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Nucleophilic heterocyclic carbenes (NHCs) have been used for the first time as catalysts in the cyclopropanation of ethyl cyanocinnamates with phenacyl bromide by Michael-initiated ring-closure (MIRC).

Two series of new pyridines bearing thiazoline (3a-n) and thiazolidinone (5a-e) moieties were prepared via the cyclization of the corresponding substituted pyridyl thiourea (2a-g) with an appropriately substituted phenacyl bromide or chloroacetic acid, respectively. The antimicrobial activity was determined for representative compounds and most of them showed moderate activity against Gram-positive bactera.

A one-pot, three-component reaction between pyridine, phenacyl bromide, and thiocyanate is described. The reaction afforded the corresponding special type of fully substituted imidazo[1,2-a]pyridine derivatives in good yields without using any catalyst or activation.

Ammonium 1,1,3-tricyano-2-methylprop-2-enide 1a and sodium 2-amino-1,1,3-tricyanoprop-2-enide 1b are treated with H2S in absolute ethanol to afford 3,4,6-trisubstituted pyridine-2(1H)-thione 3a,b; their structures are confirmed by reaction with phenacyl bromide to give 4a,b; also 3a,b reacts with DMFDMA to give 6a,b, and on treatment of 6a with phenacyl bromide affords 8; reaction of 4b with DMFDMA gave 9 while methylation of 3a,b by methyl iodide in ethanolic sodium hydroxide gives 10a,b.

A new and easy synthetic route to furo[2,3-b]furans 7a-d and furo[2,3-b]pyrroles 8a-d has been achieved by the C-phenacylation/cyclization reactions of 2-amino-4,5-dihydro-3-furancarbonitrile (5). Thermal treatment of the key intermediate 3-phenacylated tetrahydro-2-imino-3-furancarbonitriles 6a-d, which were prepared from compound 5 and phenacyl bromides, e.g. phenacyl bromide, 4-chlorophenacyl bromide, 4-methylphenacyl bromide and 4-methoxyphenacyl bromide, with acetic anhydride caused intramolecular cyclization to yield the corresponding furo[2,3-b]furans 7a-d. On the other hand, methanolic sodium methoxide-assisted cyclocondensation of compounds 6a-d gave the corresponding furo[2,3-b]pyrroles 8a-d.

The reactions of 3-[((( a-phenyllmethyl)benzylidene )amino )oxy ]methyllethyl-4-amino-5-mercapto-4(H)1 .2,4-triazoles la-d. with various aliphatic/aromatic acids 2a-d-5a-d. oxalic acid 6a-d. cyanogen bromide 7a-d, carbon disulphide 8a-d. hydrazine hydrate (99%) 9a-d. monochloroacetic acid IOa-d, phenacyl bromide Ba-d, benzoin 12a-d, dimidone 13a-d and chalcone 14a-d are described. The characterisation of the compounds have been done on the basis of elemental analysis and spectral (IR, IHNMR and mass) data. All the newly synthesised compounds have been screened for antimicrobial activity against B. cirroflagellosus, E. coli, A. niger and R. bataticola. Most of the compounds have also been screened for antitu­ berculosis activity against M. tuberculosis. H37Rv strain. Results of antimicrobial screening revealed that majority of the newly synthesised N-bridged heterocycles exhibit better antimicrobial activity than the standards cotrimoxazole and fluco­ nazole. A few of the compounds exhibit significant antituberculosis activity in comparison with rifampin, the standard used.

The synthetic route for a uterine relaxant, bis(2-{[(2S)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl}amino)-1, 2, 3, 4-tetrahydronaphthalen-7-yl]oxy}-N, N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.

The reaction of benzopyrano[2,3-c]pyrazol-3-one (1) with some active halo compounds, afforded compounds 4, 8 and 12, respectively. The cyanoethyl derivative 19 was synthesized and treated with active methylenes and sulfur or benzoylisothiocyanate and phenacyl bromide, to give compounds 24a,b and 27. Compounds 25a,b and 28 were obtained through the reaction of compounds 24a,b with acrylonitrile or compound 27 with maleic anhydride. Thiation of compound 1 afforded the corresponding thio derivative 29. The reaction of 4-benzylidene-2-methyloxazolin-5-one with compounds 1 or 29 gave products 30a,b , respectively.

