Malononitrile Derivatives Research Articles

A Green Protocol for the Synthesis of 2-((2-Chloroquinolin-3-yl)Methylene) Malononitrile Derivatives

A Green Protocol for the Synthesis of 2-((2-Chloroquinolin-3-yl)Methylene) Malononitrile Derivatives

A catalyst-free approach to synthesis of spiroacenaphthylene-pyranopyrazole derivatives in water media.

A simple approach for the synthesis of spiroacenaphthylene-pyranopyrazole derivatives was achieved via the reaction between acenaphthoquinone, pyrazolones, and activated methylene compounds (malononitrile derivatives) in water as a green solvent without using any catalyst in order to avoid the use of transition metal. This method has the advantages of mild reaction condition, short reaction time, easy workup, excellent yields, and avoidance of environmentally hazardous solvents.

Acceptor-π-Acceptor-Acceptor/Donor systems containing dicyanovinyl acceptor group with substituted 1,2,3-triazole motif – synthesis, photophysical and theoretical studies

An efficient synthetic route (target products obtained with yields 65–85%) for obtaining of malononitrile derivatives containing triazole motif substituted in the way providing the electronic architecture Acceptor-π-Acceptor-Acceptor/Donor (–CH2(CN)2/–C6H4–/triazole/substituent) is presented. As the substituents phenyl (A1), p-pentyloxyphenyl (A2), pyrid-2-yl (A3), 9,9-dimethylfluoren-2-yl (A4), 9-octyl-9H-carbazol-3-yl (A5), dibenzo[b,d]thiophen-2-yl (A6) and 2,2′-bithiophenyl-5-yl (A7) were used. The structures of compounds were confirmed by 1H and 13C NMR spectroscopy. The thermal, optical and photophysical properties of obtained target compounds were checked. Understanding of obtained data was supported by quantum-chemical calculations based on DFT methods (time-dependent calculations, NTO analysis, structural parameters). Moreover, the druglikeness analysis was performed based on the commonly known rules.

Chiral-at-Metal Rh(III) Complex Catalyzed Cascade Reduction-Michael Addition Reaction.

An enantioselective three-component cascade reduction-Michael addition reaction catalyzed by chiral-at-metal Rh(III) complexes has been developed. With a Hantzsch ester as the hydride source, a number of malononitrile derivatives were prepared in good yields and excellent enantioselectivities. A model that accounts for the origin and influence factors of the stereoselectivity has been proposed based on experiments.

One-pot of Three-component Synthesis of Novel Biologically Important 5-Amino-1,3-diaryl-1H-pyrazole-4-carbonitriles Using L-Proline Catalyst and their Antimicrobial Activity

An expeditious three-component synthesis of various biologically important heterocyclic compounds 5-amino-1,3-diaryl-1H-pyrazole-4-carbonitriles by condensation of aryl aldehydes, malononitrile and phenylhydrazine derivatives is described. This greener protocol was catalyzed by L-Proline and proceeded efficiently in solvent at room temperature within 2-15 min.

Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents

A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 ± 0.51 μM), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.

A transition metal free expedient approach for the C[dbnd]C bond cleavage of arylidene Meldrum's acid and malononitrile derivatives

A transition metal free expedient approach for the CC bond cleavage of electron deficient alkenes such as arylidene Meldrum's acid and malononitrile derivatives are discussed. The CC bond of these compound were cleaved to benzoic acid in good yield at high temperature. Most importantly, with oxone in CH3CN/H2O at 45 °C or m-CPBA in DCM or NaClO2 in THF/H2O or PIDA in THF at room temperature furnished benzaldehyde derivatives selectively in excellent yields.

Acceptor-donor-acceptor small molecules based on fuse ring and 2-(2-oxindolin-3-ylidene)malononitrile derivatives for solution-processed n-type organic field-effect transistors

The di-cyanovinyl-based small molecules were successfully used as non-fullerene acceptors in high-performance organic solar cells. However, the field-effect performances of these types of small molecules are still rarely studied. In this paper, two acceptor-donor-acceptor (A–D–A) small molecules with fuse ring as donor and strong electron-withdrawing 2-(2-oxindolin-3-ylidene)malononitrile derivatives as acceptors were synthesized and characterized for use in solution-processed organic field-effect transistors (OFETs). The new molecules had deep lowest unoccupied molecular orbital energy level (˜ –4.0 eV) for marching the electron transport and exhibited n-type charge transport characteristics. The OFETs based on the small molecules exhibited the highest electron mobility of over 3 × 10–3 cm2V–1s–1. This work indicates that di-cyanovinyl-based small molecules can also be applied in n-type OFETs.

