Dibromo Derivatives Research Articles

Dibromo- and Dichlorotriphenylphosphino N-Acyclic Carbene Complexes of Platinum(II)—Synthesis and Cytotoxicity

Some new dichloro- and dibromotriphenylphosphino isonitrile and N-acyclic (NAC) carbene complexes of platinum(II) were synthesized, starting from suitable dinuclear precursors. The reaction of cyclohexylisonitrile with trans-[Pt(μ-X)X(PPh3)]2, followed by the addition of N,N-diethylamine afforded the corresponding N-acyclic carbene (NAC)derivatives cis-[PtX2(PPh3)(NAC)] in 61–64% isolated yield. The cis geometry was attributed based on the comparison with known structures. The stability of the complexes in pure DMSO, DMSO/H2O, and DMSO/NaClaq mixtures was evaluated. While pure DMSO, as well as DMSO/H2O, did not affect the nature of either dichloro- or dibromo-compounds, dibromo derivatives were not stable in the presence of chloride ions. Since a high concentration of chloride ions is essential to perform in vitro cell assays, only dichlorocomplexes were tested as cytotoxic agents against HepG2 and human tumor cells. Among the tested complexes, NAC derivatives showed a moderate effect on MSTO-211H.

Reactivity of 2,2‐disubstituted quinazolinone towards electrophilic substitution: First in silico design to verify experimental evidence of quinazolinone‐based new organic compounds

AbstractIn a previous report, we have already synthesized dinitro and dibromo derivatives of 2,2‐disubstituted‐quinazolin‐4(1H)‐one by a facile method. In order to give insight to our experimental results, we herein report on the theoretical investigations of reactivity of synthesized quinazolinone toward bromination and nitration by using density functional theory (DFT) calculations. The optimized molecular geometries of these compounds by using the B3LYP/6–31G(d, p) method have been compared with their X‐ray structures, which are in good agreement. The correlation between the experimental and computational geometrical data is above 90% and root mean square deviation (RMSD) is low ranging from 0.04% to 0.9% except N1‐H1 and N2‐H2 bond where RMSD goes to 1% due to hydrogen bonding between N1‐H1 …..O1 = C1 and N2‐H2 … .O1 = C1. The Mullikan charge distributions at the different atomic sites have been computed and nucleophilic site are guessed by molecular electrostatic potential (MEP) map. In addition, frontier molecular orbitals of these compounds were discussed at the same level of theory, confirming the nucleophilic sites at position 6 and 8 of 4‐quinazolinone.

Chalcogenacalix[4]dithienoselenophene: Synthesis and Properties of Cyclic Thio- and Selenoether of Dithienoselenophene

Abstract Two kinds of thia- and selenacalix[4]dithienoselenophene, a cyclic dithieno[3,2-b:2′,3′-d]selenophene (DTS) oligomers bridged with divalent chalcogen atoms (S or Se), were successfully prepared via a one-pot cyclization protocol. A palladium-catalyzed coupling of dibromo DTS derivative and (Bu3Sn)2Ch (Ch = S or Se) afforded the cyclic compounds in moderate yield. We have also developed a preparation strategy for the starting DTS derivatives in multi-gram quantity. X-ray analysis revealed that these macrocyclic compounds have different conformations depending on the linker atoms. Thiacalix derivatives form an annular geometry consisting of two sets of vertical and horizontal DTS pairs, while selenacalix derivatives forms a highly symmetrical alternate arrangement of DTS units. The latter macrocycle gave a channel framework to form cavity assembled porous material. Cyclic voltammetry and differential pulse voltammetry measurements for these macrocycles indicated lower redox potentials compared to those of dithienothiophene analogues reported before. Both compounds form a 1:2 complex with C60 in the solid state through face-to-face and S⋯π interactions between DTS and C60. Two guest C60 molecules were captured in the identical space formed by a symmetrical 1,3-alternate conformer.

Bilateral Aromatic Extension of Corannulene Nucleus

AbstractHerein we show that a dibromo imide derivative of corannulene could be subjected to a palladium‐catalyzed Heck reaction in order to install aryl vinylene groups in a bilateral fashion on the C5‐symmetric aromatic nucleus. A photochemically‐induced oxidative cyclization then affords π‐extended structures in isolated overall yields of 35–44 %. Due to the aromatic area extension and the presence of electron withdrawing groups, the synthesized molecules exhibit an anodic shift of ≈1 V in their first reduction potential as compared to pristine corannulene. The bilateral growth of the aromatic scaffold, therefore, represents a viable strategy to prepare π‐extended corannulenes with an electron deficient character.

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings.

