NMR "Finger Prints" of N-Heterocyclic Carbenes, DFT Analysis: Scopes and Limitations.

The scopes and limitations of theoretical methods for estimating various NMR metrics of NHCs are considered on a wide range of model NHCs and their derivatives, using a number of computational approximations. On the whole, the most reliable, from the point of view of predictability and insusceptibility to additional effects, are 31P/13C NMR shifts of NHC-phosphinidene adducts and 13C CSs of carbenes themselves. The method based on the analysis of 77Se CS NHC-selenoureas has some limitations since the observed NMR parameters can also be modulated by exchange effects due to their formation with non-classical hydrogen bonds. As for HEP, since the delicate balance of electron distribution between Pd and two carbon centers can nonlinearly affect relativistic spin-orbit effects, the accuracy of the estimation of this metric may still be limited. 13C CSs of NHC-azolium salts do not seem to be reliable, since the observed values are strongly influenced by the effects of the exchange between different forms with counterions, which are difficult to estimate correctly.

DFT Calculations of 31P NMR Chemical Shifts in Palladium Complexes.

In this study, comparative analysis of calculated (GIAO method, DFT level) and experimental 31P NMR shifts for a wide range of model palladium complexes showed that, on the whole, the theory reproduces the experimental data well. The exceptions are the complexes with the P=O phosphorus, for which there is a systematic underestimation of shielding, the value of which depends on the flexibility of the basis sets, especially at the geometry optimization stage. The use of triple-ζ quality basis sets and additional polarization functions at this stage reduces the underestimation of shielding for such phosphorus atoms. To summarize, in practice, for the rapid assessment of 31P NMR shifts, with the exception of the P=O type, a simple PBE0/{6-311G(2d,2p); Pd(SDD)}//PBE0/{6-31+G(d); Pd(SDD)} approximation is quite acceptable (RMSE = 8.9 ppm). Optimal, from the point of view of "price-quality" ratio, is the PBE0/{6-311G(2d,2p); Pd(SDD)}//PBE0/{6-311+G(2d); Pd(SDD)} (RMSE = 8.0 ppm) and the PBE0/{def2-TZVP; Pd(SDD)}//PBE0/{6-311+G(2d); Pd(SDD)} (RMSE = 6.9 ppm) approaches. In all cases, a linear scaling procedure is necessary to minimize systematic errors.

Synthesis and Mechanistic Insights of the Formation of 3-Hydroxyquinolin-2-ones including Viridicatin from 2-Chloro-N,3-diaryloxirane-2-carboxamides under Acid-Catalyzed Rearrangements.

N-Benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, easily obtained from aromatic aldehydes and anilides of dichloroacetic acid under Darzens condensation conditions, proved to be excellent starting compounds for the synthesis of 3-hydroxyindolin-2-ones, cyclohepto[b]pyrrole-2,3-diones, and 1-azaspiro[4.5]deca-3,6,9-triene-2-ones via the C(sp2)-C(sp2) bond formation in the first case and C(sp2)-C(sp3) bond formation in the second and third cases. Under optimized reaction conditions, 3-hydroxyindolin-2-ones are obtained in a one-pot process, which involves the treatment of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides with CF3CO2H or AcOH/H2SO4. In the case of intramolecular cyclization, the detailed reaction channels depend strongly on the substituents present in the anilide component and in the aromatic ring of the aldehyde component of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, as well as the temperature and duration of the reaction. A combined experimental and DFT mechanistic study of the formation of 1-benzyl-3-hydroxy-4-arylquinolin-2(1H)-ones showed that there are three competing reaction channels: (a) ring-closure via the ipso site, (b) ring-closure via the 1,2-Cl shift, and (c) ring-closure via the ortho site. Such mechanistic insights enabled an effective one-pot gram-scale synthesis of viridicatin from benzaldehyde and 2,2-dichloro-N-(4-methoxybenzyl)-N-phenylacetamide.

Platinum(II) Complexes with 10-(Aryl)phenoxarsines: Synthesis, Cis/Trans Isomerization, and Luminescence.

Synthesis and structural and photophysical characterization of platinum dihalogenide complexes formulated as [PtHal2L2], where Hal = Cl and I, with different 10-(aryl)phenoxarsine ligands such as 10-(p-chlorophenyl)phenoxarsine, 10-(p-tolyl)phenoxarsine, and 10-(phenyl)phenoxarsine are reported. The structures of complexes were determined by NMR spectroscopy, mass spectrometry, and X-ray analysis. Cis/trans isomerism of the complexes in solution was studied by NMR spectroscopy. In the solid state, under UV irradiation, platinum diiodide trans complexes exhibit an intense orange-red emission, which was attributed to a metal halide-centered triplet state. The UV/vis absorption and emission properties were studied and rationalized by density functional theory (DFT) and time-dependent DFT calculations.

