P-substituted Benzaldehydes Research Articles

Antibacterial potentials and DNA study of cobalt(II) complexes containing aminophenol Schiff base moiety

The present study was carried out to investigate the effect of substituent groups on the antibacterial activities of 2-aminophenol Schiff bases and their cobalt (II) complexes. Development of new compounds with potential effects against pathogenic organisms has become necessary due to the increase in microbial resistance reported for existing antiseptics and disinfectants. In line with this, new cobalt (II) complexes with Schiff bases derived from 2-aminophenol and p-substituted benzaldehydes were synthesized. The compounds were characterized using elemental analysis, mass spectrometry, atomic absorption spectroscopy, electrospray ionization mass spectrometry, infrared spectroscopy, 1H NMR and electronic absorption spectroscopy. Results indicate that all metal complexes had a 1:2 metal ligand ratio with magnetic moments characteristic of tetrahedral geometry around the metal ion. The Schiff bases and their metal complexes were screened for in-vitro antibacterial activities against 6 human pathogenic bacteria usually found around the hospitals and homes; Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 19582), Bacillus cereus (10702), Enterococcus faecalis (ATCC 29212) and Kribsella pneumonia (ATCC 10031) with ampicillin used as the reference compound. DNA binding study using calf thymus DNA revealed intercalative mode of activity. The result showed that Schiff bases exhibited moderate inhibitory activity against the tested microorganisms while Schiff base metal complexes exhibited higher antibacterial activity when compared to ampicillin. Our results indicate that these complexes can be employed as active ingredients in development of broad-spectrum antibacterial agents.

Unprecedented linear products by a mechanochemically activated Biginelli reaction using lawsone

The Biginelli reaction, a crucial multicomponent reaction, was investigated involving 2-hydroxy-1,4-naphthoquinone (lawsone), p-substituted benzaldehydes, and ureas.

Design, synthesis and biological evaluation of a new series of arylidene indanones as small molecules for targeted therapy of non-small cell lung carcinoma and prostate cancer

In an attempt to identify small molecules for targeted therapy of non-small cell lung carcinoma (NSCLC) and prostate cancer (PCa), new arylidene indanones (1–10) were synthesized via the Claisen-Schmidt condensation of 5,6-methylenedioxy-1-indanone with p-substituted benzaldehyde. Compounds 1–10 were assessed for their cytotoxic effects on human lung adenocarcinoma (A549) and human pancreatic ductal carcinoma (PANC-1) cells as well as human normal lung fibroblast (CCD-19Lu) and human normal pancreatic ductal epithelial (hTERT-HPNE) cells. Among them, compounds 2, 4 and 10 were more effective on A549 and PANC-1 cells than cisplatin. Compounds 1 and 9 also showed more potent cytotoxic activity towards PANC-1 cells than cisplatin. In vitro assays were performed to assess their effects on DNA synthesis, apoptosis, caspase-3, mitochondrial membrane potential, intracellular calcium levels, morphological changes in cancer cells. Furthermore, all compounds were investigated for their inhibitory effects on cathepsin L (CatL) and cathepsin D (CatD). Compounds 2 and 4 exerted potent anti-NSCLC action through caspase-independent apoptosis induced by an increase in intracellular calcium level and correspondingly the disruption of the ΔΨm. These compounds also caused apoptotic morphological alterations in A549 cells. Compound 4 also inhibited both cathepsins but its inhibitory potency on CatL was more significant. Based on in vitro mechanistic assays, compound 4 was identified as a promising anticancer agent for targeted therapy of NSCLC. On the other hand, the marked anti- PCa activity of compound 1 mediated by apoptotic cell death is also noteworthy, but further enzymatic assays are required to elucidate its main mechanism of action.

Experimental and theoretical study of three newly-synthesized iminochalcones: An example of dual emission induced by polarity changes

A series of iminochalcones derived from 3-(4-aminophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, were synthesized using different p-substituted benzaldehydes (R = –N(CH3)2 (2a), –H (2b) and –NO2 (2c)). The melting points of these compounds depend on the substituent (2c > 2a > 2b) as a function of the intermolecular interactions. The absorption spectra of the iminochalcones present two bands and are very sensitive to solvent polarity due to the ICT character of the π → π* transition on the cinnamoyl group. The relative intensity between the two main absorption bands of 2c is induced by solvent polarity and depends on the character of the orbitals. Excitation and fluorescence experiments showed that iminochalcone 2a presents dual fluorescence. Together with DFT calculations, these results corroborate the polarity-induced change model in the energy order of the emissive states, indicating that both emission bands are derived from LE and ICT excited states.

