C–N Coupling of 1,2‐Dihydro‐2,2,4‐trimethylquinoline Derivatives via a Silver(I)‐Catalyzed Direct Functionalization of a C–H Bond

Two C,N‐linked dimeric 1,2‐dihydro‐2,2,4‐trimethylquinolines, namely 6‐chloro‐1‐(6‐chloro‐1,2‐dihydro‐2,2,4‐trimethylquinolin‐8‐yl)‐1,2‐dihydro‐2,2,4‐trimethylquinoline ( 3a ) and 6‐ethoxy‐1‐(6‐ethoxy‐1,2‐dihydro‐2,2,4‐trimethylquinolin‐8‐yl)‐1,2‐dihydro‐2,2,4‐trimethylquinoline ( 3b ), have been prepared through a silver‐catalyzed dimerization of their corresponding monomers. The effect of different silver salts on the reaction was also investigated, and the obtained results suggest that silver ions effectively catalyzed the formation of a C–N bond under these mild conditions. This represents one of the rare reports on the silver‐catalyzed C–N bond formation through a coupling of a secondary amine and an activated aromatic system, via a direct C–H functionalization. Theoretical studies showed that these dimeric structures favor a conformation in which their monomer units are oriented approximately perpendicular to each other, with an intramolecular hydrogen bond (N–H distance of 2.33 Å) forming between the hydrogen atom of the amine in one of the monomeric units and the tertiary nitrogen atom of the other one.     

N-terminal derivatization and fragmentation of neutral peptides via ion--molecule reactions with acylium ions: toward gas-phase Edman degradation?

The gas-phase ion-molecule reactions of neutral alanylglycine have been examined with various mass-selected acylium ions RCO(+) (R= CH(3), CD(3), C(6)H(5), C(6)F(5) and (CH(3))( 2)N), as well as the transacylation reagent O-benzoylbenzophenone in a Fourier transform ion cyclotron resonance mass spectrometer. Reactions of the gaseous dipeptide with acylium ions trapped in the ICR cell result in the formation of energized [M + RCO](+) adduct ions that fragment to yield N-terminal b-type and C-terminal y-type product ions, including a modified b(1) ion which is typically not observed in the fragmentation of protonated peptides. Judicious choice of the acylium ion employed allows some control over the product ion types that are observed (i.e., b versus y ions). The product ion distributions from these ion--molecule reactions are similar to those obtained by collision-activated dissociation in a triple quadrupole mass spectrometer of the authentic N-acylated alanylglycine derivatives. These data indicate that derivatization of the peptide in the gas-phase occurs at the N-terminal amine. Ab initio molecular orbital calculations, performed to estimate the thermochemistry of the steps associated with adduct formation as well as product ion formation, indicate that (i) the initially formed adduct is energized and hence likely to rapidly undergo fragmentation, and (ii) the likelihood for the formation of modified b(1) ions in preference to y(1) ions is dependent on the R substituent of the acylium ion. The reaction of the tetrapeptide valine--alanine--alanine--phenylalanine with the benzoyl cation was also found to yield a number of product ions, including a modified b(1) ion. This result suggests that the new experimental approach described here may provide a tool to address one of the major limitations associated with traditional mass spectrometric peptide sequencing approaches, that is, determination of the identity and order of the two N-terminal amino acids. Analogies are made between the reactions observed here and the derivatization and N-terminal cleavage reactions employed in the condensed-phase Edman degradation method.     

Extradiol oxidative cleavage of catechols by ferrous and ferric complexes of 1,4,7-triazacyclononane: insight into the mechanism of the extradiol catechol dioxygenases.

The major oxygenation product of catechol by dioxygen in the presence of FeCl(2) or FeCl(3), 1,4,7-triazacyclononane (TACN), and pyridine in methanol is the extradiol cleavage product 2-hydroxymuconic semi-aldehyde methyl ester (Lin, G.; Reid, G.; Bugg, T. D. H. J. Chem. Soc. Chem. Commun. 2000, 1119--1120). Under these conditions, extradiol cleavage of a range of 3- and 4-substituted catechols with electron-donating substituents is observed. The reaction shows a preference in selectivity and rate for iron(II) rather than iron(III) for the extradiol cleavage, which parallels the selectivity of the extradiol dioxygenase family. The reaction also shows a high selectivity for the macrocyclic ligand, TACN, over a range of other nitrogen- and oxygen-containing macrocycles. Reaction of anaerobically prepared iron-TACN complexes with dioxygen gave the same product as monitored by UV/vis spectroscopy. KO(2) is able to oxidize catechols with both electron-donating and electron-withdrawing substituents, implying a different mechanism for extradiol cleavage. Saturation kinetics were observed for catechols, which fit the Michaelis--Menten equation to give k(cat)(app) = 4.8 x 10(-3) s(-1) for 3-(2',3'-dihydroxyphenyl)propionic acid. The reaction was also found to proceed using monosodium catecholate in the absence of pyridine, but with different product ratios, giving insight into the acid/base chemistry of extradiol cleavage. In particular, extradiol cleavage in the presence of iron(II) shows a requirement for a proton donor, implying a role for an acidic group in the extradiol dioxygenase active site.     

All Titration Indicators are Not Created Equal—A Lecture Demonstration

This demonstration provides a simple method for emphasizing the importance of indicator selection to determine the end point of a titration involving the common weak base household ammonia. By using phenolphthalein and methyl red as the indicators in the titration of two samples of aqueous household ammonia with hydrochloric acid, students can discover that there is a difference between the two apparent termination points. There is clearly a visible difference in the sharpness of the color changes that take place, and the presence of ammonia at the apparent phenolphthalein endpoint is also detected by olfactory means. By showing the different termination ranges on a titration curve, the students can readily see that phenolphthalein does a poor job of showing the proper termination point,; whereas methyl red shows the proper titration end point.     

