A quantitative structure-activity relationship study of antifungal analogues of 3,4-substituted 5-((1H-1, 2, 4-triazol-1-yl)methyl)-4H-1,2,4-triazole

A series of 5-((1H-1, 2, 4-triazol-1-yl)methyl)-4H-1,2,4-triazole derivatives were prepared and evaluated for their antifungal activities. Quantitative structure–activity relationship studies were performed on these compounds using physicochemical parameters as independent parameters and antifungal activity as a dependent parameter, where antifungal activity correlated best (correlation coefficient r > 0.8) with physicochemical parameters (Hammett’s constants σ _p , F) and van der Waals volume V ₁. Results are interpreted on the basis of multiple regression and cross-validation methodology. Furthermore, the domain of applicability which indicates the area of reliable predictions is defined. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Chemical structures of A1–26 and A39; synthetic procedures; synthesis schemes; mps, yields, ¹H NMR; elemental analyses of compounds and single crystal X-ray diffraction of compounds.     

Hydrogen-bonded mononuclear nickel(II) benzoate complexes: synthesis and structural studies

[Tp^Ph,MeNi(Cl)Pz^Ph,MeH] (1) has been synthesized by the reaction of hydrotris(3-phenyl-5-methyl-pyrazol-1-yl) borate [Tp^Ph,Me], NiCl₂ · 6H₂O and 3-phenyl-5-methyl-pyrazole [Pz^Ph,MeH]. The reaction of 1 with variously substituted sodium p–X–benzoates resulted in the formation of complexes of the type [Tp^Ph,MeNi(p–X–OBz)Pz^Ph,MeH] (X = H for 2, F for 3, Cl for 4, NO₂ for 5, Me for 6, OMe for 7, OH for 8, CHO for 9 and CN for 10). Single crystal X-ray studies suggest that all these complexes have a five-coordinate metal center and the benzoate groups are monodentate in a square pyramidal geometry. The X-ray studies also reveal that the uncoordinated oxygen atom of the benzoate forms intramolecular hydrogen-bonds with the NH group of the coordinated pyrazole. The substituents present on the benzoate ring are involved in different types of intermolecular interactions and the complexes exhibit different crystal packing. Complexes 2–10 were tested for superoxide dismutase activity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis and bactericidal activities of novel pyrazole-1-carbothioamide derivatives

4-(2-Hydroxy-phenyl)-but-3-en-2-one (1) was prepared via condensation of salicylaldehyde with acetone, and then reaction of the ketone 1 with thiosemicarbazide was accompanied by cyclization to give substituted pyrazole (2). Seven new 5-(2-hydroxy-phenyl)-3-methyl-4,5-dihydropyrazole-1-carbothioamide derivatives (3a–3g) were synthesized by the acylation of 2 and characterized by means of elemental analysis, infrared (IR), and ¹H nuclear magnetic resonance (NMR). The compounds 3c, 3d, and 3g showed certain bactericidal activity against E. coli; while compound 3g showed certain bactericidal activity against P. vulgaris. Translated from Chinese Journal of Applied Chemistry, 2006, 23(12): 1355–1358 [译自: 应用化学]     

Structural studies of seven homoisoflavonoids, six thiohomoisoflavonoids, and four structurally related compounds

¹H and ¹³C NMR chemical shifts have been determined and assigned based on PFG ¹H, ¹³C HMQC, and HMBC experiments for 3-(4′-X-benzyl)-4-chromenones (Ia, X = CN and Ib, X = NO₂), 3-(4′-X-benzyl)-4-thiochromenones (IIa, X = Cl and IIb, X = Br), (E)-3-(4′-X-benzylidene)-4-chromanones (IIIa–IIIe, X = OCH₃, CH₃, Cl, N(CH₃)₂, Br), (Z)-3-(4′-X-benzylidene)4-thiochromanones (IVa–IVd, X = Cl, Br, F, OCH₃), 2-benzyl-1,2,3,4-tetrahydro-1-naphthol (V), 2-benzyl- and (E)-2-benzylidene-1-tetralones (VI and VII), and (E)-2-benzylidene-1-benzosuberol (VIII). The crystal structures have been determined for the following seven compounds: derivatives of 4-chromanones (IIIa–IIId), 1-tetrahydronaphtol (V), and 1-tetralones (VI and VII). The molecular features and intermolecular interactions in crystal state have been discussed.     

