Keto-enamine Tautomeric Form Research Articles

Design, synthesis, antimicrobial, antibiofilm evaluation and Z/E-isomerization of novel 6-((arylamino)methylene)benzo[a] phenazin-5(6H)-ones induced by organic solvent.

New 6-((arylamino)methylene)benzo[a]phenazin-5(6H)-one derivatives were synthesized, and good-to-high yields were achieved through one-pot, four-component condensation of 2-hydroxy-1,4-naphthoquinone, 1,2-phenylenediamine, aromatic amines and triethyl orthoformate using formic acid as catalyst under solvent-free conditions at 90 °C. The structure of these new compounds was confirmed using FT-IR and 1H-NMR as well as MS spectroscopy. Investigation of spectroscopy data indicated that the synthesized compounds exist in the keto-enamine tautomeric form and undergo Z/E-isomerization around the C[double bond, length as m-dash]C bond in DMSO-d6 at room temperature. Furthermore, intramolecular hydrogen bond has been observed in the synthesized E- and Z-ketoenamines. The noticeable features of the present procedure availability of starting materials, very simple operation, easy work-up, short reaction times, good to high yields and no need for column chromatography separation of benzophenazine enamines. The newly synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antibiofilm activities against some of the tested microorganisms. The results demonstrated that compound 6b showed the maximum antibacterial activity, 6d exhibited the maximum antifungal activity and 6b had the most efficiency to inhibit biofilm formation of Bacillus subtilis (80%) at 200 μg mL-1 concentration.

Evaluation of the protolytic equilibria and catalytic activity of sugar-based Schiff base ligands with VO2+ and MoO22+ cations in sulfoxidation and epoxidation reactions

Based on the two anomeric methyl 3-amino-2,3-dideoxy-d-arabino-hexopyranosides ten new sugar-modified Schiff base ligands have been synthesized after monocondensation reaction with five o-hydroxyaromatic aldehydes, i.e. salicylaldehyde and its five para-substituted derivatives. The acidity constants and acid-base equilibria processes in polar solution were calculated from data obtained after spectrophotometric titrations at room temperature. The first acidity constant is found to be associated with the deprotonation of an enamine nitrogen and the second constant correspond to the deprotonation of the phenolate oxygen. The contribution of the enol-imine and keto-enamine tautomeric forms and prototropic 1,5-rearrangement has been discussed with the help of the spectroscopic IR, UV–Vis and NMR techniques. Finally, in situ generated catalysts were carried out by mixing separately all synthesized sugar-based Schiff bases with VO(acac)2 or MoO2(acac)2, and have been tested in asymmetric sulfoxidation of thioanisole and the epoxidation of styrene, cyclohexene and S(−)-limonene using tert-butyl hydroperoxide (TBHP) as the terminal oxidant.

Crystal structure and Hirshfeld surface analysis of (Z)-6-[(2-hy-droxy-5-nitro-anilino)methyl-idene]-4-methyl-cyclo-hexa-2,4-dien-1-one.

The title compound, C14H12N2O4, is a Schiff base that exists in the keto-enamine tautomeric form and adopts a Z configuration. The mol-ecule is almost planar, the rings making a dihedral angle of 4.99 (7)°. The mol-ecular structure is stabilized by an intra-molecular N-H⋯O hydrogen bond forming an S(6) ring motif. In the crystal, inversion-related mol-ecules are linked by pairs of O-H⋯O hydrogen bonds, forming dimers with an R 2 2(18) ring motif. The dimers are linked by pairs of C-H⋯O contacts with an R 2 2(10) ring motif, forming ribbons extended along the [20] direction. Hirshfeld surface analysis, two-dimensional fingerprint plots and the mol-ecular electrostatic potential surfaces were used to analyse the inter-molecular inter-actions present in the crystal, indicating that the most important contributions for the crystal packing are from H⋯H (33.9%), O⋯H/H⋯O (29.8%) and C⋯H/H⋯C (17.3%) inter-actions.

