Keto Amine Research Articles

Crystal Structure of Zwitterionic (E)-9-(((3-hydroxyphenyl)iminio)methyl)-1,2,3,5,6,7- Hexahydropyrido[3,2,1-ij]Quinolin-8-Olate

The title compound (1), C19H20N2O2, crystallized with single molecule in the asymmetric unit and is present in the zwitterionic form. The compound was synthesized from the condensation reaction of 8-hydroxyjulolidine-9-carbaldehyde and 3-aminophenol. In solid state compound adopts the keto–amine tautomeric form, with the H atom attached to the N atom, which participates in an intramolecular N—H···O hydrogen bond with an S(6) ring motif. The conformation about the C=N bond is E. The aromatic ring of the julolidine moiety is inclined to the phenol ring by 13.00 (10)°. The fused non-aromatic rings of the julolidine moiety adopts a screw-boat conformations. In the crystal, the molecules are connected by N—H···O and O—H···O hydrogen bonds, with adjacent molecules related by a 21 screw axis, generating– A–B–A–B–zigzag chains extending along [010]. Furthermore, adjacent molecules are linked by pairs of C—H···O interactions, forming a ladder-like structure propagating along the a-axis direction. Density functional theory (DFT) optimized structures at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined molecular structure in the solid state.

Structural studies of a novel tautomeric Schiff base derived from 4-(N,N’-diethylamino)salicylaldehyde and 2-amino-4-methyl phenol: An experimental and theoretical study

A novel Schiff base, LMAP synthesized from 4-(N,N’-diethylamino)salicylaldehyde and 2-amino-4-methyl phenol has been characterized by single crystal X-ray diffraction and spectroscopic methods. DFT methods is used to investigate the enol-imine (EI) ⇄ keto-amine (KA) tautomeric behavior with respect to phase and in solvent media. The synthesized Schiff base crystallizes in the keto-amine (KA) form in the orthorhombic lattice and Pna21space group with four atoms per unit cell (Z = 4). Bond length analysis indicates that the KA form possesses significant zwitter ionic character. Study of electronic absorption and emission properties was conducted in the solid state as well as in different solvents. The UV–Vis result reveals the varied structural preference of the compound depending on the solvent media: polar protic solvents stabilize the KA form, while nonpolar and polar aprotic solvents favor the EI form. Quantum mechanical computations using DFT and TD-DFT also confirm these findings. Fluorescence emission spectra show multiple emission bands which indicate both excited state intramolecular proton transfer (ESIPT) and charge transfer (CT) phenomena occur simultaneously within the molecule. DFT predicted NLO responses of KA and EI were compared and found that the NLO response of KA is superior to that of EI.

Iron(III) Complexes Derived From Azo-Containing Salicylaldoxime Ligands: Synthesis, Structures and Biological Evaluations

Two novel mononuclear Fe(III) complexes derived from azo-containing salicylaldoxime ligands were synthesized and characterized by elemental analyses, spectroscopic data i.e. IR, 1H NMR, UV-Vis, electrospray ionization mass spectra, molar conductivity, and magnetic susceptibility measurements. Both the experimental and theoretical results strongly suggest that the ligands have a major contribution to the azo enol imine form instead of the hydrazo keto imine and azo keto amine forms in solution/solid-state. The electronic spectra of the ligands and their iron(III) complexes were calculated theoretically for the band assignments by using DFT and TD-DFT/CPCM methods. DNA binding, cleavage, and antioxidative activities of the investigated compounds were studied. It has been shown that the ligands and their iron (III) complexes tested bind to DNA via the intercalative mode. One of the most striking results among the antioxidant activity tests is that the hydroxyl radical scavenging activities of the ligands and complexes are higher than the standard antioxidant mannitol.