A wide range of derivatives with new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)3SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl)-4-(ortho-iodophenyl)pyrrol-3-yl)pyridinium bromide makes it possible to obtain a monocyclization product, and the bicyclization product from the dibromo derivative. The procedure is also applicable to obtain 3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinoline derivatives including 2-unsubstituted skeletons that are inaccessible via Pd-catalyzed cyclization.

Investigation of the K4[Fe(CN)6]-Mediated Mono- and Bis-Palladium-Catalyzed Cyanation of the Benzothioxanthene Core.

The pallado-catalyzed cyanation of benzothioxanthene imide (BTXI) derivatives is explored herein. Once optimized on the monobromo BTXI, mild reaction conditions were successfully applied to the dibromo derivative affording two regioisomers that have been isolated and structurally solved. Additional hydrogen-deuterium exchange experiments were carried out to support a proposed mechanism involving the formation of a five-membered palladacycle intermediate in the bay area. As well as impacting the structural, photo physical and electrochemical properties of the BTXI core, nitrile moieties were successfully used as orthogonal protecting groups, thus opening doors to new design principles.

Complexes of carboxylato pillar[6]arene with Brooker-type merocyanines: Spectral properties, pKa shifts and the design of a displacement assay for trimethyl lysine

The supramolecular complexes of three strongly solvatochromic dyes, Brooker’s merocyanine (M1) and its two derivatives (M2, M3) with carboxylato pillar[6]arene (WP6) were studied in aqueous solutions. The dye-WP6 mixtures were described in terms of four equilibrium reactions: the acidic dissociations of the pyridinium phenols into the zwitterionic phenolates, the acidic dissociations of the complexed phenols, the bindings of the phenol form dyes to WP6 and the bindings of the phenolates to WP6. The equilibrium constants were determined by an analysis of the absorption spectra. It was found that the acidity of the phenol form merocyanines were largely reduced on complexation, pKa shifts of 1.1–1.6 units were observed. In neutral solutions, the complexes of the phenol forms of M1 and M2 were dominant, in contrast to the more acidic M3 (a dibromo derivative), of which the phenolate complex was more stable. Comparing the spectral properties, the binding constants and the pKa-s of the dye-WP6 complexes, the complex M3⋅WP6 was chosen to be tested as a displacement assay. It was demonstrated that this complex functioned as a colorimetric indicator displacement assay which discriminated trimethyl lysine from other lysine derivatives.

Design, Synthesis, and Anti-Breast Cancer Activity of Some Hybrid Molecules Containing Coumarin Moiety

(Benzimidazol-2-yl)-7-hydroxycoumarin and N-(2-hydroxyphenyl)-7-hydroxycoumarin-3-carboxamide have been synthesized by the condensation of ethyl 7-hydroxycoumarin-3-carboxylate in acetic acid. Acetylation with acetic anhydride and halogenation with bromine in acetic acid’s presence of the previous compounds has yielded the corresponding acetoxy and dibromo derivatives. The synthesized molecules that contain coumarin ring have been evaluated for their activities against breast cancer and they have shown good in vitro antiproliferative activities against a human breast cancer line (MCF-7). The results have shown that 3-(benzimidazol-2-yl)-7-acetoxycoumarin had a significant cytotoxic effect compared to the standard DOX (doxorubicin) drug.

Determination of the Mono and Dibromo Derivatives Ratio Resulting from Semiconductor Bromination Using Ultraviolet-visible Absorption Spectroscopy and Gaussian Peak Fitting.

The chemical-industrial production of organic semiconductors urgently needs a cheap and fast approach to determine the components' proportion of the reaction system. In the present work, the Gaussian peak fitting method was applied to process monobromo and dibromo-substituted perylene diimide mixed solutions' ultraviolet-visible absorption curves. The functional relationship formula between the peak-intensity ratio and the component ratio is then concluded. Finally, field experiments of the perylene imide brominating reaction can be used to confirm that such a formula is able to accurately calculate the proportion of ingredients in the synthesis reaction solution system.

Antitubercular polyhalogenated phenothiazines and phenoselenazine with reduced binding to CNS receptors

Targeting energy metabolism in Mycobacterium tuberculosis (Mtb) is a new paradigm in the search for innovative anti-TB drugs. NADH:menaquinone oxidoreductase is a non-proton translocating type II NADH dehydrogenase (NDH-2) that is an essential enzyme in the respiratory chain of Mtb and is not found in mammalian mitochondria. Phenothiazines (PTZs) represent one of the most known class of NDH-2 inhibitors, but their use as anti-TB drugs is currently limited by the wide range of potentially serious off-target effects.In this work, we designed and synthesized a series of new PTZs by decorating the scaffold in an unconventional way, introducing various halogen atoms. By replacing the sulfur atom with selenium, a dibromophenoselenazine 20 was also synthesized. Among the synthesized poly-halogenated PTZs (HPTZs), dibromo and tetrachloro derivatives 9 and 11, along with the phenoselenazine 20, emerged with a better anti-TB profile than the therapeutic thioridazine (TZ). They targeted non-replicating Mtb, were bactericidal, and synergized with rifampin and bedaquiline. Moreover, their anti-TB activity was found to be related to the NDH-2 inhibition. Most important, they showed a markedly reduced affinity to dopaminergic and serotonergic receptors respect to the TZ.From this work emerged, for the first time, as the poly-halogenation of the PTZ core, while permitting to maintain good anti-TB profile could conceivably lead to fewer CNS side-effects risk, making more tangible the use of PTZs for this alternative therapeutic application.