Crystal structure and Hirshfeld surface analysis of (Z)-6-[(2-hy-droxy-4-methyl-anilino)-methyl-idene]-4-methyl-cyclo-hexa-2,4-dien-1-one.

The title compound, C15H15NO2, is a Schiff base that exists in the keto-enamine tautomeric form and adopts a Z configuration. The mol-ecule is almost planar, with the two phenyl rings twisted relative to each other by 9.60 (18)°. There is an intra-molecular N-H⋯O hydrogen bond present forming an S(6) ring motif. In the crystal, pairs of O-H⋯O hydrogen bonds link adjacent mol-ecules into inversion dimers with an R 2 2(18) ring motif. The dimers are linked by very weak π-π inter-actions, forming layers parallel to (01). Hirshfeld surface analysis, two-dimensional fingerprint plots and the mol-ecular electrostatic potential surfaces were used to analyse the inter-molecular inter-actions, indicating that the most important contributions for the crystal packing are from H⋯H (55.2%), C⋯H/H⋯C (22.3%) and O⋯H/H⋯O (13.6%) inter-actions.

Crystal structure and Hirshfeld surface analysis of a Schiff base: (Z)-6-[(5-chloro-2-meth-oxy-anilino)methyl-idene]-2-hy-droxy-cyclo-hexa-2,4-dien-1-one.

The title compound, C14H12ClNO3, is a Schiff base that exists in the keto-enamine tautomeric form and adopts a Z configuration. In the crystal, the dihedral angle between the planes of the benzene rings is 5.34 (15)°. The roughly planar geometry of the mol-ecule is stabilized by a strong intra-molecular N-H⋯O hydrogen bond. In the crystal, pairs of centrosymmetrically related mol-ecules are linked by O-H⋯O hydrogen bonds, forming R 2 2(10) rings. Besides this, the mol-ecules form stacks along the [001] direction with C-H⋯π and C-H⋯Cl contacts between the stacks. The inter-molecular inter-actions in the crystal were analysed using Hirshfeld surfaces. The most significant contribution to the crystal packing is from H⋯H contacts (30.8%).

Conjugated prototropic and ring opening rearrangements in Schiff base derivatives of formyl functionalized 2-oxaindane series spiropyran: synthesis, NMR, IR, UV/Vis, and DFT study

Condensation reaction products of formyl derivative of the 2-oxaindane series spiropyran (7-hydroxy-3′,3′-dimethyl-3’H-spiro [chromene-2,1′-isobenzofuran]-8-carbaldehyde) with several 2-amino-4-R-phenols (R = H, tBu, Сl, NO2) were synthesized and studied with the help of IR, UV/Vis, and NMR spectroscopy. It was shown that in contrast with mother spiropyran existing in closed spiro-form, all the compounds in the solution (DMSO, acetonitrile) and in solid state exist in thermodynamically stable merocyanine keto-enamine tautomeric form due to migration of the proton of 7-hydroxy group to azomethine nitrogen, conjugated with electrocyclic opening of the spirounit in the non-stable Schiff bases. In DMSO solution of merocyanine keto-enamines (R = H, tBu, Сl), dynamic equilibrium of Z,E-isomers in respect to C=C-N exocyclic double bond is observed (of which Z-one is the major component); in case of R = NO2, two additional isomers are registered. Upon protonation, strong absorption bands with maxima at the 580–590-nm spectral region are developed, while second protonation leads to hypsochromic shift of the longest wavelength absorption band to ca. 480 nm. Experimental results are supported with the DFT quantum chemical modeling of possible isomers of the obtained substances and their spectral properties (B3LYP/6-311++G(d,p) level of theory for geometry optimizations and spectra modeling).

