Imino Moiety Research Articles

One‐Pot Synthesis of Sulfonylated 5‐Aroyl‐2‐Arylpyridines via Ruthenium‐Catalyzed and K2S2O8‐Mediated Domino Annulation of β‐Ketosulfones with DMF

AbstractRuthenium‐catalyzed and K2S2O8‐mediated synthesis of diverse sulfonylated 5‐aroyl‐2‐arylpyridines was developed through one‐pot stepwise annulation of two molecules of β‐ketosulfones and N,N‐dimethylformamide (DMF) under the sealed tube conditions. In the overall process, DMF acts as the synthon of one carbon and one imino moiety in the construction of pyridine skeleton via cascade formation of single (C−C/C−N) and double (C=C/C=N) bonds under refluxing DMF conditions. Plausible reaction mechanism is proposed and discussed.

Protonation of Imino Moiety in Aminoguanidine by Heterolytic O–H Bond Cleavage on Phthalic Acid: Theoretical, Experimental and DNA Binding Studies

Aqueous neutralization reaction between aminoguanidine hydrogencarbonate and phthalic acid yielded the crystals of aminoguanidine hydrogenphthalate monohydrate (AHPMH). The crystal quality is further improved by repeated recrystallization and single crystals were obtained. The single crystal XRD data reveals that the compound crystallizes in the monoclinic crystal system with the Cc space group. The unit cell consists of four molecules (z = 4) and in the crystal lattice they are linked by O–H···O and N–H···O intermolecular hydrogen bonding. Geometrical and vibrational analyses were performed by B3LYP/6311G(d,p) basis set and compared with the single crystal XRD values. The Mulliken charge and molecular electrostatic potential (MEP) analyses have been used to predict the reaction behaviour and bond cleavage fashion during the reaction. The heterolytic O-H bonding electrons are shifted towards the oxygen atom (-0.6112 e) and it possesses high electronegative which influenced the formation of strong hydrogen bond. The binding constant (Kb) of the AHPMH indicates that strong interactions are developed between the title compound and CT-DNA.

Phenol-Benzoxazolone bioisosteres: Synthesis and biological evaluation of tricyclic GluN2B-selective N-methyl- d-aspartate receptor antagonists.

Tricyclic tetrahydrooxazolo[4,5-h]-[3]benzazepin-9-ols 22 were designed as phenol bioisosteres of tetrahydro-3-benzazepine-1,7-diols. Key features of the synthesis are the introduction of the trifluoromethylsulfonyl and allyl protective groups at the heterocyclic N-atoms. Two methods were developed to convert the triflyl-protected ketone 16 into tricyclic alcohols 21 bearing various N-substituents. According to the first method, trifluoromethanesulfinate was removed by K2 CO3 . Following the selective reduction of the imino moiety of 17 with NaBH(OAc)3 afforded the aminoketone 18, which was reductively alkylated and reduced. According to the second method, both the imine and the ketone of the iminoketone 17 were reduced with NaBH4 to yield the aminoalcohol 20, which was alkylated or reductively alkylated to form tertiary amines 21f-21r. In the last step, the allyl protective group of 21 was removed with RhCl3 and HCl to obtain oxazolones 22. In receptor binding studies using [3 H]ifenprodil as radioligand ketone, 22m showed the highest GluN2B affinity (Ki = 88 nM). However, a reduced affinity towardGluN2B subunit-containing N-methyl- d-aspartate(NMDA) receptors was observed for oxazolones 22 compared to bioisosteric 3-benzazepine-1,7-diols. High selectivity of 22m for the ifenprodil binding site of GluN2B-NMDA receptors over the 1-(1-phenylcyclohexyl)piperidine binding site and σ2 receptors was observed, but only negligible selectivity over σ1 receptors. In two-electrode voltage clamp experiments, the 4-phenylbutyl derivative 22d (Ki = 422 nM) demonstrated 80% inhibition of ion flux at a concentration of 1 µM. The differences in GluN2B affinity and inhibitory activity are explained by docking studies. In conclusion, 22d is regarded as a novel scaffold of highly potent GluN1/GluN2B antagonists.

