Halogen Moieties Research Articles

Influence of chemical structure on absolute odour thresholds and odour characteristics of ortho‐ and para‐halogenated phenols and cresols

ABSTRACTHalogenated phenols and cresols belong to a group of volatiles consistently reported as off‐flavour compounds. For example, 2‐iodophenol and 2‐iodo‐4‐methylphenol with their typical medicinal smell were found to negatively affect bottled mineral water. Even though these compounds are widespread in nature no comprehensive information about their chemo‐analytical as well as odour properties is available. Therefore, the objective of this study were (1) to provide systematic chemo‐analytical data on these substances, such as mass spectral data and retention parameters in gas chromatographic analysis, and (2) to determine, on a direct comparative basis, the sensory properties of eight mono‐halogenated phenols, four di‐halogenated phenols and four halogenated cresols. Evaluations focused on the determination of odour quality and odour threshold concentration in air and water. With regard to the relationship between substitution pattern and odour character, the location of an iodine atom in the ortho‐position was demonstrated to obviously be an important prerequisite for medicinal, plaster‐like or ink‐like smell. Faecal or horse stable‐like odour notes were predominantly related to compounds being substituted either by halogen moieties or by a methyl group in the para‐position. The 2‐halogenated 4‐methylphenols were found to be the odorants with the lowest odour threshold concentrations of all the compounds investigated in this study, and that, generally, compounds with ortho‐halogenation exhibited exceptionally low odour threshold concentrations. Copyright © 2012 John Wiley & Sons, Ltd.

Ru-catalyzed highly chemo- and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters under neutral conditions

Finely-tuned ruthenium-catalyzed highly chemoselective and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters at the carbonyl group was achieved under neutral reaction conditions (ee up to 97%). Both olefin and alkenyl halogen moieties, which are labile under hydrogenation conditions, remained untouched during the reaction.

Structure–activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI

Several 5,10-dihydroindeno[1,2-b]indole derivatives incorporating methoxy, hydroxyl, and halogen (F, Cl, and Br) moieties on the indene fragment of the molecule were prepared and tested against five carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The inhibitory potencies of these compounds against the human (h) isoforms hCA I, II, IV, VI and bovine (b) isoform bCA III were assessed. Most of them exhibited low micromolar inhibition of these enzymes. KI values of these compounds against hCA I and hCA II were in the range of 2.14–16.32 μM, and 0.34–2.52 μM, respectively. Isozyme hCA IV was inhibited with KI-s in the range of 0.435–5.726 μM, while hCA VI with KI-s of 1.92–12.84 μM bCA III was inhibited with KI-s in the range of 2.13–17.83 μM. The structurally related compounds, 1,2-dimethoxybenzene, catechol and indole were also tested in order to understand the structure activity relationship. In silico docking studies of some derivatives within the active site of hCA I and II were also carried out in order to rationalize the inhibitory properties of these compounds and understand their inhibition mechanism.

ChemInform Abstract: Bystanding F+ Oxidants Enable Selective Reductive Elimination from High‐Valent Metal Centers in Catalysis

AbstractReview: ca. 100 refs.

Bystanding F+ oxidants enable selective reductive elimination from high-valent metal centers in catalysis.

Reductive elimination from partially or completely oxidized metal centers is a vital step in a myriad of carbon-carbon and carbon-heteroatom bond-forming reactions. One strategy for promoting otherwise challenging reductive elimination reactions is to oxidize the metal center using a two-electron oxidant (that is, from M((n)) to M((n+2))). However, many of the commonly used oxidants for this type of transformation contain oxygen, nitrogen, or halogen moieties that are subsequently capable of participating in reductive elimination, thus leading to a mixture of products. In this Minireview, we examine the use of bystanding F(+) oxidants for addressing this widespread problem in organometallic chemistry and describe recent applications in Pd(II) /Pd(IV) and Au(I) /Au(III) catalysis. We then briefly discuss a rare example in which one-electron oxidants have been shown to promote selective reductive elimination in palladium(II)-catalyzed C-H functionalization, which we view as a promising future direction in the field.

Synthesis, characterization and electrochemical properties of new functional polythiophenes

Novel fully soluble polythiophene derivatives containing halogen or ester moieties at the end of a tetramethylenic side chain were synthesized using either the direct oxidative polymerization procedure of functionalized thiophene or the post polymerization functionalization of the preformed polymeric precursor. The structures of the polymers were characterized and their physical properties carefully investigated. High average molecular weights ( M ¯ n up to 30,550 g/mol) and thermostable products were obtained. The absorption wavelength of the polymers in different solvents can be tuned up by varying the composition of solvent mixtures. Cyclic voltammetry measurements displayed good charge transport properties, strongly related to the kind of substituent linked to the side chain.

