Aromatic Methyl Ketones Research Articles

Mechanochemical Organocatalysis: Simple Chiral Primary Diamine‐TfOH‐catalysed Asymmetric Aldol and Robinson Annulation Reactions

AbstractMechanochemical organocatalysis, which integrates mechanochemistry and organocatalysis to provide a metal‐and solvent‐free synthetic method for synthesizing chiral products, has garnered significant interest recently due to its importance in green chemistry. In this study, simple, unmodified commercially available chiral primary diamines with TfOH were employed as catalysts in mechanochemical direct asymmetric aldol and Robinson annulation reactions. This protocol demonstrated high efficiency, atom economy and high stereoselectivity. Notably, direct asymmetric aldol reactions involving unreactive aromatic methyl ketones, which still is a challenge for mechanochemical organocatalysis, proceeded smoothly. Additionally, chiral 3,5‐diaryl‐cyclohexenones were efficiently synthesized using this mechanochemical asymmetric catalytic protocol and afforded high‐to‐excellent enantioselectivities. These findings highlight the potential of mechanochemical organocatalysis for asymmetric catalysis.

Aromatic Methyl Ketones in the Synthesis of Biologically Active Chalcones

Aromatic Methyl Ketones in the Synthesis of Biologically Active Chalcones

β-Ketoallylic methylsulfones synthesis via inert C(sp3)–H bond activation by magnetic Ag–Cu MOF

Herein, the one-pot tandem synthesis of β-ketoallylic methylsulfones has been achieved from readily available dimethyl sulfoxide and acetophenones as coupling partners in one step. In this procedure, dimethyl sulfoxide serves as a triple role including solvent, dual synthon and as an oxidant agent. The use of magnetic Ag–Cu MOF as a bimetallic catalyst is the key to the progress of the reaction due to its accessible active sites. It provides facile access to various β-ketoallylic methylsulfone derivatives from direct C(sp3)–H bond activation and functionalization of aromatic methyl ketones especially acetophenones with electron-rich and electron-poor groups. Moreover, the present work offers a synthetically powerful strategy to form products in good to excellent yields (74–96%) with the atom, step, and pot economics. It has also delivered a new chromane-4-one derivative from 2-hydroxy acetophenone with intramolecular Michael-addition of related β-ketoallyl methylsulfone product. In the final step, the electronic properties of some products have been predicted with the theoretical studies.

Chemoenzymatic Synthesis of Enantiopure Amino Alcohols from Simple Methyl Ketones

AbstractThis study highlights the straight‐forward synthesis of substituted 1,2‐amino alcohols from simple and readily available aromatic methyl ketones. Starting from acetophenone derivatives, the straight‐forward synthesis strategy involved an initial bromination of the alpha‐positioned methyl group in the first step, followed by a simple hydrolysis to the hydroxyketone (2‐hydroxyacetophenone). The hydroxylated intermediate was subsequently converted from Silicibacter pomeroyi to the final 1,2‐amino alcohol by using the transaminase. The transaminase‐catalyzed reaction proceeded with yields up to 62 % and always excellent enantiomeric excess of >99 %. Interestingly, the keto‐enol‐tautomerism of the hydroxyl ketone yields an unexpected amino alcohol isomer.

Effect of the Position and Amount of the Electron‐Donating Groups in Substituted 2,4,6‐Triphenylpyrimidines on their Thermal, Optical and Electrochemical Properties

Abstract2,4,6‐Triphenylpyrimidine derivatives have been synthesized from the corresponding aromatic aldehydes and methyl ketones via a two‐step procedure, which include an aldol‐crotonic condensation followed by the reaction of the resulting chalcones with ammonium acetate in the presence of a catalytic amount of trifluoromethanesulfonic acid with DMF as a solvent The compound structures have been identified by NMR and IR spectroscopy and elemental analysis. The thermal, optical and electrochemical properties of the compounds obtained have been studied. The synthesized 2,4,6‐triphenylpyrimidines are characterized by blue emission. It has been shown, that these compounds have narrow band gaps and high fluorescence quantum yields.

Nanostructured Na2CaP2O7: A New and Efficient Catalyst for One-Pot Synthesis of 2-Amino-3-Cyanopyridine Derivatives and Evaluation of Their Antibacterial Activity

A facile and novel synthesis of thirteen 2-amino-3-cyanopyridine derivatives 5(a–m) by a one-pot multicomponent reactions (MCRs) is described for the first time, starting from aromatic aldehydes, malononitrile, methyl ketones, or cyclohexanone and ammonium acetate in the presence of the nanostructured diphosphate Na2CaP2O7 (DIPH) at 80 °C under solvent-free conditions. These compounds were brought into existence in a short period with good to outstanding yields (84–94%). The diphosphate Na2CaP2O7 was synthesized and characterized by different techniques (FT-IR, XRD, SEM, and TEM) and used as an efficient, environmentally friendly, easy-to-handle, harmless, secure, and reusable catalyst. Our study was strengthened by combining five new pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by intermolecular cyclization of 2-amino-3-cyanopyridines 5(b, c, g, h, j) with formamide. The synthesized products were characterized by FT-IR, 1H NMR, and 13C NMR and by comparing measured melting points with known values reported in the literature. Gas chromatography/mass spectrometry was used to characterize the newly synthesized products and evaluate their purity. The operating conditions were optimized using a model reaction in which the catalyst amount, temperature, time, and solvent effect were evaluated. Antibacterial activity was tested against approved Gram-positive and Gram-negative strains for previously mentioned compounds.

