Acrylonitrile Derivative Research Articles

Modulation of Heterotypic and Homotypic Interactions to Visualize the Evolution of Organic Aggregates in a Fluorescence Turn-on Manner.

The abnormal evolution of membrane-less organelles into amyloid fibrils is a causative factor in many neurodegenerative diseases. Fundamental research on evolving organic aggregates is thus instructive for understanding the root causes of these diseases. In-situ monitoring of evolving molecular aggregates with built-in fluorescence properties is a reliable approach to reflect their subtle structural variation. To increase the sensitivity of real-time monitoring, we presented organic aggregates assembled by TPAN-2MeO, which is a triphenyl acrylonitrile derivative. TPAN-2MeO showed a morphological evolution with distinct turn-on emission. Upon rapid nanoaggregation, it formed non-emissive spherical aggregates in the kinetically metastable state. Experimental and simulation results revealed that the weak homotypic interactions between the TPAN-2MeO molecules liberated their molecular motion for efficient non-radiative decay, and the strong heterotypic interactions between TPAN-2MeO and water stabilized the molecular geometry favorable for the non-fluorescent state. After ultrasonication, the decreased heterotypic interactions and increased homotypic interactions acted synergistically to allow access to the emissive thermodynamic equilibrium state with a decent photoluminescence quantum yield (PLQY). The spherical aggregates were eventually transformed into micrometer-sized blocklike particles. Under mechanical stirring, the co-assembly of TPAN-2MeO and Pluronic F-127 formed uniform fluorescent platelets, inducing a significant enhancement in PLQY. These results decipher the stimuli-triggered structural variation of organic aggregates with concurrent sensitive fluorescence response and pave the way for a deep understanding of the evolutionary events of biogenic aggregates.

Elasto-plastic behaviour with reversible thermosalient expansion in acrylonitrile-based organic crystals

We synthesised a molecular crystal based on an acrylonitrile derivative, showcasing a distinctive blend of elasticity, plasticity, and reversible thermal expansion, thereby resembling shape memory characteristics.

Synthesis, X-ray crystal structure, Hirshfeld analysis and computational investigation of bis(methylthio)acrylonitrile with antimicrobial and docking evaluation

In this investigation, we studied the reactivity of 3-oxopropanenitrile derivatives 3 with CS2 in the presence of sodium hydride to give the acrylonitrile potassium salt intermediate 4 which the easily reacted with methyl iodide to afford the corresponding 2-(3-methylbenzofuran-2-carbonyl)-3,3-bis(methylthio)acrylonitrile (5). The reactants were optimized utilized B3LYP/6-311(G) to elucidate their physical descriptors of them and confirm the stability of compound 5 and its reactivity due to presence of different reactive sites using FMO, ESP and MEP. Moreover, the crystal structure of bis(methylthio)acrylonitrile derivative 5 showed a triclinic structure and P-1 space group, also Hirshfeld analysis of 5 reveled contacts (H….H) with (43.1%), H….C/H….N/H…O/H….S with contributed 4.8%, 5.2, 3.5 and 4.0%, respectively. It also showed higher intramolecular interaction in its molecular packing of strong acceptor-donor interaction in C4—H4A···N1i with distance of 3.423Å and angle = 134.58o. The comparative study between experimental and theoretical results according to its bond length, bond angles, 1HNMR and 13CNMR were in strong correlation with DFT/B3LYP/6-311(G) basis set. Moreover, compound 5 exhibited higher antimicrobial activities when compared with different standard drugs which was confirmed via molecular docking with different types of proteins.

The Importance of Polymorphism Dependent Aggregation Induced Enhanced Emission of the Acrylonitrile Derivative: Helical J Type and Antiparallel H Type Stacking Modes

AbstractIn this study to analyze the structure‐property relationship of synthesized π‐conjugated acrylonitrile derivative in terms of polymorphism dependent emission and conformational polymorphism, single crystal x‐ray diffraction method, photophysical and theoretical studies were performed. The fluorescent molecule with two polymorphic structure were presented to demonstrate the effect of the molecular conformation and stacking type on the polymorphism dependent emission in aggregate state. According to results of crystallography and photophysical studies, both form of the molecule displayed aggregation induced enhanced emission (AIEE) property in the solid phase due to the restricted intramolecular rotation (RIR) and favourable stacking interactions including the antiparallel H type, J type stacking modes and intramolecular charge transfer (ICT) process. As a result, J type and antiparallel H type stacking mode with the restricted intramolecular rotation make the crystals higly emissive in solid phase. We believe that, studied two polymorphs will be best candidates for the π‐conjugated acrylonitrile derivatives in the optoelectronic field. Moreover, this study will provide an overview of the importance of conformational polymorphism, stacking type on fluorescence properties of the polymorphic structures and propose new ways for targeted polymorphic molecular design strategies in acrylonitrile derivatives.