Rhodium-Catalyzed 1,2-Addition of Sb-Phenyl-1,5-azastibocines to Functionalized Aldehydes

Simple and efficient addition of a phenyl group to aldehydes was accomplished by the rhodium-catalyzed reaction of Sb-phenyl-1,5-azastibocines. Because of the soft nucleophilic character of 1,5-azastibocines, arylation of functionalized aldehydes having ketone, ester, and halogen moieties can be achieved to afford aryl alcohols. The reaction can be carried out under aerobic conditions, in striking contrast to the reactions with hard nucleophiles such as organolithium and Grignard reagents.

Design, synthesis, biological evaluation and molecular modelling studies of novel quinoline derivatives against Mycobacterium tuberculosis

We herein describe the synthesis and antimycobacterial activity of a series of 27 different derivatives of 3-benzyl-6-bromo-2-methoxy-quinolines and amides of 2-[(6-bromo-2-methoxy-quinolin-3-yl)-phenyl-methyl]-malonic acid monomethyl ester. The antimycobacterial activity of these compounds was evaluated in vitro against Mycobacterium tuberculosis H37Rv for nine consecutive days upon a fixed concentration (6.25 μg/mL) at day one in Bactec assay and compared to untreated TB cell culture as well as one with isoniazide treated counterpart, under identical experimental conditions. The compounds 3, 8, 17 and 18 have shown 92–100% growth inhibition of mycobacterial activity, with minimum inhibitory concentration (MIC) of 6.25 μg/mL. Based on our molecular modelling and docking studies on well-known diarylquinoline antitubercular drug R207910, the presence of phenyl, naphthyl and halogen moieties seem critical. Comparison of docking studies on different stereoisomers of R207910 as well as compounds from our data set, suggests importance of electrostatic interactions. Further structural analysis of docking studies on our compounds suggests attractive starting point to find new lead compounds with potential improvements.

Insertion of arynes into carbon–halogen σ-bonds: regioselective acylation of aromatic rings

Arynes were found to insert into carbon-halogen sigma-bonds of various acid halides, enabling acyl and halogen moieties to be introduced simultaneously into adjacent positions of aromatic rings.

Induced Super-halogen Behavior of Metal Moieties in Halogen-Doped Clusters: LinI(-) and AlnI(-), n = 13, 1, 2, 3

A comparative density functional theory (DFT) study of a series of neutral and negative-ionic lithium and aluminum clusters doped with iodine atom is presented. The I atom is found to preserve the same position at Li13 with and without the negative charge and Li13 to vary its shape from prolate to oblate with changing spin state of Li13I. Both the Mulliken and natural charges are considered, the natural-charge separation between the metal and halogen moieties being generally much larger (except for Al13I-). In LinI-, the additional electron is strongly localized on the metal moiety starting from n = 1, even though the electron affinity of Lin is much smaller than that of I. Such a super-halogen behavior of Lin is induced by highly electronegative iodine making the two components charged in LinI and leading to a charge-dipole interaction with the additional electron. In AlnI-, similar factors result in Aln being more negative than I already for n = 3, even though the electron affinity of I is higher, the effect escalating for n = 13.

Plasma etching treatment for surface modification of boron-doped diamond electrodes

Boron-doped diamond (BDD) thin film surfaces were modified by brief plasma treatment using various source gases such as Cl 2, CF 4, Ar and CH 4, and the electrochemical properties of the surfaces were subsequently investigated. From X-ray photoelectron spectroscopy analysis, Cl and F atoms were detected on the BDD surfaces after 3 min of Cl 2 and CF 4 plasma treatments, respectively. From the results of cyclic voltammetry and electrochemical AC impedance measurements, the electron-transfer rate for Fe(CN) 6 3−/4− and Fe 2+/3+ at the BDD electrodes was found to decrease after Cl 2 and CF 4 plasma treatments. However, the electron-transfer rate for Ru(NH 3) 6 2+/3+ showed almost no change after these treatments. This may have been related to the specific interactions of surface halogen (C–Cl and C–F) moieties with the redox species because no electrical passivation was observed after the treatments. In addition, Raman spectroscopy showed that CH 4 plasma treatment of diamond surfaces formed an insulating diamond-like carbon thin layer on the surfaces. Thus, by an appropriate choice of plasma source, short-duration plasma treatments can be an effective way to functionalize diamond surfaces in various ways while maintaining a wide potential window and a low background current.

