- Deuterium Nuclear Magnetic Resonance Spectroscopy. II. Distribution of Deuterium in some Labelled Nitrogen Heterocyclic Compounds
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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.
- Al-Rawi, Jasim M. A.,Behnam, George Q.,Taha, Nihad I.
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- Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals
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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.
- Chaudret, Bruno,Daniel-Bertrand, Marion,Derdau, Volker,Fazzini, Pier-Francesco,Feuillastre, Sophie,Garcia-Argote, Sébastien,Mustieles Marin, Irene,Palazzolo, Alberto,Pieters, Grégory,Tricard, Simon
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supporting information
p. 21114 - 21120
(2020/09/21)
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- Iridium Hydride Complexes with Cyclohexyl-Based Pincer Ligands: Fluxionality and Deuterium Exchange
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Two hydride compounds with aliphatic pincer ligands, (PCyP)IrH2 (PCyP = {cis-1,3-bis[(di-tert-butylphosphino)methyl]cyclohexane}- (1) and (PCyP)IrH4 (2), have been studied, with emphasis on features where such systems differ from arene-based analogues. Both compounds reveal relatively rapid exchange between α-C-H and Ir-H, which can occur via formation of carbene or through demetalation, with nearly equal barriers. This observation is confirmed by deuterium incorporation into the α-C-H position. Complex 1 can reversibly add an N2 molecule, which competes with the α-agostic bond for a coordination site at iridium. The hydrogen binding mode in tetrahydride 2 is discussed on the basis of NMR and IR spectra, as well as DFT calculations. While the interpretation of the data is somewhat ambiguous, the best model seems to be a tetrahydride with minor contribution from a dihydrido-dihydrogen complex. In addition, the catalytic activity of 1 in deuterium exchange using benzene-d6 as a deuterium source is presented.
- Polukeev, Alexey V.,Marcos, Rocío,Ahlquist, M?rten S. G.,Wendt, Ola F.
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p. 2600 - 2608
(2016/09/04)
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- Kinetics, mechanism, and thermochemistry of the gas-phase reaction of atomic chlorine with pyridine
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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.
- Zhao,Huskey,Olsen,Nicovich,McKee,Wine
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p. 4383 - 4394
(2008/09/20)
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- General method of obtaining deuterium-labeled heterocyclic compounds using neutral D2O with heterogeneous Pd/C
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A protocol of a versatile H-D exchange reaction of heterocyclic compounds catalyzed by heterogeneous Pd/C in D2O is described. The reaction of various nitrogen-containing heterocycles with 10% Pd/C (10 wt % of the substrate) under hydrogen atmosphere in D2O as a deuterium source at 110-180 °C for 24 h afforded the corresponding deuterated compounds with satisfactory efficiency of deuteration in moderate to excellent isolated yields. Furthermore, the Pd/C-H2-D2O system can be extended to the direct deuteration of biologically active compounds such as sulfamethazine, which is used as a synthetic antibacterial drug for fat stocks and would be applied as a general method for the preparation of the standard materials for the analysis of residual chemicals in foods and so on.
- Esaki, Hiroyoshi,Ito, Nobuhiro,Sakai, Shino,Maegawa, Tomohiro,Monguchi, Yasunari,Sajiki, Hironao
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p. 10954 - 10961
(2007/10/03)
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- Experimental and theoretical study of the secondary equilibrium isotope effect (SEIE) in the proton transfer between the pyridinium-d5 cation and pyridine
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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.
- Munoz-Caro,Nino,Davalos,Quintanilla,Abboud
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p. 6160 - 6167
(2007/10/03)
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- Can transacylation reactions occur via SN2 pathways in the gas phase? Insights via ion-molecule reactions of N-acylpyridinium ions and ab initio calculations
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(equation presented) The gas-phase identity exchange reactions of N-acylpyridinium ions with pyridine have been examined experimentally in an ion trap mass spectrometer through the use of isotope labeling experiments. The nature of the acyl group plays a crucial role, with the bimolecular rates following the order acetyl > benzoyl > N,N-dimethylaminocarbamyl. The experimental results correlate with ab initio calculations on the simple model system RC(O)NH3+ + NH3, which also demonstrates that these are SN2 like processes.
- O'Hair, Richard A. J.,Androutsopoulos
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p. 2567 - 2570
(2007/10/03)
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- Protonation Dynamics of 2(μ-CO)(μ-C=CH2) and Decomposition Processes for 2(μ-CO)(μ-C=CH2)H(+) in the Gas Phase
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The proton affinity (PA) and site of protonation of 2(μ-CO)(μ-C=H2) (2), as well as the decomposition processes for 2(μ-CO)(μ-C=CH2)H(+) (7), are studied in the gas phase by using Fourier transform mass spectrometry (FTMS).The
- Jacobson, D. B.
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p. 1626 - 1634
(2007/10/02)
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- Protonium-deuterium exchange of substituted pyridines in neutral D2O at elevated temperatures
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H-D exchange of a series of pyridines 1-15, 10H-pyridinobenzothiazine (16), phenothiazine (17), and aniline has been carried out in neutral D2O at elevated temperatures.The substrates undergo selective exchange and are generally isolated in good yield.Cyanopyridines 4, 5 and 6 hydrolyze readily in D2O at elevated temperatures, and the resultant carboxylic acids decarboxylate.This reaction provides a convenient one-step route to selectively labelled pyridines.Possible mechanisms of exchange are presented.Key words: protium-deuterium exchange, substituted pyridines, temperature effect
- Werstiuk, Henry Nick,Ju, Chen
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