A number of molecular quantities were tested as reactivity indexes for the alkaline hydrolysis reaction of a series of 15 N-phenylacetamides para substituted in the aromatic ring. The Hammett σ constants and the shifts of carbonyl stretching mode frequencies correlate satisfactorily with the predicted Hartree-Frock (HF)/ 6-31+G(d) and density functional theory B3LYP/6-31+G(d,p) energy changes for the rate-determining stage of the reaction, namely, the addition of a hydroxide ion and formation of a tetrahedral intermediate. Natural bond orbital atomic charges at the carbonyl carbon atom, the site of the nucleophilic attack, also offer a satisfactory basis for discussing the reactivity of the carbonyl compounds studied. The electrophilicity index ω describes well the overall tendency of the changing reactivity of the studied compounds. A quantitative description of the reactivity of the studied amides in the reaction considered is provided by the theoretically estimated electrostatic potential at the carbonyl carbon atom. The linear regression correlation coefficients for the connection between the energy changes for the rate-determining stage of the amide hydrolysis and the electrostatic potential at the carbonyl carbon atom are over 0.99 with both levels of theory employed. The electrostatic potential at the nuclei is recommended as an accurate local reactivity index.

The quality of reactivity predictions coming from alternative theoretical approaches as well as experimental reactivity constants is examined in the case of the ester aminolysis process. The aminolysis of a series of para-substituted phenyl acetates is studied. The barrier heights for the rate-determining stage of the aminolysis of 16 phenyl acetate derivatives were predicted by employing density functional theory at the B3LYP/6-31+G(d,p) level. Experimental kinetic studies were carried out for the n-butylaminolysis of seven p-substituted phenyl acetates in acetonitrile. The results show that the electrostatic potential at the carbon atom of the carbonyl reaction center provides an excellent description of reactivities with regard to both theoretical barrier heights and experimental rate constants. The performance of other reactivity indices, Mulliken and NBO atomic charges, electrophilicity index, and Hammett constants, is also assessed.

Our computational and experimental investigation of the reaction of anisole with Cl 2 in nonpolar CCl 4 solution challenges two fundamental tenets of the traditional S E Ar (arenium ion) mechanism of aromatic electrophilic substitution. Instead of this direct substitution process, the alternative addition-elimination (AE) pathway is favored energetically. This AE mechanism rationalizes the preferred ortho and para substitution orientation of anisole easily. Moreover, neither the S E Ar nor the AE mechanisms involve the formation of a σ-complex (Wheland-type) intermediate in the rate-controlling stage. Contrary to the conventional interpretations, the substitution (S E Ar) mechanism proceeds concertedly via a single transition state. Experimental NMR investigations of the anisole chlorination reaction course at various temperatures reveal the formation of tetrachloro addition by-products and thus support the computed addition-elimination mechanism of anisole chlorination in nonpolar media. The important autocatalytic effect of the HCl reaction product was confirmed by spectroscopic (UV-visible) investigations and by HCl-augmented computational modeling.organic chemistry | reaction mechanisms | alternative computed routes | autocatalysis

Experimental evidence is reported for the first intermediate in the classic SEAr reaction of benzene nitration with mixed acid. The UV/Vis spectroscopic investigation of the reaction showed an intense absorption at 320 nm (appearing as a band shoulder) arising from a reaction intermediate. Our theoretical modeling shows that the interaction between the two principal reactants with solvent (H2SO4) molecules significantly affects the structure of the initial complex. In this complex, a larger distance between the aromatic ring and nitronium ion precludes the possibility for electronic charge transfer from the benzene π-system to the electrophile. The computational modeling of the potential energy surface reveals that the reaction favors a stepwise mechanism with intermediate formation of π- and σ-(arenium ion) complexes.

The electronic effect of polar substituents on the barrier of internal rotation around the amide carbon-nitrogen bond in a series of 10 p-substituted acetanilides is studied by applying density functional theory at the B3LYP/6-31G(d,p) level. The theoretical results are supplemented by experimental data on the amide C=O and N-H stretching mode frequency shifts. It is shown that computations at the theoretical level employed provide a valuable approach in studying the factors determining the conformational stability of the studied series of compounds. It is found that an excellent linear dependence between the barriers of rotation and frequency shifts exists. It is concluded that the variations of the amide C=O stretching mode frequency can be used for quantitative characterization of the amide group conformational flexibility in the studied series of acetanilides.