Electron-deficient Ring Research Articles

The anti-malarial activity of bivalent imidazolium salts

A series of compounds containing bivalent imidazolium rings and one triazolium analog were synthesized and evaluated for their ability to inhibit the replication of Plasmodium falciparum cultures. The activity and selectivity of the compounds for P. falciparum cultures were found to depend on the presence of electron-deficient rings that were spaced an appropriate distance apart. The activity of the compounds was not critically dependent on the nature of the linker between the electron-deficient rings, an observation that suggests that the rings were responsible for the primary interaction with the molecular target of the compounds in the parasite. The bivalent imidazolium and triazolium compounds disrupted the process whereby merozoites gain entry into erythrocytes, however, they did not appear to prevent merozoites from forming. The compounds were also found to be active in a murine Plasmodium berghei infection, a result consistent with the compounds specifically interacting with a parasite component that is required for replication and is conserved between two Plasmodium species.

A new role for coenzyme F420 in aflatoxin reduction by soil mycobacteria

Hepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxal 5'-phosphate synthases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin-dependent oxidoreductases. F420-dependent members of this family appear to share a common mechanism of hydride transfer from the reduced, low-potential deazaflavin to the electron-deficient ring systems of their substrates.

2-Amino-6-(3,4-ethylenedioxythiophen-2-yl)-4-(2-thienyl)-pyrimidine: Synthesis and properties

In 1988 poly(ethylenedioxythiophene) (PEDOT, BAYETRON P) was synthesized for the first time [5, 6] from ethylenedioxythiophene (EDOT) [7, 8]. The doped polymer showed a high conductivity (about 300 S/cm); its oxidized films were almost transparent and thermally stable. Molecular conductors containing fragments of electron-rich [9–12] and electron-deficient aromatic carboand heterocycles [13–15] in addition to EDOT fragments were prepared. Synthesis of such compounds attracts undoubted interest for the design of light-emitting devices [16]. In the present communication we describe the synthesis of a new heterocyclic compound containing an electron-deficient pyrimidine ring linked to two electron-donating fragments, thiophene and ethylenedioxythiophene rings. The synthetic procedure was based on a convenient approach including initial preparation of 2-acetyl-3,4-ethylenedioxythiophene (II) [8] which was brought into condensation with thiophene-2-carbaldehyde in alkaline medium to obtain previously unknown chalcone III. Cyclization of the latter in the presence of guanidine sulfate in alkaline medium according to the procedure described in [17] gave dihydropyrimidine IV, which was oxidized in situ to target product V.

3-Hydroxypyrrolo[2,3-b]pyridine and related compounds – indoxyl analogues with fused electron deficient rings

Flash vacuum pyrolysis (FVP) of 4-acetyltetrazolo[1,5-a]pyridine 5 at 400 °C provides 3-methyl isoxazolo[3,4-b]pyridine 6 whose structure was confirmed by X-ray crystallography. At higher pyrolysis temperatures, the unstable heteroindoxyl 8 was obtained, which exists as the keto form (1,2-dihydropyrrolo[2,3-b]pyridin-3-one) 8K in CDCl(3) solution and the enol tautomer (3-hydroxypyrrolo[2,3-b]pyridine) 8E in DMSO. The heteroindoxyl 8 oxidatively dimerises to the heteroindigotin 9, undergoes condensation reactions at the 2-position and reacts with methoxymethylene Meldrum's acid at the 1-position. FVP of the corresponding acetyltetrazolo[1,5-a]quinoline 19 was much more complex, with 2-(cyanophenyl)acetonitrile 30 (rather than a heteroindoxyl) the major product at 750 °C. FVP of 3-acetyl-4-azidoquinoline 24 at 400 °C gave 3-methylisoxazolo[4,3-c]quinoline 33, but rearrangement to the heteroindoxyl was not observed at higher temperatures.