Facile one-pot three-component strategy for the synthesis of 2-amino-4-arylthiazoles via elemental sulfur source

A novel and facile metal-free method for the green synthesis of 2-amino-4-arylthiazole derivatives through the three-component cascade reaction of aromatic methyl ketones, elemental sulfur and cyanamide is reported. One CN bond and two CS bonds were formed in one-pot protocol without using catalysts.

Silver‐Catalyzed One‐Pot Access to Diastereoselective Benzo[5,6]oxepino[2,3‐c]pyrroles via Formal (5+2)‐Annulation of Donor‐/Acceptor‐Type Aryl Vinyl Diazosuccinimide with Ketones

AbstractA silver triflimide catalyzed one‐pot protocol for the diastereoselective synthesis of dihydrobenzoxepines has been developed. Silver triflimide was found to be an efficient catalyst for the formal (5+2)‐cycloaddition to access dihydrobenzoxepines as a single diastereomer using vinyl diazosuccinimides as 5‐C‐synthons and ketones. An unmet challenge of utilizing the donor‐/acceptor‐type vinyl diazosuccinimides as 5‐C‐synthons under silver‐catalysis is presented. This protocol was found to be highly regio‐, chemo‐ and diastereoselective, and works well with aliphatic as well as aromatic methyl ketones bearing electron deactivating as well as donating groups to afford dihydrobenzo[5,6]oxepino[2,3‐c]pyrroles. The control experiments and time‐dependent NMR studies revealed the plausible mechanism of this transformation. The protocol also proved to be scalable on the gram‐scale synthesis.

Synthesis of benzo[f]pyrido[1,2-a]indole-6,11-diones via the I2-promoted reactions of methyl ketones with pyridines and 1,4-naphthoquinone

An effective synthesis of benzo[f]pyrido[1,2-a]indole-6,11-diones has been achieved via the I2-promoted reactions of methyl ketones, pyridines and 1,4-naphthoquinone. In this reaction, either aromatic or aliphatic methyl ketones proceeded well. The advantages of this method include a broad substrate scope, metal-free reaction conditions, and high atom- and step-economy.

Sustainable Four-Component Annulation for the Synthesis of 2,3,4,6-Tetraarylpyridines.

A one-pot, four-component annulation of 2,3,4,6-tetraarylpyridines from aromatic aldehydes, methyl ketones, diaryl ethanones, and ammonium acetate is described. The reaction features high functional group compatibility in air under solvent-free conditions without any additive and only water as the nontoxic byproduct, providing a strategy for the facile, economical, and eco-friendly construction of multiaryl-substituted pyridines from simple and readily available reactants.

Oxidant/Solvent-Controlled I2-Catalyzed Domino Annulation for Selective Synthesis of 2-Aroylbenzothiazoles and 2-Arylbenzothiazoles under Metal-Free Conditions.

A simple and practical domino protocol for the selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothiazoles catalyzed by I2 is developed under metal-free conditions. The reaction outcomes are exclusively controlled by the reaction oxidant/medium. With DMSO employed as both the solvent and the oxidant, an oxidation of aromatic methyl ketones takes precedence over the condensation with 2-aminobenzenethiols. On the other hand, when the reaction was carried out in PhNO2 or in 1,4-dioxane containing PhNO2, the condensation of aromatic methyl ketones with 2-aminobenzenethiols has priority to form imines which is followed by an oxidation of the methyl group from ketones to afford 2-arylbenzothiazoles as a sole product. The PhNO2/I2 co-catalytic system is proposed first time.

CuBr2‐Promoted Multicomponent Aerobic Reaction for the Synthesis of 1,2,3‐Triaroylindolizines

An efficient synthesis of 1,2,3‐triaroylindolizines has been developed via CuBr2‐promoted reaction of three molecules of aromatic methyl ketones and one molecule of pyridine derivative. A wide range of methyl aryl ketones and methyl heteroaryl ketones took part in the reaction and generate 1,2,3‐triaroylindolizines in good yields. This protocol also features such advantages as mild reaction conditions and high atom economy and step economy.

Iron-Catalyzed Tandem Three-Component Alkylation: Access to α-Methylated Substituted Ketones.

