Benzylidene Research Articles

Nitrile Imine Cyclizations and Rearrangements: N-Phenyl-C-styrylnitrile Imine and N-Phenyl-C-phenylethynylnitrile Imine.

The formation and rearrangements of nitrile imines are of ongoing synthetic and theoretical interest. In this paper, we report a computational investigation at the M06/6-311 + G(d,p) level of the formation and rearrangement of propargylic N-phenyl-C-styrylnitrile imine 3 from 2-phenyl-5-styryltetrazole 1 by flash vacuum pyrolysis (FVP). Nitrile imine 3 cyclizes to 3aH-3-styrylindazole 4, which is also generated by H-shifts in the FVP of 3-styrylindazole 8. Tautomerization of 4 and N2-elimination afford cyclohexadienylidene 14, which by cyclization followed by H-shifts yields the primary pyrolysis product, 3-phenylindene 5. An alternate path via 7aH-3-styrylindazole, phenyl(styryl)diazomethane, and phenyl(styryl)carbene is potentially possible. The analogous pyrolysis of 2-phenyl-5-phenylethynyltetrazole 1' afforded cyclopenta[fg]fluorene and cyclopenta[def]phenanthrene via N-phenyl-C-phenylethynylnitrile imine 3' and 3aH-3-phenylethynylindazole 4'. In both cases, 3 and 3', rearrangement to diazocyclohexadienes and cyclohexadienylidenes (e.g., 14) is energetically preferred over alternate aryldiazomethane and arylcarbene intermediates.

Design, Synthesis of a Novel Banana-Shaped Compounds via Esterification

Schiff's Bases were synthesized from the reaction of p-amino benzoic acid and alkoxybenzaldehyde in absolute ethanol and reacted with (E)-3-((4-hydroxybenzylidene) amino) phenol used DCC (N,N'-Dicyclocarbodiimide) and DAMP (4-(Dimethylamino) pyridine ) to 3-(((E)-4-((4-(((E)-4 alkoxy benzylidene) amino) benzoyl) oxy) benzylidene) amino) phenyl4- (E)- 4-alkoxy benzyli dene ) amino) benzoate. The structures of the products were confirmed by their melting points, FT-IR, 1HNMR spectra.

