Vinyl Bromide Research Articles

Design, synthesis and evaluation of halogenated furanone derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa

The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.

SYNTHESIS OF INDIVIDUAL ISOMERS OF 2-(3-CHLOROPROP-2-EN-1-YL)CYCLOHEXANONE

Recently, vinyl chlorides has been increasingly used as electrophilic partners in various cross-coupling reactions. In contrast to inaccessible and expensive vinyl bromides and iodides, in many cases vinyl chlorides are highly active in the presence of not only traditional palladium complexes, but also economical and safe compounds of iron, cobalt and nickel. Earlier, we reported on the development of new approaches to the getting of stereochemically pure (E)- and (Z)-vinyl chlorides and their successful use at the synthesis of medicines and insect pheromones. Continuing this work, an effective method of the synthesis of (E)- and (Z)-isomers of 2-(3-chloroprop-2-en-1-yl)cyclohexanone - convenient precursors of 2-(alk-2-en-1-yl)cyclohexanones, known flavors and intermediates in the synthesis of polycyclic compounds was developed. In the reaction of ethyl 2-oxocyclohexanecarboxylate with the (E)- and (Z)-isomers of 1,3-dichloropropene under the phase-transfer catalysis conditions in the presence of K2CO3, the corresponding (E)- and (Z)-isomers of ethyl 1-(3-chloroprop-2-en-1-yl)-2-oxocyclohexanecarboxylate were obtained in high yields (80-86%), without allyl rearrangement. The complete retention of the configuration of the chlorovinyl group is observed. Standard methods of the decarboxylation of isomers of ethyl 1-(3-chloroprop-2-en-1-yl)-2-oxocyclohexanecarboxylate under acidic or basic conditions result in very average yields of the corresponding chlorovinyl ketones. The best results were obtained by their decarbalkoxylation in slightly modernized Krapcho conditions. Carrying out reaction in N-methylpyrrolidone at 140-150 °C in the presence of 3 eq. LiCl and 2 eq. of H2O leads to individual (E)- and (Z)-isomers of 2-(3-chloroprop-2-en-1-yl)cyclohexanone in 79-82% yields and a stereochemical purity of ~ 99%. The structure of the obtained compounds were confirmed by HRGC, NMR, and GC/MS data. The configuration of the vinyl group was proved by the coupling constants of the vinyl hydrogens, equal to 13.2-13.4 and 7.0-7.3 Hz for the (E)- and (Z)-products, respectively, as well as by the downfield shift of the allyl carbon atom of trans-isomers by ~4 ppm as compared to the cis-analogs.

Metal-Free Transfer Hydrobromination of C-C Triple Bonds.

A transfer hydrobromination of C-C triple bonds inititated by Brønsted acids is reported. Hydrogen bromide is released stepwise from a bench-stable cyclohexa-1,4-diene-based surrogate, generating biphenyl and ethylene as waste. A range of vinyl bromides was prepared from terminal and internal, mainly acceptor-substituted alkynes with good functional-group tolerance.

Synthesis of a C1–C12 Fragment of Gulmirecin B

The synthesis of a C1–C14 fragment of the macrolide antibiotic gulmirecin B through formation of the C7–C8 bond by addition of a vinyllithium intermediate to a C1–C7 aldehyde was investigated. This crucial coupling was successful with a vinyllithium reagent corresponding to a C8–C12 fragment. The C8–C12 vinyl bromide was prepared from l-malic acid. The C1–C7 aldehyde building block was synthesized from hex-5-enoic acid by using an Evans alkylation, a cross-metathesis, and an asymmetric dihydroxylation as key steps.

Ni-Catalyzed Cross-Electrophile Coupling for the Synthesis of Skipped Polyenes.

Skipped polyenes featuring high ( E)-selectivity and varying methyl substitution patterns are synthesized using a nickel-catalyzed cross-coupling reaction between allyl trifluoroacetates and vinyl bromides. The utility of this cross-electrophile coupling is showcased in part by the synthesis of the RST fragment of the marine ladder polyether, maitotoxin. Construction of this fragment is particularly challenging due to the alternating methyl substitution pattern.