Green Synthesis and Z/E-Isomerization of Novel Coumarin Enamines Induced by Organic Solvents

An efficient and straightforward synthesis of novel (Z/E)-3-[(heteroarylamino)methylidene]chromane-2,4-dione derivatives via a one-pot three-component condensation of 4-hydroxycoumarin, triethyl orthoformate, and heteroaryl amines in the presence of guanidinium chloride as organocatalyst under solvent-free conditions is described. Investigation of spectroscopy data indicated that coumarin enamines exist in the ketoenamine tautomeric form and undergo Z/E-isomerization in respect to the C=C bond in CDCl3 and DMSO-d6 at room temperature. Furthermore, intramolecular hydrogen bonds have been observed in the synthesized compounds. Also, 1H NMR spectra indicated that E-ketoenamines are the major isomers. High to excellent yields, short reaction times, simple workup, and very easy purification of products by non-chromatographic methods are advantages of this synthetic procedure.

Coordination properties of a Schiff base probe for Zn2+ ion in aqueous media having no Cu2+ ion interference

The coordination properties and acid–base behavior of 2-[{(1S,2R)-1-hydroxy-1-phenylpropan-2-ylimino}methyl]-4-bromophenol Schiff base probe (L1) were characterized by UV–Vis and fluorescence titrations in water. The dissociation constants for the ligand account for a keto–enamine tautomer at pH 7. Detailed complexation studies were carried out, observing the formation of stable 1:1 complex for Zn2+, where a “turn-on” fluorescence effect is obtained. More importantly, no Cu2+ interference is observed, which is a typical problem for Zn2+ probes, this is awarded to the keto–enamine tautomeric form of the probe L1 according to UV–Vis and X-ray structure data. Also, the Zn2+vs. Cd2+ ion discrimination for L1 is proved. Finally, TD-DFT theoretical calculations were conducted in order to stablish the detection mechanism of the probe.

A hybrid QM/MM simulation study of intramolecular proton transfer in the pyridoxal 5'-phosphate in the active site of transaminase: influence of active site interaction on proton transfer.

Pyridoxal 5'-phosphate (PLP) Schiff base, a versatile cofactor, exhibits a tautomeric equilibrium that involves an intramolecular proton transfer between the N-protonated zwitterionic ketoenamine tautomer and the O-protonated covalent enolimine tautomer. It has been postulated that for the catalytic activity, the PLP has to be in the zwitterionic ketoenamine tautomeric form. However, the exact position of the tautomeric equilibrium of Schiff base in the active site of PLP-dependent enzyme is not known yet. In the present work, we investigated the tautomeric equilibrium for the external aldimine state of PLP aspartate (PLP-Asp) Schiff base in the active site of aspartate aminotransferase (AspAT) using combined quantum mechanical and molecular mechanical simulations. The main focus of the present study is to analyze the factors that control the tautomeric equilibrium in the active sites of various PLP-dependent enzymes. The results show that the ketoenamine tautomer is more preferred than the enolimine tautomer both in the gas and aqueous phases as well as in the active site of AspAT. Current simulations show that the active site of AspAT is more suitable for the ketoenamine tautomer compared to the enolimine tautomer. Interestingly, the Tyr225 acts as a proton donor to the phenolic oxygen in the ketoenamine tautomer, while in the covalent enolimine tautomer, it acts as a proton acceptor to the phenolic oxygen. Finally, the metadynamics study confirms this result. The calculated free energy barrier is about 7.5 kcal/mol. A comparative analysis of the microenvironment created by the active site residues of three different PLP-dependent enzymes (aspartate aminotransferase, Dopa decarboxylase, and Ala-racemase) has been carried out to understand the controlling factor(s) of the tautomeric equilibrium. The analysis shows that the intermolecular hydrogen bonding between active site residues and the phenolic oxygen of PLP shifts the tautomeric equilibrium toward the N-protonated ketoenamine tautomeric form.

Theoretical studies on charge transport and optical properties of tris(N-saclicylideneanilines)

The structural, charge transport and optical properties of the discotic liquid crystalline molecule tris(N-saclicylideneanilines) (TSANs) have been studied using quantum chemical methods. The TSANs have enol-imine and keto-enamine tautomeric forms, and the relative energy calculations show that the keto form is more stable than the enol form. The effective charge transfer integral and site energy corresponding to the hole and electron transport in TSAN molecules were calculated directly from the matrix elements of Kohn–Sham Hamiltonian. The calculated charge carrier mobility using the Monte Carlo simulation of the polaron hopping transport method shows that the TSAN molecules are n-type organic semiconductors and the charge transport strongly depends on the substituted functional groups and the orientation of the π-stacked molecules. The absorption and emission spectra of TSANs have been analyzed using a time-dependent density functional theory (TDDFT) method. The results obtained from this study will reveal the relationships between the molecular structure and charge transport as well as the optical properties of the TSAN molecules.

