Enol Imine Research Articles

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.

Crystal structure and Hirshfeld surface analysis of (Z)-2-{[(2,4-di-methyl-phen-yl)imino]-meth-yl}-4-methyl-phenol.

The title compound, C16H17NO, is a Schiff base that exists in the enol-imine tautomeric form and adopts a Z configuration. The mol-ecule is non-planar, with the twisted rings making a dihedral angle of 39.92 (4)°. The intra-molecular O-H⋯N hydrogen bond forms an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯π inter-actions and very weak π-π stacking inter-actions also help to consolidate the crystal packing. A Hirshfeld surface analysis was performed to investigate the contributions of different inter-molecular contacts within the supra-molecular structure. The major contributions are from H⋯H (65%), C⋯H (19.2%) and O⋯H (6.6%) inter-actions.

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.

Synthesis, XRD, HAS, in silico molecular docking studies and biological assessment of novel Schiff base compounds as anti-cancer and antimicrobial agents

In this study, versatile multifunctional Schiff base (SB) derivatives were synthesized. Compounds 1–8 were prepared by a mild condition and were pharmacologically assessed for their role in vitro anti-cancer and their impact on human fibrosarcoma (HT-1080) and cervical cancer cells (HeLa), in addition to their antimicrobial activity regarding fungal strains, gram-positive and gram-negative bacteria. Preliminary in silico study of 1–8 and the standard compound (5-Fluorouracil) was accomplished, using Drug2Way and PASS software. Besides, docking investigations were carried out using Schrödinger software to determine the interaction of p53-MDM2 and pf-DHFR binding affinity for all the compounds. The antimicrobial results exhibited that these novel compounds have modest to good inhibitory action against the tried bacterial and fungal strains. The crystal structures of 2 and 7 have been determined. Hirshfeld Surface Analysis (HSA) is in agreement with the XRD studies. Both compounds have shown enol–imine tautomeric forms as EE isomer.

(E)-2-{[(2-Amino-phen-yl)imino]-meth-yl}-5-(benz-yl-oxy)phenol and (Z)-3-benz-yl-oxy-6-{[(5-chloro-2-hy-droxy-phen-yl)amino]-methyl-idene}cyclo-hexa-2,4-dien-1-one.

The title Schiff base compounds, C20H18N2O2 (I) and C20H16ClNO3 (II), were synthesized from 4-benz-yloxy-2-hy-droxy-benzaldehyde by reaction with 1,2-di-amino-benzene for (I), and condensation with 2-amino-4-chloro-phenol for (II). Compound (I) adopts the enol-imine tautomeric form with an E configuration about the C=N imine bond. In contrast, the o-hy-droxy Schiff base (II), is in the keto-imine tautomeric form with a Z configuration about the CH-NH bond. Neither mol-ecule is planar. In (I), the central benzene ring makes dihedral angles of 46.80 (10) and 78.19 (10)° with the outer phenyl-amine and phenyl rings, respectively, while for (II), the corresponding angles are 5.11 (9) and 58.42 (11)°, respectively. The mol-ecular structures of both compounds are affected by the formation of intra-molecular contacts, an O-H⋯N hydrogen bond for (I) and an N-H⋯O hydrogen bond for (II); each contact generates an S(6) ring motif. In the crystal of (I), strong N-H⋯O hydrogen bonds form zigzag chains of mol-ecules along the b-axis direction. Mol-ecules are further linked by C-H⋯π inter-actions and offset π-π contacts and these combine to form a three-dimensional network. The density functional theory (DFT) optimized structure of compound (II), at the B3LYP/6-311+G(d) level, confirmed that the keto tautomeric form of the compound, as found in the structure determination, is the lowest energy form. The anti-oxidant capacities of both compounds were determined by the cupric reducing anti-oxidant capacity (CUPRAC) process.

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.

