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International audience; Newly synthesized indanedione derivatives combined with an iodonium salt, N-vinylcarbazole, amine, phenacyl bromide, or 2,4,6-tris- (trichloromethyl)-1,3,5-triazine have been used as photoinitiating systems upon very low visible light intensities: blue lights (e.g., household blue LED bulb at 462 nm) or even a halogen lamp exposure. One of them (ID2) is particularly efficient for cationic, radical and thiol−ene photopolymerizations as well as for the synthesis of interpenetrated polymer networks (IPNs). It can be useful to overcome the oxygen inhibition. ID2 based photoinitiating systems can also be selected for the reduction of Ag+ and the in situ formation of Ag(0) nanoparticles in the synthesized polymers. The (photo)chemical mechanisms are studied by electron spin resonance spin trapping, fluorescence, cyclic voltammetry, laser flash photolysis, and steady state photolysis techniques.

A novel C 3-symmetric arsine was employed in the one-pot cyclopropanation of olefins with carbonyl-stabilized arsonium ylides formed in situ from phenacyl bromide in the presence of NaHCO3. This new arsine demonstrates good stereoselectivity and activity in the one-pot cyclopropanation of arylidenemalononitrile. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Alkylation of alkaloid D-pseudoephedrine with bromoacetophenone results in a morpholine derivative. Structural and energy characteristics of the molecules of the starting, intermediate, and final reaction products were calculated by ab initio method in the HF/6-31G(d,p) approximation. The spatial structure of the final reaction product was determined by X-ray diffraction analysis.

The article describes a convenient and efficient synthetic route for the construction of 2-aroylbenzofuran-3-ols from readily available diverse methyl salicylates and phenacyl bromides using K2CO3 as catalyst in dimethylformamide as solvent at room temperature. The reaction involves two steps, which occur in quick succession within 1 h to deliver the product with reasonably high yields. All the synthesized 2-aroylbenzofuran-3-ols (4a–u) were subjected for their antimicrobial studies, and some of these have shown prominent activity. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

New route for the synthesis of 2-(benzothiazol-2-ylthio)-1-phenylethanone (6) and 2-(acetonylthio)benzothiazole (1) by using phenacyl bromide and α-chloroacetone, respectively, through carbon–sulfur bond cleavage reactions in a basic medium has been generated. Treatment of 1 with malononitrile and elemental sulfur afforded the corresponding derivative of 2-amino-3-cyanothiophene (12), whereas treatment of 1 with cyanoacetohydrazide afforded the corresponding derivative of cyanoacetylhydrazone derivative (13). The structure of the synthesis compounds has been established on the basis of elemental analyses, 1H-NMR, 13C-NMR, correlation spectroscopy, heteronuclear single quantum coherence, MS spectra, and X-ray crystallographic investigations.

A series of substituted benzylidene-2-(4-phenylthiazol-2-yl) hydrazines (2a–q) have been synthesized, characterized and evaluated for their anti-inflammatory activity by carrageenin-induced hind paw edema (acute inflammation) and cotton pellet granuloma (chronic inflammation) methods in rats. In carrageenin-induced hind paw edema method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg−1 body weight, p.o. showed excellent inhibitions (51.80–86.74 %) in between 1 and 4 h. Similarly, in cotton pellet granuloma method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg−1 body weight, p.o. inhibited the granuloma formation (71.71–90.19 % inhibition) which was comparable to that of standard drug, ibuprofen (90.36 % inhibition of paw volume at 3 h and 94.02 % inhibition of granuloma formation). Structure activity relationship studies showed excellent activity of the compounds containing electron withdrawing group (fluoro, chloro, bromo or nitro) in phenyl ring at C2 and/or C4 position of thiazole ring.

An efficient regioselective synthesis of 3-aryl imidazo[1,2-a]pyridines, 5-aryl imidazo[2,1-b]thiazoles, and 3-aryl benzo[d]imidazo[2,1-b][1,3]thiazoles is described by the reaction of phenacyl bromide with heterocyclic amine in the presence of DABCO under aqueous medium. The method is applicable for a variety of substituted phenacyl bromides as well as 2-amino-heterocycles. An aqueous reaction medium, regioselectivity, mild reaction condition, and high yield of products are the important features of this protocol.