Self-Assembly of Hekates-Tris(N-salicylideneaniline)s into Columnar Structures: Synthesis and Characterization

Two series of new, photoluminescent star-shaped discotic liquid crystals, recently termed as "hekates", derived from tris(N-salicylideneaniline)s (TSANs), were synthesized by the facile threefold condensation of 3,4-bis(alkoxy)phenyl 4-aminobenzoates/3,4,5-tris(alkoxy) phenyl 4-aminobenzoates with 1,3,5-triformylphloroglucinol and characterized. These two series of discotics with six and nine peripheral n-alkoxy tails were especially designed and accomplished to understand the relation between mesomorphic/photophysical properties and molecular structure. Proton NMR spectral analysis revealed their existence as an inseparable mixture of two keto-enamine tautomeric forms featuring C(3h) and C(s) rotational symmetries. A systematic study into the thermotropic liquid crystal behavior using polarizing optical microscopy, differential scanning calorimetry, and X-ray scattering confirmed the presence of columnar (Col) phase in vast majority of the TSANs prepared. The two-dimensional (2D) lattices of these fluid columnar phases were found to be characteristic of hexagonal Col (Col(h)), rectangular Col (Col(r)), or oblique Col (Col(ob)) phases depending on the number/length of the peripheral flexible chains. The stabilization of the Col(ob) phase, a less commonly found fluid columnar structure, and the first of its kind in TSAN systems, implies very intensive intermolecular (face-to-face) interactions among the TSAN cores within the column. The photophysical properties were investigated both in solution and the columnar states by UV-vis absorption and photoluminescence; markedly, the solution state emits light in the blue region. The light-emitting ability of the Col phase is particularly significant given the possibility that, in such cores, the protons and electrons interact with each other through the H-bonding environment.

Light emitting, star-shaped tris(N-salicylideneaniline) discotic liquid crystals bearing trans-stilbene fluorophores: synthesis and characterization

Star-shaped tris(N-salicylideneaniline) discotics possessing trans-stilbene fluorophores have been synthesized by condensing 1,3,5-triformylphloroglucinol with 4-(alkoxystyryl)benzen-amines, and characterized. 1H and 2D 1H–1H COSY NMR experiments reveal their occurrence in two inseparable keto-enamine tautomeric forms featuring C3h and Cs rotational symmetries. Their columnar liquid crystal behavior has been ascertained unequivocally with the aid of a polarizing optical microscope and a differential scanning calorimeter. Photoluminescence property has been examined both in solution and columnar states. Green light emission observed in the solution state is especially noteworthy. Thus, intrinsic self-assembly into a fluid columnar state exhibiting light emission property clearly illustrates their significance in technological applications.

Triple hydrogen bonding in a circular arrangement: ab initio, DFT and first-principles MD studies of tris-hydroxyaryl enamines.

First-principles Car-Parrinello molecular dynamics, ab initio (MP2) and density functional schemes have been used to explore the tautomeric equilibrium in three tris(amino(R)methylidene)cyclohexane-1,3,5-triones (R = hydrogen, methyl or phenyl group). The dynamic nature of the cyclic hydrogen bonding has been studied by the first-principles MD method. The comparison of the results obtained by aforesaid methods has been accomplished on the basis of calculations of structural and spectroscopic characteristics of the compounds. The conformational analysis of the studied compounds has been carried out at the MP2/6-31+G(d,p) and B3LYP/6-31+G(d,p) levels of theory. The influence of steric and electronic effects on the cyclic hydrogen bonding has been analysed. The extent of the proton delocalization has been modified by the substituents according to the sequence: hydrogen < phenyl < methyl. This fact is verified by the spectroscopic and structural data as well as the energy potential curve. A prevalence of the keto-enamine tautomeric form has been observed in the static ab initio and DFT models, and confirmed by the first-principles MD.Electronic supplementary materialThe online version of this article (doi:10.1007/s10822-012-9597-3) contains supplementary material, which is available to authorized users.

