Substituent effects and aromaticity of six-membered heterocycles

Structure, aromaticity, relative stability, and conformational flexibility of nitro and amino substituted monoheterocyclic analogous of benzene were studied by ab initio quantum-chemical method at MP2/aug-cc-pvDZ level of theory. Amino derivatives were found to be slightly less aromatic than nitro derivatives. Strong push–pull interactions were found in α- and γ-aminochalcogenopyrylium cations and, in less extent, in α- and γ-aminopyrydines. These molecules are less aromatic but more stable, as compare to their β-isomers. All heterocycles with 3rd and 4th row heteroatoms reveal C–NO₂ bond elongation accompanied by C–Heteroatom bond shortening in β-nitro isomers, and strong inequality of two endocyclic C–Heteroatom bonds in α-amino isomers.     

Substituent effects on the bond dissociation enthalpies of aromatic amines

Bond dissociation enthalpy differences, Z-X DeltaBDE = BDE(4-YC(6)H(4)Z-X) - BDE(C(6)H(5)Z-X), for Z = CH(2) and O are largely independent of X and are determined mainly by the stabilization/destabilization effect of Y on the 4-YC(6)H(4)Z(*) radicals. The effects of Y are small (< or =2 kcal/mol for all Y) for Z = CH(2), but they are large for Z = O, where good correlations with sigma(p)(+)(Y) yield rho(+) = 6.5 kcal/mol. For Z = NH, two sets of electrochemically measured N-H DeltaBDEs correlate with sigma(p)(+)(Y), yielding rho(+) = 3.9 and 3.0 kcal/mol. However, in contrast to the situation with phenols, these data indicate that the strengthening effect on N-H BDEs of electron-withdrawing (EW) Y's is greater than the weakening effect of electron-donating (ED) Y's. Attempts to measure N-H DeltaBDEs in anilines using two nonelectrochemical techniques were unsuccessful; therefore, we turned to density functional theory. Calculations on 15 4-YC(6)H(4)NH(2) gave N-H DeltaBDEs correlating with sigma(p)(+) (rho(+) = 4.6 kcal/mol) and indicated that EW and ED Y's had comparable strengthening and weakening effects, respectively, on the N-H bonds. To validate theory by connecting it to experiment, the N-H DeltaBDEs of four 4,4'-disubstituted diphenylamines and five 3,7-disubstituted phenothiazines were both calculated and measured by the radical equilibration EPR technique. For all compounds, theory and experiment agreed to better than 1 kcal/mol. Dissection of N-H DeltaBDEs in 4-substituted anilines and O-H DeltaBDEs in 4-substituted phenols into interaction enthalpies between Y and NH(2)/OH (molecule stabilization/destabilization enthalpy, MSE) and NH*/O* (radical stabilization/destabilization enthalpy, RSE) reveals that for both groups of compounds, ED Y's destabilize the molecule and stabilize the radical, while the opposite holds true for EW Y's. However, in the phenols the effects of substituents on the radical are roughly 3 times as great as those in the molecule, whereas in the anilines the two effects are of comparable magnitudes. These differences arise from the stronger ED character of NH(2) vs OH and the weaker EW character of NH* vs O*. The relatively large contributions to N-H BDEs in anilines arising from interactions in the molecules suggested that N-X DeltaBDEs in 4-YC(6)H(4)NH-X would depend on X, in contrast to the lack of effect of X on O-X and CH(2)-X DeltaBDEs in 4-YC(6)H(4)O-X and 4-YC(6)H(4)CH(2)-X. This suggestion was confirmed for X = CH(3), H, OH, and F, for which the calculated NH-X DeltaBDEs yielded rho(+) = 5.0, 4.6, 4.0, and 3.0 kcal/mol, respectively.     

