Quantitative Estimation of the Hydrogen-Atom-Donating Ability of 4-Substituted Hantzsch Ester Radical Cations

Abstract

The purpose of this study is to investigate thermodynamic and kinetic properties on the hydrogen-atom-donating ability of 4-substituted Hantzsch ester radical cations (XRH •+ ), which are excellent NADH coenzyme models. Gibbs free energy changes and activation free energies of 17 XRH •+ releasing H • [denoted as Δ G HD o (XRH •+ ) and Δ G HD ≠ (XRH •+ )] were calculated using density functional theory (DFT) and compared with that of Hantzsch ester (HEH 2 ) and NADH. Δ G HD o (XRH •+ ) range from 19.35 to 31.25 kcal/mol, significantly lower than that of common antioxidants (such as ascorbic acid, BHT, the NADH coenzyme, and so forth). Δ G HD ≠ (XRH •+ ) range from 29.81 to 39.00 kcal/mol, indicating that XRH •+ spontaneously releasing H • are extremely slow unless catalysts or active intermediate radicals exist. According to the computed data, it can be inferred that the Gibbs free energies and activation free energies of the core 1,4-dihydropyridine radical cation structure (DPH •+ ) releasing H • [Δ G HD o (DPH •+ ) and Δ G HD ≠ (DPH •+ )] should be 19–32 kcal/mol and 29–39 kcal/mol in acetonitrile, respectively. The correlations between the thermodynamic driving force [Δ G HD o (XRH •+ )] and the activation free energy [Δ G HD ≠ (XRH •+ )] are also explored. Gibbs free energy is the important and decisive parameter, and Δ G HD ≠ (XRH •+ ) increases in company with the increase of Δ G HD o (XRH •+ ), but no simple linear correlations are found. Even though all XRH •+ are judged as excellent antioxidants from the thermodynamic view, the computed data indicate that whether XRH •+ is an excellent antioxidant in reaction is decided by the R substituents in 4-position. XRH •+ with nonaromatic substituents tend to release R • instead of H • to quench radicals. XRH •+ with aromatic substituents tend to release H • and be used as antioxidants, but not all aromatic substituted Hantzsch esters are excellent antioxidants.

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics

“…As can be seen from Scheme , the oxidation potentials of common organic single-electron reductants [ E ox o (XH 2 )] span a very large range about 2.777 V [∼64.0 kcal/mol] from −2.298 V [ E ox o (H • )] to 0.479 V [ E ox o (HEH 2 )] . Since HEH 2 has always been used as a classical electron donor in chemical reactions, especially the photocatalytic reaction, − HEH 2 is assigned as a medium strong electron donor. Compared with common organic single-electron reductants (−2.298 to 0.479 V), all YH – (−0.350 to −0.134 V) with lower oxidation potentials have strong electron-donating abilities, even better than HEH 2 (0.479 V) and BNAH (0.219 V) …”

Thermodynamics of the elementary steps of organic hydride chemistry determined in acetonitrile and their applications

“…In recent years, computational chemistry has developed rapidly to clarify reaction mechanisms, design catalysts or reagents and reveal structure–activity relationships by energy or interaction calculations. 132–137 Compared with the experimental method, computational chemistry has unique advantages in thermodynamic examination including easy operation, running reliability, good economy and high efficiency. 132–134 Given that the Δ H H − D (XH 2 ) values of many organic hydrides have been measured in acetonitrile using the experimental method to date, 26–50 without a doubt, the thermodynamic database is a foundation of bond energy calculation, which can guide chemists to build and optimize new computation models for accurate thermodynamic results.…”

Theoretical study for evaluating and discovering organic hydride compounds as novel trifluoromethylation reagents

“…[22][23][24] 4-Substituted Hantzsch esters (XRH) have typical 1,4-dihydropyridine core structures, which also are classical NADH models and important organic hydride compounds (Scheme 2). 25,26 In organic synthesis, XRHs are used as alkylation reagents which are activated to give the key active intermediate XRH •+ , and the followed key elementary step is the C-C bond breakage of XRH •+ to give R • . [27][28][29][30] A variety of 4-substi-tuted Hantzsch esters (XRH) with different R groups have been investigated in detail for alkylation reactions, such as aminealkyl • , alkyl • , RCO • , etc., as well as the alkylation substrates including olefins, alkynes, halohydrocarbons, imines, aldehydes/ketones, aromatics, etc.…”

“…Besides, XHs also have many intrinsic advantages such as high stability, good solubility in organic solvents, moderate oxidation potential (which facilitates the activation), and convenient chiral modification. 26,31 Therefore, XH should have the potential to become novel trifluoromethylation reagents and deserve further investigation.…”