Experimental and theoretical investigation of the molecular and electronic structure of 3-ethoxy-4-isopropylaminocyclobut-3-ene-1,2-dione

The title compound, 3-ethoxy-4-isopropylaminocyclobut-3-ene-1,2-dione (EIAC) has been synthesized and characterized by NMR, FT-IR, UV–vis spectroscopy and single-crystal X-ray diffraction. The 1H NMR spectra were recorded at 300K and 315K in CDCl3 to determine syn/anti conformers of the compound EIAC. Density functional theory (DFT) calculations, optimized geometrical parameters, vibrational frequencies and chemical shift values of syn/anti conformer in CDCl3 have been performed at B3LYP/6-311G(d) level, and compared with the experimental data. The values provided with the calculations support the experimental data of the compound EIAC. The presence of NH⋯O type intermolecular H bond can be perceived from the difference between experimental calculations and results of FT-IR and NMR calculations. In addition, B3LYP/6-311G(d) basis set has been used to calculate the molecular electrostatic potential, frontier molecular orbitals and electronic absorption spectra. HOMO–LUMO electronic transition of 5.12eV is derived from the contribution of the bands n→σ* or π→π*. FT-IR, NMR and X-ray spectral results and additionally DFT calculations exhibit that the compound EIAC exists in keto-enamine tautomeric form. The experimental 1H NMR spectra recorded at 300K and 315K and theoretical 1H NMR data indicate that the compound EIAC is in syn conformer.

Methyl 2-{[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-ylidene)(4-nitrophenyl)methyl]amino}-3-phenylpropanoate

The mol­ecule of the title compound, C27H24N4O5, exists in the keto–enamine tautomeric form, stabilized by an intra­molecular N—H⋯O hydrogen bond. An intra­molecular C—H⋯·O hydrogen bond also occurs. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules into chains.

Diorganotin(IV) complexes of polyaromatic azo‐azomethine ligand derived from salicylaldehyde and ortho‐aminophenol: Synthesis, characterization, and molecular structures

AbstractThe diorganotin(IV) complexes of methyl 2‐{4‐hydroxy‐3‐[(2‐hydroxy‐phenylimino)‐methyl]‐phenylazo}‐benzoate (H2L) were obtained by the reaction of ortho‐aminophenol, R2SnO (R = Me, nBu, or Ph) and methyl 2‐[(E)‐(3‐formyl‐4‐hydroxy)diazenyl]benzoate (H2PL2) in ethanol, which led to diorganotin(IV) compounds of composition [Me2SnL]2 (1), nBu2SnL (2), and Ph2SnL (3) in good yield. The 1H, 13C, and 119Sn NMR, IR, the mass spectrometry along with elemental analyses allowed establishing the structure of ligand (H2L) and compounds 1–3. In all the three cases, 119Sn chemical shifts are indicators of five‐coordinated Sn atoms in a solution state. The crystal structures of ligand H2L and complexes 1 and 2 were determined by a single crystal X‐ray diffraction study. In the solid state, the ligand H2L exists as a keto‐enamine tautomeric form. The molecular structure of complex 1 in the solid state shows a distorted octahedral geometry around a tin atom due to additional coordination with an oxygen atom from a neighboring molecule leading to a four‐membered ring with Sn‐O···Sn‐O intermolecular coordination, leading to a dimeric species. On the other hand, complex 2 is a monomer with trigonal bipyramidal geometry surrounding the tin atom. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:457–465, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21037

Low temperature X-ray diffraction analysis, electronic density distribution and photophysical properties of bidentate N,O-donor salicylaldehyde Schiff bases and zinc complexes in solid state