Conversion of Aldehydes to Branched or Linear Ketones via Regiodivergent Rhodium-Catalyzed Vinyl Bromide Reductive Coupling-Redox Isomerization Mediated by Formate.

A regiodivergent catalytic method for direct conversion of aldehydes to branched or linear alkyl ketones is described. Rhodium complexes modified by P tBu2Me catalyze formate-mediated aldehyde-vinyl bromide reductive coupling-redox isomerization to form branched ketones. Use of the less strongly coordinating ligand, PPh3, promotes vinyl- to allylrhodium isomerization en route to linear ketones. This method bypasses the 3-step sequence often used to convert aldehydes to ketones involving the addition of pre-metalated reagents to Weinreb or morpholine amides.

Key Mechanistic Features in Palladium-Catalyzed Methylcyclopropanation of Norbornenes With Vinyl Bromides: Insights From DFT Calculations.

DFT calculations were performed to elucidate mechanistic details of an unusual palladium-catalyzed methylcyclopropanation from [2 + 1] cycloadditions of (Z)-2-bromovinylbenzene and endo-N-(p-tolyl)-norbornenesuccinimide. The reaction proceeds via oxidative addition (OA), intermolecular alkene insertion, deprotonation/protonation, intramolecular alkene insertion, β-H elimination and reductive elimination (RE). Protonation is the rate-limiting step and requires an overall barrier of 28.5 kcal/mol. The sources of two protons for protonation and exchange have also been clarified and the calculations agree with experimental observations.

MPTGs: Thioglycoside Donors for Acid-Catalyzed O-Glycosylation and Latent-Active Synthetic Strategies.

4-( p-Methoxyphenyl)-4-pentenylthioglycosides (MPTGs) undergo acid-catalyzed O-glycosylation with a range of alcohol acceptors in the presence of 10 mol % of triflic acid at room temperature. Particularly encouraging is the reactivity of MPTGs toward unreactive acceptors. MPTGs can be synthesized from the requisite vinyl bromides using the Suzuki reaction, and this chemistry can be leveraged toward a "latent-active" strategy for oligosaccharide synthesis.

Quantum chemical study on isomerization and transformation of hexabromocyclododecanes

Hexabromocyclododecanes (HBCDs) have been frequently detected in environment. The isomerization between HBCDs and thermodynamic properties of unimolecular and bimolecular decomposition reactions of (−)-α-HBCD and (−)-γ-HBCD have been investigated using the quantum chemical method. The results show that isomerization via 1,2-shift of Br atoms occurs between the (−)-α/(−)-γ, (+)-α/(+)-γ, and (+)-β/(−)-β counterparts of HBCDs. Self-decomposition of HBCDs to pentabromocyclododecenes and HBr progresses slowly at low temperature but becomes competitive with the isomerization reactions at high temperature. The generated products are also toxic pollutants to the aquatic organisms. The reaction of two commonly detected HBCDs, (−)-γ-HBCD and (−)-α-HBCD, with OH radical and H atom have been studied. (−)-γ-HBCD has bigger rate constants in the reaction with OH radical and H atom than (−)-α-HBCD all over studied temperature. After a series of unimolecular or bimolecular reactions, the formed pentabrominated intermediate can decompose into ethane, vinyl bromide, and 1,2-dibromoethylene after sufficient heat adsorption.

A study of thermal decomposition of bromoethane

The pyrolysis of bromoethane under dilute atmosphere and quasi-atmospheric pressure was studied at temperatures from 600 to 975 K using a fused silica jet stirred reactor (JSR) and an alumina tubular reactor (TR). In the JSR, a complete conversion was observed at a residence time of 2 s, a temperature of 975 K and an inlet mole fraction of bromoethane of 0.01. In the TR, the full conversion was observed from 925 K. In both reactors, the following species were quantified: methane, ethylene, acetylene, ethane, 1,3-butadiene, vinylacetylene and vinyl bromide. A new detailed kinetic model was developed and gave a good prediction for both reactors of the global reactivity and the major products. Flow rate and sensitivity analyses have been performed to better understand the important reaction pathways during bromoethane pyrolysis. They showed, in contrast to previous studies, that the radical mechanism is far from being negligible and that the sole analysis of reaction products can be misleading as the radical mechanism mainly lead to ethylene and HBr which are also the two products from the molecular decomposition reaction of bromoethane.