Substituent and solvent effects on tautomeric equilibria of barbituric acid derivatives and isoterically related compounds

N-Mono and N,N-dialkyl/diarylbarbituric acids exist in solution as a single tautomer. The ¹³C nmr spectroscopy shows that they are present in the triketo form in a number of polar and non-polar solvents. 2-Thiobarbituric acid derivatives, however, show extensive tautomerization. Their ¹³C chemical shift assignments were achieved by utilizing models 11a , 11c , 12b and 12d and from which relative tautomer distribution ratios were determined. These ratios were correlated with the dielectric constant of the various solvents (?). Thio-barbituric acids also formed adducts with solvents having carbonyl groups, characteristic observed only with barbiturates possessing the thione or thiophenolic group. 6-Amino and 6-methyluracils and thiouracils exist in DMSO solution as stable “ene” forms as do orotic acid, 24 , and its thio analogue 25. Compound 25 undergoes disproportionantion and tautomerization when heated or on prolonged standing in solution. Literature contradictions regarding the structure of “4,6-dihydroxypyrimidine,” 26 , were resolved and its tautomers in solution correctly assigned by ¹³C nmr. Anions of barbiturics and related systems exist in one of the two possible types A and B, depending on whether ring nitrogens are substituted (type A), or not (type B). Rapid H/D exchange at C₅ was evident from C-deuterium coupling. The redistribution of charge through C₄(C₆) carbonyl groups shown by ¹³C shifts of carbonyl carbon atoms of up to 10 ppm as compared to the CO carbons of the neutral species was evident.     

Molar enthalpies of formation of LnAl2 compounds

The enthalpy of solution of Eu in Al and the standard molar enthalpy of formation of LnAl₂ (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) were determined by dissolution calorimetry, using a calorimeter based on liquid aluminium. Experimental results are compared with model predictions.     

CORAL: QSPRs of enthalpies of formation of organometallic compounds

Available on the Internet the CORAL software gives reasonable good prediction for standard enthalpy of formation for selected organometallic compounds (n = 132). The approach is tested using five random splits of the considered data into the sub-training set (n = 32–49), calibration set (n = 36–51), test set (n = 10–29), and the validation set (n = 22–41). Compounds of the validation set are not involved in building up the models. The average statistical quality of prediction is the following: correlation coefficient ( $\overline{R^{2}} )$ R 2 ¯ ) $0.991\pm 0.005$ 0.991 ± 0.005 and standard error of estimation ( $\overline{s} )$ s ¯ ) $22.9 \pm 5.6$ 22.9 ± 5.6  kJ/mol.     

The standard enthalpies of formation of alkoxy-NNO-azoxy compounds

The standard enthalpies of combustion Δ_c H ^o and formation Δ_f H ^o of seven alkoxy-NNO-azoxy compounds containing the-N⁺(O^?)=NO-characteristic group were determined by combustion in a calorimetric bomb in the atmosphere of oxygen. The contribution of this group to the Δ_f H ^o enthalpies of the substances studied was calculated. The Δ_f H ^o enthalpies found by the method of group contributions were in satisfactory agreement with experimental data.     

Liquid-phase synthesis of 2-substituted benzimidazoles, benzoxazoles and benzothiazoles

A novel acid fluoride for use in the liquid-phase synthesis of substituted benzimidazoles, benzoxazoles and benzothiazoles was developed. Its synthetic utility is exemplified by a structurally diverse set of aromatic heterocycles. Final cleavage is achieved by treatment with sodium methoxide in methanol for 12 h. The corresponding benzimidazoles, benzoxazoles and benzothiazoles were obtained in good isolated yields (22-62%, four steps).     

(Alpha-aminoacyl)amino-substituted heterocycles and related compounds

N-Protected-(aminoacyl)benzotriazoles 1a-e, g, i, j, 1a'-c' convert heterocyclic amines of the following series: thiazoles (3a and 3a'), benzothiazoles (3b and 3b'), benzimidazoles (3c and 3c'), thiadiazoles (3d), pyrimidones (9a, b, a'), pyrazoles (11a, b), and pyridines (13a-g, 13d') under microwave irradiation, into N-substituted amides in yields of 40-98% (average 76%). N-Protected peptidoylbenzotriazoles 6a, b similarly afforded C-terminal N-protected dipeptidoyl amides 7a, b (52-60%).     