Functionalization of [60]fullerene through the anionic route

Abstract The reactivity of C602– anion, easily generated upon chemical reduction of the C60 core by sodium methanethiolate, has been systematically investigated versus a great number of saturated halogenated compounds RX or X–CH2–R′–CH2–X (X = I or Br), while these halo-compounds are unreactive with C60 itself. Various C60-derivatives in the series of bis-adducts R2C60 and fused cycloadducts R′(CH2)2C60 are thus obtained in fair to good yields, the R or R′ groups bearing functionalities such as ethylenic double bond, halogen, ketone, alcohol, or ester moieties. On the other hand a judicious utilization of the overall mechanism of the reaction between C602– anion and well chosen different RX and R′X compounds allow to extend this methodology to the preparation of mixed adducts RR′C60. Functional adducts in the series R2C60 and R′(CH2)2C60 are new attractive building blocks in C60 chemistry, and can lead to novel highly functionalized C60-based molecules. Some examples of such covalent ensembles are presented, the specific physical properties of which are typical of organic materials. To cite this article: J. Cousseau et al., C. R. Chimie 9 (2006).

Interaction of indole derivatives and tryptophan peptides with interfaces of sodium dodecyl sulfate micelles

The free energies of transfer for indole and tryptophan derivatives and pentapeptides having single tryptophan residues from aqueous to sodium dodecyl sulfate (SDS) micellar phases have been systematically studied using the conventional method of ultraviolet absorption spectrophotometry. The free energies for the position isomers of methyl indoles varied depending on the substitution positions. Thus, the contribution of the methyl group to the binding affinity of the 4-methyl indole to the micelle was about twice that of the 2- and 7-methyl indoles. The free energy changes with the introduction of halogen groups to the indole rings were correlated to the nonpolar water-accessible surface area (DeltaA(np)) of the halogen moieties, which were regarded as hydrophobic. The relationships followed straight lines passing through the origins. Position dependence having tendencies similar to the methyl indoles was observed among the magnitudes of the slopes of the straight lines. These results strongly suggest that the indole rings of the derivatives residing in the micellar interface regions direct their imino moieties --NH-- toward the micellar surfaces. Experiments using model tryptophan pentapeptides showed that the magnitude of free energy change per methylene unit of an alkyl amino acid residue in the pentapeptide increased with elongation of the alkyl moiety and was not a constant value as reported for various alkyl compounds. When the peptides distribute to the SDS micelles, the peptide backbones are anchored in aqueous phases and the amino acid side chains in the interfaces extend their alkyl groups toward the micellar centers. Thus, the free energy changes can be connected to the positions of the alkyl groups of the amino acid residues in the micelles.

Discovery of a simple picomolar inhibitor of cholesteryl ester transfer protein.

A novel series of substituted N-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]-N-(3-phenoxyphenyl)-trifluoro-3-amino-2-propanols is described which potently and reversibly inhibit cholesteryl ester transfer protein (CETP). Starting from the initial lead 1, various substituents were introduced into the 3-phenoxyaniline group to optimize the relative activity for inhibition of the CETP-mediated transfer of [3H]-cholesteryl ester from HDL donor particles to LDL acceptor particles either in buffer or in human serum. The better inhibitors in the buffer assay clustered among compounds in which the phenoxy group was substituted at the 3, 4, or 5 positions. In general, small lipophilic alkyl, haloalkyl, haloalkoxy, and halogen moieties increased potency relative to 1, while analogues containing electron-donating or hydrogen bond accepting groups exhibited lower potency. Compounds with polar or strong electron-withdrawing groups also displayed lower potency. Replacement of the phenoxy ring in 1 with either simple aliphatic or cycloalkyl ethers as well as basic heteroaryloxy groups led to reduced potency. From the better compounds, a representative series 4a-i was prepared as the chirally pure R(+) enantiomers, and from these, the 4-chloro-3-ethylphenoxy analogue was identified as a potent inhibitor of CETP activity in buffer (4a, IC50 0.77 nM, 59 nM in human serum). The simple R(+) enantiomer 4a represents the most potent acyclic CETP inhibitor reported. The chiral synthesis and biochemical characterization of 4a are reported along with its preliminary pharmacological assessment in animals.

ナイロン・イソブチレン共重合体動的架橋物における界面形成とその構造

The structure of interphase between nylon 11 and brominated Isobutylene/p-methylstyrene copolymer(BIMS)containing the small amount of halogen moieties at the mixing temperature of dynamic vulcanization was discussed. The graft-reaction between nylon 11 and BIMS occurred below the melting temperature of nylon 11. The lower contact angle and the better adhesion properties of this system were observed at the mixing temperature at 200-220°C. The surface of the copolymer, after the thermal elimination of bromine atom, may rapidly react with nylon 11 to make chemical bonds and to promote the formation of a micro-dispersion system.