FTIR studies of intermolecular hydrogen bonding in halogenated ethanols

The effect of halogen substitution on intermolecular hydrogen-bonding in ethanol is studied. Specifically, Fourier-transform infrared (FTIR) spectra of ethanol, 2,2,2-trifluoroethanol (TFE), and 2,2,2-trichloroethanol dissolved in carbon tetrachloride are reported as a function of temperature and concentration. The spectral intensities corresponding to monomer, dimer, and multimer formation are used to determine the effect of halogen substitution on intermolecular hydrogen-bonding. The enthalpy for dimerization was found to evolve from -4.2+/-0.3 kcal/mol in ethanol to -6.8+/-1.0 kcal/mol in TFE. An opposite trend was observed for multimer formation with enthalpies of -3.7+/-0.5 in ethanol and -2.1+/-1.4 kcal/mol in TFE. The majority of this evolution is assigned to the ability of ethanols to form intramolecular hydrogen bonds involving the hydoxyl proton and the halogen substituents.     

Crystal structures of two isomeric oximes. (EE)-2-methyl-3-phenyl-3-thiocyanatopropenaldoxime and (Z)-5-methyl-6-phenyl-1,3-thiazin-2-one oxime

The crystal structure of two isomeric oximes, C₁₁N₁₀N₂OS have been studied by X-ray diffraction. The open-chain thiocyanato derivative is somewhat'less dense and crystallizes with the orthorhombic space group Pbcn;a,b,c=18.718(1), 10.601(3), 11.528(1) Å,Z=8. The heterocyclic isomer occurs as pseudo-orthorhombic (Cmma)twinned crystals of space group P2₁/n, a, b, c, =12.11(1), 7.46(1), 12.12(1) Å, 100.09(1)^o,Z=4. Twinning occurs as a result of the near-equality of the monoclinica andc cell constants.     

Mu+H2 and Mu+D2 reaction kinetics from 480 To 675 K

This paper reports preliminary new measurements of the thermal reaction rate constants of muonium (Mu) with hydrogen and deuterium gases in the range 480–675 K. From Arrhenius plots of the measured reaction rate constants new values of the pre-exponential factors log₁₀ (A) and activation energies E_a have been determined for these reactions, representing a significant improvement over earlier results.     

Radiofluorination of a Pre‐formed Gallium(III) Aza‐macrocyclic Complex: Towards Next‐Generation Positron Emission Tomography (PET) Imaging Agents

As part of a study to investigate the factors influencing the development of new, more effective metal‐complex‐based positron emission tomography (PET) imaging agents, the distorted octahedral complex, [GaCl(L)]?2 H₂O has been prepared by reaction of 1‐benzyl‐1,4,7‐triazacyclononane‐4,7‐dicarboxylic acid hydrochloride (H₂L?HCl) with Ga(NO₃)₃?9 H₂O, which is a convenient source of Ga^III for reactions in water. Spectroscopic and crystallographic data for [GaCl(L)]?2 H₂O are described, together with the crystal structure of [GaCl(L)]?MeCN. Fluorination of this complex by Cl^?/F^? exchange was achieved in high yield by treatment with KF in water at room temperature over 90 minutes, although the reaction was complete in approximately 30 minutes if heated to 80 °C, giving [GaF(L)]?2 H₂O in good yield. The same complex was obtained by hydrothermal synthesis from GaF₃?3 H₂O and Li₂L, and has been characterised by single‐crystal X‐ray analysis, IR, ¹H and ¹⁹F{¹H} NMR spectroscopy and ESI⁺ MS. Radiofluorination of the pre‐formed [GaCl(L)]?2 H₂O has been demonstrated on a 210 nanomolar scale in aqueous NaOAc at pH 4 by using carrier‐free ¹⁸F^?, leading to 60–70 % ¹⁸F‐incorporation after heating to 80 °C for 30 minutes. The resulting radioproduct was purified easily by using a solid‐phase extraction (SPE) cartridge, leading to 98–99 % radiochemical purity. The [Ga¹⁸F(L)] is stable for at least 90 minutes in 10 % EtOH/NaOAc solution at pH 6, but defluorinates over this time scale at pH of approximately 7.5 in phosphate buffered saline (PBS) or human serum albumin (HSA). The subtle role of the Group 13 metal ion and co‐ligand donor set in influencing the pH dependence of this system is discussed in the context of developing potential new imaging agents for PET.     

Quantum dynamics in ultracold atomic physics

We review recent developments in the theory of quantum dynamics in ultracold atomic physics, including exact techniques and methods based on phase-space mappings that are applicable when the complexity becomes exponentially large. Phase-space representations include the truncated Wigner, positive-P and general Gaussian operator representations which can treat both bosons and fermions. These phase-space methods include both traditional approaches using a phase-space of classical dimension, and more recent methods that use a non-classical phase-space of increased dimensionality. Examples used include quantum Einstein-Podolsky-Rosen (EPR) entanglement of a four-mode BEC, time-reversal tests of dephasing in single-mode traps, BEC quantum collisions with up to 106 modes and 105 interacting particles, quantum interferometry in a multi-mode trap with nonlinear absorption, and the theory of quantum entropy in phase-space. We also treat the approach of variational optimization of the sampling error, giving an elementary example of a nonlinear oscillator.