Metal‐Free Synthesis of β‐Bromoalkenyl Sulfides via Deoxygenative Bromination/Olefination/Sulfenylation of Ketones with Sulfonyl Hydrazides and Pyridinium Tribromide

AbstractA novel metal‐free method for synthesis of β‐bromoalkenyl sulfides via deoxygenative bromination/olefination/sulfenylation process using commercially available ketones, sulfonyl hydrazides and pyridinium tribromide as starting materials has been developed. In this reaction, pyridinium tribromide plays the role of oxidant and substrate, wherein water and molecular nitrogen are generated as environmentally benign by‐products. Preliminary investigation revealed that vinyl bromides were critical intermediate. Importantly, this protocol not only obviates the use of alkynes and traditional sulfenylating agents, but also reveals that ketones can be used as precursors of vinyl bromides.

Stereoselective Alkyne Hydrohalogenation by Trapping of Transfer Hydrogenation Intermediates.

A catalytically generated vinylcopper complex, the reactive intermediate of a copper(I)-catalyzed alkyne transfer hydrogenation, can be trapped by commercially available halogen electrophiles. In this manner, internal alkynes can stereoselectively be hydrohalogenated to the corresponding vinyl chlorides, bromides, and iodides.

Pd‐Polypyrrole Nanocomposite in Environmentally Friendly Synthesis of Vinylnitriles Using K4Fe(CN)6

AbstractAn efficient cyanation of vinyl bromides, activated chlorides and mesylates with K4Fe(CN)6 has been performed using palladium polypyrrole nanocomposite. The reactions are clean and high yielding. They are highly stereoselective furnishing (E)‐nitriles from (E)‐halides and Z‐nitriles from Z‐halides. Chemoselective cyanation of sp2(vinyl)‐Br bond in the presence of sp2(aryl)‐Br is possible. The additional advantages offered by the suggested catalytic system are operational simplicity and the environmentally friendly synthetic methodology (no toxic ligands and the possibility to use environmentally benign aqueous solutions). The catalyst is active under heating and under MW irradiation; it can be reused at least three times.

Multimetallic Ni- and Pd-Catalyzed Cross-Electrophile Coupling To Form Highly Substituted 1,3-Dienes.

The synthesis of highly substituted 1,3-dienes from the coupling of vinyl bromides with vinyl triflates is reported for the first time. The coupling is catalyzed by a combination of (5,5'-bis(trifluoromethyl)-2,2'-bipyridine)NiBr2 and (1,3-bis(diphenylphosphino)propane)PdCl2 in the presence of a zinc reductant. This method affords tetra- and penta-substituted 1,3-dienes that would otherwise be difficult to access and tolerates electron-rich and -poor substituents, heterocycles, an aryl bromide, and a pinacol boronate ester. Mechanistically, the reaction appears to proceed by an unusual zinc-mediated transfer of a vinyl group between the nickel and palladium centers.

N-Vinylation of Imidazole and Benzimidazole with a Paramagnetic Vinyl Bromide

An N-vinylation of imidazole and benzimidazole with a paramagnetic vinyl bromide was investigated. Among the tested procedures, Pd-catalyzed reaction was the most powerful one. The N-vinylation of 2-aminobenzimidazole with a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde offered 1,1,3,3-tetramethyl-1H-benzimidazo[1,2-a]pyrrolo[3,4-e]pyrimidin-2(3H)-yloxyl radical and the corresponding non-cyclized Schiff base. The reaction of a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde with imidazole gave β-imidazo-α,β-unsaturated pyrroline nitroxide aldehyde, which was reduced to the alcohol and converted to an unstable allyl chloride.

Cross‐Coupling of Sodium Sulfinates with Aryl, Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis

AbstractAn efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.

Cross-Coupling of Sodium Sulfinates with Aryl, Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis.