YENİ BENZİMİDAZOL-HİDRAZON TÜREVLERİNİN TASARIMI, SENTEZİ VE KOLİNESTERAZ İNHİBİTÖR AKTİVİTESİ

Yetersiz kolinerjik transmisyon, Alzheimer hastalığında bilişsel, işlevsel ve davranışsal belirtilerin ortaya çıkmasında önemli bir rol oynamaktadır. Dolayısıyla, tedaviler genellikle ya reseptör agonisti ya da asetilkolinesteraz inhibitörleri (AChEI) ile kolinerjik sistemin işlevini arttırmaya yönelik planlanmaktadır. Bu çalışmada, yedi orijinal benzimidazol-hidrazon türevi bileşik sentezlenmiş ve bu bileşiklerin asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) inhibisyon aktiviteleri değerlendirilmiştir. Sentezlenen bileşiklerin kimyasal yapıları, 1H-NMR ve LCMS-IT-TOF verileri ile aydınlatılmıştır. Sentezi gerçekleştirilen bileşiklerin AChE ve BuChE inhibitör aktivitelerinin değerlendirilmesinde spektrofotometrik Ellman yöntemi kullanılmıştır. Sentezlenen bileşiklerden en yüksek AChE inhibitör aktiviteyi 96±3,37 nMIC50 değeri ile bileşik 4g (2-(4-etoksifenil)-N’-(4-(morfolin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) gösterirken, bu bileşik Bu ChE üzerinde düşük aktivite göstermiştir. Bileşik 4c (2-(4-etoksifenil)-N’-(4-(4-metil-piperidin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) ve bileşik 4e (2-(4-etoksifenil)-N’-(4-(4-metil-piperazin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) türevlerinde de belirgin AChE inhibitör aktivite gözlenmiştir.Sonuç olarak, bu çalışma Alzheimer hastalıkları gibi nörodejeneratif hastalıklar için yeni ajanlar geliştirmek için önemli sonuçlar sunmaktadır.Yetersiz kolinerjik transmisyon, Alzhemier hastalığında bilişsel, işlevsel ve davranışsal belirtilerin ortaya çıkmasında önemli bir rol oynamaktadır. Dolayısıyla, tedaviler genellikle ya reseptör agonisti ya da asetilkolinesteraz inhibitörleri (AChEI) ile kolinerjik sistemin işlevini arttırmaya yönelik planlanmaktadır. Bu çalışmada, yedi orijinal benzimidazol-hidrazon türevi bileşik sentezlenmiş ve bu bileşiklerin asetilkolinesteraz (AChE) ve butirilkolin esteraz (BuChE) inhibisyon aktiviteleri değerlendirilmiştir. Sentezlenen bileşiklerin kimyasal yapıları, 1H-NMR ve LCMS-IT-TOF verileri ile aydınlatılmıştır. Sentezi gerçekleştirilen bileşiklerin AChE ve BuChE inhibitör aktivitelerinin değerlendirilmesinde spektrofotometrik Ellman yöntemi kullanılmıştır. Sentezlenen bileşiklerden en yüksek AChE inhibitör aktiviteyi 0.096±0.003 IC50 değeri ile bileşik 4g (2-(4-Etoksifenil)-N’-(4-(morfolin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) gösterirken, bu bileşik BuChE üzerinde düşük aktivite göstermiştir. Bileşik 4c (2-(4-Etoksifenil)-N’-(4-(4-metil-piperidin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) ve bileşik 4e (2-(4-Etoksifenil)-N’-(4-(4-metil-piperazin-1-il)-benziliden)-1H-benzo[d]imidazol-6-karbohidrazit) türevlerinde de belirgin AChE inhibitör aktivite gözlenmiştir.

Exploring the potential of iron to replace ruthenium in photosensitizers: a computational study.

In an effort to replace the widely used ruthenium metal complexes with low-cost, earth abundant iron complexes as photosensitizers for dye-sensitized solar cell (DSSC) applications, herein we report the computational design of heteroleptic iron complexes (FC1-3) coordinated with benzimidazole-phenylcarbene (C^N) ligands. DFT and TDDFT calculations predicted the stronger σ-donating and π-accepting nature of phenyl carbene ligands substituted with electron-withdrawing CF3, donating -N(CH3)2, and benzothiazine annulation than the imidazole carbene ligands (FC4); consequently, the metal-ligand bond distances and interactions that influence the ordering of charge transfer states with respect to metal centered states are altered in FC1-3 complexes. Detailed analysis based on energy decomposition analysis, spin density distribution analysis, and ab initio ligand field theory parameters were enabled to understand the nature of heteroleptic ligand interactions with the rest of the metal complex. The results from the study shed light on the judicious choice of ligands, as the same non-innocent ligand that is experimentally proven as favorable for Ru-dyes (TC1) is found to be detrimental for Fe-dyes (FC1). Among the complexes studied, the FC3 complex is a promising sensitizer for DSSC with 1,3MLCT energy level well separated from 3,5MC, thereby preventing the deactivation of MLCT. The outcome of the study is therefore an important step toward the development of photosensitizers based on iron metal. Graphical abstract Potential photosensitzers based on earth-abundant, low cost iron metal have been designed for dye sensitized solar cell applications.

Crystal structure of 1-{4-[(2-hydroxy-5-methyl benzylidene)amino]phenyl}ethanone O-ethyl-oxime, C18H20N2O2

Abstract C18H20N2O2, monoclinic, Pc (no. 7), a = 17.8843(15) Å, b = 7.1821(6) Å, c = 6.3086(6) Å, β = 98.487(3)°, Z = 2, V = 801.45(12) Å3, R gt(F) = 0.0533, wR ref(F 2) = 0.1411, T = 296(2) K.

