Aryl Aldehydes Research Articles

NHC‐Catalyzed C3‐Acylation of 2‐Oxindoles by Selective Aerobic Oxidation of Aryl Aldehydes

AbstractWe here report an effective NHC‐catalyzed acylation of 2‐oxindoles using aldehydes with the aid of aerobic oxidation to prepare 3‐alkylideneoxindoles ‐ a biologically active moiety. This protocol is the first report on the use of oxidized Breslow intermediate for the carbon nucleophile and applies to a wide variety of aryl aldehydes, cyclohexanal, and metallocene‐aldehyde. Lower catalyst loading, milder base, greener oxidant, easily available substrates, and ambient reaction temperature exemplify this as a sustainable methodology.

Template Assisted Formation of 32 and 34π Octaphyrins Embedded with Dithienopyrrole Cores: A New Scaffold to Unravel Proton Coupled Redox Switching and (Anti)Aromaticity.

Herein, we report two distinct octaphyrins obtained by the condensation of new dithieno[3,2-b:2',3'-d]pyrrole based tetrapyrrane under two different acidic conditions. Fourfold meso-substituted octaphyrin was the major product when the reaction was performed in the presence of an aryl aldehyde using trifluoroacetic acid. Whereas, the sixfold meso-substituted octaphyrin was obtained when the precursor was condensed with pentafluorobenzaldehyde using para-toluenesulfonic acid. Such a template effect of aryl aldehydes in oxidative coupling reactions is realized for the first time in literature. Experimental and theoretical studies suggested that the oxidized form of fourfold meso-substituted octaphyrin is 32π antiaromatic and undergoes proton-coupled electron transfer (PCET) to the protonated form of 34π aromatic congener upon treatment with protic acids. Furthermore, small organic molecules such as alcohols and amines were also found to promote chemical reduction. Single crystal X-ray structure revealed that the aromatic counterpart is highly planar and stabilized by several intermolecular H-bonding and F-F interactions, leading to a large 3D supramolecular arrangement and exhibited colorimetric sensing for fluoride and hydroxide anions. On the other hand, sixfold meso-substituted octaphyrin did not show (anti)aromatic features, PCET or anion sensing, but its intriguing absorption features associated with protonation could make it an ideal candidate for pH-dependent bioimaging.

Synthesis of All Regioisomers of 2-Arylazaindole-3-acetic Acid Derivatives

AbstractA novel protocol was developed for synthesizing 2-aryl-substituted azaindole-3-acetic acid derivatives from 2-aminoazacinnamic acid derivatives and aryl aldehydes through an imino-Stetter reaction. Condensation of 2-aminoazacinnamic acid derivatives with aldehydes forms the corresponding aldimines, which are then treated with cyanide to yield the desired 2-aryl-substituted azaindole-3-acetic acid derivatives. Notably, this protocol could be employed for the synthesis of all regioisomers of azaindole-3-acetic acid derivatives by using the appropriate azacinnamic acid derivatives.

Nickel/photoredox dual-catalyzed reductive cross-coupling of aryl halides and aldehydes

A photoredox-assisted nickel-catalyzed reductive coupling of aryl halides and aldehydes to afford silyl-protected alcohols is reported. Key to success of this strategy is to identify α-silylamines as efficient organic reductants.

Aryl carbonyls and carbinols as proelectrophiles for Friedel-Crafts benzylation and alkylation.

Friedel-Crafts benzylation/alkylation using benzylic, tertiary, and homobenzylic alcohols; aryl aldehydes, aryl ketones, and the highly challenging aryl carboxylic acids and esters as proelectrophiles has been achieved using borane-ammonia and TiCl4, greatly broadening the scope of useable substrates. Incorporation of deactivated aromatic proelectrophiles and specificity for substitution at the benzylic position are demonstrated in the synthesis of various di- and triarylalkane products. Dual protocols allow for the use of standard nucleophilic solvents (benzene, toluene, etc.) or for stoichiometric addition of more valuable nucleophiles including furans, thiophenes, and benzodioxoles.

FeBr3-catalysed synthesis of 3-aroylimidazo[1,2-a]pyridine and 3,3'-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives from 2-arylimidazo[1,2-a]pyridines and aromatic aldehydes: an investigation about mechanistic insights.

In a new approach, a series of 3-aroylimidazo[1,2-a]pyridine derivatives were prepared in high yields. This approach revealed the direct Fe-catalyzed functionalization of imidazo[1,2-a]pyridine derivatives with aryl aldehydes via an aerobic oxidative cross-dehydrogenative coupling process. This transformation occurred in the presence of air, and FeBr3 served as a homogeneous Lewis catalyst. O2 was found to be the principal oxidant responsible for the method's success. Interestingly, when these reactions were carried out under an argon atmosphere, 3,3'-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives were prepared in good yields.

Gold(I)-catalyzed homologation of aryl aldehydes with trimethylsilyldiazomethane.