Syntheses,spectroscopic and crystallographic characterizations of 4-nitrobenzyloxy derivatives and benzofurans from <Emphasis Type="Italic">ortho</Emphasis>-substituted benzaldehydes and 4-nitrobenzyl bromide

A series of benzyloxybenzaldehyde derivatives (1–3) were prepared by the reactions of 4-nitrobenzyl bromide with 4-hydroxy-3-methoxybenzaldehyde (vanillin), 2-hydroxy-3-methoxybenzaldehyde (o-vanillin) and 2-hydroxy-4-methoxybenzaldehyde. When the reaction time is quite long, benzofuran derivatives (4 and 5) were obtained by the reactions of ortho-hydroxyaldehydes with the 4-nitrobenzyl bromide. Condensation reactions among the three benzyloxybenzaldehyde derivatives (1–3) with 2-aminomethylfuran (furfurylamine) yielded the new imine compounds (6–8). The structures of these aldehydes (1–3), benzofuran derivatives (4 and 5) and imine compounds (6–8) were confirmed on the basis of elemental analyses, IR, ¹H NMR and ¹³C NMR and mass spectroscopy. The solid-state structures of compounds 4–6 were determined by single-crystal X-ray crystallography.     

Effects of fused benzene rings on tautomerizations and inversions of benzo, azabenzo, and oxabenzocycloheptatrienes at theoretical levels

Biologically important bicyclic species, including 6H-, 6H-6-aza-, and 6-oxabenzocycloheptatrienes (in which the benzene moiety is fused meta with respect to the tetrahedral constituents: –CH₂–, –NH–, and –O–, respectively), show strong shifts of tautomerizations in favor of the corresponding tricyclic benzonorcaradienes (with ΔH values of −11.49, −14.55, and −19.20 kcal mol⁻¹, respectively), at B3LYP/6-311++G**//B3LYP/6-31G*, and MP2/6-311++G**//MP2/6-31G* levels, and at 298 K. In contrast, such shifts are strongly disfavored by the isomeric bicyclic species in which the benzene moieties are fused ortho or para with respect to –CH₂–, –NH–, and –O–, respectively. Hence for species with ortho benzene rings including 5H-, 5H-5-aza- and 5-oxabenzocycloheptatrienes, tautomerization ΔH values are 30.76, 31.89, and 25.27 kcal mol⁻¹, respectively, while for species with para fused benzene moieties including 7H-, 7H-7-aza-, and 7-oxabenzocycloheptatrienes, tautomerization ΔH values are 24.12, 26.00, and 19.55 kcal mol⁻¹, respectively. NICS calculations are successfully used to rationalize these results. The calculated energy barriers for inversion of the seven-membered rings of bicyclic species predict a dynamic nature for all the structures except for the virtually planar 6H-6-aza- and 6-oxabenzocycloheptatrienes. Finally, our theoretical data are compared to the experimental results where available. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Iron Pentacarbonyl Promoted Addition of CO and MeOH to 1,4-Disubstituted-1,3-butadiyne and Formation of Vinylallyl and Butatriene Ligand Systems

Abstract  Photochemical reaction of methanol solution containing 1,4-diferrocenyl- or 1,4-diphenyl-1,3-butadiynes and iron pentacarbonyl into which CO was constantly bubbled, yielded diiron hexacarbonyl complexes of cumulene ligand systems, [η¹: η³-{RCHC₂CR(COOMe)}Fe₂(CO)₆] (1; E, R = Fc, 2; Z, R = Fc, 5; E, R = Ph, 6; Z, R = Ph) and [η³: η³-{RCHC₂CR(COOMe)}Fe₂(CO)₆] (3; E, R = Fc, 7; E, R = Ph), formed by 1,4-addition of –COOMe and –H to the butadiynes. Additionally, diferrole, [Fe(CO)₄{C(O)CC(Fc)C(O)}₂],4 was obtained in minor quantity. Compounds 1, 2, 5 and 6 contain vinylallyl carbon framework which is stabilized by MeOC=O → Fe bond along with η¹: η³ coordinated Fe₂(CO)₆ unit. Compounds 3 and 7 contain butatriene units which are stabilized by η³: η³ coordinated Fe₂(CO)₆ unit. Characterization of the new compounds was carried out by IR and ¹H and ¹³C NMR spectroscopy and by mass spectrometry. Molecular structures of 2–7 were established by single crystal X-ray diffraction methods. Graphical Abstract  Diiron hexacarbonyl complexes of cumulene ligand systems, [η¹: η³ {RCHC₂CR(COOMe)}] (1; E, R = Fc, 2; Z, R = Fc, 5; E, R = Ph, 6; Z, R = Ph) and [η³: η³-{RCHC₂CR(COOMe)}] (3; E, R = Fc, 7; E, R = Ph) were obtained from photochemical reactions between Fe(CO)₅, CO and methanol. Yield of the minor product, the diferrole, 4, was improved when the photoreaction was carried out in hexane in place of methanol      