Zinc complexes (ZnL2) with bidentate N,O-donor Schiff bases (HL=HSH1, HSH2, HSH3) derivatives of salicylaldehyde and para-substituted anilines were synthesized and fully characterized. The crystallographic parameters of HSH2 and ZnL2 were refined. Low temperature X-ray diffraction analysis including topological analysis of electron density function for crystals of ZnL2 reveals that the geometrical parameters of all investigated compounds as well as the charges in chelate rings of complexes remain almost unchanged upon variation of the substituents (R) in para-position of the aniline fragment, going from –CH3 (HSH1) to –N(CH3)2 (HSH2) and –OCH3 (HSH3). Zinc complexes are thermally stable up to ∼190°C as shown by thermogravimetric analysis under nitrogen atmosphere. The photoluminescent (PL) properties of HL and ZnL2 were investigated in the solid state while its absorption spectra were measured in methanol. The theoretical calculation of the investigated compounds confirmed firstly the existence of enol-imine and keto-enamine tautomeric forms; and secondly the influence of the introduction of R on the PL properties of the compounds. The study of excited state dynamics of ZnL2 in the solid state shows bi-exponential fluorescence decays and relatively high PL quantum yield, making them potentially adequate for being used as manifold optical materials. The interpretation of photophysical properties are substantiated by DFT and TD-DFT theoretical calculations of the Schiff bases and zinc complex species.

E/Z(C=C)-Isomerization of enamines of 3-formyl-4-hydroxycoumarin induced by organic solvents

According to 1? and 13? NMR data, enamines of 3-formyl-4-hydroxycoumarin exist in the keto enamine tautomeric form and undergo Z/E-isomerization around the C=C bond in CDCl3, DMSO-d6, and CD3OD at room temperature. The activation energies of ?/Z-isomerization were measured experimentally and calculated by the B3LYP/6-311++G(d,p) method. An X-ray diffraction study showed that 3-(benzyliminomethyl)chromane-2,4-dione in the crystalline state exists as a mixture of two keto enamine isomers.

Neutral penta-coordinated diorganotin(IV) complexes derived from ortho-aminophenol Schiff bases: Synthesis, characterization and molecular structures

The one pot reactions carried among ortho-aminophenol, R 2SnO (R = Me or Ph) and acetyl acetone, 2-hydroxyacetophenone and 2-hydroxy-3-methylacetophenone led to six new diorganotin(IV) compounds Me 2SnL1 ( 1), Ph 2SnL1 ( 2), Me 2SnL2 ( 3) Ph 2SnL2 ( 4), Me 2SnL3 ( 5) and Ph 2SnL3 ( 6) ( H2L1 = 2-(3-hydroxy-1-methyl-but-2-enylideneamino)-phenol, H2L2 and H2L3 = 2-[1-(2-hydroxyaryl)alkylideneamino]-phenol) in good yields. Combination of IR, 1H, 13C and 119Sn NMR and X-ray diffraction techniques along with elemental analyses evidenced the formation of penta-coordinated monomeric species. The crystal structures of ligand H2L1 and complexes 1, 3 and 4 were determined by single crystal X-ray diffraction study. In the solid state, the ligand H2L1 exists as keto-enamine tautomeric form. There are N–H…O intra-molecular hydrogen bonds between amine and carbonyl groups. Diorganotin(IV) complexes 1, 3 and 4 are monomers with TBP (trigonal bipyramidal) geometry surrounding the tin atom. The O, N, O- tridentate ligand places its two oxygen donating atoms in the axial positions, and the nitrogen atom occupies one equatorial position. The two R groups attached to tin occupy the other two equatorial positions. The solution structures were predicted by 119Sn NMR spectroscopy.

4-[(Z)-Allylamino(phenyl)methylene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one

The title compound, C20H19N3O, exists in a keto–enamine tautomeric form. The pyrazolone ring makes dihedral angles of 20.52 (10) and 77.73 (5)° with the two phenyl rings and an intra­molecular N—H⋯O hydrogen bond occurs. A weak inter­molecular C—H⋯O hydrogen bond is observed in the crystal structure. The allyl group is disordered over two positions, with site-occupancy factors of 0.533 (5) and 0.467 (5).