The three-component domino reactions of pyridine/isoquinoline, phenacyl bromide, and substituted (E)-N-hydroxyarylimidoyl chloride in the presence of triethylamine afforded a series of 2-arylimidazo[1,2-a]pyridines and 2-arylimidazo[2,1-a]isoquinolines. This one pot three-component transformation presumably proceeds via ylide generation/annulation/fragmentation/dehydration domino sequence of reactions.

Synthesis of 9-methyl-1-phenyl-7H-furo[3,2-f]chromen-7-one and 4,9-dimethyl-3-phenyl-7H-furo[2,3-f]chromen-7-one as angular furocoumarin derivatives were carried out through Williamson reaction of hydroxycoumarins with phenacyl bromide followed by cyclization in polyphosphoric acid. The photooxygenation of synthesized furocoumarins in the presence of tetraphenylporphine as singlet oxygen sensitizer at room temperature gave the photo-cleaved product, o-benzoylhydroxy derivatives, through [2+2] cycloaddition of singlet oxygen with the double bond of the furan moiety. o-Benzoylhydroxy derivatives were prepared through the photooxygenation reactions and Fries rearrangement.

1,2-Bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)benzene (3) was synthesized from the reaction of phthalic acid with thiocarbohydrazide. Reaction of 3 with ethylbromoactate or ethylchloroacetate afforded compound 4. Heating of 3 with chloroacetyl chloride or chloroacetic acid gave triazolothiadiazinone 5 and 8, respectively. Refluxing of 3 with phenacyl bromide resulted in benzoylmethylthiotriazole 9. Treatment of 3 with chloroacetamide or benzyl chloride yielded 11 and 13, respectively. Condensation of 3 with benzaldehyde or m-nitrobenzaldehyde gave the products 14a and 14b in the ratio 1:2, and 15, respectively.

Treatment of ethyl β-aryl-α-cyanoacrylate (2a, b) with thiourea, guanidine hydrochloride, and thiosemicarbazide in presence of anhydrous potassium carbonate in methanol led to formation of pyrimidine derivatives 3 and 5 and thiosemicarbazone derivative 9. Thiazole derivative 10 was prepared via cyclization of thiosemicarbazone derivative 9 with 4-methoxy phenacyl bromide. Acetylation of 3a, 5, and 10 with acetic anhydride yielded the acetoxy and N-acetyl derivatives 4, 6, and 11. The mass-spectral fragmentation patterns of nitrogen heterocycles were investigated to elucidate the structure of the prepared compounds. Biological studies of nitrogen heterocycles were carried out to investigate their antimicrobial and anticancer activities; it was found that compounds 5, 10, and 11 were highly active against bacteria and fungi, and compounds 3a and 3b were also active against bacteria and fungi.

A simple and efficient protocol has been developed for the synthesis of quinoxalines. In the synthesis, the reaction of 1,2-phenylenediamines and phenacyl bromide were carried out using pyridine as a catalyst in THF at room temperature to give quinoxalines. This method is applicable to a variety of substrates to afford the corresponding derivatives in excellent yields.

Gibberllic acid () is one of gibberellins (GAs) that are a class of plant growth hormones that exert profound and diverse effects on plant growth and development. is essentially non-UV absorbing and is difficult to assay by UV-detector. For effective extraction of gibberellic acid from fruits by using liquid-liquid extraction, optimized pH and extraction solvent were established. The selective and sensitive derivative of for HPLC/UV-vis was derivatized using phenacyl bromide, and the experimental factors, including reaction time, reaction temperature and amount of derivatizing reagent and base were investigated for the effective synthesis. The derivatized with phenacyl bromide was effectively analyzed by HPLC/UV-vis. The structure of derivatized was confirmed by HPLC/ESI-MS. For apple, LOD and LOQ were 0.008 mg/kg and 0.027 mg/kg, respectively. For pear, LOD and LOQ were 0.003 mg/kg, 0.012 mg/kg, respectively. The established method can be applied to more effective analysis of from plant and food.