Light-fueled rapid macroscopic motion of a green fluorescent organic crystal

We report here a new green fluorescent organic crystal of an amide functionalized acrylonitrile derivative (E-ArF2) that displays various types of macroscopic response when illuminated with UV light (390 nm).

Synthesis and In Vitro Antibacterial Evaluation of Some Novel Annulated Quinazolinone Derivatives

A series of novel substituted quinazoline derivatives are synthesized. Antibacterial tests demonstrate their high activity against Gram-positive and Gram-negative bacteria. 3-[4-(2-Bromoacetyl)-phenyl]-2-phenylquinazolin-4(3H)-one 2 and 3-oxo-3-{[4-(4-oxo-2-phenylquinazolin-3(4H)-yl]phenyl}propanenitrile 3 are used as intermediates in the synthesis of functionalized heterocyclic derivatives such as 3-[4-(2-amino-thiazol-5-yl)phenyl]-2-phenylquinazolin-4(3H)-one 4, Schiff base 5, 3-{5-(4-[4-oxo-2-phenylquinazolin-3(4H)-yl]phenyl)thiazol-2-yl}-2-phenylthiazolidin-4-one 6, and N-phenyl acetohydrazonoyl derivatives 7a, 7b. The latter react with ethyl cyanoacetate with formation of 9a, 9b. Chalcone 10 is the key intermediate in the synthesis of N-acetylpyrazole derivative 11 and 1-thiocaramoyl pyrazole derivative 12. Treatment of 12 with chloroacetyl chloride and compound 2 leads to formation of compounds 13 and 14, respectively. Treatment of compound 3 with phenyl isothiocyanate affords the corresponding quinazolin-3(4H)-yl acrylonitrile derivative 15, which reacts with phenyl hydrazine to give the corresponding product 16. The synthesized compounds are characterized by IR, MS and 1H NMR spectra.

Chemo- and Stereoselective Cross Rauhut-Currier-Type Reaction of Tri-substituted Alkenes Containing Trifluoromethyl Groups.

A chemoselective cross Rauhut-Currier-type reaction has been developed involving a tri-substituted alkene (trifluoromethyl-containing acrylonitrile derivative) with a di- or tri-substituted alkene to yield tetra-substituted double bonds in RC-type products. This approach can support the synthesis of trifluoromethylated tetra-substituted olefins and synthetically important, structurally complex 3-allylic-type oxindole skeletons. The asymmetric version of this RC-type reaction can be realized by combining a Brønsted acid and Lewis base for bifunctional H-bonding-tertiary amine catalysis. Subsequent transformation of multi-functionalized RC-type product leads to pharmacologically interesting cyclohexane-based spiro-pyrazolones bearing six contiguous chiral centers and two highly congested, vicinal quaternary carbon centers.

A NOVEL ACRYLONITRILE DERIVATIVE HAVING PHOTOVOLTAIC PERFORMANCE

A new acrylonitrile derivative 3 (BPCPFA) which offer potential application as organic solar cell material was synthesized with three steps. The structures of the molecules synthesized in these steps were characterized using various spectral analyses. BPCPFA was investigated as an electron acceptor molecule in next generation organic solar cells. Theoretical prediction and experimental studies for photovoltaic performance were performed. Based on these results, it is concluded that BPCPFA with extended conjugated system has good and promising photovoltaic performance with Voc value as 0.96 V.

Theoretical and experimental investigations of the 2-(4-chlorophenyl)-3-{[5-(2-cyano-2-phenylethenyl)]furan-2-yl}acrylonitrile molecule as a potential acceptor in organic solar cells

A novel soluble asymmetric acrylonitrile derivative, 2-(4-Chlorophenyl)-3-{[5-(2-cyano-2-phenylethenyl)]furan-2-yl}acrylonitrile (CPCPFA, 3) was synthesized in three steps by Knoevenagel condensation. The structure of the CPCPFA was characterized using UV–vis, FTIR, 1H NMR, 13C NMR, and LC-MS. CPCPFA was evaluated as an electron acceptor in bulk heterojunction organic solar cells. Its optical and electronic properties as well as photovoltaic performance were investigated.