Samarium diiodide promoted formation of 1,2-diketones and 1-acylamido-2-substituted benzimidazoles from N-acylbenzotriazoles

N-Acylbenzotriazoles, when treated with samarium diiodide in THF, undergo self-coupling reaction to afford 1,2-diketones in good to excellent yields; while when treated with samarium diiodide in CH₃CN, they undergo ring-opening reaction to afford 1-acylamido-2-alkyl (or aryl) benzimidazoles in reasonable to good yields. A plausible mechanism was suggested.     

Imidazolium chloride-catalyzed synthesis of benzimidazoles and 2-substituted benzimidazoles from o-phenylenediamines and DMF derivatives

A facile, general, and economical synthesis of diversely functionalized benzimidazoles and 2-substituted benzimidazoles has been realized via the imidazolium chloride-catalyzed cyclization of o-phenylenediamines with DMF derivatives. This protocol shows a broad substrate scope for aliphatic, aromatic, and heteroaromatic amides. A series of benzimidazoles and 2-substituted benzimidazoles have been obtained in moderate to excellent yields.     

Substituent effects in second row molecules : Silicon-containing compounds

Substituent interaction energies are calculated by ab initio molecular orbital methods for the two series SiH₂X^- and SiH₃X for the directly bound substituents X = BH₂, CH₃, NH₂, OH, F and the results compared with those for the corresponding first row species. Interactions with the groups NH₂, OH, F are as large in the neutral as in the anionic series and this is attributed to the presence of important π-bonding interactions, supplementing the effects of inductive withdrawal of σ-electrons. The restoration of charge neutrality by π-donation to silicon is more important in the neutral molecules, σ-electron transfer from silicon in the anions. π-Bonding with the π-acceptor substitutent BH₂ is favourable, as it is in the CH₃X and CH₂X^- systems, but with π-donor substituents the interactions are always destabilizing.     

Standard enthalpies of formation of selected XYZ half-Heusler compounds

The standard enthalpies of formation of selected ternary half-Heusler type compositions XYZ (X = Au, Co, Fe, Ir, Ni, Pd, Pt, Rh, Ru; Y = Hf, Mn, Ti, Zr; Z = Ga, Sn) were measured using high temperature direct reaction calorimetry. The measured standard enthalpies of formation (in kJ/mole of atoms) of the half-Heusler compounds (prototype MgAgAs, Pearson symbol cF12, space group F-43m) are, IrMnSn (−29.4 ± 1.8); NiTiSn (−52.6 ± 2.4); PtHfSn (−98.8 ± 3.4); PtMnSn (−55.8 ± 2.6); PtTiSn (−93.6 ± 3.3); PtZrSn (−104.9 ± 3.8); for the B2 compound (prototype CsCl, Pearson symbol cP2, space group Pm-3m), RuMnGa (−26.9 ± 1.7); for the C1 structured (prototype CaF₂, Pearson symbol cF12, space group Pm-3m) or the C1_b structured compound IrMnGa (−40.9 ± 1.7). Indicative standard enthalpies of formation of the following compounds were obtained, half-Heusler compounds AuMnSn, CoTiSn, IrZrSn, NiHfSn, NiZrSn, PdHfSn, PdZrSn, RhTiSn; Heusler compound (prototype Cu₂MnAl, Pearson symbol cF16, space group Fm-3m) RhMnSn; hexagonal compound (prototype BeZrSi, Pearson symbol hP6, space group P6₃/mmc) PtMnGa and another type of hexagonal compound (prototype RhHfSn, Pearson symbol hP18, space group P-62c) RhHfSn, IrZrsn, RhZrSn. Values were compared with ab initio calculations from AFLOW and OQMD. Lattice parameters of these compounds were determined using X-ray diffraction (XRD) analysis. Microstructures were characterized using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Selected alloys were further annealed to investigate phase transformations and phase relationships.     