Tautomeric preference in lumazines, deazalumazines, isoalloxazines and pyrimidines and its effect on the reactivity of alkyl groups.

In lumazines, deazalumazines and pyrimidines, there are extremely low-energy "rare" tautomers (<2.3 kcal/mol), this fact perfectly explains the observed mobility of usually "non-labile" protons of methyl groups in such systems. In general, the dependence of tautomeric preference on structure correlates well with experimental findings. Thus, the activity of alkyl groups during biological transformations may be due to the presence of the corresponding thermodynamically stable tautomers.

Acid-Catalyzed Multicomponent Rearrangements via 2-((Quinoxalin-3(4H)-on-2-yl)(aryl)methylene)malononitriles, Generated In Situ, for Divergent Synthesis of Pyrroles with Different Substitution Patterns.

New three-component domino reactions, providing divergent approaches to multifunctionalized pyrroles with different substitution patterns, have been established (47 examples). In this work, a new rearrangement of quinoxalinones with the participation of the in situ-generated 2-en-1-imine moiety of the substituent at C3 makes it possible to construct two new heterocyclic systems, namely, a benzimidazolone and a pyrrole, simultaneously under one-pot reaction conditions. The reaction is easy to perform simply by mixing three common reactants of acetic acid with heating. Secondary amines or primary alcohols as the third component of the reaction, along with quinoxalin-3(4H)-ones and malononitrile, not only initiate the rearrangement but also are responsible for the nature of substituents at position 5 of the pyrrole ring in the newly formed new biheterocyclic system. The reaction proceeds smoothly and can be finished within 7 h, which makes workup convenient to give up to 97% chemical yields.

Acid-Catalyzed Rearrangement of 3-Cyanoquinoxalin-2(1H)-ones When Exposed to 1,2-Diaminobenzenes: Synthesis of 2,2'-Bibenzimidazoles.

A novel and efficient protocol for the synthesis of diversely substituted 2,2'-bibenzimidazoles from the reaction of 3-cyanoquinoxalin-2(1H)-ones with 1,2-diaminobenzenes has been developed, which proceeds through sequential nucleophilic addition and electrophilic substitution followed by a Mamedov rearrangement. The synthetic utility of this strategy was illustrated by the concise, one-pot synthesis of 5,5'-bi(2,2'-bibenzimidazoles) and aza-analogues of 2,2'-bibenzimidazole.

N-Methyl-d-glucamine-Calix[4]resorcinarene Conjugates: Self-Assembly and Biological Properties.

Deep insight of the toxicity of supramolecular systems based on macrocycles is of fundamental interest because of their importance in biomedical applications. What seems to be most interesting in this perspective is the development of the macrocyclic compounds with biocompatible fragments. Here, calix[4]resorcinarene derivatives containing N-methyl- d-glucamine moieties at the upper rim and different chemical groups at the lower rim were synthesized and investigated. These macrocycles showed a tendency to self-aggregate in aqueous solution, and their self-assembly abilities depend on the structure of the lower rim. The in vitro cytotoxic and antimicrobial activity of the calix[4]resorcinarenes revealed the relationship of biological properties with the ability to aggregate. Compared to macrocycles with methyl groups on the lower rim, calix[4]resorcinarenes with sulfonate groups appear to possess very similar antibacterial properties, but over six times less hemolytic activity. In some ways, this is the first example that reveals the dependence of the observed hemolytic and antibacterial activity on the lipophilicity of the calix[4]arene structure.

One-Pot Synthesis of 7-(Benzimidazol-2-yl)thioxolumazine and -lumazine Derivatives via H2SO4-Catalyzed Rearrangement of Quinoxalinones When Exposed to 5,6-Diamino-2-mercapto- and 2,5,6-Triaminopyrimidin-4-ols.

