Ritter-enabled catalytic asymmetric chloroamidation of olefins

Intermolecular asymmetric haloamination reactions are challenging due to the inherently high halenium affinity (HalA) of the nitrogen atom, which often leads to N-halogenated products as a kinetic trap. To circumvent this issue, acetonitrile, possessing a low HalA, was used as the nucleophile in the catalytic asymmetric Ritter-type chloroamidation of allyl-amides. This method is compatible with Z and E alkenes with both alkyl and aromatic substitution. Mild acidic workup reveals the 1,2-chloroamide products with enantiomeric excess greater than 95% for many examples. We also report the successful use of the sulfonamide chlorenium reagent dichloramine-T in this chlorenium-initiated catalytic asymmetric Ritter-type reaction. Facile modifications lead to chiral imidazoline, guanidine, and orthogonally protected 1,2,3 chiral tri-amines.

Intermolecular haloamination reactions are challenging due to the high halenium affinity of the nitrogen atom. This is circumvented by using acetonitrile as an attenuated nucleophile, resulting in an enantioselective halo-Ritter reaction.     

Synthesis of new imidazole derivatives as potential inhibitors of thromboxane synthetase

The preparation of new imidazole derivatives containing a carboxylic moiety such as succinic, adipic or benzoic into the side chain, is reported starting from the suitable imidazole intermediates.     

Spectral Properties of Effective Dynamics from Conditional Expectations

The reduction of high-dimensional systems to effective models on a smaller set of variables is an essential task in many areas of science. For stochastic dynamics governed by diffusion processes, a general procedure to find effective equations is the conditioning approach. In this paper, we are interested in the spectrum of the generator of the resulting effective dynamics, and how it compares to the spectrum of the full generator. We prove a new relative error bound in terms of the eigenfunction approximation error for reversible systems. We also present numerical examples indicating that, if Kramers–Moyal (KM) type approximations are used to compute the spectrum of the reduced generator, it seems largely insensitive to the time window used for the KM estimators. We analyze the implications of these observations for systems driven by underdamped Langevin dynamics, and show how meaningful effective dynamics can be defined in this setting.     

Iron(II) promoted direct synthesis of dibenzo[b,e]oxepin-11(6H)-one derivatives with biological activity. A short synthesis of doxepin

A novel and efficient synthesis of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular ortho-acylation from readily available 2-(phenoxymethyl)benzoic acids was developed. The method takes advantage of a newly developed cooperative system consisting of sustainable FeCl₂ and Cl₂CHOCH₃ as the key components. This methodology is compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The synthetic application of new protocol was extended to the synthesis of known tricyclic drug doxepin as well as a small library of oxepin based derivatives. For the first time, the obtained dibenzo[b,e]oxepinone derivatives were evaluated for their biological activities on the free-living nematode Caenorhabditis elegans as an effective and cost-efficient model system for anthelmintic discovery.     

The protonation thermodynamics of cyclodextrin-containing polymers for drug inclusion

A poly(amido-amine), PAA, bearing β-CD units in the side chain was synthesized by a polyaddition reaction of 1,4-bis-acryloyl-piperazine with 6-monodeoxy-6-monoamino-β-cyclodextrin (β-CD-NH₂). Unlike the simple β-CD-NH₂ with a greater basicity constant (log K = 8.60), the polymer revealed an unusual polyelectrolyte behaviour with a lower basicity constant (log K° = 6.29) of the tertiary nitrogen atom, that is strongly dependent on the degree of protonation α of the whole macromolecule. It follows the modified Henderson–Hasselbalch equation with n = 1.75, in a wide α-range. The greater (?46.1 kJ/mol) and the lower (?27.6 kJ/mol) enthalpy (ΔH°) changes of the compounds were in line with the protonation of a primary or a tertiary nitrogen atom. The calorimetric data suggested that the PAA protonation destroyed a packing structure formed by two rigid β-CD side chains interacting head-to-head. The UV spectrophotometric data showed that the PAA exhibits affinity towards the l-ascorbic acid at low pH (pH 2.46) with an isosbestic point at 241 nm and a slight blue shift of the maximum absorption of the ascorbic acid (244 nm) on PAA additions.     

Spectroelectrochemical Study of 9‐Substituted Acridines with Potential Antitumor Activity

The electrochemical and spectroelectrochemical behavior of 9‐substituted with ? CN and ? COOH acridine N‐oxides with potential antitumor activity was investigated. In SER spectra of the investigated compounds, the ring stretching vibration at 1568 cm^?1 for 9‐CN‐substituted compound respectively 1639 cm^?1 for 9‐COOH‐substituted compound was analyzed. Cyclic voltammograms indicates that the reduction potential ?0.766 V for ? CN substituted compound increase towards ?0.745 V for ? COOH substituted compound. The proposed theoretical method in the electrochemical impedance spectroscopy uses a reference redox dielectrode and a multielectrode containing the compound. To account for the change of electrochemical impedance we have considered two theoretical quantities: a pseudocapacitance and a pseudo inductance. Two possible arrangements of them: in series, respective in parallel can be used like criteria of drug classification.     