Synthesis, crystal structure studies and solvatochromic behaviour of two 2-{5-[4-(dimethylamino)phenyl]penta-2,4-dien-1-ylidene}malononitrile derivatives.

The synthesis, crystal structure studies and solvatochromic behavior of 2-{(2E,4E)-5-[4-(dimethylamino)phenyl]penta-2,4-dien-1-ylidene}malononitrile, C16H15N3 (DCV[3]), and 2-{(2E,4E,6E)-7-[4-(dimethylamino)phenyl]hepta-2,4,6-trien-1-ylidene}malononitrile, C18H17N3 (DCV[4]), are reported and discussed in comparison with their homologs having a shorter length of the π-conjugated bridge. The compounds of this series have potential use as nonlinear materials with second-order effects due to their donor-acceptor structures. However, DCV[3] and DCV[4] crystallized in the centrosymmetric space group P21/c which excludes their application as nonlinear optical materials in the crystalline state. They both crystallize with two independent molecules having the same molecular conformation in the asymmetric unit. The series DCV[1]-DCV[4] demonstrated reversed solvatochromic behavior in toluene, chloroform, and acetonitrile.

Towards the critical understanding of selected vibrational features in biologically important dicyano aromatic conjugated molecules: Importance of electron donating/withdrawal groups and geometry associated with dicyano group.

The Raman spectra of a series of synthesized DC molecules (benzylidene malononitrile derivatives) with different electron donating (EDG) and electron withdrawing (EWG) group have been presented and analyzed with DFT calculated spectra. In particular, different functional groups effect on cyano stretching (∼2200 cm-1), phenyl ring breathing and alkenic double bond stretch which often appears mixed up (1475-1650 cm-1) are studied systematically for several aromatic conjugated DC derivatives. Interestingly, symmetric stretching frequency of the DC compounds having two CN groups at geminal position appears at higher wavenumber (by 11-15 cm-1) compared to their corresponding asymmetric stretch frequency. Angle (between dicyano group) dependent theoretical study indicates that the relative appearance of cyano symmetric/anti-symmetric stretching frequency depends on whether dicyano groups are at the geminal or vicinal position and the angle between them. Complete band assignments of observed Raman frequencies have been performed by potential energy distributions (PEDs) available in GAR2PED software. Our results will help to understand the vibrational feature of this important class of compounds in biological medium when used as probe.

Chitosan: A Natural and Sustainable Polymeric Organocatalyst for C-C Bond Formation During the Synthesis of 5-amino-2,3-dihydrobenzo[d] thiazole-4,6-dicarbonitriles

Background: A green, recyclable and reusable chitosan catalyst has been utilized for the synthesis of 5-amino-2,3-dihydrobenzo[d]thiazole-4,6-dicarbonitrile and its derivatives. Methods and Results: Three-component reaction protocol incorporates the reaction of aldehydes, malononitrile and rhodanine derivatives. This is examined as an efficient route for the synthesis of dicarbonitriles utilizing a green, biodegradable, environmentally benign, and easily available chitosan catalyst. In the reported protocol, catalyst can be recycled and not any substantial dropping in its catalytic activity during the recycling steps was obtained. Conclusion: A green and environmentally benign, one pot three-component protocol has been illustrated for the synthesis of 5-amino-2,3-dihydrobenzo[d]thiazole-4,6-dicarbonitrile derivatives. Adequately yield products were gained via the natural catalytic approach with the recyclability of the catalyst. The use of chitosan represents this procedure as an attractive substitute for the synthesis of biaryls complex by multicomponent reaction condition.

Several Derivatives of 6-(Tert-Butyl)-4H-Pyran-4-Ylidene Malononitrile with Different Amorphous Phase Promoting Substituents for Light-Amplification Systems

A series of glassy 6-(tert-butyl)-4H-pyran-4-ylidene malononitrile (DCM) derivatives with covalently attached amorphous state promoting bulky 1,1,1-triphenylmethyl (trityl) moieties through several chemical design approaches have been synthesized and investigated for suitability in organic solid state laser applications. Results showed that the bonding type of such functional groups had a considerable influence on glass structure forming dye thermal properties and a slight influence on their optical properties. Thermal stability up to 346 °C was achieved with glass transitions in the range from 39 to 138 °C. Incorporation of bulky triphenyl substituents via ester groups showed remarkable amplified spontaneous emission (ASE) threshold energy value reduction by 1.7 times in comparison to other bonding approaches with excitation threshold energy density up to 91 µJ/cm2. Synthesized dyes show potential as the light-amplification medium component in organic solid state lasers.