Task specific [bmim]BF4 was found to be reusable, alternative, and effective reaction media for multicomponent synthesis of highly functionalized pyrroles. Generality of the procedure was established by synthesizing various pyrroles from wide range of aromatic/aliphatic amine, phenacyl bromide, and electrophilic alkynes by utilizing this protocol without any acid or metal catalyst. Ecocompatibility, short reaction time, excellent yield, recyclability of [bmim]BF4, low cost, easy work-up, and mild reaction conditions are additional advantages of the procedure in the context of sustainable and green chemistry.

5-(P-tolyl)-2-[(3-bromo-4-methoxy benzylidene) hydrazino]-thiazole 3, 3-[(3-bromo-4-mehtoxy benzylidine) amino]-2-thiohydantion 5, and 4,6-disubstituted-3-[(3-bromo-4-methoxybenzyliden) amino]-2-thioxo pyrimidines 10 have been prepared via cyclization of 3-bromo-4-methoxy benzaldehyde thiosemicarbazone 2 with 4-methyl phenacyl bromide, ethyl chloroacetate, and dicarbonyl compounds in different conditions. Acetylation of 3 and 5 with acetic anhydride gave the corresponding monoacetyl derivatives 4 and 6, while the acetylation of 5 with acetic anhydride in the presence of fused sodium acetate gave diacetyl derivative 7. Condensation of compound 5 with benzaldehyde in the presence of piperidine yielded the corresponding 3-substituted-5-benzylindene 2-thiohydation 8. Acetylation of compound 8 with acetic anhydride gave the corresponding 1-acetyl-3-substituted-5-benzylidene-2-thiohydantion 9. The mass spectral fragmentation patterns of some prepared compounds are investigated in order to elucidate the structure of the synthesized nitrogen heterocycles.

A series of novel 2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles have been prepared by a three-component cyclo-condensation of various chalcones, thiosemicarbazide and phenacyl bromide. The easy work-up of the products, rapid reaction, and mild conditions are notable features of this protocol. The reaction was efficiently catalyzed in one-pot by a few drops of HCl in EtOH under reflux conditions providing the title compounds in moderate to high yields. The antibacterial activity of the selected products was examined. Some products exhibit promising activities.

Reactions of liquid-phase parallel synthesis are subject to quite stringent requirements by quite different criteria. Collections of starting reagents should be cheap and diverse while the reaction conditions should be simple and mild, and the products should be obtained in high yields and without complicated purification. For biological tests, the final molecule should contain a predetermined “pharmacophore” fragment. Many reactions fail to meet such criteria. For example, certain C–C bond formation reactions can be considered unsuitable. (Diels–Alder reactions and even condensations produce a lot of admixtures; cross-coupling makes use of hardly accessible reagents, etc.) Much more suitable are reactions involving nucleophilic nitrogen atom (formation of amides, sulfamides, hydrazides, or hydrazones), the best of which is the formation of compounds with an aminoalkyl group. Substituted aminoalkyl group (NHRCH2– or NR2CH2–) is a well-known pharmacophore group in a great variety of medicines and natural compounds.

Current research is based on the synthesis of novel ( E )-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives ( 3 – 15 ) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde ( 1 ) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate ( 2 ). While in second step, cyclization between the intermediate ( 2 ) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1 H NMR and 13 C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2 – 15 were subjected for in vitro β -glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC 50 = 3.10 ± 0.10–40.10 ± 0.90 μM and found to be even more potent than the standard d -saccharic acid 1,4-lactone (IC 50 = 48.38 ± 1.05 μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds.

An efficient one-pot multicomponent synthesis of 3-(2-(1H-indol-3-yl)ethyl)-4-hydroxy-4-arylthiazolidine-2-thione and 3-(2-(1H-indol-3-yl)ethyl)-4-arylthiazole-2(3H)-thione has been developed from a multicomponent reaction of tryptamine, carbon disulfide and phenacyl bromide. This protocol has an advantage such as operational simplicity, short reaction time, and affording good to excellent yields.