A facile approach to a range of substituted 7-(benzimidazol-2-yl)thioxolumazines [7-(benzimidazol-2-yl)-2-thioxo-2,3-dihydropteridin-4(1 H)-ones] and 7-(benzimidazol-2-yl)lumazines [7-(benzimidazol-2-yl)pteridine-2,4(1 H,3 H)-diones] is described. These new biheterocyclic systems are obtained via H2SO4-catalyzed rearrangement of quinoxalin-2-ones in the presence of 5,6-diamino-2-mercapto- and 2,5,6-triaminopyrimidin-4-ols. Thus, benzimidazole and pteridine rings are constructed in one synthetic step. A plausible ANRORC ( addition of nucleophile, ring opening and ring closure)-type reaction mechanism is proposed. Applying the rearrangement to the aza-analogue of 3-benzoylquinoxalin-2(1 H)-one-i.e., 3-benzoylpyrido[2,3- b]pyrazin-2(1 H)-one-with 5,6-diamino-2-mercaptopyrimidin-4-ol makes it possible to synthesize inaccessible 7-(1 H-imidazo[4,5- b]pyridin-2-yl)-6-phenyl-2-thioxo-2,3-dihydropteridin-4(1 H)-one. 7-(Benzimidazol-2-yl)-6-(2-fluorophenyl)-2-thioxo-2,3-dihydropteridin-4(1 H)-ones undergoes intramolecular nucleophilic substitution of fluorine by a nitrogen of the benzimidazole fragment with the formation of benzo[4',5']imidazo[1',2':1,2]quinolino[4,3- g]pteridine-2,4(1 H,3 H)-diones as new heterocyclic systems.

Synthesis of 3-Hydroxy-4-arylquinolin-2-ones Including Viridicatol via a Darzens Condensation/Friedel-Crafts Alkylation Strategy.

The new efficient synthesis of biologically important 3-hydroxy-4-arylquinolin-2-ones through the Darzens condensation (epoxidation) of dichloroacetanilides with aromatic aldehydes followed by one-pot dechlorative epoxide-arene cyclization is described. This methodology has been utilized for the synthesis of naturally occurring viridicatol, a fungal metabolite isolated from the penicillium species.

Rearrangement of quinoxalin-2-ones when exposed to enamines generated in situ from ketones and ammonium acetate: method for the synthesis of 1-(pyrrolyl)benzimidazolones.

The reaction of 3-benzoylquinoxalin-2(1H)-ones with enamines (generated in situ from ammonium acetate and the corresponding methylaryl(hetaryl)ketones) proceeds smoothly to give the corresponding substituted 1-(pyrrolyl)benzimidazolone derivatives in moderate yields through the novel rearrangement of 3-benzoylquinoxalin-2(1H)-ones involving a dual cleavage of the C3═N4 and C2-C3 bonds under mild conditions.

Quantum chemical calculations of (31)P NMR chemical shifts: scopes and limitations.

The aim of this work is to convince practitioners of (31)P NMR methods to regard simple GIAO quantum chemical calculations as a safe tool in structural analysis of organophosphorus compounds. A comparative analysis of calculated GIAO versus experimental (31)P NMR chemical shifts (CSs) for a wide range of phosphorus containing model compounds was carried out. A variety of combinations (at the HF, DFT (B3LYP and PBE1PBE), and MP2 levels using 6-31G(d), 6-31+G(d), 6-31G(2d), 6-31G(d,p), 6-31+G(d,p), 6-311G(d), 6-311G(2d,2p), 6-311++G(d,p), 6-311++G(2d,2p), and 6-311++G(3df,3pd) basis sets) were tested. On the whole, it is shown that, in contrast to what is claimed in the literature, high level of theory is not needed to obtain rather accurate predictions of (31)P CSs by the GIAO method. The PBE1PBE/6-31G(d)//PBE1PBE/6-31G(d) level can be recommended for express estimation of (31)P CSs. The PBE1PBE/6-31G(2d)//PBE1PBE/6-31G(d) combination can be recommended for routine applications. The PBE1PBE/6-311G(2d,2p)//PBE1PBE/6-31+G(d) level can be proposed to obtain better results at a reasonable cost. Scaling by linear regression parameters significantly improves results. The results obtained using these combinations were demonstrated in (31)P CS calculations for a variety of medium (large) size organic compounds of practical interest. Care has to be taken for compounds that may be involved in exchange between different structural forms (self-associates, associates with solvent, tautomers, and conformers). For phosphorus located near the atoms of third period elements ((CH3)3PS and P(SCH3)3) the impact of relativistic effects may be notable.

Reaction for the synthesis of benzimidazol-2-ones, imidazo[5,4-b]-, and imidazo[4,5-c]pyridin-2-ones via the rearrangement of quinoxalin-2-ones and their aza analogues when exposed to enamines.

A synthetically useful protocol has been developed for the preparation of highly functionalized N-pyrrolylbenzimidazol-2-ones. The reaction of variously substituted 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with commercially available enamines in acetic acid results in a rapid rearrangement and formation of N-pyrrolylbenzimidazol-2-ones in modest to excellent yields. The key step of the rearrangement involves the novel ring contraction of 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with enamines. In this case, the atom of carbon which is displaced from the pyrazine ring of quinoxalin-2(1H)-one becomes the fourth carbon atom of the newly formed pyrrole ring. The method is applicable for the aza analogues of quinoxalin-2(1H)-ones.