Experimental (X-ray, FT-IR and UV–vis spectra) and theoretical methods (DFT study) of (E)-3-methoxy-2-[(p-tolylimino)methyl]phenol

A suitable single crystal of (E)-3-methoxy-2-[(p-tolylimino)methyl]phenol, formulated as C15H15N1O2, reveals that the structure is adopted to its E configuration about the azomethine CN double bond. The compound adopts a enol–imine tautomeric form with a strong intramolecular OH⋯N hydrogen bond. The single crystal X-ray diffraction analysis at 296K crystallizes in the monoclinic space group P21/c with a=13.4791(11) Å, b=6.8251(3) Å, c=18.3561(15) Å, α=90°, β=129.296(5)°, γ=90° and Z=4. Comprehensive theoretical and experimental structural studies on the molecule have been carried out by FT-IR and UV–vis spectrometry.Optimized molecular structure and harmonic vibrational frequencies have been investigated by DFT/B3LYP method with 6-31G(d,p) basis set. Stability of the molecule, hyperconjugative interactions, charge delocalization and intramolecular hydrogen bond has been analyzed by using natural bond orbital (NBO) analysis.Electronic structures were discussed by TD-DFT method and the relocation of the electron density were determined. The energetic behavior of the title compound has been examined in solvent media using polarizable continuum model (PCM). Molecular electrostatic potential (MEP), Mulliken population method and natural population analysis (NPA) have been studied. Nonlinear optical (NLO) properties were also investigated. In addition, frontier molecular orbitals analysis have been performed from the optimized geometry. An ionization potential (I), electron affinity (A), electrophilicity index (ω), chemical potential (μ), electronegativity (χ), hardness (η), and softness (S), have been investigated.

2-{(E)-[(2-Methyl-3-nitrophenyl)imino]methyl}-4-nitrophenol

The title compound, C14H11N3O5, is a Schiff base that adopts the enol–imine tautomeric form in the solid state. The dihedral angle between the aromatic rings is 37.4 (3)° and the dihedral angles between the nitro groups and their attached rings are 4.0 (6) and 46.2 (8)°. The mol­ecular structure is stabilized by an intra­molecular O—H⋯N hydrogen bond, which generates an S(6) ring motif. In the crystal, molecules are linked by C—H⋯O interactions, forming a two-dimensional network parallel to the bc plane.

Liquid crystalline bis(N-salicylideneaniline)s: synthesis and thermal behavior of constitutional isomers

Abstract The first examples of mesogenic bis( N -salicylideneaniline)s (BSANs), wherein two lipophilic (half-disk shaped) entities are interlinked through the dihydroxydiformylbenzene core, were synthesized and characterized. In particular, three constitutional (positional) isomeric BSANs were prepared by the facile twofold condensation of 3,4,5-tris(alkoxy)anilines with 2,3-dihydroxyterephthalaldehyde, 4,6-dihydroxyisophthalaldehyde, and 2,5-dihydroxyterephthalaldehyde and their structures were established by elemental analyses, FT-IR, 1 H NMR, and 13 C NMR. Proton NMR experiments demonstrated their existence in enol–imine (OH) form solely. Polarizing optical microscopic, differential scanning calorimetric, and powder X-ray diffraction studies evidenced the occurrence of columnar mesomorphism in two sets of isomers.

(E)-1-[(3-Iodophenyl)iminomethyl]naphthalen-2-ol

In the title mol­ecule, C17H12INO, the dihedral angle between the naphthaldeyde plane and the 3-iodo­aniline plane is20.07 (13)°. It exists in the solid state as an enol–imine tautomer with a strong intra­molecular O—H⋯N hydrogen bond.

Design of molecular switching and signaling based on proton transfer in 2-hydroxy Schiff bases: a computational study

The present work aims to exploit the possibility of using the tautomerism in 2-hydroxy Schiff bases for molecular switching. The enol imine (E)⇔ enaminone (K) tautomerization in a series of 2-hydroxy Schiff bases have been investigated theoretically at the DFT/B3LYP/6-311G** level of theory. The intramolecular proton transfer processes have been explored, transition structures have been located and characterized. The kinetics and thermodynamics of the proton transfer process, and its time scale have been computed and discussed in the framework of the suitability as molecular switches. Substituent effects have been computed and its effect on the enthalpy changes (∆H*) and activation energies (∆G*) have been analyzed and discussed. Nonspecific solvent effects have also been taken into account by using the polarized continuum model (IPCM) of two different solvent. The tautomerization energies are decreased and hence the endothermic nature of the enol imine ⇔ enaminone tautomerization. The potential energy barriers, on the other hand, are increased due to the relative destabilization of the transition states. The NBO charge populations show that there is a high positive charge on the hydrogen atom during the process in all cases, which confirms that the proton transfer proceeds through a three-center interaction. The proton transfer processes, in all cases studied are kinetically allowed. The low potential energy barrier suggests that interconversion between the two tautomeric forms is spontaneous and the two forms may coexist.