A Close Look at the Molecular Structure, Prototropic Behavior and Supramolecular Architecture of (E)-4-Bromo-2-[(phenylimino)methyl]-5-methoxyphenol by Spectroscopic, Crystallographic, and Computational Methods

In this study, the molecular structure, prototropic behavior and supramolecular architecture of a new Schiff base have been studied in depth using spectroscopic (UV-vis), crystallographic (XRD) and computational (HOMA and DFT) methods. Regarding the molecular structure and prototropy, the XRD, DFT and HOMA results show that the compound exists in phenol-imine form. The HOMA indices for the structural evaluation show that the compound has a pure aromatic structure in solid state. UV-vis spectra of the compound dissolved in four different solvents were investigated in order to determine which tautomeric form of the compound is dominant in the solution. It is found that the compound prefers only phenol-imine form in apolar solvents while both phenol-imine and keto amine forms appear in polar solvents. This is because polar solvent decrease the activation energy, and thus, it becomes possible to observe both forms in the solution. For an energetic approach, the tautomeric conversion between two forms of the compound was investigated by a PES scan process and close energy values were obtained for two tautomers. Investigation of non-covalent interactions underlines the active roles of C–H···O H-bonds and C···Br interactions in constructing the supramolecular network of the compound.

2'-Deoxyribose Mediated Glycation Leads to Alterations in BSA Structure Via Generation of Carbonyl Species.

The non-enzymatic glycosylation is a very common phenomenon in the physiological conditions which is mediated by distinct chemical entities containing reactive carbonyl species (RCS) and participates in the modification of various macromolecules particularly proteins. To date, various carbonyl species, i.e., glucose, fructose, D-ribose and methylglyoxal have been used frequently to assess the in-vitro non-enzymatic glycosylation. Similarly, 2'-Deoxyribose is one of the most abundant reducing sugar of the living organisms which forms the part of deoxyribonucleic acid and may react with proteins leading to the production of glycation intermediates, advanced glycation end products (AGEs) and highly reactive RCS. Thymidine phosphorylase derived degradation of thymidine contributes to the formation of 2'-Deoxyribose, therefore, acting as a major source of cellular 2'- Deoxyribose. Since albumin is a major serum protein which plays various roles including binding and transporting endogenous and exogenous ligands, it is more prone to be modified through different physiological modifiers; therefore, it may serve as a model protein for in-vitro experiments to study the effect of 2'Deoxyribose mediated modifications in the protein. In this study, Bovine Serum Albumin (BSA) was glycated with 50 and 100 mM 2'-Deoxyribose followed by examining secondary and tertiary structural modifications in BSA as compared to its native (unmodified) form by using various physicochemical techniques. We evident a significant modification in 2'-Deoxyribose-glycated BSA which was confirmed through increased hyperchromicity, keto amine moieties, carbonyl and hydroxymethylfurfural content, fluorescent AGEs, altered secondary structure conformers (α helix and β sheets), band shift in the amide-I region and diminished free lysine and free arginine content. These modifications were reported to be higher in 100 mM 2'-Deoxyribose-glycated BSA than 50 mM 2'- Deoxyribose-glycated BSA. Our findings also demonstrated that the rate of glycation is positively affected by the increased concentration of 2'-Deoxyribose. The results of the performed study can be implied to uncover the phenomenon of serum protein damage caused by 2'-Deoxyribose leading towards diabetic complications and the number of AGE-related diseases.

New azo‐azomethine‐based transition metal complexes: Synthesis, spectroscopy, solid‐state structure, density functional theory calculations and anticancer studies

A novel tetradentate azo‐Schiff base ligand (H2L) was synthesized by 2:1 molar condensation of an azo‐aldehyde and ethylenediamine. Its mononuclear Cu(II), Ni(II), Co(II) and Zn(II) complexes were prepared and their structures were confirmed using elemental analysis, NMR, infrared and UV–visible spectroscopies and molar conductivity measurements. The results suggest that the metal ion is bonded to the tetradentate ligand through phenolic oxygens and imine nitrogens of the ligand. The solid‐state structures of the azo‐Schiff base ligand and its Cu(II) complex were determined using single‐crystal X‐ray diffraction studies. The azo‐Schiff base ligand lies on a crystallographic inversion centre and thus the asymmetric unit contains half of the molecule. X‐ray data revealed that keto–amine tautomer is favoured in the solid‐state structure of the ligand. In the structure of the Cu(II) complex, the Cu(II) ion is coordinated to two phenolate oxygen atoms and two imine nitrogen atoms of the azo‐Schiff base ligand with approximate square planar geometry. The anticancer activity of the synthesized complexes was investigated for human cancer cell line (MCF‐7) and cytotoxicity of the synthesized compounds was determined against mouse fibroblast cells (L929). The ligand and its complexes were found to show antitumor activity. The synthesized metal complexes were optimized at the B3LYP/LANL2DZ level and a new theoretical formula for MCF‐7 cells was also derived.