The borrowing hydrogen strategy has been applied in the synthesis of α-branched methylated ketones via a tandem three-component reaction catalyzed by a diaminocyclopentadienone iron tricarbonyl complex. Various alkyl and aromatic methyl ketones underwent dialkylation with various primary alcohols and methanol as alkylating agents in mild reaction conditions and good yields. Deuterium labeling experiments suggested that the benzylic alcohol was the hydrogen source in this tandem process.

Synthesis, characterization and in silico biological activity of some 2-(N,N-dimethyl guanidinyl)-4,6-diaryl pyrimidines.

Introduction:As pyrimidine is a basic nucleus in DNA and RNA, it has been found to be associated with diverse biological activities. Pyrimidine derivatives were reported to possess anticonvulsant, antimicrobial, anti-inflammatory, antitumor, and antihistaminic. Recently, our team reported the anti-inflammatory and antimicrobial evaluation of some pyrimidines.Objective:To synthesize, predict and evaluate biological activity of some 2-(N,N-dimethyl guanidinyl)-4,6-diaryl pyrimidines.Experimental:seven new pyrimidines were synthesized by following the standard procedures using substituted aromatic aldehydes, methyl ketones and metformin. After the biological activity was predicted using PASS, Molinspiration and Osiris property explorer, their anthelmintic activity was evaluated using Pheretima posthuma. The structural assignment of the title compounds (P1-7) has been made on the basis of elemental analysis, infrared, 1H-nuclear magnetic resonance and Mass spectral studies.Results:All the synthesized compounds were found to obey Lipinski's rule. All the synthesized compounds scored good bioactivity values as GPCR ligands and kinase inhibitors. Among the test compounds, P5 was found to be more potent anthelmintic inducing paralysis in 36-48 minutes and death in 40-51 minutes.Conclusion and Recommendation:The synthesized compound (P5) possessing methoxy group at position-4 of the benzene ring located at position-4 of pyrimidine exhibited good anthelmintic activity. The study revealed the necessity of synthesizing many more compounds with other substituents at position-4 of the benzene ring located at position-4 of pyrimidine.

One-Step Conversion of Methyl Ketones to Acyl Chlorides

Treatment of aromatic and heteroaromatic methyl ketones with sulfur monochloride and catalytic amounts of pyridine in refluxing chlorobenzene leads to the formation of acyl chlorides. Both electron-rich and electron-poor aryl methyl ketones can be used as starting materials. The resulting C1-byproduct depends on the precise reaction conditions chosen.

ChemInform Abstract: Synthesis of Substituted Quinoline via Copper‐Catalyzed One‐Pot Cascade Reactions of 2‐Bromobenzaldehydes with Aryl Methyl Ketones and Aqueous Ammonia.

AbstractThe reaction fails using aliphatic methyl ketones such as acetone, but succeeds with excellent efficiency for aromatic methyl ketones, thus providing an alternative approach to synthetically and medicinally relevant aryl‐substituted quinolines.

ChemInform Abstract: Iodine‐Promoted Efficient Synthesis of Diheteroaryl Thioethers via the Integration of Iodination/Condensation/Cyclization/Dehydration Sequences.

Abstract A novel method for the construction of diheteroaryl thioethers from aromatic methyl ketones and thiourea is described. Iodine is the unique catalyst in this protocol. The transformation is free of foul-smell thiols and transition metal. In addition, this method could synthesize two thiazole rings and a sulfur bridge in one pot.

Iodine-promoted efficient synthesis of diheteroaryl thioethers via the integration of iodination/condensation/cyclization/dehydration sequences

A novel method for the construction of diheteroaryl thioethers from aromatic methyl ketones and thiourea is described. Iodine is the unique catalyst in this protocol. The transformation is free of foul-smell thiols and transition metal. In addition, this method could synthesize two thiazole rings and a sulfur bridge in one pot.

I2–DMSO catalyzed synthesis of 1,2,2-triarylethanones via dual C–H activation of aryl methyl ketones

An I2–DMSO promoted domino protocol was developed for the synthesis of 1,2,2-triarylethanones from readily available aromatic methyl ketones and methoxybenzenes. The 1,2,2-triarylethanones are important precursors for the synthesis of Tamoxifen and Droloxifene. The use of mild reaction conditions, high yield, and single step synthesis are the advantages of the present protocol.

Chemoselective Oxidative C(CO)C(methyl) Bond Cleavage of Methyl Ketones to Aldehydes Catalyzed by CuI with Molecular Oxygen

Aldehyde Termination: A novel copper-catalyzed transformation from methyl ketones into aldehydes has been accomplished. This method is applicable to a wide range of aromatic and aliphatic methyl ketones and chemoselectively produces aldehydes, accompanied by the release of hydrogen (H2 ) and carbon dioxide (CO2 ) as by-products.