DOCKING STUDIES ON IMIDAZOLIDINE ANALOGUES FOR MANAGEMENT OF DIABETES

Glycogen synthase kinase-3I² (GSK-3I²) has recently emerged, in the field of medicinal chemistry, as one of the most attractive therapeutic targets for type II diabetes. Phenylmethylene hydantoins (PMHs) forms strong interactions with the hinge region of GSK-3I²; carbonyl oxygen at position 2 form a H-bonding with backbone nitrogen of Val135 and the NH at position 3 to the carbonyl oxygen of Asp133. The hydantoin ring was sandwiched between Ala83, on top, and Leu188, on the bottom. The aromatic ring is rotated out of plane from the hydantoin plane, allowing extensive interactions with the nucleotide-binding loop. Furthermore, the substituted benzylidene ring system builds an H-bonding interaction with the guanidine moiety of Arg141. Targeting Arg141 is important to improve the activity in the process of designing new derivatives because it is considered the selectivity residue for GSK-3I².

Multi-branched benzylidene ketone based photoinitiators for multiphoton fabrication

In this article, we report the synthesis of a series of multi-branched benzylidene (BI) ketone-based photo-initiators for two-photon polymerisation based 3D printing/additive manufacturing. Resins prepared by the addition of 1wt.% of these initiators were processed in a commercial 2 photon polymerisation system to fabricate 3D woodpile structures, the qualities of which were examined to determine the efficiencies of the initiators. The results showed that compared to commercial initiator Irgacure 369, the four-branched initiator 4-BI exhibited excellent performance with higher writing speeds and broader ideal processing windows. The successful fabrication of complex 3D structures at high writing speeds (up to 100mm/s) indicated that the four-branched initiator 4-BI could potentially increase the fabrication efficiency and hence become a promising initiator for two-photon polymerisation.

Convenient synthesis of 1,3-disubstituted-2-thioxo-imidazolidin-4-ones as potential anti-tumor agents

1-(Arylidene)amino-2-thioxo-imidazolidine-4-ones ( 3 a,b) have been synthesized via cyclization of 1-(arylidene)amino-3-(chloroacetyl)thiourease ( 2 a,b) in ethanol in presence of fused sodium acetate under heating. Acetylation of compounds ( 3 a,b) with acetic anhydride yielded the corresponding 1-(arylidene)amino-2-thioxo-3-acetylimidazolidin-4-ones ( 4 a, b). Condensation of compounds ( 3 a,b) with aromatic aldehydes in presence of piperidine yielded the corresponding aryl-[1-(arylidine)amino-2-thioxo-4-oxo-imidazolidin-3-yl)carbanols ( 6 a-d). Halogenation of 1-(phenylethylidene)amino-2-thioxoimidazolidin-4-one ( 3 b) with one mole of bromine produced N-bromo- 2- thioxoimidazolidin-4-one ( 9 ), while brominating 1-(benzylidene)amino-2-thioxoimidazolidin-4-one ( 3 a) with two mole of bromine gave the corresponding 3,5-dibromo-2-thioxoimidazolidin-4-one derivative ( 10 ). The characterization of all synthesized compounds were done by elemental analysis and spectral studies. Moreover, the cytotoxic activities of the synthesized compounds were evaluated against human hepatocellular carcinoma cell line (HePG2) using MTT viability test. The results showed that the investigated compounds have a significantly cytotoxic effect.

Chemistry of Metal (Benzylidene) Picramate-Part III Benzylidene Picramates of Zinc Cadmium and Mercury

Benzylidene picramates of zinc, cadmium and mercury have been prepared by treating the corresponding aqueous sulphate and chloride solutions with sodium salt of 4'-dimethylaminobenzylidence-2-hydroxy-3, 5-dinitroaniline. A metal: ligand ratio of 1:2 has been established in all these cases. I.R. spectral studies of metal benzylidene picramates show N-M coordination (where M is zinc, cadmium or mercury). Explosive properties of these benzylidene picramates have also been studied and it was found that the thermal stability increases as the atomic radius decreases or ionization potential increases.

