Jack Hirst

The effect of ortho substituents on the mechanism of aromatic nucleophilic substitution reactions in dipolar aprotic solvents

The reactions of 2,6-dinitrophenyl phenyl ether and of 6-methyl-2,4-dinitrophenyl phenyl ether with piperidine, morpholine, butylamine and benzylamine are base catalysed in both dimethyl sulfoxide and acetonitrile. The reaction of 2-phenoxy-3,5-dinitropyridine with aniline is base catalysed in acetonitrile, but not in dimethyl sulfoxide, and its reactions with piperidine, morpholine, butylamine and benzylamine in acetonitrile are also base catalysed. The results are discussed in terms of the prevailing theories of aromatic nucleophilic substitution reactions. Increase in activation of the substrate increases the k2/k–1 and k3/k–1 ratios. For ortho substituents, steric/steroelectronic effects in the transition state reduce both k–1, the rate constant for the decomposition of the zwitterionic intermediate to reactants, and k2 and k3, the rate constants for its decomposition to products. When the substrate has two ortho groups the different behaviour of primary and secondary amines found with substrates containing only one ortho-nitro group is not observed.

The origins of the dichotomy of amine effects in aromatic nucleophilic substitution reactions

The reactions of 2-trifluoromethyl- and 2-cyano-4-nitrofluoro-benzenes with piperidine, n-butylamine and benzylamine in acetonitrile are not base catalysed, but the reactions with morpholine are catalysed. In benzene, the reactions of the 2-cyano-substrate with all four nucleophiles are catalysed. In acetonitrile, the reaction of 2-cyano-4-nitrophenyl phenyl ether with piperidine is base catalysed, whereas that of n-butylamine is not. In benzene, the reactions of this substrate with both nucleophiles are catalysed. The reasons why the reactions of secondary amines in aromatic nucleophilic substitution reactions are more prone to base catalysis than the corresponding reactions with primary amines of the same basicity are discussed.

Kinetics of the reactions of aniline and 2,2,2-trifluoroethylamine with 1,3,5-trinitrobenzene in dimethyl sulphoxide and acetonitrile, and of 2,2,2-trifluoroethylamine with 1-fluoro- and 1-chloro-2,4-dinitrobenzenes in these solvents

Meisenheimer complex formation between 1,3,5-trinitrobenzene (TNB) and the primary amines aniline and 2,2,2-trifluoroethylamine (TFE) has been studied in dimethyl sulphoxide and acetonitrile. The reaction with aniline is catalysed in both solvents by 1,4-diazabicyclo[2.2.2]octane (DABCO). With TFE, catalysis by both TFE and DABCO was observed in acetonitrile, but not in dimethyl sulphoxide. The reactions of TFE with 1-fluoro- and 1-chloro-2,4-dinitrobenzenes are not base catalysed in dimethyl sulphoxide or acetonitrile.

Catalysis of the aromatic nucleophilic substitution reactions of anilines in aprotic solvents

The reaction of 1-chloro-2,4-dinitrobenzene with p-anisidine in benzene is catalysed by the nucleophile and by tetra-n-butylammonium chloride. When the nucleophile is N-methyl-p-anisidine the reaction is not catalysed by the nucleophile, tetra-n-butylammonium chloride, DABCO, or pyridine. The reactions of both p-anisidine and N-methyl-p-anisidine with 1-fluoro-2,4-dinitrobenzene have been shown to be catalysed by the nucleophile, tetra-n-butylammonium chloride, and (in the case of N-methyl-p-anisidine) by DABCO and pyridine. Mechanisms are proposed to rationalize the results.

Base catalysis of aromatic nucleophilic substitution reactions in aprotic and dipolar aprotic solvents

For base-catalysed aromatic nucleophilic substitution reactions in benzene, catalysis by added base is observed irrespective of whether the catalyst is a stronger or a weaker base than the nucleophile. In acetonitrile, catalysis is only observed if the catalyst has either approximately the same strength or is a stronger base than the nucleophile. These observations are shown to indicate a difference in the mechanism of catalysis in the two solvents.