A methodology is described herein for the synthesis of 2-aryl acetaldehydes from aryl aldehydes using TMSCHN2 under Au(I) catalysis. A diazoorgano Au(I) complex was shown to be an intermediate that reacts with ArCHO to give ArCH2CHO products. This homologation protocol was used to synthesize a wide range of 2-aryl acetaldehydes with high functional group compatibility.

L-Proline-catalysed synthesis of chromeno[2,3-b]chromene from 4-hydroxy-2H-chromene-2-thione and an anti-proliferative study.

The reactivity of 4-hydroxy-2H-chromene-2-thione is investigated with aryl aldehydes and 5,5-dimethylcylohexane-1,3-dione (dimedone) in the presence of 20 mol% L-proline in toluene at 90 °C. Instead of the expected linear product with a sulphur atom in the ring provided by 4-hydroxydithiocoumarin or an angular product obtained from 4-hydroxycoumarin, the hitherto unreported products, 12-aryl substituted chromeno[2,3-b]chromenes (4), were obtained in good to excellent yields. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with an aromatic aldehyde followed by Michael addition with 4-hydroxy-2H-chromene-2-thione. In addition, a molecular docking study of all the derivatives was performed and among them, four compounds exhibited anti-proliferative activity and elevated ROS generation in breast cancer (MCF7) cell lines.

COMPUTATIONAL STUDIES AND GREEN SYNTHESIS OF BENZIMIDAZOLES THROUGH SEQUENTIAL OXIDATIVE CYCLISATION OF ARYLDIAMINES IN SOLVENT-FREE CONDITIONS

Benzimidazoles were synthesized under solvent-free conditions using Ionic Liquids (IL), specifically 1-Pentyl-3- methylimidazolium bromide ([pmim]Br), derived from aryl aldehydes and phenylenediamine. A comparative study of yields was conducted by reacting aryl aldehydes with both electron-donating and electron-withdrawing groups with substituted o-phenylenediamines, resulting in the formation of 2-phenylbenzimidazoles via cyclization. The yield of final products, optimum reaction conditions, plausible mechanism of the reaction, and the effect of substitutions at various positions of either of the reactants are presented in this paper. Computational studies have been done to explore the possibility of synthesized compounds for anticancer activity. Molecular docking studies were conducted to explore the inhibitory effects of steroidal derivatives against the estrogen receptor-derived Mutants [PDB ID: 2ITO]. The docking results of all compounds revealed significant inhibitory activity against the estrogen receptor 2ITO, with binding energy (ΔG) values for compounds 3a, 3b, 3c, 3d, 3e, 3f, and 3g against protein 2ITO recorded as -7.1 Kcal/mole, -7.3 Kcal/mole, -7.2 Kcal/mole, -7.8 Kcal/mole, -7.5 Kcal/mole, -7.6 Kcal/mole, and -7.6 Kcal/mole respectively.

Guanidine hydrochloride (GuHCl)-catalysed microwave-mediated solvent- and metal-free synthesis of pyrimido[1,2-a]benzimidazole from aryl aldehyde and aryl methyl ketone

The rapid, eco-friendly, solvent- and metal-free microwave-assisted synthesis of pyrimido[1,2-a]benzimidazole in high yields was achieved using the green organocatalyst guanidine hydrochloride using simple and inexpensive starting materials.

Carbonate-assisted selectively deoxygenative cross-coupling reaction between aryl and aliphatic aldehydes: a straightforward route to access α-alkylated aryl ketones

A novel reductive cross-coupling reaction of two different aldehydes for rapidly assembling α-alkylated aryl ketones has been developed. The inexpensive carbonate served not only as a base but also as an efficient electron donor.

Ionic liquid mediated efficient synthesis of 2,4,5-triarylimidazoles via green economical multicomponent reaction

In the present work, a new protocol was developed for the synthesis of 2,4,5-triaryl imidazoles via three component condensation of aryl aldehyde, benzil and ammonium acetate in the presence of 1-butyl-3-methyl-imidazolium hexafluoro phosphate ([BMIM][PF6]) as a catalyst under reflux in ethanol. The present protocol has many beneficial advantages such as excellent yields, easy workup procedure, green catalyst and purification of the targeted molecules without the use of column chromatography which increases the green chemistry value of the present work.

Mechanistic study of NHC-catalyzed oxidative N vs. O chemoselective acylation of aldehydes with alkanolamines

We studied the mechanism of NHC-catalyzed oxidative amidation of aryl aldehydes and amines, the sources of chemoselectivity, and the role of additives through DFT calculations.

Efficient and reusable Pumice supported perchloric acid catalyst for concise and effective synthesis of 1,8-dioxo-octahydroxanthenes under solvent free condition

In the present investigation, a library of 1,8-dioxo-octahydroxanthene derivatives have been synthesised by the cyclo-condensation reaction of aryl aldehyde with two moles of dimedone under solvent free condition in the presence of Novel Pumice supported perchloric acid (Pumice@HClO4) as a less expensive, recyclable, thermodynamically stable and non-toxic catalyst. The significant advantages of this novel protocol are experimental simplicity, easy work-up procedure, good to excellent yields of product and more sustainable as the efficiency of the readily available catalytic material.

