Structure - reactivity patterns in nucleophilic addition to activated aromatic compounds

Abstract

Kinetic and equilibrium data for the reactions of some aromatic nitro compounds with nucleophiles have been investigated using various spectrophotometric techniques (UV/visible, stopped-flow and temperature jump) and nmr spectroscopy. Kinetic and equilibrium data are reported for the formation of 1:1 and 1:2 adducts in aqueous solutions from 1,3,5-trinitrobenzene (TNB) and 2,4,6-trinitro- toluene (TNT) with thiolate ions derived from thioglycolic acid, thiomalic acid and glutathione. The results are used to determine intrinsic reactivities, kg, for the thiolate ions in adduct-forming reactions at the nitro-aromatic ring. The values for the three thiolate ions are all ca. 5x10(^4) and are considerably higher than comparable values, calculated from literature data, for the sulphite ion (500) and the hydroxide ion (10). Kinetic and equilibrium data are reported for the reactions in water of ethane- thiolate, thioglycolate and thiomalate ions with l-X-2,4,6-trinitrobenzenes (X=H, SEt, OEt and Cl). The thiolate ions show strong kinetic preference for attack at unsubstituted ring positions. However, the isomeric 1:1 adducts have similar thermodynamic stabilities. This is in marked contrast with the corresponding reactions of alkoxides. 1:2 adducts are formed by thiolate attack at two unsubstituted ring positions. A 1:3 adduct has been identified by reaction of ethanethiolate ions with TNB and the kinetic data recorded. (^1)H nmr measurements in DMSO have been used to examine the structures of intermediates and reaction products; they show the irreversible displacement of nitro groups by thiolate ions. The initial reaction of l-X-2,4,6-trinitrobenzenes (X=H, CI, CH(_3)) in methanol with the anions of dimethylmalonate, ethylcyanoacetate and a selection of substituted phenylacetonitriles yield σ-adducts by carbanion attack at un substituted ring positions. With ethylcyanoacetate there was evidence for the ionisation of the remaining exocychc hydrogen and this process is increasingly favoured as the X-substituent becomes more electron-withdrawing (CI > H > CH(_3)). An acidity function approach is used to determine the equilibrium acidities of the substituted phenylacetonitriles in methanol. The data are well correlated with a- values (7 points) and the plot is used to estimate the acidities of three further phenylacetonitriles. However, the equilibrium acidity of 4-nitrophenyl- acetonitrile is shown to be anomalous. For the most strongly basic anions, derived from the most weakly acidic phenylacetonitriles, reaction with TNB was found to proceed at or near the diffusion controlled limit. The kinetic and equilibrium data are used to determine values of intrinsic rate constants, ko, for reaction at an unsubstituted position of the trinitro-aromatic ring. The values are dimethyl malonate (200), ethylcvanoacetate (200), 4-nitrophenylacetonitrile (280), 4-cyano- phenylacetonitrile (10(^3)) and 2-cyanophenylacetonitrile (l0(^3)).Kinetic and equilibrium measurements are reported for the reactions of l-X-2,4- dinitrobenzenes (X=F, Br) with hydroxide ions in 80/20 (v/v) DMSO/H(_2)O. The results provide evidence for two types of steric effects: (i) increasing size of the halogen results in disruption of the planarity of the nitrogroups giving a general decrease in reactivity at both unsubstituted and halogen-substituted positions and (ii) unfavourable steric and electrostatic repulsions between entering and leaving groups. Hydrogen exchange experiments were carried out with l-fluoro-2,4-dinitro- benzene and OD(^-) in [(^2)H(_6)]-DMSO/D(_2)O. The results show that there is slightly more hydrogen exchange at the 3-position of the substituted product (the phenoxide) than there is at the 3-position of the unreacted starting material. However, these observations do not necessarily require the formation of an intermediate on the pathway to σ-adduct formation.