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.

Synthesis of the Tetracyclic Structure of Batrachotoxin Enabled by Bridgehead Radical Coupling and Pd/Ni-Promoted Ullmann Reaction.

The steroidal ABCD-ring system of the potent neurotoxin batrachotoxin was efficiently assembled in a convergent fashion. Bridgehead radical coupling between the simple AB-ring and D-ring fragments (3 and 4) formed the sterically congested linkage at the C9-oxygen-attached tetrasubstituted carbon. The C-ring was then cyclized by the Pd/Ni-promoted Ullmann reaction of the vinyl triflate and vinyl bromide of 19, giving rise to tetracyclic structure 1.

Direct and Delayed Dynamics in Electron-Induced Surface Reaction.

The electron-induced reaction of physisorbed vinyl bromide (ViBr) and allyl bromide (AllBr) on Cu(110) at 4.6 K was studied experimentally by scanning tunneling microscopy and theoretically by molecular dynamics. ViBr and AllBr were found to react by two pathways: "Direct", in which the molecule reacted under the tip, and "Delayed", in which reaction occurred spontaneously after the molecule had diffused across the surface away from the tip. The novel pathway of Delayed reaction constituted a major route for both vinyl bromide (68%) and allyl bromide (53%). The observed reaction dynamics for ViBr and AllBr gave evidence of a long-lived vibrationally excited intermediate for both Direct and Delayed reactions. Molecular dynamics simulations with reagent excitation by way of selected vibrational normal modes resulted in either Direct or Delayed reaction, depending on the vibrational mode.

Variable dual carbon-bromine stable isotope fractionation during enzyme-catalyzed reductive dehalogenation of brominated ethenes

The potential of compound-specific stable isotope analysis (CSIA) to characterize biotransformation of brominated organic compounds (BOCs) was assessed and compared to chlorinated analogues. Sulfurospirillum multivorans and Desulfitobacterium hafniense PCE-S catalyzed the dehalogenation of tribromoethene (TBE) to either vinyl bromide (VB) or ethene, respectively. Significantly lower isotope fractionation was observed for TBE dehalogenation by S. multivorans (εC = −1.3 ± 0.2‰) compared to D. hafniense (εC = −7.7 ± 1.5‰). However, higher fractionation was observed for dibromoethene (DBE) dehalogenation by S. multivorans (εC = −16.8 ± 1.8‰ and −21.2 ± 1.6‰ for trans- and cis-1,2- (DBE) respectively), compared to D. hafniense PCE-S (εC = −9.5 ± 1.2‰ and −14.5 ± 0.7‰ for trans-1,2-DBE and cis-1,2-DBE, respectively). Significant, but similar, bromine fractionation was observed for for S. multivorans (εBr = −0.53 ± 0.15‰, −1.03 ± 0.26‰, and −1.18 ± 0.13‰ for trans-1,2-DBE, cis-1,2-DBE and TBE, respectively) and D. hafniense PCE-S (εBr = −0.97 ± 0.28‰, −1.16 ± 0.36‰, and −1.34 ± 0.32‰ for cis-1,2-DBE, TBE and trans-1,2-DBE, respectively). Variable CBr dual-element slopes were estimated at Λ (εC/εBr) = 1.03 ± 0.2, 17.9 ± 5.8, and 29.9 ± 11.0 for S. multivorans debrominating TBE, cis-1,2-DBE and trans-1,2-DBE, respectively, and at 7.14 ± 1.6, 8.27 ± 3.7, and 8.92 ± 2.4 for D. hafniense PCE-S debrominating trans-1,2-DBE, TBE and cis-1,2-DBE, respectively. A high variability in isotope fractionation, which was substrate property related, was observed for S. multivorans but not D. hafniense, similar as observed for chlorinated ethenes, and may be due to rate-limiting steps preceding the bond-cleavage or differences in the reaction mechanism. Overall, significant isotope fractionation was observed and, therefore, CSIA can be applied to monitor the fate of brominated ethenes in the environment. Isotope effects differences, however, are not systematically comparable to chlorinated ethenes.