Benzyl Phenyl Ketone Research Articles

Antioxidant Activity, Molecular Docking and Quantum Studies of New Bis‐Schiff Bases Based on Benzyl Phenyl Ketone Moiety

AbstractIn the current research work novel bis‐Schiff base products of benzyl phenyl ketone nucleus were synthesized via two step reactions in excellent yields. Using FTIR, EI‐MS and 1H‐NMR spectroscopic procedures, the structures of synthesized derivatives were confirmed and finally evaluated them for DPPH free radical scavenging activity. In the synthetic series, compounds 2 c (IC50=26.11±0.12 μM), 2 b (IC50=30.33±0.22 μM), 2 d (IC50=38.19±0.65 μM), and 2 a (IC50=40.12±0.42 μM) exhibited excellent activity better than standard drug ascorbic acid (IC50=44.01±1.41 μM) while the rest of derivatives revealed good to moderate activity. Frontier molecular orbitals, like HOMO and LUMO, which show charge transfer from molecule to biological transfer, and MEP maps, which show the chemically reactive zone suited for drug action, are calculated using DFT study. Non bonding orbitals (NBO), the electron localization function (ELF) and atoms in molecule (AIM) charges is also calculated. Strong hydrogen bonding interactions with crucial amino acid residues of the peroxidase structure are revealed by the molecular docking analysis of the drug with DPPH for efficient inhibition.

Synthesis, molecular structure and urease inhibitory activity of novel bis-Schiff bases of benzyl phenyl ketone: A combined theoretical and experimental approach

BackgroundUrease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus. ObjectiveSynthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors. MethodIn the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives. ResultsThe prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3–9) showed excellent to less inhibitory activity when compared with standard thiourea (IC50 = 21.15 ± 0.32 µM). Compounds 3 (IC50 = 22.21 ± 0.42 µM), 4 (IC50 = 26.11 ± 0.22 µM) and 6 (IC50 = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.

Iodine/DMSO promoted oxidation of benzylic Csp3–H bonds to diketones – A mechanistic investigation

This article describes a mechanistic investigation into the I2/DMSO mediated benzylic Csp3–H oxidation of an α-methylene ketone. The electron paramagnetic resonance (EPR) spectrum centred at g = 2.0011 supports the involvement of iodine and benzylic radicals, as the α-iodinated compound 2-iodo-1,2-diphenylethanone was isolated as a key reactive intermediate. The oxidation reaction relies, primarily, on DMSO as a source of oxygen in benzil, proven by the reaction of benzyl phenyl ketone with diphenyl sulfoxide (DPSO).

New antibacterial and 5-lipoxygenase activities of synthetic benzyl phenyl ketones: Biological and docking studies

We investigated twelve benzyl phenyl ketone derivatives which are synthetic precursors of isoflavonoids that are shown be good 5-hLOX inhibitors, especially those that have the catechol group, but these precursors never have been assayed as 5-hLOX inhibitors being a novelty as inhibitors of the enzyme, due to sharing important structural characteristics. Screening assays, half maximal inhibitory concentration (IC50) and kinetic assays of all the studied molecules (5 µg/ml in media assay) showed that 1-(2,4-dihydroxy-3-methylphenyl)-2-(3-chlorophenyl)-ethanone (K205; IC50 = 3.5 µM; Ki = 4.8 µM) and 1-(2,4-dihydroxy-3-methylphenyl)-2-(2-nitrophenyl)-ethanone (K206; IC50 = 2.3 µM; Ki = 0.7 µM) were potent, selective, competitive and nonredox inhibitors of 5-hLOX. Antioxidant behavior was also assayed by DPPH, FRAP, and assessing ROS production, and those with antibacterial and antiproliferative properties relating to 1-(2,4-dihydroxy-3-methylphenyl)-2-(2-chlorophenyl)-ethanone (K208) established it as the most interesting and relevant compound studied, as it showed nearly 100% inhibition of bacterial growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Finally, docking studies were done that helped to characterize how the inhibitor structures correlated to decreased 5-hLOX activity.

Reaction of 11 C-benzoyl chlorides with metalloid reagents: 11 C-labeling of benzyl alcohols, benzaldehydes, and phenyl ketones from [11 C]CO.

In this article, we describe the carbon-11 (11 C, t1/2 =20.4minutes) labeling of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step synthesis in which 11 C-carbon monoxide is used in an initial palladium-mediated reaction to produce 11 C-benzoyl chloride as a key intermediate. In the second step, the obtained 11 C-benzoyl chloride is further treated with a metalloid reagent to furnish the final 11 C-labeled product. Benzyl alcohols were obtained in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent. Changing the metalloid reagent to either tributyltin hydride or sodium borohydride, allowed for the reliable syntheses of 11 C-benzaldehydes in RCYs ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to obtain 11 C-phenyl ketones in high RCYs (77%-95%). The developed method provides a new and efficient route to 3 different classes of compounds starting from aryl iodides or aryl bromides.