Enantioselective Catalyzed Synthesis of Amino Derivatives Using Electrophilic Open‐Chain N‐Activated Ketimines

AbstractN‐Activated ketimines are characterized by the presence of acyl, sulfonyl, and phosphinoyl groups linked to the nitrogen atom of the azomethine system. These electron‐withdrawing groups enhance the electrophilic character of the imino moiety allowing the addition of even weak nucleophilic reagents. The presence of the oxygen atoms in these activating groups with its coordinating and Lewis or Brønsted properties is of paramount importance in asymmetric catalyzed reactions. This review collects the results that have appeared in the literature during the last two decades on the utilization of open‐chain N‐activated ketimines for the synthesis of optically active α‐disubstituted and α‐trisubstituted amino derivatives including nitrogen‐containing heterocyclic compounds.magnified image

Iminopyridine Ni(II) Catalysts Affording Oily Hyperbranched Ethylene Oligomers and/or Crystalline Polyethylenes Depending on the Reaction Conditions: Possible Role of In Situ Catalyst Structure Modifications

Nickel-based ethylene polymerization catalysts have unique features, being able to produce macromolecules with a variable content of branches, resulting in polymers ranging from semicrystalline plastics to elastomers to hyperbranched amorphous waxes and oils. In addition to Brookhart’s α-diimine catalysts, iminopyridine Ni(II) complexes are among the most investigated systems. We report that Ni(II) complexes bearing aryliminopyridine ligands with bulky substituents both at the imino moiety and in the 6-position of pyridine afford either hyperbranched low molecular weight polyethylene oils or prevailingly linear crystalline polyethylenes or both, depending on the ligand structure and the reaction conditions. The formation of multiple active species in situ is suggested by analysis of the post-polymerization catalyst residues, showing the partial reduction of the imino function. Some related arylaminopyridine Ni(II) complexes were also synthesized and tested, showing a peculiar behavior, i.e., the number of branches of the produced polyethylenes increases while ethylene pressure increases.

Synthesis, Characterization, Biological and Molecular Docking Studies of 1,3-Diphenyl-1H-pyrazole Terminated Imino Derivatives

Herein, the novel pyrazole derivatives with imino moiety were synthsized, characterized using IR, NMR, mass spectroscopy, elemental analysis and screened their biological activities. Molecular docking studies were also carried out by the software Arguslab 4.0.1. The synthesized compounds showed moderate to good biological activities both experimentally and theoretically.

Efficient Cobalt Catalyst for Ambient-Temperature Nitrile Dihydroboration, the Elucidation of a Chelate-Assisted Borylation Mechanism, and a New Synthetic Route to Amides.

N,N-Diborylamines have emerged as promising reagents in organic synthesis; however, their efficient preparation and full synthetic utility have yet to be realized. To address both shortcomings, an effective catalyst for nitrile dihydroboration was sought. Heating CoCl2 in the presence of PyEtPDI afforded the six-coordinate Co(II) salt, [(PyEtPDI)CoCl][Cl]. Upon adding 2 equiv of NaEt3BH, hydride transfer to one chelate imine functionality was observed, resulting in the formation of (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co. Single-crystal X-ray diffraction and density functional theory calculations revealed that this compound possesses a low-spin Co(II) ground state featuring antiferromagnetic coupling to a singly reduced imino(pyridine) moiety. Importantly, (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co was found to catalyze the dihydroboration of nitriles using HBPin with turnover frequencies of up to 380 h-1 at ambient temperature. Stoichiometric addition experiments revealed that HBPin adds across the Co-Namide bond to generate a hydride intermediate that can react with additional HBPin or nitriles. Computational evaluation of the reaction coordinate revealed that the B-H addition and nitrile insertion steps occur on the antiferromagnetically coupled triplet spin manifold. Interestingly, formation of the borylimine intermediate was found to occur following BPin transfer from the borylated chelate arm to regenerate (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co. Borylimine reduction is in turn facile and follows the same ligand-assisted borylation pathway. The independent hydroboration of alkyl and aryl imines was also demonstrated at 25 °C. With a series of N,N-diborylamines in hand, their addition to carboxylic acids allowed for the direct synthesis of amides at 120 °C, without the need for an exogenous coupling reagent.