Synthesis and characterization of palladium(II) complexes of thioureas. X-ray structures of [Pd( N , N ′-dimethylthiourea)4]Cl2?·?2H2O and [Pd(tetramethylthiourea)4]Cl2

Palladium(II) complexes of thiones having the general formula [Pd(L)₄]Cl₂, where L = thiourea (Tu), methylthiourea (Metu), N,N′-dimethylthiourea (Dmtu), and tetramethylthiourea (Tmtu) were prepared by reacting K₂[PdCl₄] with the corresponding thiones. The complexes have been characterized by elemental analysis, IR and NMR spectroscopy, and two of these, [Pd(Dmtu)₄]Cl₂ · 2H₂O (1) and [Pd(Tmtu)₄]Cl₂ (2), by X-ray crystallography. An upfield shift in the >C=S resonance of thiones in ¹³C NMR and downfield shift in N–H resonance in ¹H NMR are consistent in showing sulfur coordination with palladium(II). The crystal structures of the complexes show a square-planar coordination environment around the Pd(II) ions with the average cis and trans S–Pd–S bond angles of 89.64° and 173.48°, respectively. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

Complete basis set,hybrid-DFT study,and NBO interpretations of the conformational behavior of 1,2-dihaloethanes

The conformational behavior of 1,2-difluoroethane (1), 1,2-dichloroethane (2), 1,2-dibromoethane (3), and 1,2-diiodoethane (4) have been analyzed by means of complete basis set CBS-QB3, hybrid-density functional theory (B3LYP/Def2-TZVPP) based methods and natural bond orbital (NBO) interpretation. Both methods showed the expected greater stability of the gauche conformation of compound 1 compared to its anti conformation. Contrary to compound 1, the anti conformations of compounds 2–4 are more stable than their gauche conformation. The stability of the anti conformation compared to the gauche conformation increases from compound 1 to compound 4. The NBO analysis of donor–acceptor (σ → σ*) interactions showed that the generalized anomeric effect (GAE) is in favor of the gauche conformation of compound 1. Contrary to compound 1, GAE is in favor of the anti conformations of compounds 2–4. The GAE values calculated (i.e., GAE_anti − GAE_gauche) increase from compound 1 to compound 4. On the other hand, the calculated dipole moment values for the gauche conformations decrease from compound 1 to compound 4. In the conflict between the GAE and dipole moments, the former succeeded in accounting for the increase of the anti conformation stability from compound 1 to compound 4. There is a direct correlation between the calculated GAE, ∆[r _c–c(G) − r _c–c(A)] and ∆[r _c–x(A) − r _c–x(G)] parameters. The correlations between the GAE, bond orders, total steric exchange energies (TSEEs), ΔG _{Anti–Gauche}, ΔG ^‡(Gauche → Gauche′, C _2v), ΔG ^‡(Anti → Gauche, C ₂), dipole–dipole interactions, structural parameters, and conformational behaviors of compounds 1–4 have been investigated.     

Experimental and theoretical studies on the functionalization reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid and-acid chloride with various aminophenols

The 1H-pyrazole-3-carboxylic acid 1 was converted via reactions of its acid chloride 2 with various aminophenol derivatives 3a--d into the corresponding N-(hydroxyphenyl)-1H-pyrazole-3-carboxamides 4a--d, respectively, in good yields (34–53%). The reactions of 1 or 2 with 3 in benzene or toluene for 5–7 h with no catalytic amounts of base lead to the formation of the products 4. The structures of all new synthesized compounds were established by the ¹³C NMR,¹H NMR, IR, masss spectroscopic data and elemental analyses. The reaction mechanism of 2 with 3 was studied by means of the RHF/3-21G and RHF/6-31G method.     

1H,13C NMR spectral data for α-, β-, and γ-lewisites and identification ofcis,trans, trans-γ-lewisite as a new isomer

The¹H and¹³C NMR spectral parameters of α-, β-, and y-lewisites1–5 were obtained and a new isomer,cis,trans,trans-γ-lewisite5, was isolated and identified on the basis of chemical shifts, relative intensities of the signals, and the intra-chain (³ J _hh ,³ J _ch ) and interchain (³ J _casch ) coupling constants. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1833–1835, October, 1993.     