Ethyl 2-(quinoxalin-2(1H)-on-3-yl)acetate and its mono- and dibromo derivatives in the synthesis of 2,2′-biquinoxalin-3,3′(4H,4’H)-diones

The synthetic scope of ethyl 2-(quinoxalin-2(1H)-on-3-yl)acetates and their mono- and dibromo derivatives in the synthesis of 2,2’-biquinoxaline-3,3’(4H,4’H)-diones was examined.

Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones.

Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

The effect of the structure of a cross-linking reagent of the alkylating type on the properties of chitosan granules

The reactivity of chitosan in the form of granules towards a series of cross-linking reagents of alkylating type is compared. The following cross-linking reagents were considered: alkyl dihalides (1,2-dichloroethane, 1,2-dibromoethane, 1,3-dibromopropane, 1,4-dichlorobutane, 1,5-dibromopentane), 2,2′-dichlorodiethylamine, 2,2′-dichlorodiethyl ether, 2,2-diethoxy-1-bromoethane, epichlorohydrin, diglycidyl ethers of ethylene glycol, and butane-1,4-diol. The composition and structural features of the obtained materials were characterized by elemental analysis and FTIR spectroscopy. On the basis of a number of characteristics of the granules such as degree of crosslinking, degree of swelling, static exchange capacity, sorption capacity towards CuII ions, it is shown that among the studied dihaloalkanes, chitosan reacts more efficiently with dibromo derivatives, and 1,3-dibromopropane is found to be the best cross-linking reagent. On the basis of the data on degree of swelling of the cross-linked granules, the cross-link density and the degree of crosslinking were calculated for different cross-linking reagents.

Unveiling a Masked Polymer of Dewar Benzene Reveals trans-Poly(acetylene)

A dibromo derivative of Dewar benzene, trans-5,6-dibromobicyclo[2.2.0]hex-1-ene, was polymerized using ring-opening metathesis polymerization (ROMP). The reaction proceeded in a controlled manner as changing the initial monomer-to-catalyst ratio afforded monodispersed polymers with tunable molecular weights and growing polymer chains were extended upon subsequent exposure to additional monomer. Treatment of the halogenated polymers with an alkyllithium reagent resulted in elimination followed by isomerization to afford trans-poly(acetylene). Based on a series of mechanistic and spectroscopic studies, the transformation was proposed to proceed through a cyclobutenyl intermediate that undergoes rearrangement. The methodology was found to be versatile as triblock copolymers containing the halogenated homopolymer were prepared and converted to their poly(acetylene)-containing derivatives. The polymers were characterized using gel permeation chromatography as well as a range of spectroscopic (NMR, FT-IR, UV–vi...

Chemical shift assignment of mono- and di-bromo triimidazo[1,2-a:1',2'-c:1″,2″-e][1,3,5]triazine derivatives by DFT/NMR integrated approach.

Mono- and di-bromo derivatives of triimidazo[1,2-a:1',2'-c:1″,2″-e][1,3,5]triazine have been proposed as new organic molecules presenting a very rich and complex photophysical behavior. Thus, we afforded the correct chemical shift assignment by integrating the experimental data with DFT calculation of NMR parameters. Our findings lay foundation for a structural reference in the organic synthesis and characterization of new congeners of this intriguing class of molecules.

Synthesis and Electrochemical Characterization of Acetylacetone (acac) and Ethyl Acetate (EA) Appended β-Trisubstituted Push-Pull Porphyrins: Formation of Electronically Communicating Porphyrin Dimers.