Reactions of 3-aryloxymethyl-4-amino-5-mercapto-1 ,2,4-triazoles 1 with aromatic carboxylic acids, furoic acid, oxalic acid, monoch10roacetic acid and phenacyl bromide furnish various N-bridged heterocycles viz., triazolothiadiazoles, bis­ triazolothiadiazoles, triazolothiadiazinones and triazolothiadiazines . The structures of these N-bridged heterocycles are characterized on the basis of elemental analyses, IR, NMR and mass spectral data. Some of these compounds are also subjected to antibacterial screening studies. The pharmacological importance of nitrogen bridged heterocycles derived from 1,2,4-triazoles paved the way towards active research in triazole chemistry. As a result, variety of new compounds were being added to this field every year. A number of attempts were made to improve the activity of these compounds by varying the substituents on the triazole nucleus. The literature survey reveals that many N-bridged heterocycles such as triazolothiadiazoles , triazolothiadiazinones and tria­ zolothiadiazines derived from 1,2,4-triazoles display broad spectrum of biological activities l • 15

The reaction of 3-hydrazino-4,5,6-triphenylpyridazine with phenacyl bromide afforded triazolopyridazine, while the reaction with different aldehydes gave the corresponding 3-arylidene hydrazinopyridazine derivatives which, on reaction with Br 2/ Na 2 CO 3 , gave the corresponding triazinopyridazines. Also, fusion with ethyl acetoacetate, ethyl bertzoylacetate, diethyl malonate, or ethyl phenylacetoacetate gave the corresponding pyrazolo- and triazinopyridazine derivatives. The antimicrobial activity of some of the new compounds has been discussed.

A one-pot synthesis of functionalized benzofurans has been developed via O-alkylation, carbon–carbon coupling/cyclization, and dehydration/olefination tandem reactions from phenacyl bromide and phenols under microwave irradiation and solvent-free conditions in the presence of mineral-supported reagent and inorganic base. The best selectivity for forming benzofuran product has been achieved with Na2CO3 as a base. The order of activity of inorganic base is as follows: K2CO3 > NaHCO3 > Na2CO3 > KHCO3 > Na2SO3 > KOH > K3PO4 > NaOH > KH2PO4 > KOAc. This novel synthesis features three new bonds and one ring system assembled in a single step.

The reaction of N,N’-diarylselenoureas 16 with phenacyl bromide in EtOH under reflux, followed by treatment with NH3 , gave N,3-diaryl-4-phenyl-1,3-selenazol-2(3H)-imines 13 in high yields (Scheme 2). A reaction mechanism via formation of the corresponding Se-(benzoylmethyl)isoselenoureas 18 and subsequent cyclocondensation is proposed (Scheme 3). The N,N’-diarylselenoureas 16 were conveniently prepared by the reaction of aryl isoselenocyanates 15 with 4-substituted anilines. The structures of 13a and 13c were established by X-ray crystallography.

A series of thiazolo[3,2- b ][1,2,4]triazole incorporating diphenylsulfone moieties were synthesized starting from 5-[4-(4-X-phenylsulfonyl)phenyl]-4 H -1,2,4-triazole-3-thioles 3a – c , X = H, Cl, Br. Thus, alkylation of 1,2,4-triazoles 3 with phenacyl bromide or 4-bromophenacyl bromide afforded S-substituted 1,2,4-triazoles 4 , 5 . These new intermediates 4 and 5 , in the presence of H 2 SO 4 (c), were cyclized to 2-[4-(4-X-phenylsulfonyl)phenyl]-6-(4-Y-phenyl)[1,3]thiazolo[3,2- b ]-[1,2,4]-triazoles 6 , 7 (I) and not to isomeric thiazolo[2,3- c ][1,2,4]-triazoles 6 , 7 (II). The newly synthesized compounds were characterized by IR, 1 H, 13 C NMR and elemental analysis. MS spectra confirmed the formation of thiazolo[3,2- b ][1,2,4]triazole 6 , 7 (forms I) in detriment of [2,3- c ] isomeric compounds (forms II). The potential antibacterial effects of the synthesized compounds were investigated using standard bacterial strains: Acinetobacter baumannii ATCC 19606, Citrobacter freundii ATCC 8090, Escherichia coli ATCC 11775, Pseudomonas aeruginosa ATCC 9027, Enterococcus faecalis ATCC 19433, Staphylococcus aureus ATCC 12600, Staphylococcus epidermidis ATCC 14990, Bacillus cereus ATCC 14579.