Substituent effects in formally quintuple-bonded ArCrCrAr compounds (Ar = terphenyl) and related species

The effects of different terphenyl ligand substituents on the quintuple Cr-Cr bonding in arylchromium(I) dimers stabilized by bulky terphenyl ligands (Ar) were investigated. A series of complexes, ArCrCrAr (1-4; Ar = C6H2-2,6-(C6H3-2,6-iPr2)2-4-X, where X = H, SiMe3, OMe, and F), was synthesized and structurally characterized. Their X-ray crystal structures display similar trans-bent C(ipso)CrCrC(ipso) cores with short Cr-Cr distances that range from 1.8077(7) to 1.8351(4) A. There also weaker Cr-C interactions [2.294(1)-2.322(2) A] involving an C(ipso) of one of the flanking aryl rings. The data show that the changes induced in the Cr-Cr bond length by the different substituents X in the para positions of the central aryl ring of the terphenyl ligand are probably a result of packing rather than electronic effects. This is in agreement with density functional theory (DFT) calculations, which predict that the model compounds (4-XC6H4)CrCr(C6H4-4-X) (X = H, SiMe3, OMe, and F) have similar geometries in the gas phase. Magnetic measurements in the temperature range of 2-300 K revealed temperature-independent paramagnetism in 1-4. UV-visible and NMR spectroscopic data indicated that the metal-metal-bonded solid-state structures of 1-4 are retained in solution. Reduction of (4-F3CAr')CrCl (4-F3CAr' = C6H2-2,6-(C6H3-2,6-iPr2)2-4-CF3) with KC8 gave non-Cr-Cr-bonded fluorine-bridged dimer {(4-F3CAr')Cr(mu-F)(THF)}2 (5) as a result of activation of the CF3 moiety. The monomeric, two-coordinate complexes [(3,5-iPr2Ar*)Cr(L)] (6, L = THF; 7, L = PMe3; 3,5-iPr2Ar* = C6H1-2,6-(C6H-2,4,6-iPr3)2-3,5-iPr2) were obtained with use of the larger 3,5-Pri2-Ar* ligand, which prevents Cr-Cr bond formation. Their structures contain almost linearly coordinated CrI atoms, with high-spin 3d5 configurations. The addition of toluene to a mixture of (3,5-iPr2Ar*)CrCl and KC8 gave the unusual dinuclear benzyl complex [(3,5-iPr2Ar*)Cr(eta3:eta6-CH2Ph)Cr(Ar*-1-H-3,5-iPr2)] (8), in which a C-H bond from a toluene methyl group was activated. The electronic structures of 5-8 have been analyzed with the aid of DFT calculations.     

One-pot synthesis of nitrogen heterocycles initiated by regio- and diastereoselective carbon-carbon bond formation of bifunctional carbonyl compounds

We report a one-pot synthesis of nitrogen heterocyclic compounds initiated by the allylation of the formyl group of bifunctional carbonyl compounds accompanying chemo-, regio-, and diastereoselective carbon-carbon bond formation in side chain moieties.     

Benzazoles. 3*. Synthesis and arylsulfonylation of 2-substituted benzimidazoles

2-Alkylbenzimidazoles have been obtained from o-nitroaniline and aliphatic carboxylic acids by reductive cyclization. Interaction of the former with arenesulfonyl chlorides led to the synthesis of 2-alkyl-1-arylsulfonylbenzimidazoles, the yield of which depended on the structure of the substituent in position 2.     