Exploration of Ruthenium (III) Chloride catalysis on oxidative conversion of aryloximes to arylaldehydes with bromamine-B: A kinetic and mechanistic approach

Conversion of aryloximes to corresponding arylaldehydes is an important oxidative transformation in synthetic chemistry. In the course of this research, optimum conditions for the facile oxidation of benzaldehyde oxime and p-substituted benzaldehyde oximes viz., p-hydroxybenzaldehyde oxime, p-methoxy benzaldehyde oxime, p-bromobenzaldehyde oxime and p-nitrobenzaldehyde oxime (aryloximes) with bromamine–B (BAB) catalyzed by ruthenium (III) chloride (RuCl3) in perchloric acid (HClO4) medium have been kinetically investigated at 303 K. All the five aryloximes follow identical kinetics with a first-order dependence of rate on [BAB]o, fractional-order each on [aryloximes]o and [RuCl3], and an inverse fractional-order on [H+]. Activation parameters have been evaluated. Oxidation products were characterized by spectral analysis. Under the identical set of experimental conditions, the kinetics of catalyzed reactions has been compared with uncatalyzed reactions and found that the catalyzed reactions are 4–6 folds faster. Isokinetic temperature is found to be 338 K. The catalytic constants (Kc) have been calculated at different temperatures and the values of activation parameters with respect to the catalyst have been evaluated. Spectroscopic evidence for the formation of 1:1 complex between BAB and RuCl3 has been obtained. The observed results have been explained by a plausible mechanism and the related rate law has been deduced. The present method offers many advantages including high conversion, short reaction times and the involvement of non-toxic reagents.

Synthesis and Characterization of New Series of 1,3-5-Triazine Hydrazone Derivatives with Promising Antiproliferative Activity.

A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01–18.20 µM in MCF-7 and 0.97–19.51 µM in HCT-116. The best results were obtained with 4,4’-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a–e showed more potent antiproliferative in MCF-7 compared to their analogs 7a–f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a–f showed better IC50 values in the range 10.4–22.2 µM. On the other hand, compounds containing two-piperidine rings 7a–f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8–19.5 µM) than their analogs 8a–e and 9a–f.

Synthesis and Evaluation of a New Series of Arylidene Indanones as Potential Anticancer Agents.

Arylidene indanones have attracted a great deal of interest due to their outstanding therapeutic applications. In particular, considerable research has pointed out the importance of arylidene indanones in the field of cancer research. The aim of the current work was to design and synthesize arylidene indanone-based anticancer agents. New arylidene indanones were obtained via the Claisen-Schmidt condensation of 5-chloro-6-methoxy- 2,3-dihydro-1H-inden-1-one with p-substituted benzaldehyde derivatives. MTT assay was performed to evaluate their cytotoxic effects on MCF-7 human breast adenocarcinoma, HeLa human cervix carcinoma and NIH/3T3 mouse embryonic fibroblast cell lines. The most effective derivatives were evaluated for their DNA synthesis inhibitory and apoptotic effects. The most apoptotic compounds were also investigated for their effects on caspase-3 activation in HeLa cells. The binding interactions of the most effective caspase-3 activator at the active site of caspase-3 were confirmed through molecular docking studies using Schrodinger's Maestro molecular modeling package. Compounds 2, 3, 4, 5, 6 and 7 exhibited selective anticancer activity against HeLa cells, whilst compounds 7 and 10 showed selective anticancer activity against MCF-7 cells. Compound 10 caused significant DNA synthesis inhibition on MCF-7 cells, whereas compound 3 caused significant DNA synthesis inhibition on HeLa cells. Compounds 2 and 3 were determined as the most apoptotic agents against HeLa cells, whereas compounds 7 and 10 showed apoptotic activity against MCF-7 cells. Besides, compound 2 was identified as the most effective compound on caspase-3 activation in HeLa cells. Docking studies showed that compound 2 interacted with the residues His121 and Tyr204 forming π-π stacking interactions.