The reaction of 2-chloro-4,6-dimethylpyridine-3-carbonitrile with hydrazine hydrate, hydroxylamine, and anthranilic acid afforded the corresponding pyrazolo, isoxazolo, and pyridoquinazoline derivatives. Alkylation of 2-mercapto-4,6-dimethylpyridine-3-carbonitrile with ethyl chloroacetate or phenacyl bromide followed by cyclization in NaOH gave thienopyridine derivatives. Diazotization of ethyl 3-amino-4,6-dimethylthiеno[2,3-b]pyridine-2-carboxylate followed by the reaction with thiourea, guanidine carbonate, and hydroxylamine hydrochloride gave the corresponding thienopyridine derivatives. The biological activity of some new compounds has been discussed.

Nucleophilic heterocyclic carbenes (NHCs) have been used for the first time as catalysts in the cyclopropanation of ethyl cyanocinnamates with phenacyl bromide by Michael-initiated ring-closure (MIRC).

WOS: 000279893600003 The synthesis of 4-amino-2-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (2) and 4-amino-2-[(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (5) was performed starting from 2-[4-amino-3-(4-methylphenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetohydrazide (1). The treatment of 2 and 5 with 4-fluorobenzaldehyde (for 8) or salicylaldehyde (for 6) afforded the corresponding Schiff bases (6 and 8). The condensation of 5 with phenacyl bromide produced 4-amino-5-(4-methylphenyl)-2-[(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (7). The alkylation of 2 and 8 was carried out by using methyl iodide in basic media. Compounds 3 and 10a,b were prepared by aminoalkylation of 2 and 8 with 4-fluorophenyl piperazine, morpholine, or 4-methyl piperazine in the presence of formaldehyde. The synthesized compounds were screened for their antimicrobial activities and, with the exception of 2, 4, 7, and 9, were found to possess good or moderate activities against the screened bacterial strains except Candida tropicalis and Candida albicans. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [107T333]; Karadeniz Technical University, BAP, TurkeyKaradeniz Teknik University [2005.111.002.4] The support provided by the Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 107T333) and Karadeniz Technical University, BAP, Turkey (Ref. No. 2005.111.002.4), is gratefully acknowledged.

Single crystal X-ray diffraction measurements on the adduct obtained from neopentyl diphenylphosphinite and phenacyl bromide show this Michaelis-Arbuzov intermediate to be a phosphonium compound, with a tetrahedral arrangement of bonds around phosphorus and a P + ⋯Br − interatomic distance of 4.229 A. The phenyl-phosphorus bonds are of normal length for single PC bonds. Although the phosphorus-oxygen bond length (1.573 A) indicates significant double bond character, the reactivity of intermediates of this type is thought to be controlled mainly by inductive effects. Rearrangement of this intermediate to the isomeric vinyloxyphosphonium bromide (Perkow intermediate) does not occur.

Various derivatives of thiophene, thiazoline and thienopyrimidine have been synthesized via the reaction of active methylene reagents (la-j) with benzoyl isothiocyanate in the presence of potassium hydroxide, followed by the subsequent treatment of the potassium salt intermediates 2a-j with phenacyl bromide or ethyl chloroacetate. The stability of the formed adducts 3 and 12 or their selective cyclization depends on both the nature of the active methylene reagent and the α-halocarbonyl compounds.

