Aralkyl Ketones Research Articles

Pyrimidine Tethered Pyrazoles: Synthesis, Biological, and Molecular Docking Studies

A series of pyrimidine integrated pyrazoles (5a?5g) has been synthesized in good yields from aryl hydrazines and aralkyl ketones through a protocol of multi-steps such as condensation/imine formation, cyclization/Vilsmeier-Haackreaction, and Knoevenagelcondensation and characterized through physical and spectral techniques. 2,2-diphenylpicrylhydrazyl radical scavenging evaluation revealed that the chemical entity possessing para-fluoro substituent on the aromatic unit tethered at the carbon of pyrazole scaffold 5g exerted the highest activity among the investigated ones. Of the results of cytotoxicity evaluation utilizing AsPC1, BxPC3, SW1990 (pancreatic cancer cells), the chemical entity possessing ortho-chlorosubstitient on the aryl unit integrated at carbon of pyrazole scaffold 5b exhibited superior activity. Besides, the molecular docking studies of the ortho-chloroaryl group possessing chemical entity 5b with BCL-2 (B-cell lymphoma 2) displayed significant binding affinity (-9.1 kcal mol-1). In addition, pharmacokinetic as well as prediction of drug-likeness for all the molecular hybrids 5a?5g have been evaluated using SwissADME tool and all the chemical entities are in good agreement of Lipinski rule with no violation.. KEYWORDS :Cytotoxicity, Molecular docking, Pyrazoles, Pyrimidines, Radical scavenging, SwissADME.

Metal‐free Catalytic Esterification of Aryl Alkyl Ketones with Alcohols via Free‐radical Mediated C(sp3)−H Bond Oxygenation

AbstractA novel metal‐free catalytic one‐pot approach has been developed for the esterification of aralkyl ketones with alcohols under open‐air atmospheric conditions. The inexpensive iodide/oxone reagent system allowed the cascade C(sp3)−H bond oxygenation, selective C−C bond cleavage and esterification through the both radical and ionic pathways in a stepwise manner in one‐pot. This mild, convenient and economically viable catalytic method tolerates the various functional groups to provide the corresponding alkyl benzoates in up to 98% yields with up to 99% selectivity. The efficiency and feasibility of scale‐up of the present catalytic system was demonstrated with gram scale experiments (up to 10 gram scale).

Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies.

Synthesis of a series of benzimidazole-ornamented pyrazoles, 6a–6j has been obtained from arylhydrazine and aralkyl ketones via a multistep synthetic strategy. Among them, a hybrid-possessing para-nitrophenyl moiety connected to a pyrazole scaffold (6a) exerted the highest anti-inflammatory activity, which is superior to the standard, diclofenac sodium. While executing the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, a hybrid-possessing para-bromophenyl unit integrated at the pyrazole structural motif (6i) exhibited the highest activity among the hybrids examined. Besides, evaluation of anticancer potency of the synthesized hybrids revealed that the one containing a para-fluorophenyl unit tethered at the pyrazole nucleus (6h) showed the highest activity against both the pancreatic cancer cells (SW1990 and AsPCl) investigated. Considerable binding affinity between B-cell lymphoma and the hybrid, 6h has been reflected while performing molecular docking studies (−8.65 kcal/mol). The outcomes of the investigation expose that these hybrids could be used as effective intermediates to construct more potent biological agents.

Microwave-assisted green synthesis of new imidazo[2,1-b]thiazole derivatives and their antimicrobial, antimalarial, and antitubercular activities

We have synthesized some imidazo[2,1-b]thiazole derivatives by reaction of 1-(2-amino-4-methylthiazol-5-yl)ethanone or ethyl 2-amino-4-methylthiazole-5-carboxylate with α-bromo aralkyl ketones (phenacyl bromides) in presence of polyethylene glycol-400 (PEG-400) as efficient, inexpensive, biodegradable, and green reaction medium and catalyst (dual nature) under Microwave Irradiation (MWI) at 300 W as well as under thermal heating at 90 °C. Moreover, we also synthesized 1-(2-amino-4-methylthiazol-5-yl)ethanone and ethyl 2-amino-4-methylthiazole-5-carboxylate by one-pot reaction of acetyl acetone/ethyl acetoacetate with N-bromosuccinimide (NBS) and thiourea in presence of PEG-400 under microwave irradiation at 180 W. All synthesized compounds were screened for antimicrobial and antimalarial activities. All compounds were found to show good to excellent antibacterial activity, and some analogs exhibited good antimalarial activity.