Novel indolin-2-one-substituted methanofullerenes bearing long n-alkyl chains: synthesis and application in bulk-heterojunction solar cells.

An easy, high-yield and atom-economic procedure of a C60 fullerene modification using a reaction of fullerene C60 with N-alkylisatins in the presence of tris(diethylamino)phosphine to form novel long-chain alkylindolinone-substituted methanofullerenes (AIMs) is described. Optical absorption, electrochemical properties and solubility of AIMs were studied. Poly(3-hexylthiophene-2,5-diyl) (P3HT)/AIMs solar cells were fabricated and the effect of the AIM alkyl chain length and the P3HT:AIM ratio on the solar cell performance was studied. The power conversion efficiencies of about 2% were measured in the P3HT/AIM devices with 1:0.4 P3HT:AIM weight ratio for the AIMs with hexadecyl and dodecyl substituents. From the optical and AFM data, we suggested that the AIMs, in contrast to [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), do not disturb the P3HT crystalline domains. Moreover, the more soluble AIMs do not show a better miscibility with the P3HT crystalline phase.

Structure and dynamics of P,N-containing heterocycles and their metal complexes in solution.

Conformations and dynamics of 1,5-diaza-3,7-diphosphacyclooctane (1) with chiral l-menthyl substituents on the phosphorus atoms and several metal complexes thereof were investigated by a variety of DNMR methods. In solution 1 adopts a C(2) symmetrical "crown"-like conformation (CW) and the conformational preference and dynamics of the complexes depend on the type of metal: for the Cu complex the CW form is preferred, whereas the Pd, Pt, or Mo complexes exist in an equilibrium of two "chair-boat"-like conformations (CB/CB*). The barriers of interconversion between these two conformations for the Pd and Pt complexes are about 2 times higher than for the Mo complex. Quantum chemical calculations (B3LYP/6-31G(d)) are in agreement with experimental findings.

Deoxygenation of some α-dicarbonyl compounds by tris(diethylamino)phosphine in the presence of fullerene C60.

The reactions of such cyclic α-diketones as acenaphthenequinone, aceanthrenequinone, and N-alkylisatins, with hexaethyltriaminophosphine in the presence of the fullerene C(60), lead to the formation of methanofullerene derivatives under mild conditions. This process proceeds via deoxygenation of the dicarbonyl compound by the P(III) derivative and is likely to involve the intermediate formation of α-ketocarbenes. The structure of some methanofullerenes has been confirmed by NMR and XRD. The electrochemical behavior of the methanofullerenes was also investigated.

Novel self-assembling system based on resorcinarene and cationic surfactant.

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties.

First representative of optically active P-L-menthyl-substituted (aminomethyl)phosphine and its borane and metal complexes.

The first representative of 1,5-diaza-3,7-diphosphacyclooctanes (1) with chiral L-menthyl substituents on the phosphorus atoms was obtained by condensation of L-menthylphosphine with formaldehyde and p-toluidine. This optically active cyclic bisphosphine readily forms a stable P,P-complex with borane (2) and P,P-chelate complexes with platinum(II) (3) and palladium(II) dichloride (4). The structure of the bisphosphine 1 in solution was elucidated by employing a variety of 1D/2D NMR correlation experiments, and the molecular structure of complex 3 was studied by X-ray crystallography.

Structure, conformation, and dynamics of P,N-containing cyclophanes in solution.

3D structures in solution of highly symmetrical N,P-containing macrocycles were established by a variety of 2D NMR correlation techniques. It was shown that a number of magnetically equivalent fragments in such symmetrical systems can be estimated by NMR diffusion measurement. The title compounds adopt a helical conformation of the macrocycles in solution. The extent of twisting and the size of the intramolecular cavity are determined by steric hindrance of the aromatic substituents on the exocyclic phosphorus atoms with phenylene and dimethylmethylene groups forming the macrocycle. In solution these macrocycles host aromatic guests inside the cavity.

GIAO DFT 13C/15N chemical shifts in regioisomeric structure determination of fused pyrazoles.

The combined use of two-dimensional NMR correlation experiments and gauge including atomic orbital density functional theory in (13)C NMR chemical shift (CS) calculations allowed reliable and simple structural determination of regioisomeric heterocyclic systems that originate from the reactions of acylquinolinones with substituted hydrazines. Moreover, the results of differential analysis between the calculated (15)N NMR CSs for hypothetical structures and the experimental data of the title azaheterocyclic systems were even more advantageous with respect to (13)C because there was no need for correlational analysis: structures of the regioisomeric compounds could be determined just by direct comparison.