Boriana Hadjieva

Predicting Reactivities of Organic Molecules. Theoretical and Experimental Studies on the Aminolysis of Phenyl Acetates

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.

Ab initio molecular orbital and infrared spectroscopic study of the conformation of secondary amides: derivatives of formanilide, acetanilide and benzylamides

Abstract Ab initio molecular orbital calculations at HF/4-31G level and infrared spectroscopic data for the frequencies are applied to analyse the grouping in a series model aromatic secondary amides: formanilide; acetanilide; o -methylacetanilide; 2,6-dimethylformanilide, 2,6-dimethylacetanilide; N -benzylacetamide and N -benzylformamide. The theoretical and experimental data obtained show that the conformational state of the molecules studied is determined by the fine balance of several intramolecular factors: resonance effect between the amide group and the aromatic ring, steric interaction between various substituents around the –NH–CO– grouping in the aromatic ring, conjugation between the carbonyl bond and the nitrogen lone pair as well as direct field influences inside the amide group.

Aminolysis of phenyl N-phenylcarbamate via an isocyanate intermediate: theory and experiment.

A comprehensive examination of the mechanism of the uncatalyzed and base-catalyzed aminolysis of phenyl N-phenylcarbamate by theoretical quantum mechanical methods at M06-2X/6-311+G(2d,2p) and B3LYP-D3/6-31G(d,p) levels, combined with an IR spectroscopic study of the reaction, was carried out. Three alternative reaction channels were theoretically characterized: concerted, stepwise via a tetrahedral intermediate, and stepwise involving an isocyanate intermediate. In contrast to dominating views, the theoretical results revealed that the reaction pathway through the isocyanate intermediate (E1cB) is energetically favored. These conclusions were supported by an IR spectroscopic investigation of the interactions of phenyl N-phenylcarbamate with several amines possessing varying basicities and nucleophilicities: n-butylamine, diethylamine, triethylamine, N-methylpyrrolidine, and trimethylamine. The reactivity of substituted phenyl N-phenylcarbamates in the aminolysis reaction was rationalized using theoretical and experimental reactivity indexes: electrostatic potential at nuclei (EPN), Hirshfeld and NBO atomic charges, and Hammett constants. The obtained quantitative relationships between these property descriptors and experimental kinetic constants reported in the literature emphasize the usefulness of theoretical parameters (EPN, atomic charges) in characterizing chemical reactivity.

Arenium ions are not obligatory intermediates in electrophilic aromatic substitution

Significance Electrophilic substitution is universally regarded as the characteristic reaction of aromatic compounds. Arenium ions are widely accepted as obligatory intermediates in the two-stage (SEAr) mechanism typically described in textbooks, monographs, and reviews. We now challenge this mechanistic paradigm. Our combined computational and experimental investigation of the exemplary halogenation of anisole with Cl2 in CCl4 finds that addition–elimination pathways compete with the direct substitution process and also account for the ortho–para orientation preferences easily. Moreover, the SEAr processes do not involve arenium ion pair intermediates, but proceed instead via concerted one-stage single transition state routes. We question not only the generality of the accepted SEAr mechanism, but also the involvement of arenium ion intermediates, when counter ions are present. Our computational and experimental investigation of the reaction of anisole with Cl2 in nonpolar CCl4 solution challenges two fundamental tenets of the traditional SEAr (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 SEAr 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 (SEAr) 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.

Reactivity of Acetanilides in the Alkaline Hydrolysis Reaction: Theory vs. Experiment

The rate constants (at 25°C) for the alkaline hydrolysis of a series of seven acetanilide derivatives were determined experimentally. The series included the parent compound acetanilide and the following para-substituents: CH3, OCH3, NH2, CHO, COCH3 and NO2. The obtained kinetic data were then correlated with the following theoretically estimated reactivity indices: Mulliken and NBO atomic charges, the Parr electrophilicity index (ω), and the electrostatic potential at the carbon and nitrogen atoms of the reaction center (V C, V N). Very good correlation between the logarithm of the rate constant, ln k, and the ω values was established. Excellent correlations between V C and V N and ln k were found. The data obtained show that the model-independent electrostatic potential at the nuclei provides a reliable quantitative approach for describing the reactivity of organic compounds.

An Experimentally Established Key Intermediate in Benzene Nitration with Mixed Acid

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.

Infrared spectroscopic study of the configuration of some alkylaryl ureas

Abstract The conformation of a series of 1-aryl-3-(n-butyl)ureas and 1-aryl-1-methyl-3-(n-butyl)-ureas having an orthohydroxyl group in the aromatic ring is studied by infrared spectroscopy. The spectral data show that in organic solvents (CHCl3, CH2Cl2, CCl4) the compounds are in a Z,Z-conformation. Conclusive evidence is obtained for the existence of an intramolecular hydrogen bond between the OH and CO groups in all N-methylated ureas.

AB INITIO MOLECULAR ORBITAL STUDY OF THE CONFORMATION OF AMIDE GROUP : O-METHYLFORMANILIDE

HF/4-31G ab initio quantum mechanical calculations on o-methylformanilide are used to analyse the conformational isomerism of the amide group in the molecule. It is known from experimental literature sources that the compound has some remarkable features: (1) pure trans and cis rotameric forms associated with the secondary amide grouping can be experimentally isolated and their properties studied; (2) for this molecule the cis ‐CO‐NH‐ conformational form predominates at ambient temperature in contrast to results for many other secondary amides. The principal results of the ab initio calculations carried out in the present study can be summarized as follows: (1) ab initio calculations employing at least HF/4-31G basis set are needed to correctly describe the conformational state of the amide group in o-methyl-formanilide; (2) the ab initio results show that the trans conformers have a planar structure while the cis isomer is nonplanar; (3) the N‐H stretching mode frequency for the trans form is estimated to be 49 cm 21 higher than the respective N‐H frequency in the cis conformer; (4) the experimental infra-red spectrum of the compound in CCl4 reveals that the cis ‐CO‐NH‐ structure predominates at ambient temperature in accord with previous experimental results; (5) the theoretically estimated barrier of rotation around the amide C‐N bond (Eaa 19.2 kcal/mol) is in accord with the experimentally detected simultaneous presence of cis and trans forms at ambient temperature. q 1999 Elsevier Science B.V. All rights reserved.

Hyperconjugative effects in π‐hydrogen bonding: Theory and experiment

Density functional theory computations with the B3LYP/6‐311++G(2df,2p) method and IR spectroscopy are employed in investigating the properties of twenty π‐hydrogen bonded complexes between substituted phenols and hexamethylbenzene. All complexes possess T‐shaped structures. The methyl hyperconjugative effects on interactions energies and OH stretching frequencies are estimated via comparisons with previously reported theoretical and experimental results for analogous phenol complexes with benzene. The theoretical computations provide excellent quantitative predictions of the OH stretching frequency shifts (ΔνOH) resulting from the hydrogen bonding. The ΔνOH shifts in the hexamethylbenzene complexes are approximately twice as large as the corresponding shifts for the benzene complexes. Hirshfeld charges, electrostatic potential at nuclei values, and molecular electrostatic potential maps are employed in gaining insights into the mechanisms of methyl hyperconjugative effects on complex formation.