7291-22-7Relevant articles and documents
Lee, Kenneth E.,Gladysz, J. A.
, p. 2209 - 2212 (1988)
Deuterium Nuclear Magnetic Resonance Spectroscopy. II. Distribution of Deuterium in some Labelled Nitrogen Heterocyclic Compounds
Al-Rawi, Jasim M. A.,Behnam, George Q.,Taha, Nihad I.
, p. 204 - 206 (1981)
Pyridine, methylpyridines, quinoline and isoquinoline have been labelled with deuterium using pre-reduced platinum dioxide (PtO2*2H2O) and heavy water.Their 2H chemical shifts from monodeuteriated TMS have been assigned.The extent of the labelling has been determined directly by 2H NMR spectroscopy.
Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals
Chaudret, Bruno,Daniel-Bertrand, Marion,Derdau, Volker,Fazzini, Pier-Francesco,Feuillastre, Sophie,Garcia-Argote, Sébastien,Mustieles Marin, Irene,Palazzolo, Alberto,Pieters, Grégory,Tricard, Simon
supporting information, p. 21114 - 21120 (2020/09/21)
Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late-stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air-stable iridium precatalyst [Ir(COD)(OMe)]2 is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa-/thia-zoles, thiophene, but also electron-rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.
Kinetics, mechanism, and thermochemistry of the gas-phase reaction of atomic chlorine with pyridine
Zhao,Huskey,Olsen,Nicovich,McKee,Wine
, p. 4383 - 4394 (2008/09/20)
A laser flash photolysis-resonance fluorescence technique has been employed to study the kinetics of the reaction of atomic chlorine with pyridine (C 5H5N) as a function of temperature (215-435 K) and pressure (25-250 Torr) in nitrogen bath gas. At T ≥ 299 K, measured rate coefficients are pressure independent and a significant H/D kinetic isotope effect is observed, suggesting that hydrogen abstraction is the dominant reaction pathway. The following Arrhenius expression adequately describes all kinetic data at 299-435 K for C5H5N: k1a = (2.08 ± 0.47) × 10-11 exp[-(1410 ± 80)/T] cm 3 molecule-1 s-1 (uncertainties are 2σ, precision only). At 216 K ≤ T ≤ 270 K, measured rate coefficients are pressure dependent and are much faster than computed from the above Arrhenius expression for the H-abstraction pathway, suggesting that the dominant reaction pathway at low temperature is formation of a stable adduct. Over the ranges of temperature, pressure, and pyridine concentration investigated, the adduct undergoes dissociation on the time scale of our experiments (10 -5-10-2 s) and establishes an equilibrium with Cl and pyridine. Equilibrium constants for adduct formation and dissociation are determined from the forward and reverse rate coefficients. Second- and third-law analyses of the equilibrium data lead to the following thermochemical parameters for the addition reaction: ΔrH°298 = -47.2 ± 2.8 kJ mol-1, ΔrH°0 = -46.7 ± 3.2 kJ mol-1, and ΔrS° 298 = -98.7 ± 6.5 J mol-1 K-1. The enthalpy changes derived from our data are in good agreement with ab initio calculations reported in the literature (which suggest that the adduct structure is planar and involves formation of an N-Cl σ-bond). In conjunction with the well-known heats of formation of atomic chlorine and pyridine, the above ΔrH values lead to the following heats of formation for C 5H5N-Cl at 298 K and 0 K: ΔfH° 298 = 216.0 ± 4.1 kJ mol-1, Δ fH°0 = 233.4 ± 4.6 kJ mol-1. Addition of Cl to pyridine could be an important atmospheric loss process for pyridine if the C5H5N-Cl product is chemically degraded by processes that do not regenerate pyridine with high yield. the Owner Societies.
Experimental and theoretical study of the secondary equilibrium isotope effect (SEIE) in the proton transfer between the pyridinium-d5 cation and pyridine
Munoz-Caro,Nino,Davalos,Quintanilla,Abboud
, p. 6160 - 6167 (2007/10/03)
In this work we present an experimental and theoretical study of the proton transfer from the pyridinium-d5 cation to pyridine. FT-ICR measurements yield, at 331 K, an equilibrium constant K = 0.809 (Δ rGmo = 0.58 kJ mol-1) for the process, favoring the pyridine form. The structural and bonding changes on protonation of pyridine are analyzed by applying the atoms in molecules theory. As a consequence of electronic density redistribution, we found that on protonation the CN and the CC bonds placed farther from the nitrogen weaken. In addition, the CH and the CC bonds closer to the nitrogen increase their strength. Thermostatistical computation of the equilibrium constant from data obtained at the B3LYP/cc-pVTZ level, within the harmonic approximation, predicts a value of 0.827 (ΔrGmo, value of 0.52 kJ mol-1), in good agreement with the 0.809 ± 0.027 experimental result for a 99.9% confidence level. A simple statistical mechanical model intended to apply under conditions close to the present ones is developed. The model allows for a fine-tuning of the thermodynamic state functions for the equilibrium. This model shows that rather than by translational and rotational variations, the reaction is driven by the changes in zero point energies and in the density of vibrational states. In addition, theoretical analysis of the enthalpic and entropic contributions shows that the ΔrGmo value is determined by the enthalpic part. It is also predicted that the ΔrG mo value decreases with temperature. We found that this effect is due to a higher density of vibrational states in the pyridine-d 5 form. A new model is developed to correct the vibrational partition function for anharmonicity. This model shows that correction for anharmonicity in the low-frequency modes reduces significantly the difference between calculated and experimental K values.
