Pd0‐Catalyzed Intramolecular α‐Arylation of Sulfones: Domino Reactions in the Synthesis of Functionalized Tetrahydroisoquinolines

A new strategy for the synthesis of tetrahydroisoquinolines based on the Pd⁰‐catalyzed intramolecular α‐arylation of sulfones is reported. The combination of this Pd‐catalyzed reaction with intermolecular Michael and aza‐Michael reactions allows the development of two‐ and three‐step domino processes to synthesize diversely functionalized scaffolds from readily available starting materials.     

Calculation of Franck-Condon factors including anharmonicity: simulation of the C2H4+X2B3u<--C2H4X1A(g) band in the photoelectron spectrum of ethylene

Our new simple method for calculating accurate Franck-Condon factors including nondiagonal (i.e., mode-mode) anharmonic coupling is used to simulate the C2H4+X2B3u<--C2H4X1A(g) band in the photoelectron spectrum. An improved vibrational basis set truncation algorithm, which permits very efficient computations, is employed. Because the torsional mode is highly anharmonic it is separated from the other modes and treated exactly. All other modes are treated through the second-order perturbation theory. The perturbation-theory corrections are significant and lead to a good agreement with experiment, although the separability assumption for torsion causes the C2D4 results to be not as good as those for C2H4. A variational formulation to overcome this circumstance, and deal with large anharmonicities in general, is suggested.     

Reactivity of pyrrole pigments,part 15: On the oxidation of bilirubins and biliverdins

Summary Characteristic oxidation reactions of bilin-1,19-diones (biliverdins) and biladien-ac-1,19-diones (bilirubins) were reinvestigated. These include bromine and iodine oxidation of biliverdin IX, bilirubin IX and their Zn(II) complexes, the reaction described by Siedel (1941) of mesobilirubin XIII dimethyl ester with nitric acid (Gmelin reaction) and Smith's oxidation (1977) of etiobiliverdin IV using Tl triacetate and Pb tetra-acetate. For some of these reaction products new structures were assigned on the basis of their spectrometric data. These structures agreed with the expected reactivity pattern of biliverdins and bilirubins.

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Reaktivität von Pyrrolpigmenten, 15 Mitt.: Über die Oxidation von Bilirubinen und Biliverdinen

Zusammenfassung Einige bekannte Oxydationen von Bilin-1,19-dionen (Biliverdinen) und Biladien-ac-dionen (Bilirubinen) wurden neuerlich untersucht, und zwar die Brom- und Jodoxydation von Biliverdin IX und Bilirubin IX sowie der entsprechenden Zn(II)-Komplexe, die Reaktion des Dimethylesters von Mesobilirubin XIII mit HNO₃ (Gmelinreaktion; Siedel 1941) und Smith's Oxydation von Etiobiliverdin IV mit Thaliumtriacetat und Bleitetraacetat. Für einige Reaktionsprodukte wurden aufgrund spektroskopischer Daten neue Strukturen-konsistent mit dem bekannten Reaktionsverhalten von Biliverdinen und Bilirubinen-formuliert.

     

Oxidative addition of the ethane C-C bond to Pd. An ab initio benchmark and DFT validation study

We have computed a state-of-the-art benchmark potential energy surface (PES) for the archetypal oxidative addition of the ethane C-C bond to the palladium atom and have used this to evaluate the performance of 24 popular density functionals, covering LDA, GGA, meta-GGA, and hybrid density functionals, for describing this reaction. The ab initio benchmark is obtained by exploring the PES using a hierarchical series of ab initio methods [HF, MP2, CCSD, CCSD(T)] in combination with a hierarchical series of five Gaussian-type basis sets, up to g polarization. Relativistic effects are taken into account either through a relativistic effective core potential for palladium or through a full four-component all-electron approach. Our best estimate of kinetic and thermodynamic parameters is -10.8 (-11.3) kcal/mol for the formation of the reactant complex, 19.4 (17.1) kcal/mol for the activation energy relative to the separate reactants, and -4.5 (-6.8) kcal/mol for the reaction energy (zero-point vibrational energy-corrected values in parentheses). Our work highlights the importance of sufficient higher angular momentum polarization functions for correctly describing metal-d-electron correlation. Best overall agreement with our ab initio benchmark is obtained by functionals from all three categories, GGA, meta-GGA, and hybrid DFT, with mean absolute errors of 1.5 to 2.5 kcal/mol and errors in activation energies ranging from -0.2 to -3.2 kcal/mol. Interestingly, the well-known BLYP functional compares very reasonably with a slight underestimation of the overall barrier by -0.9 kcal/mol. For comparison, with B3LYP we arrive at an overestimation of the overall barrier by 5.8 kcal/mol. On the other hand, B3LYP performs excellently for the central barrier (i.e., relative to the reactant complex) which it underestimates by only -0.1 kcal/mol.     

