ANS differential reactivity of biological hydrogen-bonded amines in aprotic solvent: experimental and theoretical study

C.E.S. ALVARO; F. BERGERO; F.M. BOLCIC; S. RAMOS; N. SBARBATI NUDELMAN

Villa Carlos Paz, Córdoba

Conferencia; 13° Conferencia Latinoamericana de Fisicoquímica Orgánica; 2015

Facultad de Ciencia Químicas - Universidad Nacional de Córdoba - INFIQC-CONICET

Aromatic Nucleophilic Substitutions (ANS) is a biological andindustrially important reaction type that can proceed via a number of different reaction mechanisms1. If ANS with aminesand substrates activated by electron withdrawing groups are carried out insolvents of low permittivity, weak non-covalent interactions such as hydrogenbonding (H-bonding) play a significant role and a third order in amine kineticlaw is often determined.Continuing ourstudies of ANS reactions in aprotic solvents, in this work we report kineticresults using mono- and polyfunctional biological amines, that werepurposefully designed due to their special structures that allows the formation ofintra- or intermolecular homo-dimers. Kinetic studies were performed in toluenewith 2,4-dinitrochlorobenzene (DNClB) with the polyfunctional amines: 2-amino-5-guanidinopentanoic acid(arginine), (4-aminobutyl)guanidine (agmatine), 2,6-diamino-hexanoic acid (lysine)  and a monofunctional amine: 3,4-dihydroxyphenethylamine (dopamine) and comparewith the results obtained with 2-guanidinobenzimidazole (2-GB)2 and 2-(1H-imidazole-4-yl)ethanamine(histamine)2, respectively, amines that because of its rigidgeometry molecular form intramolecular H-bond2. For arginine, agmatine, lysine anddopamine the second-order rate coefficients, kA, were found to increase rapidly with amineconcentration, [B]; these results are consistent with a third-order in amineterm in the kinetic law. For histamine and 2-GB the second-order ratecoefficient increases steadily with [B], the plots of kA vs [B] arestraight lines with a null intercept2.Toprovide valuable insight into the predominant type of H-bond formed weperformed ab initio Density Funcional Theory calculations on the abovementioned amines determining the optimal geometry and energy formation invacuum and toluene for monomers and dimers at the B3LYP/6-31++G(d) level, and weimplemented a methodology to simultaneously evaluate Counterpoise correctionsto account for basis set superposition errors (BSSE) and solvent effects3.Theoretical results show that dimerization energy decreases in order: arginine >>lysine >> dopamine > agmatine. Whereas arginine, lysine and dopaminealso form intermolecular oxygen H-bonds, their dimers are more stable thanintermolecular dimers formed with amines that have no oxygen in its structure. Experimental data and therelative stability of dimers versus monomers are discussed in light of thecurrent study.References1-F. Terrier, ?Modern Nucleophilic AromaticSubstitution?, (Hardcover), first ed. Wiley-VCH Verlag GmbH & Co, 2013, 488 pp.2-C. E. S. Alvaro, N. S. Nudelman, Phys. Chem., 2013, 3 (2), 39-47.3- F. Bergero, C. E. S. Alvaro, N. S.Nudelman, S. Ramos. J. Argent. Chem. Soc. 2013,100, 35-47