Conformational analysis of N-isopropylbenzohydroxamic acids: crystal structure, DFT, and NMR studies

X-ray crystal structure determinations together with density functional theory (DFT) calculations in vacuo and NMR studies in solution have been carried out for 4-MeOC₆H₄CONPrⁱOH 2a and 3,5-(NO₂)₂C₆H₃CONPrⁱOH 2b. The results were compared with that for the respective N-methyl benzohydroxamic acids. For crystal structures as well as for DFT-optimized geometries of 2 (both isomers) in vacuo, the effect of substituents in aromatic ring manifested by changing of charges is inconspicuous. Studies of potential energy surfaces showed that libration barrier around ω ₁ = 0° is low enough to make electron conjugation feasible, and that for 2b rotation barrier around C(O)N bond is higher by 6 kcal/mol and additionally, that rotation around N–C bond is hindered. A careful analysis of low-temperature ¹H NMR spectra confirmed the greater stability of Z-2a, the greater rigidity of E-2b and the influence of solvent on both isomers population. Despite solvent-dependent conformational alteration, both 2a and 2b crystallize exclusively as E isomers from ethyl acetate solution. Correlations of absolute ¹H, ¹³C, and ¹⁵N shielding calculations with experimental data were also analyzed. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis of 2-aryl-4-(4-<Emphasis Type="Italic">β</Emphasis>-D-allopyranosyloxyphenyl)4,6,7,8-tetrahydroquinolin-5(1<Emphasis Type="Italic">H</Emphasis>)-one derivatives under solvent-free conditions and study of sedative activity

Under solvent-free conditions, syntheses of 2-aryl-4-(4-β-D-allopyranosyloxyphenyl)-4,6,7,8tetrahydroquinolin-5(1H)-one derivatives were carried out from chalcone (2a–2e), cyclohexane-1,3-dione (3), and NH₄OAc in excellent yield without using any catalysts. The structure of the new compounds were characterized by ¹H NMR, IR, and HR-MS spectroscopy. The preliminary bioassay tests of 4a–4j indicated that compounds 4b, 4e, and 4f exhibited potent sedative and hypnotic activity.     

A new flavonol derivative from <Emphasis Type="Italic">Fagopyrum dibotrys</Emphasis>

A new flavonol derivative 3, 8-dihydroxy-10-methoxy-5-H-isochromeno[4, 3-b]chromen-7-one (1) together with four known compounds, glutinone (2), luteolin (3), acacetin 7-O-α-L-rhamnopyranosyl- (1→6)-β-D-glucopyranoside (4), and rutin (5) were isolated from the dried roots of Fagopyrum dibotrys. Their structures were determined by UV, IR, MS, ¹H, and ¹³C NMR spectroscopic analysis, including 2D NMR. Published in Khimiya Prirodnykh Soedinenii, No. 6, pp. 567–568, November–December, 2008.     

Experimental and theoretical studies on the reactions of 1-amino-5-benzoyl-4-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrimidine-2-one/-thione compounds with ethyl acetoacetate

The reaction of 1-amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidin-2(1H)-one/-thione (1a,b) with ethyl acetoacetate (EA) afforded moderate to good yields (59–63%) of ethyl 2-methyl-4-(4-methylbenzoyl)-5-(4-methylphenyl)-7-oxo/-thioxo-3,3a-dihydropyrazolo[1,5-c]pyrimidine-3-carboxylate (2a,b). The newly synthesized compounds were characterized by elemental analyses, IR, ¹H and ¹³C NMR spectral data. All were compared with their previous analogues. The reaction mechanism of 1 with EA was studied by means of the B3LYP/6-31G(d,p) method. In addition, for reactants Fukui functions were performed using the data calculated with the Becke3–Lee–Yang–Parr (B3LYP) hybrid function.     

New Molybdaborane Clusters with a Bridged Phosphido Ligand

Abstract  

Treatment of [Cp*MoCl₄], 1 (Cp* = η⁵-C₅Me₅), with [LiBH₄.thf] in toluene at −40 °C, followed by thermolysis with [(thf)Li{CH(PPh₂–BH₃)₂}] results in the formation of a new class of phosphido bridged molybdaborane [(Cp*Mo)₂B₄H₇(μ-PPh₂)], 2 which has been characterized crystallographically. In addition, the above reaction also produces known [(Cp*Mo)₂B₅H₉], 3 and an unusual molybdaborane [(Cp*Mo)₂B₅H₈(O ⁱ Pr)], 4 ( ⁱ Pr = –CH(CH₃)₂). All the new compounds have been characterized in solution by ¹H, ¹¹B, ¹³C, ³¹P NMR spectroscopy and the structural types were unambiguously established by X-ray crystallographic analysis of compounds 2 and 4.     