Insights in the antioxidant activity of diarylamines from the 2,3-dimethylbenzo[ b]thiophene through the redox profile

Cyclic voltammetry was used to evaluate the antioxidant activity of 7-aryl or 7-heteroarylamino-2,3-dimethylbenzo[ b]thiophenes previously synthesized by some of us, comparing their oxidation potentials with those of the well-known synthetic standards (BHA, BHT). Compounds with electron-donating groups on the arylamine moiety have lower E p/2 than compounds with electron-withdrawing groups or electron-deficient rings (pyridines). The position of the methoxy group on the arylamine moiety also changes the oxidation potential: lower E p/2 for the diarylamines with methoxy groups in the para position. Comparing the first peak potential with the ones of BHA and BHT, the diarylamine compounds show lower oxidation potential, and therefore higher reducing power. A reasonable inverse correlation was also observed between the E p/2 values and the pEC 50 values obtained in antioxidant activity chemical assays. It can be generalized that compounds with lower E p/2 values have better antioxidant activity (DPPH assay) and higher reducing power.

A versatile color tuning strategy for iridium(III) and platinum(II) electrophosphors by shifting the charge-transfer states with an electron-deficient core

By fusing an electron-deficient ring system with the phenyl ring of a 2-phenylpyridine (ppy)-type ligand, a new and synthetically versatile strategy for the phosphorescence color tuning of cyclometalated iridium(III) and platinum(II) metallophosphors has been established. Two robust red electrophosphors with enhanced electron-injection/electron-transporting features were prepared by using an electron-trapping fluoren-9-one chromophore in the ligand design. The thermal, photophysical, redox and electrophosphorescent properties of these complexes are reported. These exciting results can be attributed to a switch of the metal-to-ligand charge-transfer (MLCT) character of the transition from the pyridyl groups in the traditional IrIII or PtII ppy-type complexes to the electron-deficient ring core, and the spectral assignments corroborate well with the electrochemical data as well as the time-dependent density functional theory (TD-DFT) calculations. The electron-withdrawing character of the fused ring results in much more stable MLCT states, inducing a substantial red-shift of the triplet emission energy from yellow to red for the IrIII complex and even green to red for the PtII counterpart. Electrophosphorescent organic light-emitting devices (OLEDs) doped with these red emitters fabricated by using vacuum evaporation technique have been realized with reasonable performance.

Structural Versatility of Anion−π Interactions in Halide Salts with Pentafluorophenyl Substituted Cations

A series of pentafluorophenyl substituted ammonium, iminium, amidinium, and phosphonium halides are presented which show extensive anion-pi interactions. Hereby, the well-known anion-donor-pi-acceptor as well as "eta6" anion-pi-complex type interactions are observed. The latter is supported by fixation of the anion on top of the aromatic system through hydrogen bonding. This arrangement was investigated by theoretical methods showing a highly attractive anion-pi interaction. In addition an eta2-type coordination of the anions to only two C-atoms of the electron-deficient ring system is described.

Reactivity of several deactivated 3-aminobenzo[ b]thiophenes in the Buchwald–Hartwig C–N coupling. Scope and limitations

Di(hetero)arylamines were prepared in moderate to high yields by Buchwald–Hartwig C–N coupling of bromobenzenes bearing electron-withdrawing groups and of a bromobiphenyl with several methyl 3-aminobenzo[ b]thiophene-2-carboxylates, using the coupling conditions for heteroaromatic amines [Pd(OAc) 2, Xantphos, Cs 2CO 3 in dioxane, 120 °C]. The use of these aminobenzo[ b]thiophenes as coupling components avoids the step of changing the amino group into a bromine atom, like we have done before to perform C–N couplings using the corresponding 3-bromobenzo[ b]thiophenes. Nevertheless, the couplings using the methyl 3-aminobenzo[ b]thiophene-2-carboxylates were only successful with bromobenzenes bearing electron-withdrawing groups and a bromobiphenyl or with electron deficient rings such us as bromopyridines. Using the latter compounds, different substituted 6 H-benzothieno[3,2- d]pyrido[1,2- a]pyrimid-6-ones were obtained by C–N coupling followed by an intramolecular cyclization. These tetracyclic compounds may have interesting biological activity like it was already demonstrated by us for the non substituted derivative.

