Nucleophilic Aromatic Substitution Reactions in Dipolar Aprotic Solvents: The Remarkable Effect of Trifluoromethyl Group on the Reactivity of Nitrophenyl Ethers with Nucleophiles.

Abstract

Rate constants are reported for the reactions of 4-phenoxy-3-nitrobenzotrifluoride 3c, 2-phenoxy-5-nitrobenzotrifluoride 4c and 1-phenoxy-2,4-dinitrobenzene 5c activated by trifluoromethyl (CF3) or nitro (NO2) groups with n-butylamine, pyrrolidine and piperidine in DMSO.  The results are compared with results reported previously for same reactants and with the more strongly ring-activated compounds 4-phenoxy-3,5-dinitrobenzotrifluoride 1c and 2-phenoxy-3,5-dinitrobenzotrifluoride 2c in acetonitrile.  A change in reaction medium from acetonitrile to DMSO leads to a reduction in values of kAm/k-1 as the proton-transfer from zwitterionic intermediates to catalysing amine becomes less thermodynamically favourable. Overall, the reactivity order is 5c > 3c> 4c and decreasing ring-activation in the 1-phenoxy compounds 1c - 5c leads to lower values of kAm/k–1 resulting in greater susceptibility to base catalysis.  Specific steric effects leading to rate-retardation, is noted for the ortho-CF3 group. The higher reactivity of para-CF3 group in compounds 3c compared to 4c has been attributed partly to the more effective polar hyperconjugative activation by the CF3 group in 3c and to a possible participation of unfavourable electrostatic repulsion for the ortho-CF3 group between the electronegative fluorine atoms in 4c and the incoming nucleophiles.Keywords: Trifluoromethyl group, Proton transfer mechanism, Stereoelectronic effects, Nucleophilic aromatic substitution.