Comprehensive analysis of the toxic and refractory pollutants in acrylonitrile–butadiene–styrene resin manufacturing wastewater by gas chromatography spectrometry with a mass or flame ionization detector

Acrylonitrile–butadiene–styrene (ABS) resin manufacturing wastewater is a complicated, toxic and refractory industrial wastewater. Comprehensive and accurate analysis of the typical pollutants in ABS resin manufacturing wastewater is critical to develop cost-effective wastewater treatment technologies. In this paper, a comprehensively qualitative analysis combined with three complementary methods has been developed for the detection of typical pollutants in ABS resin manufacturing wastewater from three production sections, and thirty-seven compounds had been detected and further confirmed by this analysis method with standards. Simultaneous chromatographic separation and quantification of seven representative pollutants, including three mononuclear aromatics, three acrylonitrile dimers and one acrylonitrile derivative, were achieved by GC–FID system. The detection limits of this method for seven representative pollutants were in the range of 0.007–0.89mg/L. The within-day and between-day precisions of this method were less than 6.5% (RSD, n=6). The recoveries of the representative pollutants reached 90–120%. The ABS resin manufacturing wastewater from E zone was successfully determined by this method, with two mononuclear aromatics and three acrylonitrile dimers accounting for 57.73% and 40.63% of the selected seven compounds, respectively. These results reveal that the removal of mononuclear aromatics and acrylonitrile dimers is a key to treat this wastewater.

Synthesis of Quaternary Derivatives of Ortho-Coco Di-Amido Toluene and Investigation of these Compounds as Cationic Bitumen Emulsifier

Abstract Bitumen emulsions are preferred over conventional pavement systems due to their biologically and environmentally acceptable formulation, safety, low viscosity, storage stability, and cost effectiveness. The present investigation deals with the systematic study to synthesize ortho-cocodi-amido toluene and four quaternary derivatives by amidation of coconut oil and ortho toluene diamine (OTD), followed by quaternization with formaldehyde, formic acid mixture, and acrylonitrile, resulted in a new quaternary compound useful as cationic emulsifier in bitumen emulsions. The roles of temperature and reaction time in determining optimum conditions were investigated as well. Emulsifying behavior of these quaternary compounds was studied by sieve residue test, settlement and storage stability test of emulsified asphalt, and water solubility. The results show that the acrylonitrile imidazolinium derivative of o-cocodi-amido toluene (VI) can be used as a rapid-medium setting emulsifier.

(E)-3-Anilino-2-benzoyl-3-(methylsulfanyl)acrylonitrile

In the title acrylonitrile derivative, C17H14N2OS, the central amino­acryl­aldehyde O=C—C=C—NH unit, wherein an intra­molecular N—H⋯O hydrogen bond generates an S(6) ring motif, is approximately planar, with an r.m.s. deviation of 0.0234 (2) Å for the five non-H atoms. This plane makes dihedral angles of 41.04 (9) and 84.86 (10)° with the two phenyl rings. The dihedral angle between the two phenyl rings is 54.82 (10)°. An intra­molecular C—H⋯N hydrogen bond is also present. In the crystal, weak C—H⋯π and π–π inter­actions, with a centroid–centroid distance of 3.8526 (14) Å, are observed.

Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo

Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38-resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1-mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRP-transduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.

A facile tandem synthesis of α-benzyl benzimidazole acetonitriles

An efficient and convenient tandem method for the synthesis of α-benzylbenzimi dazoleacetonitriles has been developed. In this method, a benzimidazoleacetonitrile 1 was condensed with an aromatic aldehyde in the presence of basic alumina under solvent-free conditions by simple physical grinding of reactants using a mortar and pestle. Subsequent reduction of the in situ formed acrylonitrile derivative with NaBH4 in 95% ethanol at room temperature gives the corresponding 2-(1H-benzimidazol-2-yl)-3-aryl-propionitrile 3 by regiospecific reduction of the double bond.

A Practical Synthesis of a γ-Secretase Inhibitor

A practical and scaleable synthesis of the gamma-secretase inhibitor 1 is reported. The inhibitor consists of a central trisubstituted cyclohexane core with appended propionic acid, 2,5-difluorophenyl, and 4-chlorophenylsulfonyl moieties. Two alternative synthetic strategies, proceeding by way of a common disubstituted cyclohexanone derivative 5, were studied. In the preferred route, conjugate reduction of acrylonitrile derivative 4 with L-Selectride configures the desired relative stereochemistry of the cyclohexane core with >99.9:0.1 dr. A second strategy, based on catalyst-controlled hydrogenation of racemic cyclohexene derivative 2, is more convergent but less diastereoselective (up to 75:25 dr). The common cyclohexanone intermediate 5 was constructed by a regioselective Diels-Alder condensation of a 1,1-disubstituted vinyl sulfone 6 with 2-trimethylsiloxybutadiene.