The separation and determination of the major carboxylic acids in wine by liquid chromatography were optimized by using the modelling surface response method. The chromatographic response function was used as a criterion to obtain an optimum peak separation with the minimum analysis time accepted. The starting mobile phase composition (% methanol) and the change in the solvent strength of the mobile phase during the analysis time were considered as experimental parameters. Malic, tartaric, acetic, lactic, succinic and citric acid were determined by linear gradient elution of their phenacyl bromide derivatives. The optimized method was applied to a red wine sample.

The thiophene derivative 1 reacts with the active methylene reagents 2a-c to afford the thieno[2,3-d]pyrimidine derivatives 6a,b and 8, respectively. 1 reacts with phenacyl bromide 2d to afford the N-alkylation product 9 and reacts with phenacyl thiocyanate 2e to afford the N-(thiazol-2-yl) derivative 10, which was further cyclized into thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivative 12. Compound 1 reacts also with the cinnamonitriles 3a,b to afford the thieno[2,3-b]pyridines 15a,b, respectively. 1 undergoes either acetylation or hydrolysis to afford the thieno[2,3-b]pyridine derivative 19 and the thiophene derivative 22, respectively. Some of the new compounds show inhibitory effect to the production of mycotoxins and to fungal growth.

Substituted 2-alkylthio-3-cyano-4,6-dimethyl-5-phenylcarbamoyl-1,4-dihydropyridines were obtained by successive reaction of acetaldehyde with cyanothioacetamide and acetoacetanilide, α-chloracetamide or phenacyl bromide in the presence of piperidine.

epi-Androsterone 1 was converted into its hydrazone derivative through the reaction with hydrazine hydrate 80%. Hydrazonoandrostane derivative 2b reacted with hydrazonoyl halides in the presence of K(2)CO(3) forming the corresponding hydrazopyridazinoandrostane derivatives 6a-d. The 3β-acetyl-17-hydrazonoandrostane derivative 2b reacted with a halogen reagent, benzoyl chloride, to form the non-cyclic 16-benzoylated hydrazone 9. On the other hand, compound 2b produced the corresponding pyridazinoandrostane derivatives 11 and 12 via its reaction with phenacyl bromide and chloroacetone respectively. Reaction of the hydrazono derivative 2b with benzaldehyde in the presence of acetic acid drops led to the formation of the benzylidenehydrazonoandrostane derivative 13. The product 14, phosphinom-ethylenehydrazonoandrostane was obtained by the reaction of the derivative 13 with trisdimethylaminophosphine in the presence of dry benzene. The reaction of compound 2b with phenyl isothiocyanate followed by boiling in chloroacetic acid or thioglycolic acid produced the pyrazoloandrostane derivatives 17 and 18 respectively. The biological activity of compounds 6a, 6d, 11, 12, and 15 was evaluated as inhibitor of growth in a human liver carcinoma cell line and doxorubicine was used for comparison. Compounds 15 and 12 showed a higher potency than the other tested compounds.

5-Acyl-8-hydroxyquinoline-2-(3'-substituted-4'-aryl-2,3- -dihydrothiazol-2'-ylidene)hydrazones, 5a-e to 10a-c, were prepared by the reaction of appropriate 5-acyl-8-hydro- xyquinoline-4-substituted thiosemicarbazones 3a-e and phenacyl bromides 4a-e. Structures of the new compounds were verified on the basis of spectral and elemental analy- ses. Twenty-eight new compounds were tested for their possible antimicrobial activities. Most of the tested com- pounds showed weak to moderate antibacterial activity against most of the bacterial strains used in comparison with gatifloxacin as a reference drug. The test compounds showed weak to moderate antifungal activity against te- sted fungi in comparison with ketoconazole as a referen- ce drug. On the other hand, the newly synthesized com- pounds were tested for their anti-inflammatory effects and most of them showed good to excellent anti-inflamma- tory activity compared to indomethacin. Moreover, ulce- rogenicity and the median lethal dose (LD50) of the most active anti-inflammatory compounds 6b and 9e were de- termined in mice; they were non-toxic at doses up to 400 mg kg -1 after i.p. administration.