Various imidazolo[1,2-a]pyridines were synthesized from amino pyridines and aromatic phenacyl bromides by one step process in the presence of MgO in aqueous medium at room temperature. The salient feature of this method includes mild conditions, short reaction time, high yields, easy purification and simple procedure.

Two different heterocycles, thiazole-2-imines and imidazole-2-thiones, have been conveniently synthesized by just altering the sequential order (1 + 2 + 3 or 1 + 3 + 2) when combining the same components [aryl amine (1), aryl isothiocyanate (2), and phenacyl bromide (3)] in one-pot, three-component protocols. The third possible sequential order of combination (2 + 3 + 1) chemoselectively affords thiazole-2-imine. The finding is a stepping stone in the synthetic applicability of sequential one-pot, three-component protocols.

The choice of solvent in which to carry out liquid-phase organic reactions often has a large impact on reaction rates and selectivity and is thus a key decision in process design. A systematic methodology for solvent design that does not require any experimental data on the effect of solvents on reaction kinetics is presented. It combines quantum mechanical computations for the reaction rate constant in various solvents with a computer-aided molecular design (CAMD) formulation. A surrogate model is used to derive an integrated design formulation that combines kinetics and other considerations such as phase equilibria, as predicted by group contribution methods. The derivation of the mixed-integer nonlinear formulation is presented step-by-step. In the application of the methodology to a classic S N 2 reaction, the Menschutkin reaction, the reaction rate is used as the key performance objective. The results highlight the trade-offs between different chemical and physical properties such as reaction rate constant, solvent density and solid reactant solubility and lead to the identification of several promising solvents to enhance reaction performance.

(1; X = Br) [5667-47-0] C10H13BrOS (MW 261.18) InChI = InChI=1S/C10H13OS.BrH/c1-12(2)8-10(11)9-6-4-3-5-7-9;/h3-7H,8H2,1-2H3;1H/q+1;/p-1 InChIKey = MOXCZQUDEPYNKM-UHFFFAOYSA-M (2; X = BF4) [24806-57-3] C10H13OSBF4 (MW 268.08) InChI = InChI=1S/C10H13OS.BF4/c1-12(2)8-10(11)9-6-4-3-5-7-9;2-1(3,4)5/h3-7H,8H2,1-2H3;/q+1;-1 InChIKey = NYDZUKNJLPHOOF-UHFFFAOYSA-N Alternate Names: (1) dimethylphenacylsulfonium bromide; (benzoylmethyl)dimethylsulfonium bromide; (2) dimethylphenacylsulfonium tetrafluoroborate; (benzoylmethyl)dimethylsulfonium tetrafluoroborate. Physical Data: (1) hygroscopic colorless plates, d 1.559 g cm−3, mp 145 °C; (2) colorless needles, mp 170–171 °C. Solubility: (1) sol in water, DMSO, EtOH; (2) sol in DMSO, EtOH, MeOH. Preparative Methods: although dimethylphenacylsulfonium bromide can be purchased from several chemical providers, it can be readily prepared via a simple substitution reaction between phenacyl bromide and dimethyl sulfide (eq 1).1 This bromide salt can be transformed to tetrafluoroborate salt by an anion exchange reaction with sodium tetrafluoroborate in acetone.2 (1) Use of highly stench and volatile dimethyl sulfide can be avoided by employing DMSO as a sulfur source.3 DMSO is first reacted with tert-butyl bromide via a SN1 mechanism to give the bromodimethylsulfonium tert-butoxide. Then the anion is exchanged to bromide, which is derived from another t-BuBr molecule. The resulting bromodimethylsulfonium bromide reacts with acetophenone to give α-bromoacetophenone, which is transformed in situ to the title compound by the reaction with the liberated dimethyl sulfide (eq 2). (2) Later, a variant of this method was reported using 3 equiv of hydrogen bromide as a bromine source instead of t-BuBr.4 Here, the title compound is obtained in 69% yield. The corresponding sulfonium chloride can be prepared in the same manner by using HCl; however, the yield is as low as 5%.5 Dimethylphenacylsulfonium iodide is synthesized from phenacyl methyl sulfide and methyl iodide.6 Handling, Storage, and Precautions: proper safety precautions include working in a laboratory fume hood while wearing safety eyewear, appropriate gloves, and a laboratory coat. Compound causes skin and eye irritation. In case of exposure to skin, flush with copious amounts of water for at least 15 min. If irritation persists, seek medical advice.