Polymorphism for a novel phosphoramidate; NMR and X-ray crystallography

Abstract  

New phosphoramidates with formula 3-NC₅H₄C(O)NHP(O)XY (X=Y=Cl (1), X=Y=NH–C(CH₃)₃ (2a,2b), X=Y=N(C₄H₉)₂ (3), X=Cl, Y=N(C₂H₅)₂ (4) were synthesized and characterized by IR, ¹H-, ¹³C-, ³¹P-NMR spectroscopy and CHN elemental analysis. Surprisingly, the reaction of compound 2a with LaCl₃, 7H₂O in 3:1 M ratio leads to a polymorph of this compound (2b). NMR spectra indicate that ² J(PNH_amide) in 2b (7.0 Hz) is very much greater than in 2a (4.1 Hz), while δ(³¹P) values are identical for both of them. In IR spectra, υ(P=O) is weaker but υ(C=O) is stronger in 2a than in 2b. The structures of 2a, 2b were determined by X-ray crystallography. These compounds form centrosymmetric dimers via two intermolecular P=O……H–N hydrogen bonds. Strong intermolecular N–H…N, N–H…O and weak C–H…O hydrogen bonds lead to a three-dimensional polymeric cluster in the 2a while intermolecular strong N–H……N and weak C–H……O hydrogen bonds form a two-dimensional polymeric chain in 2b.     

Syntheses,spectroscopic study and crystal structures of some new <Emphasis Type="Italic">N</Emphasis>-benzoylphosphoric triamides

The reaction of N-benzoylphosphoramidic dichloride with amines afforded some new N-benzoylphos-phoric triamides with formula C₆H₅C(O)NHP(O)(X)₂, X=NH–CH(CH₃)₂ (1), NH–CH₂–CH(CH₃)₂ (2), NH–CH₂–CH(OCH₃)₂ (3), N(CH₃)[CH₂CH(OCH₃)₂] (4) and N(CH₃)(C₆H₁₁) (5) that were characterized by ¹H,¹³C,³¹P NMR, IR spectroscopy and elemental analysis. The structures have been determined for compounds 4 and 5 by X-ray crystallography. These compounds contain one amidic hydrogen atom and form centrosymmetric dimmers via intermolecular –P–O⋯H–N–hydrogen bonds besides weak C–H⋯O hydrogen bonds that lead to three-dimensional polymeric clusters in the crystalline lattice.     

Structural studies of spiroarsoranes derived from 2-aminophenols

This paper describes the structural studies of 2-phenyl-9,9′-dimethyl-2,2′-spirobis(1,3,2-λ⁵-benzoxazarsoline) 5, 2-phenyl-8,8′-dimethyl-2,2′-spirobis(1,3,2-λ⁵-benzoxazarsoline) 6 by ¹H,¹³C,¹⁵N NMR in [²H₆]DMSO and CDCl₃. The solid state studies were made by X-ray experiments. Infrared spectroscopy was obtained in CDCl₃ and the vibrational signals were assigned using DFT calculations. The nature of the As–N, As–C and As–O bonds in these compounds was established by NBO studies.     

Cytotoxic effect of some pentacyclic triterpenes and hemisynthetic derivatives of stigmasterol

Two different oxidation reactions (PCC and KMnO₄) of stigmasterol gave three products, stigmasta-4,22-dien-3-one (1a), stigmasta-4,22-diene-3,6-dione (1b), and 3-O-acetyl-5β,6β-epoxystigmast-22-ene-3-ol (1c). The cytotoxic activities of hemisynthetic compounds, stigmasterol, and four pentacyclic triterpens 2–5 previously isolated from cultivated and wild Triumfetta cordifolia and identified were investigated against human fibrosarcoma cell line (HT1080). Most of the drugs showed moderate cytotoxic activity. It was also notice that the triterpene skeleton had a range of number of OH functions in which activity was observed. Spectroscopic analyses (¹H and ¹³ C NMR) and mass were used to elucidate the structure of hemisynthetic compounds.