A series of fused and non fused 1,2,4-triazoles with (2,4-dichlorophenoxy) moiety are prepared utilizing 3-((2,4-dichlorophenoxy)methyl)-4-amino-4 H -1,2,4-triazole-5-thiol ( 3 ). The latter on reaction with carboxylic acids, ethylchloroformate, ethylcyanoacetate and sodium nitrite gives five membered fused triazole derivatives 4a – d , 5 , 6 , 7 and 10 , respectively. The six membered heterocycles 11 , 12 and 14 are prepared by cyclization of compound 3 with phenacyl bromide, chloroacetic acid and α-bromoketone respectively. Most of the newly synthesized compounds were screened for their anti-inflammatory and molluscicidal activities. The compounds 4b , 4d , 11 and 14 showed potent anti-inflammatory activities in dose dependent manner while compounds 3 , 4b , 8 and 10 exhibited promising molluscicidal activities.

Aryl, alkyl, and sugar-derived isoselenocyanates were prepared by a one-pot procedure starting from the corresponding formamides, using triphosgene as a dehydrating agent, triethylamine, and black selenium powder. The preparation of sugar selenoureas by coupling of O-protected sugar-derived isoselenocyanates with different amines, and by coupling of unprotected glycopyranosyl amines with phenyl isoselenocyanate was also accomplished. The synthesis of a glucopyranos-2-yl-selenazole starting from O-protected 2-amino-2-deoxy-d-glucose by coupling with benzoyl isoselenocyanate, Se-alkylation with phenacyl bromide, and acid-catalyzed dehydration is also reported. Unprotected N-(β-d-glucopyranosyl)-N′-phenylselenourea was transformed into a 1,2-trans-fused bicyclic isourea upon treatment with aqueous hydrogen peroxide; the same isourea was prepared by a one-pot three-step procedure from β-d-glycopyranosylamine by thiophosgenation, coupling with aniline, and HgO-mediated desulfurization.

A one-pot, three component reaction between isoquinoline, phenacyl bromide derivatives and thiocyanates leading to imidazo[2,1-a]isoquinoline derivatives in good yields is reported. Reactions are carried out in water or DMF as the solvent at reflux.

Highly versatile ethyl 3-thiosemicarbazidobutanoate was ball-milled with phenacyl bromide to afford the corresponding ethyl 3-[(4-phenyl-2-thiazolyl)hydrazono]butanoate which underwent heterocyclization by heating in ethanolic sodium acetate to give thiazolylpyrazolone that coupled chemoselectively with aromatic diazonium salts to furnish arylhydrazonothiazolylpyrazoles. Vilsmeier-Haack reaction of ethyl 3-thiosemicarbazidobutanoate furnished selectively thiazolylpyrazole. A series of pyrazolylthiosemicarbazones were synthesized by solid-state technique which allowed waste-free production. The reaction of pyrazolylthiosemicarbazones with phenacyl bromide afforded the corresponding 2-(arylidenehydrazino)-4-phenylthiazoles in quantitative yields.

A series of thiazolo[3,2- b ][1,2,4]triazole incorporating diphenylsulfone moieties were synthesized starting from 5-[4-(4-X-phenylsulfonyl)phenyl]-4 H -1,2,4-triazole-3-thioles 3a – c , X = H, Cl, Br. Thus, alkylation of 1,2,4-triazoles 3 with phenacyl bromide or 4-bromophenacyl bromide afforded S-substituted 1,2,4-triazoles 4 , 5 . These new intermediates 4 and 5 , in the presence of H 2 SO 4 (c), were cyclized to 2-[4-(4-X-phenylsulfonyl)phenyl]-6-(4-Y-phenyl)[1,3]thiazolo[3,2- b ]-[1,2,4]-triazoles 6 , 7 (I) and not to isomeric thiazolo[2,3- c ][1,2,4]-triazoles 6 , 7 (II). The newly synthesized compounds were characterized by IR, 1 H, 13 C NMR and elemental analysis. MS spectra confirmed the formation of thiazolo[3,2- b ][1,2,4]triazole 6 , 7 (forms I) in detriment of [2,3- c ] isomeric compounds (forms II). The potential antibacterial effects of the synthesized compounds were investigated using standard bacterial strains: Acinetobacter baumannii ATCC 19606, Citrobacter freundii ATCC 8090, Escherichia coli ATCC 11775, Pseudomonas aeruginosa ATCC 9027, Enterococcus faecalis ATCC 19433, Staphylococcus aureus ATCC 12600, Staphylococcus epidermidis ATCC 14990, Bacillus cereus ATCC 14579.