Ring-Closure Reactions of ortho-Vinyl-tert-anilines and (Di)Aza-Heterocyclic Analogues via the tert-Amino Effect: Recent Developments

One version of the tert-amino effect operating in tert-anilines possessing an ortho-vinyl substituent affords a fused tetrahydropyridine ring by an isomerization process with the formation of a new carbon-carbon bond between the vinyl and tert-amino moieties. Since its discovery in 1984, this type of cyclization has been efficiently used for the construction of fused-ring systems. However, it has been found that the electron-deficient heterocyclic analogues of tert-anilines, such as diazines, may undergo isomerization at considerably lower reaction rates and, as a consequence, their reactions may require harsh conditions. Recent synthetic studies have indicated that the rate and yield may be improved by incorporating the β-vinylic carbon atom into an electron-deficient ring and/or buttressing the tert-amino group, and/or performing the reaction by means of microwave irradiation.

Olefin and Enyne Cross-Metathesis - A New Tool for the Synthesis of Alkenyl-substituted Azulenes

A selective synthesis of azulenes with an extended n-electron system by olefin and enyne cross-metathesis is described. Electron-enriched five-membered ring and electron-deficient seven-membered ring of the azulene moietyaffected the reaction yield.

The Vilsmeier Reaction of Non‐Aromatic Compounds

AbstractFor Abstract see ChemInform Abstract in Full Text.

Pseudorotaxanes and Rotaxanes Incorporating Cycloheptatrienyl Stations − Synthesis and Co-Conformation

Novel [2]rotaxanes containing the tetracationic cyclophane cyclobis(paraquat-4,4′-biphenylene), linked mechanically to a dumbbell-shaped molecular thread incorporating a pair of diaryl cycloheptatriene units, have been synthesised in moderate yields of up to 35% by the acylative endcapping method, with the use of either bulky acyl chlorides or isocyanates. The pseudorotaxanes formed by the threading of the electron-rich molecular threads through the tetracationic ring were characterised by 1H NMR and UV/Vis spectroscopy. The nonplanar, boat-shaped cycloheptatriene rings do not hamper the threading process. According to the 1H NMR spectra, the tetracationic ring undergoes a fast shuttling process between the two cycloheptatriene stations in the rotaxanes. The unexpected signal dispersion of the cyclophane proton resonances is attributable to the existence of two diastereomeric rotaxanes. It was shown that interaction between the recognition sites is strongly influenced by the substitution pattern on the seven-membered ring; the interaction between the electron-deficient ring and a 1,3-diaryl-2,4,6-cycloheptatriene unit is much stronger than that with the regioisomeric 1,4-disubstituted pendant moiety.

Pseudorotaxanes and Rotaxanes Incorporating Cycloheptatrienyl Stations − Synthesis and Co-Conformation

Novel [2]rotaxanes containing the tetracationic cyclophane cyclobis(paraquat-4,4′-biphenylene), linked mechanically to a dumbbell-shaped molecular thread incorporating a pair of diaryl cycloheptatriene units, have been synthesised in moderate yields of up to 35% by the acylative endcapping method, with the use of either bulky acyl chlorides or isocyanates. The pseudorotaxanes formed by the threading of the electron-rich molecular threads through the tetracationic ring were characterised by 1H NMR and UV/Vis spectroscopy. The nonplanar, boat-shaped cycloheptatriene rings do not hamper the threading process. According to the 1H NMR spectra, the tetracationic ring undergoes a fast shuttling process between the two cycloheptatriene stations in the rotaxanes. The unexpected signal dispersion of the cyclophane proton resonances is attributable to the existence of two diastereomeric rotaxanes. It was shown that interaction between the recognition sites is strongly influenced by the substitution pattern on the seven-membered ring; the interaction between the electron-deficient ring and a 1,3-diaryl-2,4,6-cycloheptatriene unit is much stronger than that with the regioisomeric 1,4-disubstituted pendant moiety.

Nucleophilic Substitution of 4H-Imidazoles - A Key Step in the Synthesis of Fused Imidazoles and New Chromophores