Design and synthesis of some new heterocyclic benzylidene hydrazide derivatives for their antileishmanial activity

ABSTRACT: Benzylidene hydrazide is a highly active moiety against Leishmania donovani, and has become a core structure for the design of new antileishmanial agents. The 5-nitrothiophen-2-yl-benzylidene hydrazide derivative presents a potent IC50 value. With this background, it is attempted to discern the structural and physicochemical requirements for the inhibition of Leishmania donovani. The techniques of quantitative structure activity relationship and docking are valuable molecular modeling tools for drug design. In the present study, 3-DQSAR of some Leishmania donovani inhibitors was carried out using VLife MDS, while interaction studies were carried usind Schrodinger molecular modeling interface. The developed QSAR models showed q2 = 0.9849, pred_r2 = 0.6770 with kNN analysis by stepwise forward and backward method. Docking study revealed important interactions of designed compounds with the active binding site of Leishmania donovani. Designed compounds were synthesis and screened against Leishmania donovani. Three compounds exhibited IC50 values lower than standard drugs. Brief SAR analysis revealed that substitution is important to the activity. KEY WORDS: benzylidene hydrazide derivatives, antileishmanial activity, 3D-QSAR, docking

A density functional theory study on the stability and ligand properties of the different substituted phenyl carbenes

In regard to the worldwide interest in synthesis and application of stable carbenes, DFT calculations (B3LYP/6-311++G**//B3LYP/6-31+G* levels) are employed to reach at a series of phenyl carbenes. The singlet-triplet energy separations (ΔES-T), HOMO–LUMO energy gaps (ΔEHOMO-LUMO), as well as philicity indices (N and ω) and basicity of these carbenes are compared and contrasted with the synthesized N-heterocyclic carbenes. The investigations reveal that F, Cl, Br, NMe2 and PMe2 stabilize singlet states more than their corresponding triplet states. The reactivity of the species is discussed in terms of nucleophilicity, electrophilicity and proton affinity. This detailed study offers new insights into the chemistry of these classes of carbenes. Key words: Stability, phenyl carbenes, nucleophilicity and electrophilicity, proton affinity, DFT.

N-[2-(4,6-二甲氧基嘧啶-2-氧基)苯亚甲基]-2-芳氧乙酰腙的合成与除草活性

通过2-（4,6-二甲氧基嘧啶-2-氧基）苯甲醛（1）与芳氧乙酰肼2的缩合反应,合成了10个含嘧啶结构的芳氧乙酰腙化合物3,其结构经1H NMR、IR、EI-MS或ESI-MS和元素分析测试技术确证。除草活性测试（活体盆栽）结果表明,大部分目标化合物在1.5 kg/hm2浓度下,无论苗前或苗后处理对苋菜均显示出很强抑制活性,化合物3e和3h的抑制率分别为100%和97.7%,而化合物3a、3b、3d、3e、3f和3h苗后处理对苋菜的抑制率均超过97%,对马唐的除草活性最差。苯环4-位取代基性质对除草活性有规律性影响。

Growth and characterization of an organic NLO crystal:4-chloro- 4-methyl benzylidene aniline

In this paper, we report for the first time the synthesis, growth and characterization of a new organic NLO single crystal of 4 choloro-4-methyl benzylidene aniline. The title compound is synthesized and single crystals were grown by the slow evaporation technique at constant temperature. The grown single crystals have been characterized by single crystal XRD; powder XRD, FTIR, NMR, UV-Vis, thermal analysis and microhardness studies. From the XRD study, it is found that the crystals are in the monoclinic system. The FTIR spectrum was recorded to identify the various functional groups present in the group compound. The formation of the product was confirmed from NMR spectral analysis. The optical transparency was determined by UV-visible spectroscopy. The melting point is found to be 108°C from the DSC curve. The second harmonic generation (SHG) efficiency of the crystal was obtained using ND-YAG laser which is found to be 7.5 times that of KDP.