Synthesis and Antioxidant Activity of Some Novel Benzimidazole Derivatives

A series of 2-substituted-5-methylbenzimidazole derivatives (3a-e) were synthesized by reacting 4-methyl-1,2-phenylenediamine (1) with a number of p-substituted benzaldehydes (2a-e) in moderate yields (25.51- 40.21%). The synthesized compounds (3a-e) were characterized by spectroscopic data and were evaluated for antioxidant activity using DPPH free radical scavenging assay. The compounds showed significant antioxidant activity having IC50 value of 1.054-19.05 μg/ml as compared to the standard BHT (26.96 μg/ml).Dhaka Univ. J. Pharm. Sci. 16(2): 245-249, 2017 (December)

Design, synthesis and QSAR studies of 2-amino benzo[d]thiazolyl substituted pyrazol-5-ones: novel class of promising antibacterial agents

Novel analogs of 3-(4-substituted benzylideneamino)-N-(6-substituted-1,3-benzo[d]thiazol-2-yl)-4,5-dihydro-5-oxo-pyrazole-1-carboxamide (5a–s) were designed and synthesized by reacting 3-amino-N-(6-substituted-1,3-benzo[d]thiazol-2-yl)-4,5-dihydro-5-oxo-pyrazole-1-carboxamide (4a–d) with p-substituted benzaldehydes. The Infrared Spectroscopy, 1H-Nuclear Magnetic Resonance, 13C-Nuclear Magnetic Resonance, and High Resolution Mass Spectra spectral data confirmed the structures of all the novel synthesized compounds. Among the series tested, two compounds 5k and 5o displayed promising antibacterial activity especially against Staphylococcus aureus (MIC = 3.14 and 1.57 µg/mL) and Bacillus subtilis (MIC = 3.12 and 1.84 µg/mL) respectively. Further, these title compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell line using 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl-tetrazolium bromide assay, indicating that the compounds exhibit antibacterial activity at non-cytotoxic concentrations. Field based three-dimensional quantitative structure–activity relationships were also discussed based on the antimicrobial screening data. Synthesis, spectral studies, antibacterial evaluation and QSAR studies of nineteen novel Schiff bases of pyrazol-5-one derivatives derived from 2-aminobenzothiazole nucleus are described.

9-Amino(9-deoxy)epi-cinchona alkaloid-tethered aluminium phosphonate architectures for heterogeneous cooperative catalysis: asymmetric aldol and double-Michael cascade reaction

Novel aluminium phosphonate-supported organocatalysts performing the cooperative catalysis of enamine-acid and enamine/iminium-acid were easily prepared by means of the direct and rapid precipitation of 9-amino(9-deoxy)epi-cinchona alkaloid-derived phosphonate with sodium aluminate. The heterogeneous cooperative organocatalysts with multiple functionality efficiently promoted the green aqueous asymmetric aldol addition of cyclohexanone to o, m, p-substituted benzaldehydes bearing electron-withdrawing substituents (65–98% yield, anti/syn=82:18–95:5 and 92–98%ee anti) and double-Michael of α, β-unsaturated ketones to aromatic nitroalkenes (36–85% yield, trans/cis=86:14–97:3 and 78–96%ee trans). These catalysts could be quantitatively recovered from reaction mixture by centrifugation and reused without significant loss of catalytic performances for aldol addition in the tenth run (95%, anti/syn=91:9 and 92%ee anti) and double-Michael cascade reaction in the fifth run (62%, trans/syn=89:11 and 87%ee trans). Furthermore, the arm length (n) and H+ exchange capacity resulted from POH defects had significant effects on the cooperative catalysis of 9-amino(9-deoxy)epi-cinchona alkaloid and Brønsted acid.

