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

Abstract

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.

Towards physical interpretation of Hammett constants: charge transferred between active regions of substituents and a functional group

“…-electron densities at p-and m-positions in monosubstituted benzenes [34] -electrostatic potential values at the ring carbon atoms [28,35,36] -electrostatic potential values at atoms of a reaction center [28,37] -topography of electrostatic potential near the molecular surface [38][39][40][41][42] -hyperpolarizability [43] -a complexed metal chemical shift [44,45] -energy of the highest occupied orbital (E HOMO ) [46,47] -energy of the lowest unoccupied orbital (E LUMO ) [16] -ionization potential [48] -electrophilicity, being a measure of stabilization in energy when the system acquires an additional electronic charge DN from the environment [28,49,50] -core electron binding energy shifts [51,52] -intramolecular charge transfer between oxygen or sulfur lone pair and an adjacent orbital, both within the reaction active center [53,54] -the so-called quantum chemical topology descriptors constructed using properties of the bond critical points, BCP, where BCP is the saddle points in the electron density [55][56][57][58] -charge of the reaction active site [42,47,59,60] -energy of p-conjugation [61] -charge of the substituent active space [58,[62][63][64].…”

Effects of structural variations on the hydrogen bond pairing between adenine derivatives and thymine

“…Since the atoms in the vicinity of N1 and N6 atoms in adenine remain the same throughout the investigated series (Scheme 1), it can be considered that the shifts of V Y (Y = N1, H6) upon the distant structural variations (at position C8) are dominated by electron density variations near atoms Y. Numerous successful application of EPN as a reactivity index for hydrogen bonding and chemical reactivity confirm the credibility of this hypothesis [53][54][55][56][57][58][59][60][61][62][63][64][65]. Figure 1 illustrates key geometrical parameters of some optimized complexes.…”

“…Z A is the charge of nucleus A at position R A , and ρ(r) is the electron density func-tion. Following the original findings [53][54][55][56][57] that EPN values define quantitatively the ability of molecules to form hydrogen bonds, the EPN index was extensively applied in describing both hydrogen bonding and chemical reactivity of various molecular systems [58][59][60][61][62][63][64][65]. In a recent review, we surveyed the application of EPN in quantifying various molecular properties of aromatic systems [62].…”

Selective acetylation of primary amino groups with phenyl acetate; simple synthesis of N,N´-diacetyl polyamines

“…Furthermore, the reactivity of phenyl acetate could be modified by varying substituents on the aromatic ring which change the electrophiicity of the carbonyl group. 18 Thus, electron-withdrawing substituents such as -Cl or -NO 2 at para-or orthopositions lead to faster reaction rates and electron-donating substituents lower rates. However, the reaction rate of unsubstituted phenyl acetate was already high enough for our purposes, and thus, we decided to evaluate its reactivity with various primary amines in acetonitrile at room temperature (Table 1).…”