The electrophilic properties of the 4H-imidazoles 1 and their protonated derivatives 2 permit the introduction of nucleophilic building blocks, as illustrated by reactions of 1 with selected amines. Depending on the nature of the amine and the substituents R1 on the heterocycle 1, single (3) or double (4) transamination is observed. The 1H-NMR spectra of the products, as well as X-ray structure analyses of compounds 3f and 4c, confirm that the residues at the 4- and/or 5-positions of 1 are exchanged. The tautomerism between 3e-h and 3e′-h′ seems to be central to the chemistry of these mixed substituted derivatives. Using orthoesters and acetophenone dimethylacetal as cyclization partners, the imidazo[4,5-d]imidazoles 5 and the 4H-imidazo[4,5-b]pyrazines 6 are obtained, respectively. Reduction of 3e with Zn/HCl or H2S leads to the air-sensitive, strongly fluorescent leuco compounds 8. Quenching of 8 by addition of aromatic aldehydes results in a condensation reaction and, coupled with the subsequent redox disproportionation, this conversion constitutes an alternative route to imidazo[4,5-d]imidazoles of type 11. The unexpected reaction of 3e-h with Lawesson's reagent allows synthesis of the 6-azapentafulvenes 14. The relevant spectral data show 14 to be members of a new chromophoric system, in which an electron-rich five-membered ring is coupled with an electron-deficient ring.

Nucleophilic Substitution of 4H-Imidazoles - A Key Step in the Synthesis of Fused Imidazoles and New Chromophores

The electrophilic properties of the 4H-imidazoles 1 and their protonated derivatives 2 permit the introduction of nucleophilic building blocks, as illustrated by reactions of 1 with selected amines. Depending on the nature of the amine and the substituents R1 on the heterocycle 1, single (3) or double (4) transamination is observed. The 1H-NMR spectra of the products, as well as X-ray structure analyses of compounds 3f and 4c, confirm that the residues at the 4- and/or 5-positions of 1 are exchanged. The tautomerism between 3e-h and 3e′-h′ seems to be central to the chemistry of these mixed substituted derivatives. Using orthoesters and acetophenone dimethylacetal as cyclization partners, the imidazo[4,5-d]imidazoles 5 and the 4H-imidazo[4,5-b]pyrazines 6 are obtained, respectively. Reduction of 3e with Zn/HCl or H2S leads to the air-sensitive, strongly fluorescent leuco compounds 8. Quenching of 8 by addition of aromatic aldehydes results in a condensation reaction and, coupled with the subsequent redox disproportionation, this conversion constitutes an alternative route to imidazo[4,5-d]imidazoles of type 11. The unexpected reaction of 3e-h with Lawesson's reagent allows synthesis of the 6-azapentafulvenes 14. The relevant spectral data show 14 to be members of a new chromophoric system, in which an electron-rich five-membered ring is coupled with an electron-deficient ring.

Regioselectivity and stereoelectronic effects in the reactions of the dinitroaniline herbicides trifluralin and benefin with nucleophiles

The reactions of two members of the dinitroaniline class of herbicides, N,N-di-n-propyl-2,6-dinitro-4- (trifluoromethyl)aniline (trifluralin; 1) and N-ethyl-N-n-butyl-2,6-dinitro-4-(trifluoromethyl)aniline (benefin; 2), along with their analogue, N-phenyl-2,6-dinitro-4-(trifluoromethyl)aniline (3), with the nucleophiles, OD- and SO32- , have been investigated using 400 MHz 1H NMR spectroscopy. The reactions of both 1 and 2 with OD- result in formation of Meisenheimer anionic σ -complexes according to a K3T1 (kinetic preference for formation of the C-3 adduct with thermodynamic preference for formation of the C-1 adduct) reaction sequence while the reaction of 3 with OD- and that of 1 with SO32- follow a K3T3 (kinetic and thermodynamic preference for formation of the C-3 adduct) sequence. There was no observation of the C-1 adducts of 1 and 2 with OD-, but the products of SNAr displacement at C-1 were observed as the final thermodynamic products. Geometry optimization calculations support our hypothesis of n –> σ * stabilization of the C-1 adduct leading to SNAr displacement. In the reaction of 3 with OD-, initial N-deprotonation to form the anion, 3a, is followed by σ -complex formation. The final thermodynamic product observed in this system is 3,5-dinitro-4-(N-phenylamino)benzoic acid formed through hydrolysis of the trifluoromethyl group on the anion, 3a. Aryl H-D exchange has been found for the systems of 1 and 2 with OD-, but not for the SO32- system and neither for the reaction of 3 with OD-. Since dimethylpicramide showed significantly slower H-D exchange under identical conditions, it is argued that this discrepancy has as origin the ability of the amino N lone electron pair to interact with the π -system of the ring. With both 1 and 2 the larger size of the amino alkyl chains prevent the amino N lone pair from aligning with the π -system of the ring, thus hindering electron density donation to the electron-deficient ring carbons.Key words: trifluralin, benefin, herbicides, Meisenheimer complexes, stereoelectronic effects.