Oxygen migration on the graphene surface. 1. Origin of epoxide groups

It is now a widely accepted fact that oxidized graphene surfaces are populated, to a greater or lesser extent, with epoxide groups. And yet the origin of these groups has heretofore been mysterious. We report the results of a computational (DFT) analysis of this issue carried out by combining the theoretical and experimental knowledge of three seemingly unrelated fundamental processes: (i) formation of pentagon–heptagon pairs (or Thrower–Stone–Wales defects); (ii) surface diffusion of oxygen atoms on the basal plane; and (iii) graphene unzipping by oxygen insertion. We provide thermodynamic and kinetic evidence for the hypothesis that a key intermediate step in the stabilization of free adjacent zigzag sites – before they reconstruct to form an armchair site or become quinone surface functionalities upon dissociative O 2 chemisorption – is the formation of an epoxide group in the basal plane. The presence of epoxide groups on the graphene surface is therefore a result of spillover of edge oxygen (e.g., nondissociatively adsorbed O 2 on carbene-type sites), mechanistically reminiscent of the extensively investigated migration of carbon in the conversion of phenyl carbene to bicycloheptatriene.

Versatile Zirconium Reductants and Carbon–Carbon Coupling Agents Selectively Accessible from the 2:1 Molar Aggregate of n‐Butyllithium and Zirconium(IV) Salts

AbstractIn previous studies of transition metal alkyls the 2:1 molar aggregate of n‐butyllithium and zirconium(IV) salts has been found to react both with benzylic hydrocarbons and aromatic carbonyl derivatives in diverse and useful ways. In the present study the reactions of the aggregates, 2nBuLi·ZrE4 (E = Cl, OEt), with benzaldehyde have involved carbometallation, hydrometallation and reductive dimerization (paths 1–3) in THF and were selectively achievable by temperature control alone. First, at –78 °C benzaldehyde underwent carbolithiation to give upon hydrolysis 1‐phenyl‐1‐pentanol. However, short‐term reaction times and prompt D2O quenching revealed that with Zr(OEt)4 both benzaldehyde and 1‐phenyl‐1‐pentanol were deuteriated, consistent with the presence of a phenyl(lithioxy)carbene intermediate. The observed dimerization of benzaldehyde to benzyl benzoate by lithium 2,2,6,6‐tetramethylpiperidide is also consistent with such a phenyl(lithioxy)carbene intermediate. Second, at 25 °C the 2nBuLi·ZrE4 aggregate reduced benzaldehyde exclusively to benzyl alcohol, which observation is consistent with the formation of the hydrozirconating agent, H2ZrE2. Third, heating the aggregate at reflux and subsequent reaction with benzaldehyde produced solely the reduced dimer, 1,2‐diphenyl‐1,2‐ethanediol with high stereoselectivity: E = Cl, rac/meso of 93:7 and E = OEt, rac/meso of 100:0. The proposed mechanism involves the formation of ZrE2, the epizirconation of benzaldehyde and the insertion of the second benzaldehyde into the zirconaoxacyclopropane under steric control. Finally, the high selectivity in hydrozirconation and reductive dimerization shown by 2nBuLi·ZrE4 appears at this time to be superior to that attainable with analogous titanium or hafnium aggregates.

Polymer supported N-benzyl-N-nitroso-4-toluenesulfonamide: An improved reagent for the derivatization of the acidic markers of nerve agents

We report herein the synthesis, characterization, stability study of a new solid supported derivatizing agent, N-benzyl-N-nitroso-4-poly(styrene-co-divinylbenzene)sulfonamide beads, for the preparation of phenyldiazomethane (PDM). The active component loading was found to be 2.0 ± 0.1 mmol g−1. This derivatizing agent is easy to synthesize and purify. The impurities and byproducts generated during the formation of PDM remain bound to the polymer backbone. These byproducts can be easily removed by filtration. Thus, pure PDM is obtained without the need for further purification. Due to the formation of a dilute solution of PDM, the chances of explosion and intoxication are minimized. The PDM from this derivatizing agent was used for the benzylation of a variety of acids. We have evaluated this derivatizing agent for the benzylation of alkylphosphonic acids (APAs) and alkyl alkylphosphonic acids (AAPAs). Subsequently, this reagent was applied for analysis of a real sample containing pinacolyl methylphosphonic acid by onflow LC-UV-1H NMR analysis.