A novel method for thiazolyl-pyrazolone rings formation is established using the reaction of phenacyl bromide and thiosemicarbazide with ethyl acetoacetate in the presence of aryl aldehyde to give 4-arylidene-3-methyl-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5(4H)-ones in good yields.

The acidic ionic liquid, 1-(4-sulfonic acid) butyl-3-methylimidazolium hydrogen sulfate [MimC4SO3H]HSO4 catalyzed two-component condensation reaction of phenacyl bromide and o-phenylenediamine to afford corresponding quinoxaline derivatives. The inexpensive and non-toxic ionic liquids can be reused severaltimes without any perceptible loss of their activities.

Derivatives of pyrrolo[1,2-a]quinoxalines (Fig. 3.1) have valuable characteristics and, in particular, marked biological activity and are a subject of constant interest. In spite of this, however, data on the synthesis of these compounds remain disconnected.

Two different heterocycles, thiazole-2-imines and imidazole-2-thiones, have been conveniently synthesized by just altering the sequential order (1 + 2 + 3 or 1 + 3 + 2) when combining the same components [aryl amine (1), aryl isothiocyanate (2), and phenacyl bromide (3)] in one-pot, three-component protocols. The third possible sequential order of combination (2 + 3 + 1) chemoselectively affords thiazole-2-imine. The finding is a stepping stone in the synthetic applicability of sequential one-pot, three-component protocols.

The synthesis of 3-methyl-1,4-diphenyl-7-thioxo-4,6,8,9-tetrahydropyrazolo[5,4-b] pyrimidino[5,4-e]pyridine-5-one (6) was achieved by two different one-pot multi-component synthesis (one-pot three-component and one-pot four component synthesis). Mono and dialkylation of 6 under different conditions gave compounds 7–11. The hydrazine 12 produced from reaction of 9 with N2H4 was subjected to reactions with some aromatic aldehydes, ethyl acetoacetate, acetyl acetone, ethyl cyanoacetate and triethyl orthoformate to give 13–17, respectively. Compound 12 upon reaction with CS2, nitrous acid, benzoin, chloroacetone and phenacyl bromide gave 18,20,21,22. Alkylation of 18 with ethyl iodide, ethyl chloroacetate and phenacyl bromide gave 19a–c. The antibacterial and antifungal activities of selected derivatives were evaluated.

An efficient and convenient protocol of broad scope for the synthesis of quinoxaline by cyclization-oxidation of phenacyl bromide with equimolar amount of phenylenediamine at room temperature catalyzed by thiamine in the form of N-heterocyclic carbene (NHC). High efficiency, inexpensiveness, and non-toxicity are the interesting features of the catalyst, which make it eco-friendly and highly attractive.

A simple and efficient synthesis of highly substituted pyrroles was achieved in water medium via multi-component strategy, using amine, DMAD/DEAD as well as phenacyl bromide catalyzed by β-CD. Utilizing this protocol various pyrrole derivatives were synthesized in good to excellent yields.

In the present study, synthesis and antimicrobial activity of 2,5-disubstituted 1,3,4-thiadiazole derivatives 5a-f are described. The structures of the newly synthesized compounds were confirmed by FT-IR, 1 H NMR, 13 C NMR, mass and elemental analysis. All compounds were screened for antitubercular and antimicrobial activity. Molecular modeling studies were performed to dock compounds into the ecKAS III binding site, which suggested probable inhibition mechanism. The results revealed that most of the compounds showed high to moderate biological activity against tested microorganisms.

Lipase bio-catalyst or ammonium based deep eutectic mixture efficiently catalyzed aqueous phase synthesis of methyl-thiazole and amino-thiazole derivatives. The simple ammonium deep eutectic catalyst, easily synthesized from choline chloride and urea, is inexpensive, recyclable and bio-degradable, making it suitable for industrial applications. An efficient and eco-friendly process for methyl and amino-thiazole synthesis in aqueous media involving bio-catalyst or ammonium deep eutectic mixtures as catalysts is described. Both the catalysts are bio-degradable, recyclable and non-toxic.