Catalytic Asymmetric Umpolung Allylation/2-Aza-Cope Rearrangement for the Construction of α-Tetrasubstituted α-Trifluoromethyl Homoallylic Amines.

A general protocol for the preparation of enantioenriched α-tetrasubstituted α-trifluoromethyl homoallylic amines is disclosed. Despite the significant challenge in stereoselectivity control, Ir-catalyzed asymmetric cascade umpolung allylation/2-aza-Cope rearrangement of trifluoromethylated fluorenone imines with allylic carbonates was realized with excellent efficiency and remarkable stereoselectivity. These were enabled by the suitable protective imino moiety and an unexpectedly exclusive E-geometrical imine of the allylation intermediate. This methodology is also applicable to facile access to chiral α-trisubstituted α-trifluoromethyl homoallylic amines in similarly high yield and stereoselectivity.

Novel Nicotinonitrile Derivatives Bearing Imino Moieties Enhance Apoptosis and Inhibit Tyrosine Kinase.

Fused heterocyclic containing pyrazolopyridine systems have several medicinal activities including cytotoxic and carcinostatic activities. To investigate the antiproliferative activity and associated mechanism(s) of a novel series of nicotinonitrile derivatives. The series has been synthesized by the reaction of hydrazonoyl chlorides with each of 4-(4- methoxyphenyl)-3-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile and 2-amino-4-(4- methoxyphenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile in dioxane in basic medium. The assigned structures for each of the new products were identified via elemental and spectral data. Moreover, the cytotoxic activity for some selected products was screened. Derivatives 5g, 7i, 8 and 9 had their IC50 at ~ 1-3 µM and derivatives 7b, 7d, and 7f were similar to 5- fluorouracil and had their IC50 at ~ 5 µM against breast (MCF-7) and colon (HCT-116) cell lines. All derivatives were specific in action and safe to normal fibroblasts (WI38). Only derivative 9 caused some toxicity but at high concentration of 93 µM. These derivatives exerted strong antiproliferative activity through inducing intrinsic apoptosis as indicated from the significant induction of caspases 9 and 3 by 3-6 folds in colon cells and/or inhibiting tyrosine kinase (TK) and hence arresting the cell cycle. Compounds 8 and 5g were the most potent anticancer agents inhibiting the TK by 86 and 89% and their IC50 of the enzyme were 311 and 352 nM, respectively. We believe that these derivatives deserve further investigation and these chemical moieties could offer promising anticancer drugs.

Synthesis, crystal structure and luminescence properties of acenaphthene benzohydrazide based ligand and its zinc(II) complex

The complex compound of zinc(II) supported by (Z)-2-hydroxy-N′-(1-oxoacenaphthylen-2(1H) ylidene)benzohydrazide ligand (H2L1) has been reported and discussed. The reaction of zinc acetate with H2L1 ligand leads to the formation of a mononuclear zinc(ii) complex, [Zn(HL1)2H2O]. The ligand, H2L1 has been characterized by elemental analysis, 1H, 13C and 1HCOSY -NMR, IR and ESI-MS, while the complex was characterized by elemental analysis, IR, and ESI-MS. The crystal structures of the free ligand H2L1 and the complex have also been determined by single crystal X-ray diffraction. The ligand chelates with metal centre with a nitrogen atom of imino moiety and an oxygen atom of enolic group. The complex shows distorted trigonal bipyramidal geometry around the metal centre with oxygen atoms lying in the equatorial plane and imino nitrogen atoms along the axial direction. The DFT/TD-DFT calculations were performed on both the ligand and its zinc complex to get insight into the structural, electronic and optical properties. The photoluminescence, fluorescence properties of the complex have been investigated.