Eight Schiff bases derived from various salicylaldehydes: phenol-imine and keto-amine forms, conformational disorder, and supramolecular assembly in one and two dimensions.

Structures are reported for eight Schiff bases derived from various salicylaldehydes: five are newly synthesized and re-investigations are reported for three previously reported structures, leading, in each case, to some revision of previous conclusions. In (E)-N-(3,4-dimethylisoxazol-5-yl)-4-[(2-hydroxybenzylidene)amino]benzenesulfonamide, C18H17N3O4S, (I), and (E)-4-[(5-bromo-2-hydroxy-3-methoxybenzylidene)amino]-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide. C19H18BrN3O5S, (II), the isoxazole rings adopt different orientations relative to the rest of the molecules, despite the additional substituents in (II) being in the aryl ring remote from the isoxazole unit. The molecules of both (E)-4-bromo-2-[(2-hydroxyphenylimino)methyl]-6-methoxyphenol, C14H12BrNO3, (III), and (E)-4-bromo-2-methoxy-6-[(2-methoxyphenylimino)methyl]phenol, C15H14BrNO3, (IV), are both effectively planar; while (III) adopts the phenol-imine constitution, (IV) adopts the keto-amine constitution. (E)-2-Methoxy-6-[(2-methoxyphenylimino)methyl]phenol, C15H15NO3, (V), which was determined previously using powder X-ray data assuming the phenol-imine constitution, has now been refined from single-crystal X-ray data, confirming the phenol-imine constitution. In (E)-3-benzoyl-2-[(5-fluoro-2-hydroxybenzylidene)amino]-4,5,6,7-tetrahydrobenzo[b]thiophene, C22H18FNO2S, (VI), the fused carbocyclic ring exhibits conformational disorder; both disorder components, having populations of 0.705 (4) and 0.295 (4), adopt half-chair conformations. The isostructural (E)-3-benzoyl-2-[(2-hydroxybenzylidene)amino)]-4,5,6,7-tetrahydrobenzo[b]thiophene, C22H19NO2S, (VII), which was originally reported as having a fully ordered structure [Kaur et al. (2014). Acta Cryst. E70, o476-o477], has been rerefined using the original data set and found to exhibit the same type of disorder as found in (VI), with disordered populations having occupancies of 0.851 (3) and 0.149 (3). The triclinic polymorph of (E)-[(2-hydroxyphenylimino)methyl]phenol, C13H11NO2, (VIII), which crystallizes with Z' = 2 in the space group P-1, has been described variously as occurring as the keto-amine tautomer [Maciejewska et al. (1999). J. Phys. Org. Chem. 12, 875-880] and as the phenol-imine tautomer [Tunç et al. (2009). J. Chem. Crystallogr. 39, 672-676]. Rerefinement of this structure using one of the original data sets shows that both of the independent molecules exist in the keto-amine form. In the structures of compounds (I), (VI), (VII) and (VIII), hydrogen bonds generate simple chains, while a chain of rings is formed in (V). Sheets are formed by hydrogen bonds in both (II) and (III), while in (IV), the sheet structure is built from aromatic π-π stacking interactions.

Crystal structure and DFT study of the zwitterionic form of 3-{(E)-1-[(4-ethoxyphenyl)iminiumyl]ethyl}-6-methyl-2-oxo-2H-pyran-4-olate.