Reaction of 2,4-dinitrophenyl phenyl ether with morpholine in dimethyl sulphoxide, acetonitrile, tetrahydrofuran, and ethyl acetate and of 1-chloro-2,4-dinitrobenzene with morpholine in ethyl acetate

The reaction of morpholine with 2,4-dinitrophenyl phenyl ether is base-catalysed in all the solvents investigated. The values of k3/k2 provide information about the mechanism of the uncatalysed decomposition of the intermediate formed in nucleophilic aromatic substitution in solvents of high dielectric constant.The reaction of morpholine with 1-chloro-2,4-dinitrobenzene in ethyl acetate is not base-catalysed. Comments are made on the mechanism of base-catalysed nucleophilic aromatic substitution in solvents of low dielectric constant and basicity.

Kinetics of the reactions of piperidine, n-butylamine, morpholine, and benzylamine with 2,4-dinitrophenyl phenyl ether

The kinetics of the reactions designated in the title have been studied as a function of amine concentration in acetonitrile, dimethyl sulphoxide, and (for piperidine and n-butylamine only) methanol. In all the solvents studied, the reactions of the secondary amines are base-catalysed : those of the primary amines are not. The results are interpreted in terms of the generally accepted mechanism of nucleophilic aromatic substitution.

The reaction of imidazole with some 1-halogeno-2,4-dinitrobenzenes in aprotic solvents

The reactions of imidazole with 1-chloro- and 1-fluoro-2,4-dinitrobenzenes in dimethyl sulfoxide are not catalysed by imidazole. DABCO or imidazolium perchlorate. In acetonitrile these reactions are not catalysed by the nucleophile or DABCO but the second-order rate constant kA has a linear dependence on the concentration of tetrabutylammonium chloride and is depressed by the addition of imidazolium perchlorate. In this solvent the reaction of imidazole with 1-bromo-2,4-dinitro-benzene is not catalysed by the nucleophile and the kABr/kACl ratio is 0.90. These results are rationalised in terms of the conventional mechanism of aromatic nucleophilic substitution reactions in aprotic solvents of high relative permittivity, with chloride ion catalysing the formation of the intermediate in acetonitrile solution.In benzene the reaction of imidazole with 1-chloro-2,4-dinitrobenzene is strongly catalysed by the nucleophile and by tetrabutylammonium chloride and weakly by pyridine. The corresponding reaction with 1-bromo-2,4-dinitrobenzene is also strongly catalysed by imidazole and there is little difference in the reactivity of the two substrates. The catalysis of the reactions by amines observed here, and that previously reported in the literature, is explained as being due to reaction taking place via complexes formed from the reactants and catalysts.

The mechanism of aromatic nucleophilic substitution reactions in protic solvents. The reations of aniline, N-methylaniline, n-butylamine, and piperidine with some nitroaryl phenyl ethers in methanol

In methanol, the reactions of aniline with 2-phenoxy-3,5-dinitropyridine, phenyl 2,4,6-trinitrophenyl ether, and 4-nitrophenyl 2,4,6-trinitrophenyl ether and the last-named substrate with N-methylaniline are general-base catalysed. The reaction of 2,6-dinitrophenyl phenyl ether with n-butylamine is not base catalysed, but its reaction with piperidine is specific-base catalysed. The results are discussed in terms of the mechanism of aromatic nucleophilic substitution reactions in protic solvents.

Catalysis by amine salts of some aromatic nucleophilic substitution reactions

The reaction of 1-chloro-2,4-dinitrobenzene with aniline in acetonitrile is catalysed by R4NY where Y is Cl, Br, I, or toluene-p-sulphonate, but not by 1,4-diazabicyclo [2.2.2.] octane (DABCO). When the nucleophile is changed to n-butylamine or morpholine, addition of tetraethylammonium chloride has only a small effect; the reactions of all three nucleophiles are not catalysed by tetraethylammonium perchlorate. The reaction of 1-fluoro-2,4-dinitrobenzene with aniline is strongly catalysed by tetraethylammonium chloride, to a lesser extent by the bromide and toluene-p-sulphonate and also by trimethylamine hydrochloride, but not by tetraethylammonium perchlorate. The reactions of morpholine with 1-fluoro-2,4-dinitrobenzene and piperidine with 2,4-dinitrophenyl phenyl ether are not catalysed by amine salts. The results are consistent with the formation and stabilisation of the intermediate formed in aromatic nucleophilic substitution reactions by the anions of the salts, when the nucleophile is aniline.