Hydrosilylation in imino-substituded N- or C-monoanionic ligands

The reaction of HSiCl3 with 2-[N-(2,6-diisopropylphenyl)iminomethyl]indolyl lithium (DippIMIndLi) provided disubstituted (DippAMInd)(DippIMInd)SiCl (2), where one imino moiety of DippIMInd ligand was reduced to amino group by Si-H fragment. In contract the reaction of HSiCl3 with 2-[N-(2,6-diisopropylphenyl)iminomethyl]phenyl lithium (DippIMPhLi) provided stable CHN→Si coordinated silane (DippIMPh)SiHCl2 (3). Heating of the toluene solution of 3 provided the hydrosilylated compound (DippAMPh)SiCl2 (4). It has been demonstrated that the rate of CHN imino group reduction strongly depends on type of the anionic ligand.

Effect of benzimidazole configuration in polybenzimidazole chain on interaction with phosphoric acid: a DFT study.

Polybenzimidazole doped with phosphoric acid (PA) is a candidate for polymer electrolyte membranes in fuel cells. Understanding the interaction of benzimidazole in polybenzimidazole with PA is important for fuel-cell applications. Herein, the interaction of a PA-benzimidazole complex was investigated using density functional theory, with calculations performed at the ωB97X-D/6-311G(d,p) level of theory, with an aim to investigate the effects of bibenzimidazole configuration on the interaction energy. Benzimidazole and three different bibenzimidazole configurations (2,2'-bibenzo[d]imidazole (1), 2,5'-bibenzo[d]imidazole (2), and 5,5'-bibenzo[d]imidazole (3)) were used as models for bulk polybenzimidazole. Calculation of various types of hydrogen bond interaction showed that the interaction between the imino moiety of the monomer and the hydroxyl group of PA is the strongest, which agrees with previous studies. Our calculations indicated that π-H interactions between the hydrogen atoms of the PA molecule and the benzene rings should be considered, and these contribute to the interaction energy for some interaction complexes. The interaction energy between the monomer and PA is smaller than that of the PA dimer. However, the interaction energy between bibenzimidazole and PA is comparable to that of the PA dimer for bibenzimidazole configurations 1 and 2, highlighting the importance of considering the adjacent monomer unit.

Construction and Multiple Exterior Surface Functionalization of Giant Molecular Cages

AbstractBy a one‐pot reaction strategy and a stepwise fragment‐coupling approach, three types of giant cage molecules with a triangular prism shape and an approximate cavity volume of 930 Å3 were synthesized. Through efficient aromatic nucleophilic substitution reactions of chlorotriazine with functionalized amines or aliphatic substitution reactions of the linking imino moieties with allyl bromide, the giant cages were successfully functionalized on the surface with multiple hydroxy, 2‐pyridyl, or allyl groups. As evidenced by variable‐temperature 1H NMR spectroscopy, the D3h‐ and C3v‐symmetric cage molecules underwent very slow conformational changes or deformation in solution because of their giant size and their flexible building units. Their giant cavities, different electronic interiors, and facile multiple exterior surface functionalization could render the molecular cages powerful three‐dimensional macrocyclic hosts that might find wide applications in supramolecular science.

Synthesis and stability of Li/Cl carbenoids based on bis(iminophosphoryl)methanes.

