increase similar to phenyl 2,4,6-trinitrophenyl ether with the same amine. [34] Also the reaction of 2,4-dinitrofluorobenzene with piperidine [35] in benzene displayed a rate increase with added methanol while the reaction of the same substrate produced the opposite effect in its reaction with cis and trans 1,2-dinitro cyclohexylamine. [38] It can therefore be reasonably assumed that a methanol-substrate interaction is not responsible for the observed increase in rate in present case.…”

Kinetics and mechanism for the reaction of 1-chloro-2,4-dinitrobenzene with n-butylamine and piperidine in AOT/n-hexane/water reverse micelles

“…The competitive formation of an electron-donor-acceptor complex (EDA) between the reactants or the substrate with donor solvents prior to the sigma intermediate formation was suggested to explain the difference in reactivities. 11 A similar proposal has been made for other nonpolar aprotic solvents. 22.23 However, since the role of the EDA complex is kinetically undistinguishable under the reaction conditions no point will be made on this aspect.…”

“…11 The magnitude of the catalysis depends on the structure of the amine being noteworthy in the case of NBA. In micellar systems, the overall rate constant dependence with the surfactant concentration can be quantitatively treated taking into account the species distribution between the micellar pseudophase and the bulk organic solvent, assuming that the incorporation of each reactant is not affected by the presence of the other, 14 and that the S N Ar reaction is rate limiting.…”

“…The values of k´and k" used, were previously reported for the reaction in neat organic solvent (0 and 4x10 -5 for NBA, and 2.05x10 -2 and 0.118 for PIP respectively). 11 The intrinsic rate constant for the reaction at the interface k 1 b and K A , were obtained by non-linear least square fitting of the k obs versus [AOT] plots by means of eq. 4.…”