Trifluorination of sulfides and dithioketals using IF5-pyridine-HF

Abstract Stable fluorinating reagent, IF5-pyridine-HF, was used for the polyfluorination of aryl alkyl sulfides. The introduction of three fluorine atoms with a concomitant migration of the arylsulfanyl group was achieved. Carrying out the reaction at 80 °C and presence of a methyl substituent on the aryl group were found to be effective for the polyfluorination. Trifluorinated products were also obtained from dithioketals by reaction with IF5-pyridine-HF. Tetrafluorination of phenyl benzyl ketone and dibenzyl ketone dithioketals was also achieved by reaction with IF5-pyridine-HF and Et3N-6HF.

One-pot preparation of 2,5-disubstituted and 2,4,5-trisubstituted oxazoles from aromatic ketones with molecular iodine, oxone, and trifluoromethanesulfonic acid in nitriles

Alkyl aryl ketones were successfully converted into the corresponding 2,5-disubstituted and 2,4,5-trisubstituted oxazoles in good to moderate yields in a one-pot manner, utilizing iodine, Oxone®, and trifluoromethanesulfonic acid in nitriles under transition-metal-free conditions. The present method could be used for the preparation of Oxaprozin from benzyl phenyl ketone and succinonitrile. A possible reaction mechanism was proposed in which the key intermediates were α-iodoalkyl aryl ketones and α-iodosylalkyl aryl ketones.

ChemInform Abstract: Hypervalent Iodine‐Promoted α‐Fluorination of Acetophenone Derivatives with a Triethylamine·HF Complex.

The direct fluorination reaction of acetophenone using iodosylarenes and TEA·5HF was conducted under mild conditions except for use of a HF reagent. The fluorination reaction was applied to acetophenone derivatives, acetonaphthones, benzyl phenyl ketone, propiophenone, butyrophenone, 1-indanone, and phenacyl chloride, giving selectively the corresponding α-fluoroketone derivatives in good yields.

Hypervalent iodine-promoted α-fluorination of acetophenone derivatives with a triethylamine·HF complex.

The direct fluorination reaction of acetophenone using iodosylarenes and TEA·5HF was conducted under mild conditions except for use of a HF reagent. The fluorination reaction was applied to acetophenone derivatives, acetonaphthones, benzyl phenyl ketone, propiophenone, butyrophenone, 1-indanone, and phenacyl chloride, giving selectively the corresponding α-fluoroketone derivatives in good yields.

Direct Copper‐Catalyzed α‐Arylation of Benzyl Phenyl Ketones with Aryl Iodides: Route towards Tamoxifen

This is the first efficient α-arylation of non-activated deoxybenzoin derivatives with simple aryl iodides.

Direct Copper‐Catalyzed α‐Arylation of Benzyl Phenyl Ketones with Aryl Iodides: Route towards Tamoxifen

Ohne Aktivierung: Die erste effiziente direkte α-Arylierung einer nichtaktivierten oder ungeschützten Familie enolisierbarer Ketone mit einfachen Aryliodiden beruht auf einem Kupferkatalysator. Die Methode ermöglicht eine leichte und kurze Synthese von Tamoxifen, dem am häufigsten zur Behandlung von Brustkrebs verabreichten Wirkstoff. R, R′, R′′ = elektronenschiebende oder -ziehende Gruppen.

Formation of N-benzylbenzamide from benzyl phenyl ketone oxime in a system C2H2-KOH-DMSO. Key role of acetylene

Oximes rearrange into amides under the action of strong acids (Beckmann rearrangement) [1]. Only seldom this rearrangement occurs in the presence of bases, for instance, that of benzoquinosylidone Eand Z-oximes [2]. The preparation of benzamide from benzaldoxime in the system KOH–DMSO was described through hydration of the intermediate nitrile [3]. In the course of the synthesis of 1-vinyl-2,3-diphenylpyrrole (II) from benzyl phenyl ketone oxime (I) and acetylene by Trofi mov reaction [4–6] in the system KOH–DMSO at the atmospheric pressure (130°C, 7 h) alongside the expected pyrrole II (yield 14–34%) N-benzylbenzamide (III) was obtained (14–24%) (Scheme1). Besides after acidifying the reaction mixture benzoic acid was isolated (up to 56%). Special experiment showed that amide III was not a product of oxime I rearrangement under the action of KOH–DMSO (at heating oxime I under the same conditions without acetylene it was nearly completely recovered, to 95–97%). Obviously the key role in the formation of amide III from oxime I belonged to acetylene. Apparently O-vinyloxime IV, the intermediate in the synthesis of pyrroles from oximes and acetylene, was deprotonated by the superbase KOH–DMSO forming carbanion V that further replaced intramolecularly the vinyloxy anion with the closure of the azirine ring VI (Scheme 2). Its hydration into hydroxyaziridine VII followed by a rearrangement resulted in amide III. The stage of azirine formation from O-vinyloxime under the action of the superbase was suggested recently for the understanding of the assembling of 4-methylene-3oxa-1-azabicyclo[3.1.0]hexanes from ketoximes, ketones, and acetylene [7]. In essence this stage resembles the azirine synthesis from oximes or their ethers by Hoch– Campbell reaction [1, 8]. This reaction fundamentally supplements the common Scheme 1. Dedicated to Full Member of the Russian Academy of Sciences N.S. Zefi rov on occasion of his 75th anniversary