Base–modified Tunisian Smectite: Efficient Catalysts for Ultrasound- Assisted Knoevenagel Condensation under Mild Reaction Conditions

Abstract: This research work presents the use of base-modified Tunisian Smectite as catalysts for the condensation of Knoevenagel. The prepared clay-catalysts were characterized via FTIR and XRD studies. A series of condensation reactions based on ultrasonic irradiation of various types of active methylene compounds and a variety of aryl aldehydes have shown the high efficacy of prepared catalysts. The stability and catalytic performance of the clay-catalysts were excellent since they could be reused four times without considerable loss in catalytic activity

A green bio-organic catalyst (taurine) promoted one-pot synthesis of (R/S)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches.

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of (R/S)-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of (R/S)-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4R)-(+)-4S developed as a single crystal, and it was found that this crystal structure was orthorhombic.

Utilization of DMSO as a solvent-cum-reactant: synthesis of fused 2-aryl-4-methylquinolines.

Herein, we disclose the synthesis of a variety of disubstituted fused quinoline, such as 4-methyl-2-arylbenzo[h]quinolines (3a-j), 1-methyl-3-arylbenzo[f]quinolines (3k-r), 1-methyl-3-arylnaphtho[2,3-f]quinolines (3s-x), and 2-aryl-5,7-dimethoxy-4-methylquinolines (4a-c), derivatives from the reaction of an aryl aldehyde with 1-naphthylamine (1a), 2-naphthylamine (1b), 2-aminoanthracene (1c) and 3,5-dimethoxyaniline (1d), respectively, at 80 °C in the presence of 30 mol% (±)-10-camphorsulfonic acid ((±)-CSA) using DMSO as the solvent-cum-reactant. DMSO molecules regioselectively incorporate three carbon atoms into the target molecule in this distinct reaction. The other advantages of the present protocol are that it can be performed under mild reaction conditions and does not require metal catalysts, additional additives or oxidants.

NiO HETEROGENEOUS NANO-CATALYST MEDIATED SIMPLE, RAPID AND EFFICIENT SYNTHESIS OF 2-ARYL SUBSTITUTED BENZOTHIAZOLES

A variety of benzothiazole derivatives have been prepared via the reaction of aryl aldehydes and substituted o-amino thiophenol using nickel oxide as a nanocatalyst with an aqueous medium. By fabricating the recoverable heterogeneous nanocatalyst, the obtained nanocatalyst has been analyzed using various techniques such as powder XRD and SEM. There are some advantages of this protocol like the eco-friendly nature of the catalyst, loading of the low percentage of catalyst, good yield of products, reusability of the nanocatalyst, lesser reaction duration, high selectivity, and effortless workup. The corresponding product structures have been analyzed by the use of spectral techniques (IR, 1H NMR, and 13C NMR) and elemental analysis.

Semi-synthesis, α-amylase inhibition, and kinetic and molecular docking studies of arylidene-based sesquiterpene coumarins isolated from Ferula tunetana Pomel ex Batt.

Despite all the significant progresses made to enhance the efficacy of the existing bank of drugs used to manage and cure type II diabetes mellitus, there is still a need to search and develop novel bioactive compounds with superior efficacy and minimal adverse effects. This study describes the valorization of the natural bioactive sesquiterpene coumarin via the semi-synthesis of new analogs and the study of their α-amylase inhibition activity. The sesquiterpene coumarin named coladonin (1) was quantitatively isolated from the chloroform extract of endemic Ferula tunetana roots. Subsequently, the oxidation of 1via the Jones oxidation reaction, used as a key reaction, afforded precursor 2. The condensation of oxidized coladonin (2) with various aryl aldehydes provided a series of new arylidene-based sesquiterpene coumarin derivatives (3a-m), which were characterized by NMR and ESI-HRMS experiments. All derivatives evaluated in vitro for their α-amylase inhibitory potential showed interesting α-amylase inhibition with IC50 values ranging from 7.24 to 28.98 μM. Notably, compounds 3k and 3m exhibited lower IC50 values (7.24 μM and 8.38 μM, respectively) compared to the standard (acarbose: IC50 = 9.83 μM). In addition, the structure-activity relationship (SAR) for all the compounds was studied. The most active compounds were found to be mixed-type inhibitors, which was revealed by kinetic studies. Furthermore, molecular in silico docking studies were established for all synthesized analogs with the binding site for the α-amylase enzyme.

Montmorillonite K-10 catalyzed synthesis of Hantzsch dihydropyridine derivatives from methyl arenes via in situ generated ammonia under microwave irradiation in neat conditions.

An expeditious, efficient, and environmentally friendly approach has been established for the synthesis of diverse Hantzsch 1,4-dihydropyridine derivatives utilizing montmorillonite K-10 as a catalyst in solvent-free conditions. The procedure entails the reaction of methyl arynes as a sustainable surrogate of aryl aldehydes, active methylene compounds, and urea hydrogen peroxide (UHP) as an oxidising agent as well as a source of ammonia under microwave irradiation, facilitated by montmorillonite K-10.