The title Schiff base compound, C16H17NO4, crystallizes as a zwitterion, with the phenolic H atom having been transferred to the imino group. The resulting iminium and hy-droxy groups are linked by an intra-molecular N-H⋯O hydrogen bond, enclosing an S(6) ring motif. The conformation about the C=N bond is E and the dihedral angle between the benzene and pyran rings is 70.49 (6)°. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure. There are also C-H⋯π inter-actions and offset π-π inter-actions, involving the pyran rings [inter-centroid distance = 3.4156 (8) Å], which consolidate the three-dimensional structure. Quantum chemical calculations of the mol-ecule are in good agreement with the solid state keto-amine (NH) form of the title compound.

6-[(R)-(2-Hydroxy-1-phenylethyl)aminomethylidene]-4-(2-phenyldiazen-1-yl)cyclohexa-2,4-dien-1-one

The title chiral photochromic Schiff base compound, C21H19N3O2, was synthesized from (R)-(−)-2-phenylglycinol and salicylaldehyde of azobenzene derivative. The molecule exhibits the keto–amine tautomeric form and displays characteristic features of azobenzene derivatives. The diazenyl group adopts a trans (E) conformation, with N=N bond length of 1.260 (2) Å. The hydroxy group is involved in an intermolecular O—H...O hydrogen bond.

One-pot cyclization/decarboxylation of α-keto acids and acylhydrazines for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles under transition-metal-free conditions

A one-pot KI/TBHP-mediated oxidative cyclization of α-keto acids with acylhydrazines was developed. A series of functional 2,5-disubstituted 1,3,4-oxadiazoles were synthesized through a tandem keto amine condensation followed by oxidative cyclization and decarboxylation reactions. This procedure was achieved under transition-metal-free conditions and showed advantages including readily available materials, mild reaction conditions and good group tolerance.

Zwitterionic 4-bromo-6-meth-oxy-2-{[tris-(hy-droxy-meth-yl)methyl]-iminiumyl-meth-yl}phenolate: crystal structure and Hirshfeld surface analysis.

In the solid state, the title compound, C12H16BrNO5 [systematic name: 4-bromo-2-((1E)-{[1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-yl]iminium-yl}meth-yl)-6-meth-oxy-benzen-1-olate], C12H16BrNO5, is found in the keto-amine tautomeric form, with an intra-molecular iminium-N-H⋯O(phenolate) hydrogen bond and an E conformation about the C=N bond. Both gauche (two) and anti relationships are found for the methyl-hydroxy groups. In the crystal, a supra-molecular layer in the bc plane is formed via hy-droxy-O-H⋯O(hy-droxy) and charge-assisted hy-droxy-O-H⋯O(phenolate) hydrogen-bonding inter-actions; various C-H⋯O inter-actions provide additional cohesion to the layers, which stack along the a axis with no directional inter-actions between them. A Hirshfeld surface analysis confirms the lack of specific inter-actions in the inter-layer region.

Molecular structure and computational studies on 2-((2-(4-(3-(2,5-dimethylphenyl)-3-methylcyclobutyl)thiazol-2-yl)hydrazono)methyl)phenol monomer and dimer by DFT calculations

The title compound, 2-((2-(4-(3-(2,5-Dimethylphenyl)-3-methylcyclobutyl)thiazol-2-yl)hydrazono)methyl)phenol, was characterized by single-crystal X-ray diffraction. In order to calculate molecular geometry along with the infrared, Atoms in Molecules (AIM) analysis and 1H and 13C NMR chemical shift values, the density functional theory (DFT) method with 6-311G++(d,p) basis set was utilized. Experimental data were then used for comparison. While the title crystal structure is photochromic, the molecule is nonplanar. It takes on an enol form including a forceful intramolecular OH⋯N hydrogen bond as well as a forceful intermolecular NH⋯N hydrogen bond. The 6-311G++(d,p) basis function was used to examine the intramolecular tautomerism single proton transfer reaction of the hydrogen-bonded enol–imine and keto–amine monomer in the title crystal structure at the B3LYP theory level. Further, the frontier molecular orbitals (FMO), molecular docking and NLO properties were studied by using theoretical calculations. The calculated NLO properties of title compound are much greater than urea. The title compound generates a stable complex with CDK2 as is distinct from the binding energy values. These results proposed that the compound might exhibit inhibitory effect against CDK2. These are important in development of new antitumor agent.