(E)-1-[(3-Bromophenyl)iminomethyl]naphthalen-2-ol

The title compound, C17H12BrNO, exists in an enol–imine form and the mol­ecular structure features an intra­molecular O—H⋯N hydrogen bond. The dihedral angle between the benzene ring and the naphthalene ring system is 17.27 (15)°.

2-{(E)-[(3-Iodo-4-methylphenyl)imino]methyl}-4-(trifluoromethoxy)phenol

The title compound, C15H11F3INO2, adopts the enol–imine tautomeric form. The mol­ecule displays an E conformation with respect to the imine C=N double bond. The dihedral angle between the two benzene rings is 12.4 (2)°. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯N hydrogen bond, which generates an S(6) ring motif. The trifluoro­meth­oxy­phenyl group is disordered over two sites with an occupancy ratio of 0.621 (6):0.379 (6). The crystal structure features C—H⋯π inter­actions.

2-((E)-{[4-(Hydroxymethyl)phenyl]imino}methyl)phenol

The title compound, C14H13NO2, adopts the enol–imine tautomeric form, with an intra­molecular O—H⋯N hydrogen bond which generates an S(6) ring motif. The dihedral angle between the aromatic rings is 7.85 (7)°. The crystal structure is stabilized by O—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds, forming a two-dimensional array that stacks along the a axis. In addition, a C—H⋯π inter­action contributes to the stabilization of the crystal packing.

ChemInform Abstract: Intramolecular Ester Enolate—Imine Cyclization Reactions for the Asymmetric Synthesis of Polycyclic β‐Lactams and Cyclic β‐Amino Acid Derivatives.

AbstractEnolates of N‐substituted amino esters (I) and (III) undergo intramolecular cyclization reactions to afford (syn)‐aza‐anions that undergo 4‐exo‐trig cyclization onto their ester carbonyl group to afford cyclic β‐lactams (II) and (IV) in high diastereoselectivity.

2-{[(4-{[(2-Hydroxyphenyl)(phenyl)methylidene]amino}phenyl)imino](phenyl)methyl}phenol

The title mol­ecule, C32H24N2O2, has a crystallographically imposed inversion centre and exists in the crystal as an enol–imine tautomer. The mol­ecular structure is stabilized by two strong intra­molecular O—H⋯N hydrogen bonds. The dihedral angles between the central benzene ring and the mean planes of the phenyl substituents are 59.99 (1) and 62.79 (2)°. In the crystal, the mol­ecules are arranged into (010) layers via C—H⋯π inter­actions.

Intramolecular Ester Enolate–Imine Cyclization Reactions for the Asymmetric Synthesis of Polycyclic β-Lactams and Cyclic β-Amino Acid Derivatives

Enolates of chiral N-(α-methyl-p-methoxybenzyl)-ω-imino-esters undergo intramolecular cyclization reactions to afford (syn)-aza-anions of β-amino esters in high dr that cyclize to afford N-(α-methyl-p-methoxybenzyl)-β-lactams that can be readily deprotected to afford their corresponding cyclic NH-β-lactams, β-amino esters, or β-amino acids.

2-[1-(3-Aminophenylimino)ethyl]phenol

The title compound, C14H14N2O, exists as the enol–imine tautomer. A strong intra­molecular hydrogen bond between O and N atoms forms a six-membered ring with an S(6) graph-set motif, which is approximately coplanar with the phenol ring, the inter­planar angle being 3.4 (3)°. In the crystal, inter­molecular C—H⋯O hydrogen bonds and N—H⋯π inter­actions link the mol­ecules into infinite chains along [100].

3-Meth-oxy-2-[(E)-(4-meth-oxy-phen-yl)imino-meth-yl]phenol.

The title compound, C15H15NO3, adopts the enol–imine tautomeric form. The two rings are twisted with respect to each other, making a dihedral angle of 44.08 (5)°. The 3-methoxy-2-[(E)-(4-methoxyphenyl)-iminomethyl]phenol unit is almost planar, the largest deviation from the mean plane being 0.047 (2) Å. Such a planar conformation might be related to the occurrence of an intra­molecular O—H⋯N hydrogen bond. In the crystal, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into sheets parallel to (010). These sheets are inter­connected by weak C—H⋯π inter­actions.

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