ChemInform Abstract: The Use of Chiral Sulfides in Catalytic Asymmetric Epoxidation.

Abstract Non racemic epoxides with ee's of 23–41 % have been prepared from aldehydes and phenyl diazomethane using catalytic amounts of sulfides derived from camphor.

Asymmetric aziridination of N-tert-butanesulfinyl imines with phenyldiazomethane via sulfur ylides

Optically active aziridines were synthesized from the reaction of chiral nonracemic N-tert-butanesulfinyl imines with benzyl-stabilized sulfur ylides, wherein the latter were generated from a rhodium-catalyzed decomposition of phenyldiazomethane (PDM) in the presence of various sulfides. In most cases, the aziridines were formed and isolated in quantitative yield and the 2,3-trans-aziridines were found to predominate over the 2,3-cisaziridine isomers. The diastereoselectivity between the two trans-aziridines was found to vary significantly, depending upon the solvent and sulfide employed in the reaction.

The effects of PGV-1 and PGV-2 on the b-hexosaminidase release from intraceluller calcium ion-induced mast cells

PGV-1 or 2,5-bis(4'-hydroxy-3',5'-dimethylbenzylidene)cyclopentanone and PGV-2 or 2,5-bis(4'-hydroxy-3',5' diethylbenzylidene)cyclopentanone are two benzylidene cyclopentanone analogues of curcumin. In our study, we investigated the effects of these compounds on the b-hexoaminidase enzyme release from mast cell culture (RBL-2H3 cell line). Thapsigargin and ionomycin were used as intracellular calcium ion stimulants for inducing b-hexoaminidase enzyme release from mast cells. The release of b-hexoaminidase enzyme was determined by colorimetric methods with substrate, p-nitrophenyl-2-acetamido-2-deoxy-b-D-glucopyranocide, and a microplate reader at 405 nm. In present study, treatment of 0.5 mM thapsigargin or 1 mM ionomycin could stimulate the release of b-hexoaminidase enzyme from RBL-2H3 cells by 43.91 ± 1.30 % and 52.93 ± 2.07 %, respectively. PGV-1 and PGV-2 showed inhibitory effects on the b-hexoaminidase enzyme release from RBL-2H3 cells induced by the increase of intraceluller calcium ion in dose dependent manner. At the dose of 100 mM, PGV-1 and PGV-2, respectively, inhibited the b-hexoaminidase enzyme release by 73.51 ± 8.69 % and 66.42 ± 8.63 % on thapsigargin experiments; and by 89.73 ± 3.23 % and 38.57 ± 5.32 % on ionomycin experiments. The IC50 values of their effects on the b-hexoaminidase enzyme release from RBL-2H3 cells, respectively, were 22.20 mM and 22.27 mM on thapsigargin experiment; and 22.77 mM and >100 mM on ionomycin experiment. Based on the results, the inhibitory effect of PGV-1 and PGV-2 on the b-hexoaminidase enzyme release from RBL-2H3 cells involving mechanisms related to the alteration on activation processes of intracellular calcium ion on mast cells. Key words : Curcumin, PGV-1, PGV-2, mast cells, b-hexoaminidase enzyme

Tantalum−Benzylidene Complexes Supported by C5Me5 and Diazadiene Ligands: Synthesis, Kinetic Analysis of the Formation, and Reactive Studies

Reaction of half-metallocene dichloro complexes Cp*TaCl2(η4-supine-Ar-DAD) (1a: Ar = p-MeO; 1b: Ar = p-Me; 1c: Ar = p-F; 1d: Ar = p-Cl) (Cp* = pentamethylcyclopentadienyl; Ar-DAD = 1,4-di(aryl)-1,4...