Sustainable C–C bond formation through Knoevenagel reaction catalyzed by MgO-based catalysts

A study of the Knoevenagel condensation of p-substituted benzaldehydes with malononitrile or ethyl cyanoacetate over potassium, calcium and lanthanum modified MgO was carried out under thermal and microwave activation. The catalysts were fully characterized to determine their textural, structural and surface acid–base properties. The whole set of catalysts were essayed in propan-2-ol test reaction in order to gain a better understanding of their acid–base properties. As for the surface basic properties of the catalysts, the modification of MgO with Ca and K led to solids with enhanced basicity while La modification slightly reduced the basicity of bare MgO. Inductive and mesomeric effects of the substituent in p-substituted benzaldehydes were coherent with a reaction mechanism in which a nucleophilic attack to the carbon atom of the carbonyl group takes place. Malononitrile or ethyl cyanoacetate were used as the active methylene reagent and the reaction was faster in the case of malononitrile as compared to ethyl cyanoacetate, indicating that the nucleophile formation (carbanion) on the catalyst basic sites is an important issue in this reaction. As for the catalysts, the overall reactivity order in thermal Knoevenagel condensation was \({\text{MgO}}-{\text{K}}\left( {\text{I}} \right)>{\text{MgO}}-{\text{K}}\left( {\text{II}} \right)>{\text{MgO}}-{\text{Ca}}\left( {\text{I}} \right) \approx {\text{MgO}}{-}{\text{La}}\left( {\text{II}} \right) \approx {\text{MgO}}>{\text{MgO}}{-}{\text{La}}\left( {\text{I}} \right)\), which completely agrees with the catalyst basicity extracted from the propan-2-ol test reaction (yield to acetone). The above correlation confirmed that, in Knoevenagel condensation, the carbanion formation on the surface basic sites of the catalysts is a key step in the reaction mechanism. The microwave-activated Knoevenagel reaction was much faster than the conventional, thermally activated reaction. The results indicate that the nucleophilic character of the Knoevenagel condensation also prevails under microwave activation.

N-Pyrrolidine-based α/β-peptides incorporating ABOC, a constrained bicyclic β-amino acid, for asymmetric aldol reaction catalysis

A series of N-pyrrolidine-based α,β-peptide catalysts incorporating a constrained 2-aminobicyclo[2.2.2]octane carboxylic acid (ABOC) residue were synthesized and evaluated in the asymmetric aldol reaction from acetone and some p-substituted benzaldehydes. Their catalytic properties were shown to be highly dependent on the amino acid sequences and on the absolute configuration of the ABOC residue that played a determinant role. Among the peptides tested, the heterochiral tripeptide H-Pro-(R)-ABOC-Asp-OCH313, that adopts a turn conformation in the solid state, proved to be the most efficient catalyst affording β-hydroxy ketones in high yields and good enantioselectivities (up to 87%).

Pinacol coupling of benzaldehydes mediated by titanium complexes displaying amine bis(phenolate) ligands

Titanium amine bis(phenolate) complexes of general formulas [Ti(L)Cl(THF)], [Ti(L)X2] and [{Ti(L)Cl}2-μ-O] (X=Cl, OiPr) were assessed as catalysts of PhCHO pinacol coupling. In optimal conditions (7.5mol% catalyst load, 55°C and 16h of reaction time in THF) and TMSCl as additive, [Ti(L3)Cl2] (11) is the most efficient catalyst giving 100% conversion and 95% yield in diol with a ratio DL:meso=57:43 and 27% ee. Using acidic additives, lower diol yields but higher diasteriomeric ratios are obtained. No significant improvements are observed when p-substituted benzaldehydes are used. The reduction of the Ti(IV) complexes to Ti(III) species is identified by EPR and a stoichiometric reaction between a [TiIII(L1)Cl(THF)] (6) and benzaldehyde shows that the pinacol coupling occurs with a conversion in diol of 72%. Different D,L ratios obtained in the absence or in the presence of reducing metals indicate that different Ti(III) catalysts may form, namely mono- and trinuclear species.

Anomalous chemosensitivity of SOD mimetic sulfurated amino acid–phen complexes: synthesis, characterization, and DNA cleavage efficacy

The DNA interaction efficacies of mixed-ligand complexes [ML(phen)2]Cl [L = a Schiff base derived from p-substituted benzaldehyde (L1 = NO2/L2 = –OCH3) and methionine; phen = 1,10-phenanthroline, the co-ligand] have been explored by absorption, electrochemistry, viscosity measurements, and agarose gel electrophoresis. The results indicate that these complexes can bind to calf thymus DNA via an intercalative mode and show efficient cleavage activity in the presence of H2O2. They are dose dependent. The antioxidative properties reveal that one complex has a stronger radical-scavenging potency than ligands. The complexes exhibit superoxide dismutase (SOD)-like activity with their IC 50 values ranging from 0.46 to 2.93 µM. Moreover, all the complexes have shown relatively high antibacterial and antifungal potencies. The in vitro chemosensitivity of the studied complexes exhibits significant cytotoxic effects, comparable to those reported for cisplatin. These findings represent a prompting to search for the probable interaction of these complexes with other cellular elements of fundamental consequence in cell proliferation.

Unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents

In this work the synthesis and antiparasitical activity of new 1,5-diaryl-3-oxo-1,4-pentadienyl derivatives are described. First, compounds 1a, 1b, 1c and 1d were prepared by acid-catalyzed aldol reaction between 2-butanone and benzaldehyde, anisaldehyde, p-N,N-dimethylaminobenzaldehyde and p-nitrobenzaldehyde. Reacting each of the methyl ketones 1a, 1b, 1c and 1d with the p-substituted benzaldehydes under basic-catalyzed aldol reaction, we further prepared compounds 2a–2p. All twenty compounds were evaluated for antiproliferative activity, particularly for promastigote of Leishmania amazonensis and epimastigote of Trypanosoma cruzi. All compounds showed good activity while nitro compounds 2i and 2k showed inhibition activity at a few μM.

Synthesis and NMR Studies of (E)-1-Aryl-3-(2-pyrrolyl)-2-propenones and (E)-3-Aryl-1-(2-pyrrolyl)-2-propenones

Series of (E)-1-aryl-3-(2-pyrrolyl)-2-propenones, that were aldol condensation products between pyrrole-2-carbaldehyde and m- and p-substituted acetophenones, were prepared and their <TEX>$^1H$</TEX> and <TEX>$^{13}C$</TEX> NMR spectra were examined to obtain the information on the conformation of the enone system. Similar studies were carried out with (E)-3-aryl-1-(2-pyrrolyl)-2-propenones that were prepared from 2-acetylpyrrole and m- and p-substituted benzaldehydes. The substituent chemical shifts were studied by applying the Hammett relationship.

Fluorescent p-substituted-phenyl-imidazolo-cytidine analogues

The synthesis and spectral properties of modified cytidine analogues are described here. To confer fluorescent properties, the cytidine fluorophore was extended by a cinnamyl moiety at the cytidine 5-position, (analogues 1a–c), or extended by a phenyl-imidazolo ring, (analogues 3a–d). Those compounds were synthesized via the Suzuki–Miyaura coupling reaction and via condensation of 5-amino-cytidine with p-substituted benzaldehydes, respectively. All analogues were fluorescent in the blue region (λem: 402–436 nm). Among the above mentioned analogues, p-CF3–phenyl-imidazolo-cytidine, 3d, was found to be a promising fluorescent probe, exhibiting a quantum yield 7000-fold larger than cytidine (Φ=0.617) and a red-shift of ca. 108 nm of maximum emission (411 nm). Its retained Watson–Crick hydrogen bonding face allows 3d to base-pair specifically with guanosine, similar to cytidine. In addition, phenyl-imidazolo-cytidine analogues prefer anti conformation and the C3′-endo (N) sugar puckering. These properties make 3d an attractive fluorescent probe for potential use in the various facets of nucleic acid chemistry.

Synthesis of D-ring-substituted (5′R)- and (5′S)-17β-pyrazolinylandrostene epimers and comparison of their potential anticancer activities

Various steroidal benzylidenes were synthetized from pregnenolone with benzaldehyde and p-substituted benzaldehydes. The resulting 17β-chalconyl derivatives of pregnenolone were reacted with hydrazine hydrate in acetic acid solution. Regardless of the starting material, the ring-closure reaction afforded (in contrast with the literature data) a mixture of two steroidal pyrazoline epimers. The epimers were critical isomer pairs, which could be separated only in their acetylated form; their structures were investigated by NMR techniques. The in vitro inhibition of rat testicular C17,20-lyase activity and the antiproliferative effects on four human cancer cell lines were measured, and the results obtained from the two epimer series were compared.