FeCl3/PVP as Green Homogeneous Catalyst to Synthesize 5‐Amino‐1H‐Pyrazole‐4‐Carbonitriles from Malononitrile Derivatives

AbstractThe homogenous catalytic system “FeCl3/PVP” and green solvent system “water/PEG‐400” has been presented as a green pathway to synthesize 4‐amino‐1‐aryl‐1H‐pyrazole‐4‐carbonitrile and its derivatives from a series of phenyl hydrazines and malononitriles. The new approach enhanced the reaction yield of the desired product up to 97% in 2–4 h time whereas the traditional thermal method gives only 87% maximum yield in relatively longer reaction time (3‐7 h). The catalytic system has remarkable benefits such as it is inexpensive, stable, easy to prepare and very efficient with a small loading of FeCl3 (5 mol%).

Glass-forming nonsymmetric DWK-dyes with 5,5,5-triphenylpentyl and piparazine moieties for light-amplification studies

A series of 2,6-bis-styryl-4H-pyran-4-ylidene fragment containing glass-forming organic compounds with bonded amorphous phase promoting bulky triphenyl moieties through piperazine structural fragment [2-(2-(4-(bis(2-(trityloxy)ethyl)amino)styryl)-6-methyl-4H-pyran-4ylidene)malononitrile derivatives (DWK)-T dyes] in a form of (5,5,5-triphenylpentyl)piperazin-1-yl)styryl)-substituent attached to the 4H-pyran-4-yliden fragment in two-position have been synthesized and investigated as the potential light-amplification medium for organic solid-state lasers. DWK-T dye physical properties also depend on the structure of the other styryl-substituent attached to the 4H-pyran-4-ylidene backbone fragment in six-position. Thermal stability of synthesized dyes is above 312°C with the glass transitions from 97°C and up to 109°C. Obtained neat pure spin-cast films based on these compounds show photoluminescence with λmax in range from 672 to 695 nm, ASE λmax from 690 to 704 nm with ASE threshold values in range from 327 to 1091 μJ / cm2, which are mostly influenced by the nature of the electron transition characteristics of various four substituents in a 6-styryl-fragment. The proposed synthetic approach could be useful for obtaining chemically stable and covalently bonded bulky triphenyl group containing glassy dyes, while the synthetic design allows to acquire different nonsymmetric 2,6-bis-styryl-4H-pyran-4-ylidene fragment-containing compounds for red and infrared light-emitting and light amplification applications.

Thermal, spectroscopic, electrochemical, and electroluminescent characterization of malononitrile derivatives with triphenylamine structure.

Three push-pull molecules with linear, quadrupolar and tripodal arrangements, consisting of triphenylamine (electro-donor) substituted with malononitrile groups (electro-acceptor), were synthesized with high yield by a simple procedure. Impact of the number of malononitrile substituents on optoelectronic properties was investigated with cyclic voltammetry, absorption and emission spectroscopy, as well as density functional theory calculation. The derivatives formed amorphous materials and exhibited low energy band gaps ranging from 2.06 to 2.49 eV. UV-Vis absorption and photoluminescence emission spectra were investigated in solutions (CHCl3, NMP) and in solid-state as thin films and two kinds of blends (with PMMA and PVK:PBD). Quantum yield of photoluminescence was dependent on the molecule structure, solvent, and solid-state layer formulation. The compounds exhibited high photoluminescence quantum yield in the range of 15-42% and 12-59% in solid-state as film and blend with PMMA (1 wt%), respectively, being promising for applications in light emitting diodes. The diodes with active layer consisting of neat derivatives and compounds molecularly dispersed in PVK:PBD (50:50 wt%) matrix showed orange and green electroluminescence.