Two new families of "push-pull" tetraphenylporphyrins with one acetylacetone (acac) or ethyl acetate (EA) moiety at a β-pyrrole position of the macrocycle and two Br or Ph substituents at the antipodal β-positions were synthesized and structurally, spectroscopically, and electrochemically characterized. The examined porphyrins are represented as MTPP(R)2acac and MTPP(R)2EA (where R = Br or Ph and M = H2, Co, Ni, Cu, or Zn). NiTPP(Br)2acac exhibits an extremely nonplanar conformation (Δ24 = 0.44 Å, ΔCβ = 0.82 Å), while H2TPP(Br)2EA and ZnTPP(Ph)2EA exhibit a quasi-planar conformation. All of the synthesized acac-appended porphyrins show a keto-enol tautomerism in solution, which results in formation of hydrogen bonded dimers as evidenced by 1H NMR and mass spectrometry. Dimers were also detected under the electrochemical conditions for the dibromo derivatives but not the diphenyl substituted porphyrins. A facile stepwise and reversible electrogeneration of the electronically communicating porphyrin dimers is observed for MTPP(Br)2acac where M = CuII, NiII, or ZnII.

Synthesis and Biological Activity of Mono- and Dibromo Derivatives of 2-Amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carboxylic Acids

The previously unknown mono- and dibromo derivatives of 2-amino-5-(2-aryl-2-oxo-ethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carboxylic acids were synthesized. Antinociceptive and antimicrobial activity of the obtained compounds was studied.

Synthesis and Spectroscopic Characterization of Some Hydrazone and 2H‐benzopyranone Derivatives as Antitumor Agents

A new series of hydrazone, 2H‐benzopyranone‐3‐carboxamide and 2H‐benzopyranone‐3‐carbonylthiosemicarbazide derivatives were synthesized from the alkyl 7‐hydroxy‐2H‐benzopyranone‐3‐carboxylate (1a,b) and dibromo derivatives (6a,b) as a key starting materials. The structures of the synthesized new compounds were confirmed by IR, 1H, 13C‐NMR, MS, and elemental analysis. Some hydrazone derivatives and N‐substituted 2H‐benzopyranone‐3‐carboxamides were evaluated for their anticancer activity against HepG‐2 cell lines. Some of these compounds shared good cytotoxicity.

Palladium-Catalyzed Intramolecular Oxidative Arylations for the Synthesis of Fused Biaryl Sulfones.

This study unveils palladium-catalyzed intramolecular oxidative cyclizations in biaryl and heterobiaryl sulfones providing direct access to fused biaryl sulfones (dibenzothiophene-5,5-dioxides). Variously substituted dibenzothiophene-5,5-dioxides could be readily prepared in good to excellent yields under optimized conditions. In addition, bromination afforded dibromo derivative of dibenzothiophene-5,5-dioxides, providing platform for late-stage diversification. The translational applications of this current protocol have successfully been demonstrated in the synthesis of 2,8-diamino derivative of dibenzothiophene-5,5-dioxides, a α7-nicotinic acetylcholine receptor agonist analogue, and novel single fluorene-tethered dibenzothiophene-5,5-dioxide, an organic emitter.

Microwave-assisted and conventional synthesis, photophysics and electroluminescence of poly(9,9-dihexadecylfluorene-2,7-diyl-alt-2,2′-bithiophene-5,5′-diyl)

Alternating electroluminescent copolymers, poly(9,9-dihexadecylfluorene-2,7-diyl-alt-2,2′-bithiophene-5,5′-diyl)s (PFC16BTs), were synthesized using two different routes of Suzuki coupling reaction in which either dibromo derivative of fluorene was reacted with diboronic acid ester of bithiophene or vice versa, with microwave-assisted (MA) or conventional (C) heating in high boiling point solvents, chlorobenzene (CB) and xylene (Xy). PFC16BT copolymers with various molecular weights (MW) were obtained depending on the synthetic conditions, and the influence on MW is discussed. The photophysical and electrochemical properties and the electroluminescence (EL) of the PFC16BT copolymers were studied and compared with those of poly(9,9-dioctylfluorene-2,7-diyl-alt-2,2′-bithiophene-5,5′-diyl)s (PFC8BTs) to reveal the impact of MW and the length of side chains on their properties. A slight dependence on the MW was only observed in the absorption spectra in solutions. Photoluminescence (PL) of PFC16BTs solutions emitted green light with a maximum of approximately 500 nm, whereas the PL emission spectra of thin films were redshifted with the maxima at 540 nm. The ionization potential (HOMO level) and electron affinity (LUMO level) values of 5.4 eV and 2.6 eV, respectively, were evaluated for PFC16BTs, which are similar to those for PFC8BTs. The electrochemical bandgap value of 2.8 eV was higher than the value of the optical bandgap of 2.4 eV. The PFC16BT copolymers with various MW were tested as an active layer in light-emitting devices (LEDs), and the results are compared with those of PFC8BT LEDs. The PFC16BT LEDs exhibited a luminance higher than 3500 cd m–2 and low onset voltages of approximately 2 V. The shape of the EL spectra of LEDs is similar to that of PL spectra of the thin films. PL emission of PFC16BT thin films and EL emission were blue shifted compared with those of PFC8BT, indicating a more pronounced aggregation in PFC8BT.