Crystal structure of (Z)-4-[1-(4-acetyl-anilino)ethyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

In the solid state, the title compound, C20H19N3O2, adopts the keto-amine tautomeric form, with the H atom attached to the N atom, which participates in an intra-molecular N-H⋯O hydrogen bond with an S(6) ring motif. The dihedral angles between the pyrazole ring and the phenyl and benzene rings are 3.69 (10) and 46.47 (9)°, respectively. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, generating C(16) chains propagating in [301]. Weak aromatic π-π stacking inter-actions [centroid-centroid distances = 3.6123 (10) and 3.6665 (10) Å] link the chains into a three-dimensional network.

Surface selectivity competition of newly synthesized polyarylidene(keto amine) polymers toward different metal ions

ABSTRACTA new series of polyarylidene(keto amine)s (PAKAs) 3a−3e based on thiophene moieties in polymer main chains were synthesized with the solution polycondensation technique. The polymers were synthesized by the reaction of the new monomer 1,1′‐(1E,1′E)‐(2‐oxocyclohexane‐1,3‐diylidene)bis(methanylylidene)bis(thiophene‐5,2‐diyl)bis(2‐chloroethanone) (2) with different diamines. The new monomer was first synthesized under the normal conditions of the Friedel–Crafts reaction. The results obtained from both elemental and spectral analyses were consistent with the chemical structure of the new monomers and the polymers. Moreover, the identification of the polymers was carried out with different characterization techniques. The analytical competition of the newly synthesized PAKA polymers as selected examples (3d and 3e) was also evaluated for a selective extraction of metal ions, including Cd(II), Co(II), Cu(II), Cr(III), Fe(III), Ni(II), and Zn(II), before their determination by inductively coupled plasma–optical emission spectrometry. The results of the selectivity study demonstrated that the 3d and 3e polymers was the most selective toward Co(II) and Fe(III), respectively. However, the adsorption capacity of 3d for Co(II) was improved by 10.10% in comparison to that of 3e for Fe(III) after only 1 h of contact time. Moreover, the adsorption isotherm data also showed that the adsorption process was mainly monolayer on the homogeneous adsorbent surfaces of both polymers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40873.

1-{(Z)-[2-Methoxy-5-(trifluoromethyl)anilino]methylidene}naphthalen-2(1H)-one

The title compound, C19H14F3NO2, crystallizes in the keto–amine tautomeric form, with a strong intra­molecular N—H⋯O hydrogen bond. The mol­ecule is almost planar; the dihedral angle between the naphthalene ring system and the benzene ring is 4.60 (7)°. In the crystal, mol­ecules are linked into chains along the c axis by C—H⋯O hydrogen bonds. The F atoms of the trifluoro­methyl group are disordered over two positions with refined site occupancies of 0.668 (9) and 0.332 (9).

Conformational and tautomeric preferences in 3‐aminoacrylaldehyde: A theoretical study

AbstractThe conformational study of 3‐aminoacrylaldehyde were performed at various theoretical levels and the equilibrium conformations were determined. Furthermore, to have more reliable energies, the total energies of all forms recomputed at G2MP2 and CBS‐QB3. Theoretical calculations clearly show that the intramolecular hydrogen bond (IHB) is the origin of conformational preference and the resultant IHB order at HF/6‐311++G(d,p), MP2/6‐311++G(d,p), and CBS‐QB3 levels is different from the order which obtained from the B3LYP/6‐311++G(d,p), G2MP2, the geometrical parameters, AIM, and NBO analyses. Furthermore, our theoretical results reveal that the ketoamine (KA) tautomeric group is more stable than the enolimine (EI) and ketoimine (KI) ones. The IHB and tautomeric process could not rationalize the irregular stability of KA group with respect the others. But the population analyses of the possible conformations by NBO predict that the π‐electron delocalization, especially unusual π→ πcharge transfer, is the origin of tautomeric preference. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