Synthesis of Amphiphilic meso-Aryl­porphyrins in Organic Solvents and Aqueous Micellar Medium

Amphiphilic porphyrins find a remarkable place in chemistry of new materials due to their unique aromatic structure and spectral properties. Porphyrins and their metalloderivatives can be used as photoelectronic materials, sensors, electronics, photosensitized solar cells and organic light-emitting devices. Supramolecular synthetic methods and strategies rapidly develop, and porphyrins are particularly amenable to the design of complex and robust architectures because of their rigid framework. Architectural arrangement of the substituents plays an important role in such materials. Hydroxyl group side by side with carboxyl-group is often used to form supramolecular systems, and, at the other hand their asymmetry can provide interesting properties. Elaborations of the synthetic methods and obtaining of porphyrins in sufficient quantities are still in object of many researchers. In this study we have synthesized symmetrical and unsymmetrical amphiphilic tetraphenylporphyrins containing available hydroxylgroups and hydrophobic long chains. Two methods were explored – monopyrrole condensation in organic solvents mixture and in aqueous micellar medium. Initially both methods were used to produce meso-tetra(4-hydroxyphenyl) porphyrin. First method consists of the condensation of p-substituted benzaldehyde with pyrrole in mixed solvents (propionic acid, acetic acid and nitrobenzene). In this system nitrobenzene plays a role not only of the solvent, but of the efficient oxidant – the yields of porphyrins were doubled compared with those of the reaction system without nitrobenzene. The yields of this method were higher than from other general methods such as Adler method. Methodology of the isolation using mixed-solvents was fine-tuned. Yields were 39-43%. After that we have investigated the application of this method to the synthesis of the unsymmetrical amphiphilic porphyrins containing fatty alkyl residues. The aldehydes, 4-hydroxybenzaldehyde and 4-oxytetradecylbenzaldehyde, were condensed with pyrrole in ratio 3:1 and 1:3. Yields of the desired porphyrins were 10-13%, also the symmetrical porphyrins were obtained with sufficient yields 9-12%. The preparation of the meso-tetra(4-hydroxyphenyl)porphyrin using anionic sodium dodecyl sulfate micelles was the next step. Micelles act as potential wells, binding products more tightly than reactants, and may also catalyze condensation reactions. Choosing a micellar approach for the synthesis of amphiphilic porphyrins with long-chain substituents, we relied on the ability of these compounds to be embedded in micelles of various detergents, which are widely described in literature. By using this method meso-tetra(4hydroxyphenyl)porphyrin was obtained with 40% yield. In comparison with more hydrophilic aldehydes (like in the case of 4-hydroxybenzaldehyde), hydrophobic aldehydes gave much lower yields in micellar synthesis. For the first time we have proved a satisfiability of this method in condensation of the unsymmetrical aldehydes having hydroxylgroups and long alkyl substituents in phenyl rings. Yields of the porphyrins were 5-8% that is lower relatively the mixed solvents method. But it should be noted that monopyrrole condensation method in the micellar environment is easer in practice and more ecological. In the next stage of work it is planned to study the properties of these porphyrins, including liquid crystalline, and use them as syntons for subsequent functionalization of porphyrins.

Controlled Synthesis of Water‐Dispersible Faceted Crystalline Copper Nanoparticles and Their Catalytic Properties

We report a solution-phase synthetic route to copper nanoparticles with controllable size and shape. The synthesis of the nanoparticles is achieved by the reduction of copper(II) salt in aqueous solution with hydrazine under air atmosphere in the presence of poly(acrylic acid) (PAA) as capping agent. The results suggest that the pH plays a key role for the formation of pure copper nanoparticles, whereas the concentration of PAA is important for controlling the size and geometric shape of the nanoparticles. The average size of the copper nanoparticles can be varied from 30 to 80 nm, depending on the concentration of PAA. With a moderate amount of PAA, faceted crystalline copper nanoparticles are obtained. The as-synthesized copper nanoparticles appear red in color and are stable for weeks, as confirmed by UV/Vis and X-ray photoemission (XPS) spectroscopy. The faceted crystalline copper nanoparticles serve as an effective catalyst for N-arylation of heterocycles, such as the C--N coupling reaction between p-nitrobenzyl chloride and morpholine producing 4-(4-nitrophenyl)morpholine in an excellent yield under mild reaction conditions. Furthermore, the nanoparticles are proven to be versatile as they also effectively catalyze the three-component, one-pot Mannich reaction between p-substituted benzaldehyde, aniline, and acetophenone affording a 100% conversion of the limiting reactant (aniline).