A novel lipid droplets-targeting ratiometric fluorescence probe for hypochlorous acid in living cells

Lipid droplets were found to be involved in many organism activities. Here, a lipid droplets-targeted near-infrared fluorescence probe (named XHZ) for ratiometric detection of endogenous hypochlorous acid/hypochlorite (HClO/ClO-) in living cells was developed, which was constructed by a coumarin moiety and a malononitrile derivative. XHZ could detect HClO/ClO- with high selectivity and sensitivity in a ratiometric manner based on FRET (Förster Resonance Energy Transfer) mechanism. The two well-resolved emission (470/672 nm) bands could ensure accurate detection of HClO/ClO- in vitro as well as in vivo. XHZ was successfully used for ratiometric fluorescence imaging of exogenous and endogenous HClO/ClO- in RAW264.7 cells. A good linear relationship between the fluorescence intensity ratios of the two emissions and HClO/ClO- concentrations from 0 to 40 μM was obtained. Importantly, XHZ could localize mainly in lipid droplets of RAW264.7 cells. To the best of our knowledge, XHZ is the first lipid droplets-targeted ratiometric fluorescence probe for HClO/ClO-.

Multicomponent Solvent-Free Synthesis, Antibacterial Evaluation and QSAR Study of 2-(Bis(benzylthio)methylene) malononitriles

Multicomponent reaction of malononitrile, carbon disulphide and various benzyl halides was developed as an efficient strategy for the synthesis of 2-(bis(benzylthio)methylene)malononitrile derivatives via two different procedures: (a) in the presence of K2CO3 as a base in acetonitrile and (b) under solvent-free conditions in the presence of triethylamine. Higher yields with shorter reaction times were obtained from the latter procedure. Inhibitory activity of all derivatives was evaluated against 22 pathogenic bacteria including both Gram-negative and Gram-positive strains. Thioether 4b showed broad-spectrum antibacterial activities according to the antibiogram tests. DFT calculations (B3LYP/6-311++G**) were performed to determine the type of drug-receptor interactions. It was found that reversible dipole-dipole forces play a key role in most interactions.

Malononitrile derivatives as push-pull molecules: Structure - properties relationships characterization

A series of molecules with a dicyanovinyl acceptor connected with various substituted phenyls as donor blocks were synthesized and characterized. The thermal, electrochemical and photophysical properties of these compounds were investigated and compared. DSC and TGA measurements revealed that all compounds showed high both different melting transitions and the beginning of decomposition. The electrochemical studies did not show significant differences in energy band gap being between 2.41 and 2.55 eV (except for one with carbazole unit), which was also supported by the density functional theory calculations. They emitted light with higher photoluminescence quantum yield in film than in solution. Blends containing the malononitrile derivatives dispersed in a solid matrix consisting of poly(9-vinylcarbazole) and (2-tert-butylphenyl-5-biphenyl-1,3,4-oxadiazole) emitted with small or high contribution from the host, signaling efficient or incomplete energy transfer from host to guest molecules. Emission of light under external voltage by diodes based on these blends was observed.

Preparation of Trifluoromethylated (Arylaminomethylene)malononitriles Suitable for Synthesis of 4-Amino-2-(trifluoromethyl) quinoline Derivatives by Intramolecular Friedel–Crafts Reaction

An approach for the synthesis of 4-amino-2-(trifluoromethyl)quinolines via the intramolecular Friedel–Crafts reaction of 2-(1-(arylamino)-2,2,2-trifluoroethylidene)malononitrile derivatives is reported. This simple protocol provides a wide variety of 4-amino-2-(trifluoromethyl)quinolines in good to excellent yields, without any purification. Furthermore, the 2-(1-(arylamino)-2,2,2-trifluoroethylidene) malononitrile derivatives used in this project have been synthesized by the reaction of N-aryl-2,2,2-trifluoroacetimidoyl chlorides and malononitrile at ambient temperature and under microwave irradiation in excellent yields, for the first time.

A new lipid droplets-targeted fluorescence probe for specific detection of SO2 derivatives in living cells

A new lipid droplets-targeted fluorescence probe (HTF) for SO2 derivatives (HSO3−/SO32−) is developed based on FRET platform, in which a dansyl and 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene) malononitrile (TCF) derivative were combined by piperazine moiety. Besides a large Stokes shift (155 nm), probe HTF possesses high selectivity toward SO2 derivatives over other common anions or biothiols and excellent sensitivity with low detection limit (66 nM). The sensing mechanism was proposed to involve nucleophilic addition reaction of HSO3− to CC double bond, which was confirmed by 1H NMR titration and HR-MS spectra. Furthermore, HTF showed a low cytotoxicity and excellent lipid droplets-targeting in living cells. Its ratiometric fluorescence imaging hinted a good latent application for the monitor of exogenous and endogenous bisulfite in living cells.