Retention of the B(3)X (X=Br, I) bond in closo- o-carborane derivatives after nucleophilic attack. The first synthesis of [3-X-7-R-7,8- nido-C 2B 9H 10] − (X=Br, I). Crystal structure of [HNMe 3][3-I-7,8- nido-C 2B 9H 11

The synthesis of new 3-halogeno nido derivatives of o-carborane, [3-X-7-R-7,8- nido-C 2B 9H 10] − (X=Br, I; R=H, CH 3, C 6H 5) is described, through deboronation of the compounds 3-X-1-R-1,2- closo-C 2B 10H 10, previously synthesised in our laboratory. These nido products have been fully characterised using 1H-, 11B- and 13C-NMR spectroscopies, MALDI-TOF and, for [3-I-7,8- nido-C 2B 9H 11] − by an X-ray crystallographic study. The influences of the halogen moiety on both the B(3) resonance and that of the bridge proton are discussed.

Density functional theory investigation of the reactions of CH2Br–I, CH2I–Br, CH2Cl–I, and CH2I–Cl isopolyhalomethanes with ethylene

We report density functional theory calculations that examine the chemical reactivity of the iso-CH2X–I and iso-CH2I–X (where X = Br or Cl) species with ethylene and their isomerization reactions. The carbenoid properties and isomerization reactions of these CH2X–Y species were compared to those found previously for the CH2X–X species (where X = I, Br or Cl). The chemical reactivity of the iso-CH2X–I and iso-CH2I–X species varies with the electronegativity of the X atom and the position of the X atom in the carbon–halogen–halogen moiety. In addition, the C–X–I or C–I–X bond angles and I–X bond lengths (which vary more than in the iso-CH2X–X species) also appear to influence the chemical reactivity of the iso-CH2X–I and iso-CH2I–X species. We briefly discuss the properties of these cyclopropanation and isomerization reactions and likely consequences for using different isopolyhalomethanes and other species as methylene transfer agents.

Improved enantioselectivity of a lipase by rational protein engineering.

A model based on two different binding modes for alcohol enantiomers in the active site of a lipase allowed rational redesign of its enantioselectivity. 1-Halo-2-octanols were poorly resolved by Candida antarctica lipase B. Interactions between the substrates and the lipase were investigated with molecular modeling. Unfavorable interactions were found between the halogen moiety of the fast-reacting S enantiomer and a region situated at the bottom of the active site (stereoselectivity pocket). The lipase was virtually mutated in this region and energy contour maps of some variants displayed better interactions for the target substrates. Four selected variants of the lipase were produced and kinetic resolution experiments were undertaken with these mutants. Single point mutations gave rise to one variant with doubled enantioselectivity as well as one variant with annihilated enantioselectivity towards the target halohydrins. An increased volume of the stereoselectivity pocket caused a decrease in enantioselectivity, while changes in electrostatic potential increased enantioselectivity. The enantioselectivity of these new lipase variants towards other types of alcohols was also investigated. The changes in enantioselectivity caused by the mutations were well in agreement with the proposed model concerning the chiral recognition of alcohol enantiomers by this lipase.

Novel reductive Friedel-Crafts alkylation of aromatics catalyzed by indium compounds: Chemoselective utilization of carbonyl moieties as alkylating reagents

Reductive Friedel-Crafts alkylation of aromatics with ketones or aldehydes was characteristically catalyzed by indium compounds in preference to general catalysts like AlCl 3 and BF 3, where hydrosilanes would play an important role both as a hydride donor and as a co-catalyst. Chemoselective utilization of ketone moieties as alkylating reagents took place even in the presence of halogen, ester or ether moieties which are very susceptible under traditional Friedel-Crafts conditions. Discussion on a plausible intermediate was carried out by some controlled experiments.

Femtosecond Dynamics of Unimolecular and Unrestricted Bimolecular Reactions

The results of two time-resolved experiments using femtosecond laser pulses are presented. In the first, molecular photoinduced detachment of I2 from methylene iodide is studied. The progress of the reaction is monitored by selective detection of fluorescence from the iodine product; molecular dynamics are probed by depletion of the fluorescent state. Pump−probe spectroscopy of the halogen moiety following high-energy (12 eV) excitation reveals that the reaction proceeds by a concerted asynchronous mechanism. The second experiment is a real-time study of an unrestricted bimolecular reaction. In this process, gas phase mercury atoms are photoassociated to an electronically excited state using a femtosecond pulse; the real-time dynamics of the resulting excimers are probed by fluorescence depletion using a second pulse. Analysis of the rotational anisotropy in the nascent dimers reveals the degree of rotational excitation in the excited state and indicates the impact parameter selectivity of the photoassociation process.