The synthesis and stability of two bis(iminophosphoryl) substituted lithium chloride carbenoids with different N-substituents (tolyl and adamantyl) were examined. Their preparation was accomplished via the mild oxidation of the corresponding dilithio bis(iminophosphoryl) methandiides, BIPM(Tol) and BIPM(Ad), which are easily accessible by direct double deprotonation. In the case of the adamantyl substituted system the alternative preparation method via lithiation of the chlorinated precursor was found to be more selective. Here, the chlorinated precursor turned out to be highly CH acidic. Intramolecular deprotonation by the imino moiety results in the formation of the NH tautomer with a carbanionic centre as the most stable isomer. The prepared carbenoids are stable at room temperature in the solid state. Yet, in solution the stability was found to depend on the substituent bound at the imine nitrogen atom. As such, the tolyl substituted system was fairly stable in ether and hydrocarbon solvents, thus allowing crystallization. In contrast, the adamantyl derivative exhibits limited stability in ether solvents at room temperature. Decomposition resulted in LiCl elimination and transfer of the imino moiety to the carbenoid carbon atom.

Citrullination – small change with a great consequence

Citrullination is one of the possible post-translational modifications of proteins. It is based on a conversion of L-arginine residue (L-Arg) to L-citrulline residue (L-Cit). The reaction is catalyzed by peptidylarginine deiminases (PAD). The change of L-Arg imino moiety results in a loss of a positive charge. This slight modification can contribute to significant changes in physicochemical properties of proteins, which may also cause a change of their functions. Citrullination is the modification observed in physiological processes such as epidermal keratinization, regulation of gene expression and the reorganization of myelin sheaths. The changes in the efficacy of citrullination may contribute to the pathogenesis of many different diseases including: psoriasis, multiple sclerosis, rheumatoid arthritis and cancer.

Amino→Imino Tautomerization upon in Vacuo Sublimation of 2-Methyltetrazole-Saccharinate as Probed by Matrix Isolation Infrared Spectroscopy

The amino-imino tautomerization of the nitrogen-linked conjugate 2-methyltetrazole-saccharinate (2MTS) was observed upon sublimation of the compound in vacuo. As shown previously by X-ray diffraction [Ismael, A.; Paixão, J. A.; Fausto, R.; Cristiano, M. L. S. J. Mol. Struct., 2011, 1023, 128-142], in the crystalline phase the compound exists in an amino-bridged tautomeric form. Infrared spectroscopic investigation of a cryogenic matrix prepared after sublimation of a crystalline sample of 2MTS and deposition of the sublimate together with argon (in ~1:1000 molar ratio) onto an IR-transparent cold (15 K) substrate, revealed that the form of 2MTS present in the matrix corresponds to the theoretically predicted most stable imino-bridged tautomer. In this tautomer, the labile hydrogen atom is connected to the saccharine nitrogen, and the two heterocyclic fragments are linked by an imino moiety in which the double-bond is established with the carbon atom belonging to the saccharyl fragment. The observed isomeric form of this tautomer is characterized by a zusammen (Z) arrangement of the two rings around the C═N bond of the bridging group and an intramolecular NH···N hydrogen bond. The experimental IR spectrum of the matrix-isolated 2MTS has been fully assigned based on the calculated spectra for the two most stable conformers of this tautomer. A mechanism for the conversion of the tautomeric form existing in the crystal into that present in the gas phase is proposed. As a basis for the interpretation of the experimental results, a detailed theoretical [at the DFT(B3LYP) level of approximation with the 6-31++G(d,p) and 6-311++G(3df,3pd)] study of the potential energy surface of the compound was performed.

Crystal Structure Study on Non-Coplanarly Organized Accumulating Aromatic Rings Molecules: Spatial Organization of <i>C</i>,<i>C</i>,<i>N</i>-Triaryl Substituted Imines