Practical Synthesis of a Neuropeptide Y Antagonist via Stereoselective Addition to a Ketene

[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former. The coupling reaction of ethyl 4-oxocyclohexanecarboxylate (10a) with lithiated isonicotinamide 11 was investigated in detail, but even optimized conditions only provided a 45:55 ratio of trans:cis isomers (12a:12b). While selective crystallization schemes were developed to isolate the thermodynamically less stable trans isomer 2a, improved stereocontrol was subsequentially achieved by the application of ketene chemistry. The ketene formation and quench was investigated under a variety of conditions aimed at maximizing the trans:cis ratio. Reacting a mixture of carboxylic acids 2a and 2b with POCl3 in THF, followed by concomitant addition of tert-butyl alcohol in the presence of TMEDA at 35 degrees C provided a 4:1 ratio of trans:cis tert-butyl esters (18a:18b) via in situ ketene formation. Ester hydrolysis, followed by selective crystallization of undesired 2b as the HCl salt, led to isolation of 2a in 47% overall yield. Aminopyrazole intermediate 3 was synthesized via the condensation reaction of 2-fluorophenylhydrazine hydrochloride (4a) with acrylonitrile derivative 5 in 65-70% yield. Coupling of advanced intermediates 2a and 3b via activation with thionyl chloride gave a 92% yield of 1.

Structure and Stereochemistry of the Active Metabolite of Clopidogrel

Clopidogrel (SR25990C, PLAVIX) is a potent antiplatelet drug, which has been recently launched and is indicated for the prevention of vascular thrombotic events in patients at risk. Clopidogrel is inactive in vitro, and a hepatic biotransformation is necessary to express the full antiaggregating activity of the drug. Moreover, 2-oxo-clopidogrel has been previously suggested to be the essential key intermediate metabolite from which the active metabolite is formed. In the present paper, we give the evidence of the occurrence of an in vitro active metabolite after incubation of 2-oxo-clopidogrel with human liver microsomes. This metabolite was purified by liquid chromatography, and its structure was studied by a combination of mass spectometry (MS) and NMR experiments. MS results suggested that the active metabolite belongs to a family of eight stereoisomers with the following primary chemical structure: 2-[1-[1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-sulfanyl-3-piperidinylidene]acetic acid. Chiral supercritical fluid chromatography resolved these isomers. However, only one of the eight metabolites retained the biological activity, thus underlining the critical importance of associated absolute configuration. Because of its highly labile character, probably due to a very reactive thiol function, structural elucidation of the active metabolite was performed on the stabilized acrylonitrile derivative. Conjunction of all our results suggested that the active metabolite is of S configuration at C 7 and Z configuration at C 3-C 16 double bound.

Reversible interaction of a reactive intermediate derived from furazolidone with glutathione and protein

Swine liver microsomes convert the nitrofuran furazolidone into N-(4-cyano-2-oxo-3-butenylidene)-3-amino-2-oxazolidone, a reactive open-chain acrylonitrile derivative. This derivative may be trapped with such thiol-group-containing agents as glutathione and mercaptoethanol. However, this reaction is reversible; e.g., adding an excess of mercaptoethanol to an aqueous solution (pH 7.4) of the glutathione conjugate results in conversion of 43% of this compound into the mercaptoethanol conjugate. In addition, when microsomal protein is added to the glutathione conjugate or the mercaptoethanol conjugate, 36 and 44%, respectively, become covalently bound to the protein. The amount of this covalently bound radioactivity decreases again on prolonged incubation at 37 degrees C (42% disappearance within 24 hr), suggesting that the acrylonitrile derivative also reacts reversibly with thiol groups of microsomal protein. Indeed an excess of mercaptoethanol could remove covalently bound radioactivity from microsomal protein resulting in the formation of the mercaptoethanol conjugate. The reversibility of the reaction is dependent on pH, as is demonstrated for the mercaptoethanol conjugate. Below pH 2 this conjugate is stable; optimal exchange to microsomal protein is found between pH 7 and 10. At very high pH (greater than 11) no binding to protein is found, although the conjugate disappears rapidly. The mercaptoethanol conjugate exhibits mutagenic activity in the Salmonella/microsome test indicating that the acrylonitrile derivative of furazolidone also interacts with DNA.

ChemInform Abstract: REACTIVITIES OF 4‐ARYLTHIO‐2‐AZETIDINONES

AbstractDie aus den Sulfiden (I) durch Umsetzung mit Chlorsulfonylisocyanat (II) entstandenen Azetidinone (III) lassen sich mit Natriumthiosulfat unter Abspaltung der Chlorsulfonylgruppe reduzieren.

Reactivities of 4-Arylthio-2-azetidinones

Reactivities of 3-methyl-4-arylthio-2-azetidinones (IIIa and IIIb) and their N-chlorosulfonyl derivatives (IIa and IIb) are discussed. Treatment of IIIa with hexamethylphosphoramide (HMPA) gave the acrylonitrile derivative (Va). The arylthio group of IIIa was easily oxidized with m-chloroperbenzoic aicd to afford the sulfoxide (VII), and further oxidation gave sulfone derivative (IX). Treatment of IIIa with iodine or bromine in methylene chloride gave the disulfide (VI) in high yield. Reaction of IIIa with 2-methylthio-2-thiazoline gave 6-methyl-5-oxo-5H-2, 3-dihydrothiazolo [3, 2-a] pyrimidine (XII) in 16% yield.