(Z)-3-Diethylamino-6-({2-[(E)-4-(diethylamino)-2-hydroxybenzylideneamino]-4,5-dimethylphenyl}aminomethylidene)cyclohexa-2,4-dienone–5,5′-bis(diethylamino)-2,2′-[4,5-dimethyl-o-phenylenebis(nitrilomethylidyne)]diphenol

The asymmetric unit of the title Schiff base compound, C30H38N4O2, comprises two crystallographically independent mol­ecules, A and B. The structure is non-merohedrally twinned with a refined BASF ratio of 0.219 (6):0.701 (6). Mol­ecule B shows both phenol–imine and keto–amine tautomeric forms in a single structure. The dihedral angles between the central ring and the two outer rings are 5.9 (3) and 48.4 (3)° in mol­ecule A, and 48.3 (3) and 6.9 (3)° in mol­ecule B. Strong intra­molecular O—H⋯N and N—H⋯O hydrogen bonds generate S(6) ring motifs. The crystal structure is further stabilized by inter­molecular C—H⋯O, C—H⋯π and π–π inter­actions [centroid–centroid distances = 3.870 (4)–3.871 (4) Å].

Theoretical and experimental studies on electronic structure, cocrystallization, and intramolecular proton transfer of two tautomers: (E)‐2‐{[2‐(hydroxymethyl)phenylimino]methyl}‐5‐methoxyphenol and (Z)‐6‐{[2‐(hydroxymethyl)phenylamino] methylene}‐3‐methoxy‐cyclohexa‐2, 4‐dienone

AbstractIn this work, the structure of (E)‐2‐{[2‐(hydroxymethyl) phenylimino]methyl}‐5‐methoxyphenol was characterized by X‐ray single crystal diffraction technique, infrared spectroscopy, and quantum chemical computational methods as both experimental and theoretically. The compound crystallizes in the triclinic space group P1 with a = 9.4601 (5) Å, b = 11.7273 (7) Å, c = 12.4400 (8) Å, α = 88.179 (5)°, β = 71.442 (4)°, γ = 84.977 (5)°, and Z = 4. X‐Ray study shows that both enol–imine and keto–amine tautomeric forms coexist in the asymmetric unit as two independent molecules. The molecular geometry was also optimized at the B3LYP/6‐311G(d,p) level by using density functional theory started from the crystallographically achieved parameters of molecule. From the optimized geometry of the molecule, molecular electrostatic potential was evaluated, frontier molecular orbitals and natural bond orbital analysis were performed, and vibrational frequencies were computed theoretically. The polarizable continuum model calculations starting from the optimized geometry were also carried out in both gaseous and solution phase to investigate the energetic behavior and dipole moment of the title compound with the same level of theory. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

Prototropic tautomerism and solid-state photochromism of N-phenyl-2-aminotropones

N-(4-X-phenyl)-2-aminotropones (X = methoxy, chloro, or nitro substituent) and their clathrate crystals with deoxycholic acid (DCA) were prepared and their prototropic phenomena were determined. Each 2-aminotropone derivative existed as a keto–amine form in the crystal state irrespective of its substituent, which influenced the stability of keto–amine or enol–imine structure in solution. X-Ray crystal structure analysis of N-(4-methoxyphenyl)-2-aminotropone revealed the existence of bimolecular hydrogen bonds and close molecular packing, which would inhibit structural change necessary to photo-induced prototropic tautomerization. Thus, N-phenyl-2-aminotropones did not show photocoloration in the crystal state, while their clathrate crystals with DCA were found to exhibit photochromism.

2-Methoxy-3-[(3,4,5-trimethoxyanilino)methylidene]-3,4-dihydro-2H-1-benzopyran-4-one

The title mol­ecule, C20H21NO6, adopts a keto–amine tautomeric form. An intra­molecular N—H⋯O hydrogen bond, classified as a resonanse-assisted hydrogen bond, influences the mol­ecular conformation; the two benzene rings form a dihedral angle of 24.6 (1)°. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds link mol­ecules into chains propagating along [001].