Infrared study of solvent-solute interactions of 1-substituted 2-pyrrolidinones and related compounds

Summary The wavenumbers of the carbonyl stretching vibrations of 2-pyrrolidinone (P), 1-methyl-2-pyrrolidinone (MP), 1-isopropyl-2-pyrrolidinone (IPP), 1-(2-hydroxyethyl)-2-pyrrolidinone (HEP), 2-oxobenzothiazole (OBT), and 3-octyl-2-oxobenzothiazole (OOBT) were measured inn-hexane/CDCl₃, acetonitrile/D₂O, methanol/D₂O, and 2-butoxyethanol/D₂O mixtures and compared with similar data for 1-cyclohexyl-2-pyrrolidinone (CHP) and dimethylacetamide (DMA). The dependencies of the wavenumbers on the mole fraction of the less polar cosolvent in binary mixtures allow a distinction and assignment of all species resulting from weak solute-solvent and solute-solute interactions. The slopes of the dependencies of the wavenumbers on the mole fraction for similar intermolecular species inn-hexane/CDCl₃ mixtures correlate well with the relative hydrogen bond basicities (i.e. hydrogen bonding abilities with phenol) and reveal that the solvent sensitivities significantly depend on the steric requirements in the vicinity of the C=O group. On the other hand, the slopes of similar dependencies in acetonitrile/D₂O mixtures are proportional to the electron donating effects of alkyl groups attached to the nitrogen atom of the pyrrolidinone ring. In the case of mixtures formed by two strongly hydrogen bonding cosolvents (alcohols/D₂O), a competitive equilibrium occurs between the hydrogen bonding tendency of both cosolvents and 1-substituted 2-pyrrolidinones. In solutions of 1-substituted 2-pyrrolidinones in water-rich 2-butoxyethanol/D₂O mixtures, microheterogeneous domains occur before classic mixtures of two polar liquids are formed.

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Infrarotuntersuchungen über Wechselwirkungen von 1-substituierten 2-Pyrrolidinonen und verwandten Verbindungen mit Lösungsmitteln

Zusammenfassung Die Wellenzahlen der Carbonylstreckschwingungen von 2-Pyrrolidinon (P), 1-Methyl-2-pyrrolidinon (MP), 1-Isopropyl-2-pyrrolidinon (IPP), 1-(2-Hydroxyethyl)-2-pyrrolidinon (HEP), 2-Oxobenzothiazol (OBT) und 3-Octyl-2-oxobenzothiazol (OOBT) wurden inn-Hexan/CDCl₃, Acetonitril/D₂O, methanol/D₂O und 2-Butoxyethanol/D₂O gemessen und mit den entsprechenden Daten für 1-Cyclohexyl-2-pyrrolidinon (CHP) und Dimethylacetamid (DMA) verglichen. Die Abhängigkeit der Wellenzahlen vom Molenbruch des weniger polaren Lösungsmittels in binären Mischungen erlaubt eine Unterscheidung und Zuordnung aller durch schwache Wechselwirkungen zwischen gelöster Substanz und Lösungsmittel bzw. durch Wechselwirkungen der gelösten Moleküle untereinander entstehenden Spezies. Für ähnliche Moleküle inn-Hexan/CDCl₃ — Mischungen korrelieren die Steigungen der Abhängigkeiten der Wellenzahlen vom Molenbruch gut mit den relativen Basizitäten der Wasserstoffbrückenbindungen (d.h. mit der Fähigkeit zur Ausbildung von Wasserstoffbrückenbindungen mit Phenol) und beweisen, daß die Lösungsmittelabhängigkeiten wesentlich von sterischen Faktoren in der Umgebung der Carbonylgruppe abhängen. Andererseits sind die Steigungen entsprechender Korrelationen in Acetonitril/D₂O — Mischungen zur Elektronendonatorfähigkeit von an das Stickstoffatom des Pyrrolidinonrings gebundenen Alkylgruppen proportional. Im Fall von Mischungen aus zwei stark wasserstoffbrückenbildenden Lösungsmitteln (Alkohole/D₂O) stellt sich ein kompetitives. Gleichgewicht zwischen der Tendenz zur Wasserstoffbrückenbindungsbildung beider Lösungsmittel und den 1-substituierten 2-Pyrrolidinonen ein. In Lösungen von 1-substituierten 2-Pyrrolidinonen in 2-Butoxyethanol/D₂O — Mischungen mit hohem Wasseranteil treten vor der Ausbildung klassischer Mischungen zweier polarer Flüssigkeiten mikroheterogene Domänen auf.