ChemInform Abstract: Palladium-Catalyzed Cross-Coupling of Benzyl Ketones and α,β-Unsaturated Carbonyl and Phenolic Compounds with o-Dibromobenzenes to Produce Cyclic Products.

A number of carbonyl and phenolic compounds efficiently couple with o-dibromobenzenes in the presence of a palladium catalyst and a base to give the corresponding oxygen-containing heterocycles or carbocyclic compounds. Thus, from the reactions of benzyl phenyl ketones, 1-naphthols, and α,β-unsaturated aldehydes and ketones, benzofuran, benzopyran, benzocyclobutane, and indene derivatives, respectively, are produced selectively via the successive formation of C–C and C–O bonds or of two C–C bonds.

Quantum Mechanical Investigation of the Horner-Wadsworth-Emmons Reaction of Benzyl Pyridyl Ketone

The Horner-Wadsworth-Emmons (HWE) reaction is one of much versatile tools in syntheses of α ,β-unsaturated esters, α ,β-unsaturated ketones, and other conjugated systems. Mechanistically, it is generally accepted that the HWE reaction occurs with the addition of enolate derived from phosphonoacetate to aldehyde or ketone, followed by oxaphonphetane formation, pseudorotation, P-C bond cleavage, and then O-C bond cleavage. Stereochemically, the general phosphonoacetates with alkyl phosphonate substituents give E-olefins, which can be explained as a result of the predominant formation of thermodynamically more stable threo adducts. According to an ab initio calculation performed by Ando, in the transition states of the nucleophilic addition to the carbonyl group of acetaldehyde with the trimethyl phosphonoaceate enolate, a transition state leading to Z-olefin (erythro-TS-1) is more stable than threoTS-1 due to a repulsive interaction between the phosphonate moiety and the methyl substituent of aldehyde in threo-TS-1 (Fig. 1). On the other hand, the transition state for the oxaphosphetane formation favors a transition state leading to E-olefin (threo-TS-2) over erythro-TS-2 due to the steric hindrance between the ester moiety and the alkyl substituent of the carbonyl compound (Fig. 1). Based on the energy difference calculated, Ando concluded that the rate-determining transition state for the HWE reaction is TS-2 and, therefore, the threo-olefin is the product of choice. In our recent attempt to convert benzyl phenyl ketone (1, Table 1) to its corresponding olefinic compound (3 and 4, Table 1), the strong preference for E-olefin (3) was also observed (E:Z > 99:1, Table 1) regardless of the base used. However, to our surprise, benzyl 2-pyridyl ketone (2, Table 1), by the reaction with triethyl phosphonoacetate in the presence of t-BuOK, provided a 1:1 mixture of the corresponding E(5) and Z(6) olefins (Entry 4, Table 1) in fairto-good yields. Interestingly, the increased Z-selectivity was not reproduced by use of NaH or LiHMDS as a base (Entires 5 and 6, Table 1), which indicates that the counter cation of the base plays the key role in determining the stereochemi-

Purported Synthesis of 3,4,7,8‐Tetraphenyl‐1,2,5,6‐tetraazocine from Benzil and Hydrazine: Competing Cyclization and Carbon–Carbon σ‐Bond Scission