The 1,2,4-triazolyl cation: thermolytic and photolytic studies

The generation of the 1,2,4-triazolyl cation (1) has been attempted by the thermolysis and photolysis of 1-(1,2,4-triazol-4-yl)-2,4,6-trimethylpyridinium tetrafluoroborate (2) and the thermolysis of 1- and 4-diazonium-1,2,4-triazoles, using mainly mesitylene as the trapping agent. Thermolysis of 2 gave mostly 1,2,4-triazole, together with 3-(1,2,4-triazol-4-yl)-2,4,6-trimethylpyridine, 4-(1,2,4-triazol-4-ylmethyl)-2,6-dimethylpyridine, and 4-(2,4,6-trimethylbenzyl)-2,6-dimethylpyridine. Thermolysis of each of the diazonium salts in the presence of mesitylene again gave mainly triazole together with very low yields of 1-(1,2,4-triazol-1-yl)-2,4,6-trimethylbenzene and the corresponding -4-yl isomer in about the same ratio. On the other hand, photolysis of 2 in mesitylene gave mainly 1-(1,2,4-triazol-1-yl)-2,4,6-trimethylbenzene. A photoinduced electron transfer from mesitylene to 2 has been observed and preliminary laser flash photolyses of 2 and the corresponding 2,4,6-triphenylpyridinium salt have been carried out. The observed transients are explained as arising from the first excited states of the pyridinium salts rather than from 1. Ab initio MO calculations are reported and indicate that the predicted electronic ground-state of the triazolyl cation is a triplet state of B1 symmetry with five pi electrons, which corresponds to a diradical cation (1c). Possible mechanisms for the formation of the various products are proposed.     

A common method for the determination of several calcium channel blockers using an HPLC system with ultraviolet detection

We report a common HPLC method for the single or simultaneous determination of four calcium channel blockers (CCB), namely diltiazem (DTZ), verapamil (VER), nifedipine (NIF) and nitrendipine (NIT) and their active metabolites demetildiltiazem and deacetildiltiazem (MA and M1), norverapamil (NOR), and dehydronifedipine (DHN). DHN was first synthesised in our laboratory and different pH values of the mobil phase were subsequently prepared and tested for chromatographic separation. The detection system and the environmental light conditions were optimised. The best separations of all analytes were obtained using a C₁₈ column and a mobile phase of methanol, 0.04 M ammonium acetate, acetonitrile and triethylamine (2:2:1:0.04 v/v). Quantitation was performed using imipramine (IMI) as the internal standard. For DTZ and its metabolites (M1 and MA), the wavelength chosen was 237 nm; for VER and its metabolite NOR, it was 210 nm; and, finally for NIF and its metabolite DHN and NIT it was 216 nm. When a simultaneous analysis was carried out the wavelength was of 230 nm. The optimum pH were 7.90 and 7.10 when the separation of NIT and DTZ or VER and NIF were carried out, respectively, and 7.90 when a simultaneous separation was carried out. The detection limit of the assay was less than 8 ng ml⁻¹ for all compounds, with coefficients of variation less than 7% (for inter- and intra-day) over the concentration range of 1–1000 ng ml⁻¹. The retention times were less than 11 min. When NIF or NIT were studied, it was necessary to use a sodium vapour lamp in order to avoid the photodegradation which takes place under daylight conditions.