Classification of wines from five Spanish origin denominations by aromatic compound analysis

Wine is a complex matrix in which aroma compounds play an important role in the characterization of the flavor pattern of a given wine. Twelve volatile compounds were determined in 244 samples of Spanish red wines from different denominations of origin: Rioja, Navarra, Valdepe?as, La Mancha, and Cari?ena. The samples were analyzed by GC using headspace solid-phase microextraction. The concentration (mg/mL) intervals obtained were 3-methyl-butyl acetate (3.9 to 116), 3-methyl-1-butanol (93 to 724), ethyl hexanoate (0.8 to 39), 1-hexanol (0.3 to 6.7), ethyl octanoate (1.4 to 41), diethyl succinate (0.2 to 13), 2-phenyl ethyl acetate (0 to 5.3), hexanoic acid (0 to 8.3), geraniol (0 to 3.0), 2-phenylethanol (1.5 to 56), octanoic acid (0 to 20), and decanoic acid (0 to 3.3). Wines were classified by multivariate statistical methods: principal component analysis, and lineal discriminant analysis. A correct differentiation among wines according to their origin was obtained by lineal discriminant analysis.     

Novel and highly sensitive mixed-polymeric electrokinetic chromatography system for determination of contaminants and impurities of heparin samples

A mixed‐polymeric electrokinetic chromatography system has been developed for the simultaneous determination of a contaminant like oversulfated condroitin sulfate (OSCS) and impurities expressed as dermatan (Der) in heparin (Hep) samples. The EKC system consisted of 0.5% w/v polymeric β‐CD, 0.4% w/v tetronic^® 1107 and 400 mM tris‐phosphate buffer at pH 3.5. The optimized electrophoretic conditions included the use of an uncoated‐silica capillary of 50 cm of total length and 75 μm id, an applied voltage of ?7 kV, a temperature of 30°C and 200 nm UV‐detection. The highly sensitive method developed showed low values of LOD, 0.07% w/w (0.07 μg/mL) (OSCS) and 0.1% w/w (0.1 μg/mL) (Der), and values of LOQ 0.2% w/w (0.2 μg/mL) (OSCS) and 0.3% w/w (0.3 μg/mL) (Der) with a concentration level of Hep sample as low as 0.1 mg/mL. Additional parameters of validation such as specificity, linearity, accuracy, and robustness were evaluated according to international guidelines. Owing to its simplicity, high sensitivity, and reliability, the proposed method can be an advantageous alternative to the traditional methodologies for the analysis of Hep in raw material and specially in finished products because of the low amounts of Hep sample required.     

Hydrogen‐bonded nucleophile effects in ANS: the reactions of 1‐chloro and 1‐fluoro‐2,4‐dinitrobenzene with 2‐guanidinobenzimidazole, 1‐(2‐aminoethyl)piperidine and N‐(3‐aminopropyl)morpholine in aprotic solvents

The kinetics of the reactions of 2,4‐dinitrofluorobenzene (DNFB) and 2,4‐dinitrochlorobenzene (DNClB) with 2‐guanidinobenzimidazole (2‐GB) at 40 ± 0.2 °C in dimethylsulphoxide (DMSO), toluene, and in toluene–DMSO mixtures, and with 1‐(2‐aminoethyl)piperidine (2‐AEPip) and N‐(3‐aminopropyl)morpholine (3‐APMo) in toluene at 25 ± 0.2 °C were studied under pseudo first‐order conditions. For the reactions of 2‐GB carried out in pure DMSO, the second‐order rate coefficients were independent of the amine concentration. In contrast, the reactions of 2‐GB with DNFB in toluene, showed a kinetic behaviour consistent with a base‐catalysed decomposition of the zwitterionic intermediate. These results suggest an intramolecular H‐bonding of 2‐GB in toluene, which is not present in DMSO. To confirm this interpretation the reactions were studied in DMSO–toluene mixtures. Small amounts of DMSO produce significant increase in rate that is not expected on the basis of the classical effect of a dipolar aprotic medium; the effect is consistent with the formation of a nucleophile/co‐solvent mixed aggregate. For the reactions of 3‐APMo with both substrates in toluene, the second‐order rate coefficients, k_A, show a linear dependence on the [amine]. 3‐APMo is able to form a six‐membered ring by an intramolecular H‐bond which prevents the formation of self‐aggregates. In contrast, a third order was observed in the reactions with 2‐AEPip: these results can be interpreted as a H‐bonded homo‐aggregate of the amine acting as a better nucleophile than the monomer. Most of these results can be well explained within the frame of the ‘dimer nucleophile’ mechanism. Copyright © 2010 John Wiley & Sons, Ltd.     

B-decay CP-asymmetries in SUSY with a U(2)3 flavour symmetry

We study CP asymmetries in rare B decays within supersymmetry with a U(2)³ flavour symmetry, motivated by the SUSY flavour and CP problems, the hierarchies in the Yukawa couplings and the absence so far of any direct evidence for SUSY. Even in the absence of flavour-blind phases, we find potentially sizable CP violating contributions to b→s decay amplitudes. The effects in the mixing-induced CP asymmetries in B→ϕK _S and B→η′K _S , angular CP asymmetries in B→K ^∗ μ ⁺ μ ⁻ and the direct CP asymmetry in B→X _s γ can be in the region to be probed by LHCb and next generation B factories. At the same time, these effects in B decays are compatible with CP violating contributions to meson mixing, including a non-standard B _s mixing phase hinted by current tensions in the CKM fit mostly between S_yKS, e_KS_{\psi K_{S}}, \epsilon_{K} and DM_Bs/DM_Bd\Delta M_{B_{s}}/\Delta M_{B_{d}}.