The X-ray crystal structures of C,C,N-triaryl-substituted imine compounds, which have methoxy or hydroxy group adjacent to the imino moiety, are reported and discussed in comparison with those of the precursor ketone compounds, 1-(4-chlorobenzoyl)-2,7-dimethoxynaphthalene and 1-(4-chlorobenzoyl)-2-hydroxy-7-methoxynaphthalene. In crystals, three aromatic rings in a molecule of the methyl ether-retained imine compound are positioned almost perpendicularly to each other by giving non-coplanar spatial organization of the single molecular structure [dihedral angles: 85.32(18)° for C-linked phenyl ring and naphthalene ring; 79.27(17)° for N-linked phenyl ring and naphthalene ring; 84.78(17)° for C-linked phenyl ring and N-linked phenyl ring]. Spatial organization of the analogous methyl ether-cleaved imine compound has essentially same topology [dihedral angles 80.39(6)° for the C-linked phenyl ring and naphthalene ring; 82.35(6)° for the N-linked phenyl ring and naphthalene ring; 87.09(7)° for C- and N-linked phenyl rings]. These structural features of triarylimines apparently differ from those of the precursor ketones. Two aromatic rings in the methyl ether-cleaved ketone compound make smaller dihedral angle [58.10(6)°] by intramolecular hydrogen bond between ketonic carbonyl group and hydroxy group [2.5573(16) A] than that of the methyl ether-retained ketone [72.06(7)°]. In molecular packing, the methyl ether-retained imine forms tubular molecular alignments composed of R—S dimeric molecular pairs, whereas the methyl ether-retained ketone affords consecutively stacks of one configurated molecules.

Calix[4]arene-based fluorescent receptor for selective turn-on detection of Hg2+ ions

A new fluorescent molecular receptor 3 based on the cone confirmation of calix[4]arene appended with 2-[4-(N,N-dimethylaminophenyl)iminoethoxy] moieties was synthesised, which exhibits selective fluorescence ‘Turn-On’ response in the presence of only Hg2+ ions among the various metal ions tested with a detection limit up to the nanomolar range. The fluorescence behaviour of receptor 3 in the presence of Hg2+ ions is attributed to the alteration in electronic properties of 3, i.e. working of intramolecular charge transfer (ICT) phenomenon on Hg2+ ions complexation. The nitrogen atoms of the imino moieties got involved in the coordination with mercury ions, which enhances the electron-withdrawing ability of imino nitrogen atoms and, hence, leads to an ICT process consequently resulting in the appearance of an emission band at 444 nm.

Ozonation of the food dye Brilliant Blue in aqueous medium: monitoring and characterization of products by direct infusion electrospray ionization coupled to high‐resolution mass spectrometry

Dyes have been widely used to accentuate or to provide different colors to foods. However, the high concentrations of dyes in effluents from the food industries can cause serious and unpredictable damages to aquatic life in general. Furthermore, since conventional biological treatments have been shown to be ineffective, the use of advanced oxidation processes to promote the depletion of such dyes in water bodies has turned out to be mandatory. The degradation of the food dye Brilliant Blue by ozone in aqueous solution is reported herein. The overall process was monitored in real time by using direct infusion electrospray ionization high-resolution mass spectrometry in the negative ion mode, ESI(-)-HRMS. Preliminary results (visual inspection and UV-vis spectra) showed the high efficiency of ozonation in causing the decoloration of an aqueous solution of the dye whereas TOC (total organic carbon) measurements revealed that such an oxidation process was unable to promote its complete mineralization. ESI(-)-HRMS data showed that the substrate consumption occurred concomitantly with the appearance of four by-products, all of them produced by an initial attack of hydroxyl radicals (generated via the decomposition of ozone) on the two imino moieties of the dye molecule. Structures were proposed for all the by-products based mainly on the high-resolution mass measurements and on the characteristic reactivity of typical functional groups towards hydroxyl radicals. An unprecedented degradation route of Brilliant Blue by ozone in aqueous solution could thus be proposed. A greater ecotoxicity against Artemia salina was observed for the by-products than for the original dye. This indicates that the identification of by-products arising from oxidation treatments is of primary importance since such compounds can be more hazardous than the precursor itself.

ChemInform Abstract: Chemistry and Biological Activity of Platinum Amidine Complexes

AbstractReview: 106 refs.