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 amines and substrates activated by electron with drawing groups are carried out insolvents of low permittivity, weak non-covalent interactions such as hydrogen bonding (H-bonding) play a significant role and a third order in amine kineticlaw is often determined.Continuing our studies of ANS reactions in aprotic solvents, in this work we report kinetic results using mono- and polyfunctional biological amines, that were purpose fully designed due to their special structures that allows the formation of intra- or intermolecular homo-dimers. Kinetic studies were performed in toluene with 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 compare with the results obtained with 2-guanidinobenzimidazole (2-GB)2 and 2-(1H-imidazole-4-yl)ethanamine(histamine)2, respectively, amines that because of its rigid geometry molecular form intramolecular H-bond2. For arginine, agmatine, lysine and dopamine the second-order rate coefficients, kA, were found to increase rapidly with amine concentration, [B]; these results are consistent with a third-order in amine term in the kinetic law. For histamine and 2-GB the second-order ratecoefficient increases steadily with [B], the plots of kA vs [B] are straight lines with a null intercept2.To provide valuable insight into the predominant type of H-bond formed we performed ab initio Density Funcional Theory calculations on the above mentioned 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 corrections to 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 dopamine also form intermolecular oxygen H-bonds, their dimers are more stable than intermolecular dimers formed with amines that have no oxygen in its structure. Experimental data and the relative stability of dimers versus monomers are discussed in light of the current study.References1- F. Terrier, "Modern Nucleophilic Aromatic Substitution", (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