Thermodynamic, Spectroscopic, and Structural Studies of Complexation of Phenol- and Pyridine-Armed Macrocyclic Ligands with Univalent Metal Ions

Log K, {Delta}H, and {Delta}S values for interactions of a series of pyridinoazacrown ethers each bearing a phenol arm (2-6) and two macrocycles each bearing a pyridine arm (7, 8) with Na{sup +}, K{sup +}, Tl{sup +}, and Ag{sup +} have been determined in absolute methanol at 25{degrees}C by calorimetric titration. In each case, the complex stability has the sequence Na{sup +} < K {sup +} < Tl{sup +} {much_lt} Ag{sup +}. The phenol-armed macrocycles exhibit selectivity of more than 4 orders of magnitude for Ag{sup +} over Na{sup +}, K{sup +}, and Tl{sup +}. Attachment of a pendant phenol arm having various substituents to parent macrocycle 1 increases the binding abilities of the resulting ligands. Substituents on the para position of the phenol arm have an appreciable effect on cation-binding constants. Good Hammett correlations are found by plotting log K values vs {sigma}{sub p} for interactions of five phenol-armed macrocyclic ligands (2-6) with Na{sup +}, K{sup +}, and Tl{sup +}. The complexation has been characterized by means of {sup 1}H NMR and UV-visible spectroscopic, and X-ray crystallographic methods. The study indicates that the phenol OH group of 2-6 is capable of forming an intramolecular hydrogen bond with the macroringmore » nitrogen atom and that the complexation in absolute methanol generally does not deprotonate these phenols. In the crystal structure of the Na{sup +} -3 complex, the Na{sup +} is coordinated to all seven of the donor atoms of the ligand and two Na{sup +} -3 complexes join together to form a dimer. The dimer contains an intermolecular hydrogen bond formed between the phenol hydrogen atom of one ligand and the phenolate group of a centrosymmetrically related ligand and two {pi}-{pi} stacking interactions between the electron-deficient pyridine ring of one molecule and the electron-rich phenol ring of the other. 36 refs., 5 figs., 6 tabs.« less

π-π Interactions between Pyrylium and Phenyl Rings in the Crystal

Abstract The crystal structures of two isomeric phenyl-substituted pyrylium perchlorates, 2,6-di-methyl-4-phenylpyrylium (1) and 2,4-dim ethyl-6-phenylpyrylium (2), have been determined. Both cations are planar in the crystal so that the electron deficient pyrylium rings can interact strongly with the phenyl rings of adjacent molecules forming stacks along the shortest crystallographic axis. The phenyl rings may act as donors in a charge transfer interaction which is more pronounced in 1 than in 2. Charge transfer appears as a non-mandatory consequence of the π-π stacking. The structures demonstrate the electrostatic nature of these interactions conforming to the model of Hunter and Sanders [ 1 ].

Conformational analysis of colchicinoids containing an electron-deficient aromatic ring on the B ring

A dinitrophenyl substituent at the C-7 position of N-deacetylcolchicine and N-deacetylisocolchicine was shown to perturb the 1 H NMR and circular dichroic spectra of colchicinoid ring systems. The perturbations were explained by an interaction between the C-7 substituent and the A and/or C rings. Other aromatic substituents or large substituents located at the C-7 position (J. Med. Chem. 1983, 26, 1365) have not been reported to influence the aS-aR equilibrium of the phenyltropone ring junction. It was concluded that the sterically unfavored atropisomers were stabilized by the interaction of an electron-deficient ring with the more electron-rich A ring of the colchicinoid molecules

X-ray diffraction study of C-monosubstituted derivatives of o-carborane with trimethylsilyl and trimethylgermyl substituents

1. The data of a detailed x-ray-diffraction study of 1-trimethylsilyl- and trimethyl-germyl-o-carboranes show that the Si-C and Ge-C bonds between the carborane ring and the substituent are larger than the bonds in the substituent itself, and CH3 groups have a screened orientation with respect to the unsubstituted C-atom of the o-carborane skeleton. 2. The electron-deficient carborane ring appreciably influences the geometrical parameters of the bond of the polyhedron C atom with substituents.