An efficient and general method has been described for the synthesis of imidazo[2,1-b]-1,3,4-thiadiazole by the reaction of 2-aminothiadiazoles with phenacyl bromides in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO). The method is suitable for the synthesis of functionalized imidazothiadiazoles.

This paper describes the determination of fatty acid composition of coffee, citrus and rum distillery wastes using reversed-phase high-performance liquid chromatography (RP-HPLC). Lipid extracts of the waste samples are derivatized with phenacyl bromide and their phenacyl esters are separated on a C8 reversed-phase column by using continuous gradient elution with water and acetonitrile. The presence of saturated and unsaturated fatty acids in quantifiable amounts in the examined wastes, as well as the high percentage recoveries, are clear indications that these wastes have potential value as inexpensive sources of lipids. The HPLC procedures described here could be adopted for further analysis of materials of this nature.

The di- N -functionalized macrocycle 2,13-bis(2-phenacyl)-5,16-dimethyl-2,6,13,17-tetraazatricyclo[16.4.0. 1.18 0 7.12 ]docosane (H 2 L 2 ) bearing two N -CH 2 COC 6 H 5 groups has been prepared by the reaction of 3,14-dimethyl-2,6,13,17-tetraazatricyclo[16.4.0.0 7.12 ]docosane (L 1 ) with phenacyl bromide. Interestingly, H 2 L 2 reacts with Ni 2+ ion to form two geometric isomers, trans -[Ni(H 2 L 2 )] 2+ and cis -[Ni(H 2 L 2 )] 2+ . The axial Ni–O ( N -CH 2 COC 6 H 5 group) bond distance (2.080(2) A) of trans -[Ni(H 2 L 2 )](ClO 4 ) 2 ·2DMSO is shorter than the in-plane Ni–N distances (2.096(2) and 2.100(2) A). However, the Ni–O distances (2.105(2) and 2.124(2) A) of cis -[Ni(H 2 L 2 )](ClO 4 ) 2 ·H 2 O are considerably longer than the Ni–N distances (2.053(2)–2.086(2) A). Each N -CH 2 COC 6 H 5 group of trans -[Ni(H 2 L 2 )] 2+ and cis -[Ni(H 2 L 2 )] 2+ exists as its keto form in the solid state and in various solvents. Two N -CH 2 COC 6 H 5 groups of trans -[Ni(H 2 L 2 )] 2+ are readily deprotonated in basic aqueous solutions, producing the enolate form trans -[Ni(L 2 )]. On the other hand, cis -[Ni(H 2 L 2 )] 2+ undergoes deprotonation to yield cis -[Ni(HL 2 )] + , in which one N -CH 2 COC 6 H 5 group is not deprotonated, under similar conditions.

Two derivatives of pyridoxal oxime (1) were prepared by quaternization of pyridoxal oxime with phenacyl bromide and 2-methoxyphenacyl bromide. The crystal structures of the 1-phenacyl-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (2) and the novel 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(2′-methoxyphenacyl) pyridinium bromide (3) have been determined by X-ray diffraction method. The conformation of these two pyridoxal oxime phenacyl derivatives is locked by numerous intramolecular hydrogen bonds. The O–H···Br, C–H···Br and C–H···O hydrogen bonds in 2 and 3 form complex three-dimensional network. Supramolecular structure of 3 also contains C–H···π and π···π interactions which link neighbouring cations. .