AbstractThe claims that 3,4,7,8‐tetraphenyl‐1,2,5,6‐tetraazocine can be prepared by the thermal condensation of two moles of benzil monohydrazone or of an equimolar mixture of benzil and benzil dihydrazone have been thoroughly reinvestigated. When such thermolyses were conducted in moist air, neither the claimed 3,4,7,8‐tetraphenyl‐1,2,5,6‐tetraazocine nor the precedented isomeric tetraazapentalene derivative was detected. The following products were unambiguously formed from the heating of molten benzil monohydrazone (%): benzil (10), benzaldehyde (10), benzamide (22), benzyl phenyl ketone (19), benzil bis(ketazine) (11), 3,4,5,6‐tetraphenylpyridazine (9), benzil benzaldehyde azine (10), and, after column chromatography, 2,4,5‐triphenylimidazole (2). This last component had a melting point and the fluorescent properties in UV light attributed by the original investigator to the mistakenly presumed 3,4,7,8‐tetraphenyl‐1,2,5,6‐tetraazocine. Thus, the original claims for the synthesis of such a novel tetraazocine ring or even for the synthesis of the precedented isomeric zwitterionic tetraazapentalene have now been repudiated. The formation of 2,4,5‐triphenylimidazole as a side reaction in the thermolysis of benzil monohydrazone can readily be rationalized as arising from benzil, benzaldehyde, and a source of ammonia, namely, benzamide, in the long‐known Radziszewski reaction. Corroborating evidence was provided by data from the thermolysis of benzil dihydrazone. In addition, the origin of other side products is explained in terms of other possible condensations. Finally, preliminary experiments on using irreversible dehydrating agents such as titanium(IV) isopropoxide with benzil monohydrazone indicate that 3,4,7,8‐tetraphenyl‐1,2,5,6‐tetraazocine is formed at room temperature as a transitory intermediate, which eliminates dinitrogen to produce 3,4,5,6‐tetraphenylpyridazine.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Reaction Behavior of Secondary Alcohols in Supercritical Water

Abstract Benzhydrol and benzoin, which have two benzene subunits, a secondary hydroxy group, and no hydrogen atom on the β-position of the hydroxy group, were treated in supercritical water in the absence of an oxidizing agent or a catalyst. Water played a key role in the product distributions in these reactions. Each reaction proceeded smoothly to give larger amounts of oxidation products, benzophenone (3) and benzil (6), as well as smaller amounts of reduction products, diphenylmethane (4) and benzyl phenyl ketone (7), respectively, in the presence of water, while the ratios of 3:4 and 6:7 were almost 1:1 in both cases in the absence of water. The best yield of benzophenone (63%) was achieved by the reaction of benzhydrol at 460 °C for 180 min in 0.35 g mL−1 water density in the SUS 316 reactor. Hydrogen gas evolution was observed in the reaction of benzhydrol in a quartz tubular reactor.

An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole

Two new synthetic pathways to the anti-cancer agent tamoxifen and its derivatives were developed. The first route involved the aldol reaction of benzyl phenyl ketone with acetaldehyde followed by Friedel–Crafts substitution with anisole in the presence of Cl 2Si(OTf) 2 to produce 1,1,2-triaryl-3-acetoxybutane, a precursor of the tamoxifen derivatives. The second one utilized the novel three-component coupling reaction among aromatic aldehydes, cinnamyltrimethylsilane, and aromatic nucleophiles using HfCl 4 as a Lewis acid catalyst to produce 3,4,4-triarylbutene, that is also a valuable intermediate of the tamoxifen derivatives. The former strategy requires a total of 10 steps from the aldol formation to the final conversion to tamoxifen, whereas the latter needs only three or four steps to produce tamoxifen and droloxifene including the installation of the side-chain moiety and the base-induced double-bond migration to form the tetra-substituted olefin structure. This synthetic strategy seems to serve as a new and practical pathway to prepare not only the tamoxifen derivatives but also the other SERMs (selective estrogen receptor modulators) including estrogen-dependent breast cancer and osteoporosis agents.

Regioselective sonochemical synthesis of genistein derivatives

Differential functionalization of the phenolic groups in genistein was carried out in excellent yields under ultrasonic irradiation. The isoflavone ring had proved to be unstable under stirring at 60 °C and phenyl benzyl ketone was unexpectedly isolated instead of the genistein derivative.

Synthesis, Crystal Structures and Anticancer Activity of the New Chiral Mono‐ and Dinuclear Palladium(II) Complexes derived from (S)‐(‐)‐(1‐phenylethylimino)benzylphenylketone

AbstractThe enantiopure ketoimine of benzil – the (S)‐(‐)‐(1‐phenylethylimino)benzyl phenyl ketone (1) obtained under microwave irradiation in solvent‐free conditions – reacts with Na2[PdCl4] to give the new chiral mono‐ and dinuclear Pd‐complexes 2 and 3, which have been partly characterized by IR, 1H and 13C NMR spectroscopies along with MS‐FAB+ spectrometry. The crystal and molecular structures of both complexes has been fully confirmed by single‐crystal X‐ray studies. On the other hand, investigations in vitro of 2 and 3 have displayed growth inhibition against different classes of cancer: leukemia (K‐562 CML), colon cancer (HCT‐15), cancer breast (MCF‐7), central nervous system (U‐251 Glio) and prostate cancer (PC‐3) cell lines.

ChemInform Abstract: An EPR Investigation of Persistent Radicals from the Photolysis of p,p′‐Dialkyl‐Substituted Phenyl Benzyl Ketones (I)—(III) Adsorbed on MFI Zeolites.

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