Lactic acid-mediated tandem one-pot synthesis of 2-aminothiazole derivatives: A rapid, scalable, and sustainable process

AbstractEnvironmentally benign and biodegradable lactic acid is identified as alternative solvent and catalyst for the tandem one-pot synthesis of Hantzsch 2-aminothiazole derivatives (4) from readily available aralkyl ketones (1) through in situ regioselective α-bromination using N-bromosuccinimide (2) followed by heterocyclization using thiourea (3) at 90–100°C. The major advantages of the present method include short reaction times (10–15 min), practical, simple to perform, easy work-up, good yield of products (up to 96%), productive for large-scale applications, free from apply of α-bromoketones (lachrymator) as substrates, avoids column purification. Hence, the present method meets with the concepts of both Wender’s “ideal synthesis” and sustainable chemical process.

Montmorillonite K-10 Clay Mediated Green Synthesis of 2-Amino-4-aryl thiazole Derivatives from α-Brominated Aralkyl Ketones in Water

Montmorillonite K-10 clay has been identified as an efficient and green catalyst for the synthesis of 2-amino-4-aryl thiazole derivatives (3) in good to excellent isolated yields (80-96%) from α-brominated aralkyl ketones (1) and thiourea (2) in aqueous medium at 25-30°C. The present procedure offers advantages of short reaction time, simple work-up, high yields of products and the catalyst is environmentally benign and exhibits remarkable reusable activity by four times. Keywords: Montmorillonite K-10 clay, phenacyl bromides, thiourea, water, 2-amino-4-aryl thiazoles.

Solvent and Catalyst Free, Regioselective α-Bromination of Aralkyl Ketones Using N-Bromosuccinimide (NBS) Under Microwave Irradiation: An Efficient Protocol

Solvent and Catalyst Free, Regioselective α-Bromination of Aralkyl Ketones Using N-Bromosuccinimide (NBS) Under Microwave Irradiation: An Efficient Protocol

Catalytic hydrogen transfer over magnesia. Part XXV. Liquid and vapor phase reduction of ketoesters

The reactivity of two series of compounds: alkyl x-oxoalkanoates (x = 2, 3, 4 and 6), and alkyl ω-phenyl-y-oxoalkanoates (y = 2 and 4) has been studied in the catalytic transfer hydrogenation (CTH) over magnesium oxide as the catalyst. The catalytic tests have been performed either in liquid or vapor phase with secondary alcohols (2-propanol to 2-octanol) as hydrogen donors. A strong diminution of reactivity of the ketoesters in CTH has been observed, in contrast to simple aliphatic or aralkyl ketones. The occurrence of transalcoholysis between ketoesters and alcohols used as hydrogen donors resulted in the formation of new ketoesters as side products. The hydroxoesters, i.e. the products of the CTH reaction, have been obtained with only moderate to good yields (up to 50 %). It has been found that in the CTH of ketoesters with the carbonyl group in a γ position, such as alkyl levulinates and benzoylpropionates, the appropriate lactones (γ-valerolactone and 5-phenyl-γ-valerolactone) have been formed.