The mechanism generally admitted for the bioactivation of the antithrombotic prodrug, prasugrel, 1c, is its two-step enzymatic conversion into a biologically active thiol metabolite. The first step is an esterase-catalyzed hydrolysis of its acetate function leading to a thiolactone metabolite 2c. The second step was described as a cytochrome P450 (P450)-dependent oxidative opening of the thiolactone ring of 2c, with intermediate formation of a reactive sulfenic acid metabolite that is eventually reduced to the corresponding active thiol 3c. This article describes a detailed study of the metabolism of 1c by human liver microsomes and human sera, with an analysis by HPLC-MS under conditions allowing a complete separation of the thiol metabolite isomers, after derivatization with 3'-methoxy phenacyl bromide. It shows that there are two competing metabolic pathways for the opening of the 2c thiolactone ring. The major one, which was previously described, results from a P450- and NADPH-dependent redox bioactivation of 2c and leads to 3c, two previously reported thiol diastereomers bearing an exocyclic double bond. It occurs with NADPH-supplemented human liver microsomes but not with human sera. The second one results from a hydrolysis of 2c and leads to an isomer of 3c, 3c endo, in which the double bond has migrated from an exocyclic to an endocyclic position in the piperidine ring. It occurs both with human liver microsomes and human sera, and does not require NADPH. However, it requires Ca(2+) and is inhibited by paraoxon, which suggests that it is catalyzed by a thioesterase such as PON-1. Chemical experiments have confirmed that hydrolytic opening of thiolactone 2c exclusively leads to derivatives of the endo thiol isomer 3c endo.

A practical and efficient procedure for the synthesis of polysubstituted azirines and in some cases benzamides was developed through reaction of phenacyl bromides and N,N-dialkylcarbodiimides, in the presence of catalytic amount of isoquinoline in dry acetonitrile under mild conditions at ambient temperature. The salient features of this process include operational simplicity, high yields, and easily accessible starting materials.

(Z)-1-amino-4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-imidazol“5(4H)”one 2 was synthesized from the corresponding oxazolone 1. Condensation with different phenacyl bromide derivatives yielded our target compounds 4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-1-(2-oxophenyl/substitutedphenylethylamino)-1H-imidazol“5(4H)”one 3a–f. On the other hand, oxazolone 1 was allowed to react with dl-alanine to obtain (Z)-2-(4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-5-oxo-4,5-dihydroimidazol-1-yl)propanoic acid 4. Chlorination followed by reaction with appropriate aromatic amines gave our compounds 2-(4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-5-oxo-4,5-dihydroimidazol-1-yl)-N-phenyl/substitutedphenylpropanamide 6a–c. All the target compounds were evaluated for their anticonvulsant activity using mean electroshock (MES) test at an oral dose of 100 mg/Kg. Most of the compounds showed protection against seizures with a potency ranging from 70 to 96%. However, compounds 3d, 6b, and c showed excellent protection against seizures with a potency of 92.84, 96.42, 96.42%, respectively, with respect to the reference standard phenytoin with a potency of 100%. To assess the locomotor coordination and neurological deficit, animals were tested on the rotarod, the most promising compounds did not affect the stability of mice on rotarod at the same dose level.

Silica phosphoric acid has been found to be an efficient catalyst for the synthesis of 2-amino/anilino-5-aryl-1,3,4-thiadiazine bromide derivatives from the reaction of thiosemicarbazide and α-bromoketones in acetonitrile at room temperature. The catalyst can be reused for four times without any significant loss of catalytic activity. The experimental procedure is simple, and the products are obtained in high yield.

The synthesis of C-substituted and N-substituted pyrrole is described by the reaction of phenacyl bromides, pentane-2, 4-dione and amine in aqueous medium using DABCO as a catalyst. The method is very convenient and applicable for alkyl as well as aryl amines and phenacyl bromides. The procedure is amenable for the synthesis of new substituted pyrroles. Moreover, aqueous medium makes the method more eco-friendly.

The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with benzoylisothiocyanate (2) afforded the thiourea derivatives 3a,b. Cyclization of the latter products gave the annulated products 4a,b. Compounds 3a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 7a-d which underwent cyclization for compounds 7a,c afforded compound 9. On the other hand compounds 4a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 6a-d a second pathway was applied to synthesize compound 6c which underwent cyclization afforded compound 9. Also compounds 4a,b reacted with either phenacyl bromide (10) afforded compounds 11a,b or ethylchloroacetae (12) compounds 13a,b were produced. The latter products reacted with each hydrazine hydrate (5a) and phenyl hydrazine (5b) afforded compounds 14a-d. Their antitumor activities were tested using three different cell lines.