Substrate Directed Regioselective Monobromination of Aralkyl Ketones Using N-Bromosuccinimide Catalysed by Active Aluminium Oxide: α-Bromination versus Ring Bromination

Bromination of aralkyl ketones using N-bromosuccinimide in presence of active Al2O3 provided either α-monobrominated products in methanol at reflux or mononuclear brominated products in acetonitrile at reflux temperature with excellent isolated yields depending on the nature of substrate employed. The α-bromination was an exclusive process when aralkyl ketones containing moderate activating/deactivating groups were subjected to bromination under acidic Al2O3 conditions in methanol at reflux while nuclear functionalization was predominant when aralkyl ketones containing high activating groups were utilized for bromination in presence of neutral Al2O3 conditions in acetonitrile at reflux temperature. In addition, easy isolation of products, use of inexpensive catalyst, short reaction time (10–20 min), and safe operational practice are the major benefits in the present protocol.

ChemInform Abstract: Regioselective α‐Bromination of Aralkyl Ketones Using N‐Bromosuccinimide in the Presence of Montmorillonite K‐10 Clay: A Simple and Efficient Method.

Abstract A simple and more convenient method has been developed for regioselective α-bromination of various aralkyl ketones with N-bromosuccinimide (NBS) in the presence of Montmorillonite K-10 catalyst in methanol at 60–65 °C. The present procedure offers advantages of short reaction time, simple workup, good yields of products and reusability of the catalyst for four times without loss of activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Regioselective α-Bromination of Aralkyl Ketones Using N-Bromosuccinimide in the Presence of Montmorillonite K-10 Clay: A Simple and Efficient Method

A simple and more convenient method has been developed for regioselective α-bromination of various aralkyl ketones with N-bromosuccinimide (NBS) in the presence of Montmorillonite K-10 catalyst in methanol at 60–65 °C. The present procedure offers advantages of short reaction time, simple workup, good yields of products and reusability of the catalyst for four times without loss of activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Oxidative iodination of carbonyl compounds using ammonium iodide and oxone®

A simple, efficient, mild, and regioselective method for oxyiodination of carbonyl compounds has been reported by using NH4I as the source of iodine and Oxone® as an oxidant. Various carbonyl compounds such as aralkyl ketones, aliphatic ketones (acyclic and cyclic), and β-keto esters proceeded to the respective α-monoiodinated products in moderate to excellent yields. Unsymmetrical aliphatic ketones reacted smoothly yielding a mixture of 1-iodo and 3-iodo ketones with the predominant formation of 1-iodoproduct.

ChemInform Abstract: Chromic Anhydride-Chlorosilanes. An Application to Benzylic Oxidation.

Chlorotrimethylsilane reacts with chromic anhydride to form a very reactive neutral chromium (Ⅵ) oxidizing agent. The active oxidizing species is not trimethylsilyl chlorochromate as was previously reported but chromyl chloride generated in equilibrium concentration. This oxidizing agent was proved very suitable for benzylic oxidations of toluenes and alkylbenzenes to benzaldehydes and aralkyl ketones. Dichlorodimethylsilane and trichlormethylsilane also react with chromic anhydride to form chromyl chloride in an equilibrium concentration.

ChemInform Abstract: Photoinduced Electron Transfer Carbon-Carbon Bond Cleavage of Radical Cations of Carbonyl Compounds in Solution. 2,4,6-Triphenylpyrylium Salt-Sensitized Oxygenation of Aralkyl Ketones and Aldehydes.

Photosensitized electron transfer oxygenation of several aralkyl ketones and aldehydes such as 1,2,2-triphenylethanone and diphenyl- and triphenylethanal has been carried out with 2,4,6-triphenylpyrylium tetrafluoroborate (TPP + BF 4 - ) in dichloromethane. The carbonyl compounds underwent C-C bond cleavage through they cation radicals, generated via electron transfer to the excited singlet state of the pyrylium salt. For example, diphenylethanal afforded benzophenone in 80% yield

ChemInform Abstract: Asymmetric Synthesis of Amines by the Reductive Amination of Ketones Using (+)- and (-)-Norephedrine Followed by Periodate Oxidation.

A new route for the synthesis of aralkyl primary amines is reported, where the commercially available (+) or (−) norephedrine is condensed with aralkyl ketones followed by hydrogenation of the Schiff base using platinum catalyst. The chiral β-aminoalcohols thus obtained were oxidized by periodate to yield the aralkyl primary amines in 54–66% enantiomeric excess.

Experimental transition state for the B-chlorodiisopinocampheylborane (DIP-Cl) reduction

Asymmetric reductions of prochiral ketones are important transformations in the syntheses of natural products, pharmaceuticals, and fine chemicals. B-Chlorodiisopinocampheylborane (DIP-Cl), a stoichiometric reagent that is capable of reducing prochiral aralkyl ketones with high selectivity. Here, we utilize a recently developed 13C kinetic isotope effect (KIE) methodology to probe the symmetry breaking process inherent to this asymmetric reduction. Experimental KIEs and computed transition structures indicate significant roles for non-bonding interaction, specific directed orbital interactions, and hydrogen tunneling in this reaction.

Catalytic hydrogen transfer over magnesia

Abstract A comprehensive study of the reactivity of a series of mono-, di- and trisubstituted aralkyl ketones (Me, i-Pr or OMe as substituents) with straight- or branched acyl groups in the hydrogen transfer reaction over magnesium oxide as the catalyst, either in vapour or liquid phase (VP or LP) has been performed. In the VP mode of reaction, most of the studied ketones gave good conversions (60–65%), which slightly decreased with the increase of crowding in the carbonyl group region. There were five exceptions, namely isopropylphenyl and tertbutylphenyl ketones, whose conversions were very high (74–82%) and all trisubstituted ketones, in which both ortho positions were occupied, whose conversions were very low ( Based on single crystal X-ray diffraction data for some ketones and the corresponding alcohols a parameter, Δ L , has been proposed to describe the shortest intramolecular interactions between hydrogen atoms in the aforementioned molecules. This parameter was used to show that the changes in the reactivity of ketones in transfer hydrogenation might be attributed to an increase or decrease of steric strains in the appropriate alcohols. In the LP mode of reaction, 12 aliphatic alcohols have been used as hydrogen donors and the dependence of the conversion of acetophenone on their structure and boiling point has been determined. The influence of the amount of catalyst and donor–acceptor molar ratio on the conversion of the ketone has also been studied. Under optimal conditions yields of alcohols exceeding 80% and selectivity higher than 99% after 6 h of the reduction of acetophenone and its 4- and 3-alkyl derivatives have been reached. It has been found that the liquid phase mode of reaction is much more structure sensitive than the gas phase mode; only residual reactivity has been noted for all studied monortho- or diorthosubstituted acetophenones and pivalophenone.

A Facile One‐Step Synthesis of Fused Isoxazolo[4,5‐b]pyridine‐N‐oxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A new catalytic enantioselective reducing reagent system from (−)-α,α-diphenylpyrrolidinemethanol and 9-borabicyclo[3.3.1]nonane, especially effective for hindered and substituted aralkylketones

New catalytic enantioselective reduction systems were prepared from aminoalcohols and dialkylboranes, for the enantioselective reductions of prochiral aromatic ketones. Among these, the system prepared from (−)-α,α-diphenylpyrrolidinemethanol with 9-borabicyclo[3.3.1]nonane proved especially promising for such reductions. This complex catalyzes the reduction of prochiral aralkyl ketones to the corresponding alcohols with BH 3–THF, with enantioselectivities 82–99.2%. Also, this catalyst is particularly effective for the more hindered and substituted aralkyl ketones. Various modifications in this new catalytic reduction system, such as changing reaction conditions, reducing agent and dialkylborane, were also examined.

Kinetic Implications of Nonlinear Effects in Asymmetric Synthesis

Observation of a conversion-dependent enantioselectivity in asymmetric reactions with nonenantiopure catalysts or reagents may be diagnostic of kinetically complex behavior. This paper shows how reaction simulations based on parameters derived from initial enantioselectivity data provide an extension of the Kagan MLn models as powerful mechanistic tools in asymmetric synthesis. This approach is illustrated for an example of a stoichiometric reduction of aralkyl ketones with chiral borane reagents and is also discussed for several cases of catalytic reactions.