Reaction of 2-cinnamoyl-1-hydroxycarbazoles 2a - d, with phenacyl bromide, mercuric acetate and H₂O₂/NaOH under different reaction conditions yielded 2-benzoyl-3-styryl-furo[2,3-a]carbazoles 3a-d, 2-benzylidene-furo[2,3-a]carbazol-3(10H)-ones 4a - d and 3-hydroxy-2-phenylpyrano- [2,3-a]carbazol-4(11H)-ones 5a - d, respectively.

4-Chloro/methyl phenacyl bromide la-b reacted with thiourea to furnish 2-amino thiazole 2a-b through Hantzsch's process, which were converted to their thiazolidinone derivatives 4a-b, by the reaction of corresponding thiazolyl thiourea 3a-b with chloroacetic acid in the presence of sodium acetate. Subsequent treatment of 4a-b with aromatic aldehydes 5a-c, followed by condensation with ω-bromolkoxyphthalimides 7a-b afforded titled compounds 8a-l.

5-Acyl-8-hydroxyquinoline-2-(3'-substituted-4'-aryl-2,3-dihydrothiazol-2'-ylide- ne)hydrazones, 5a-e to 10a-c, were prepared by the reaction of the appropriate 5-acyl-8-hydroxyquinoline-4-substituted thiosemicarbazones 3a-e and phenacyl bromides 4a-e. Structures of the new compounds were verified on the basis of spectral and elemental analyses. Twenty-eight new compounds were tested for their possible antimicrobial activities. Most of the tested compounds showed weak to moderate antibacterial activity against most of the bacterial strains used in comparison with gatifloxacin as a reference drug. The test compounds showed weak to moderate antifungal activity against tested fungi in comparison with ketoconazole as a reference drug. On the other hand, the newly synthesized compounds were tested for their anti-inflammatory effects and most of them showed good to excellent anti-inflammatory activity compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD50) of the most active anti-inflammatory compounds 6b and 9e were determined in mice; they were non-toxic at doses up to 400 mg kg-1 after i.p. administration., 5-Acil-8-hidroksikinolin-2-(3'-supstituirani-4'-aril-2,3-dihidrotiazol-2'-ilid- ne)hidrazoni 5a-e do 10a-c pripravljeni su reakcijom odgovarajućih 5-acil-8-hidroksikinolin-4-supstituiranih tiosemikarbazona 3a-e i fenacil bromida 4a-e. Strukture novih spojeva potvrđene su na temelju spektralnih i elementarnih analiza. Dvadeset osam novih spojeva testirano je na potencijalno antimikrobno djelovanje. Većina spojeva pokazuje slabo do umjereno antibakterijsko djelovanje protiv većine testiranih bakterijskih sojeva u usporedbi s gatifloksacinom kao referentim lijekom, te slabo do umjereno antifungalno djelovanje protiv gljivica u usporedbi s ketokonazolom kao referentnim lijekom. Testovi na protuupalno djelovanje pokazuju da većina spojeva posjeduje dobro ili snažno protuupalno djelovanje u usporedbi s indometacinom. Ulcerogeno djelovanje i srednje letalne doze (LD50) najaktivnijih spojeva 6b i 9e određeni su na miševima. Rezultati pokazuju da su netoksični u dozama do 400 mg kg-1 nakon i.p. primjene.

Valproic acid (VA) is a drug used to control seizures in several epileptic conditions. In VA pharmacotherapy, therapeutic drug monitoring is recommended to obtain adequate seizure control and avoid toxicity. The aim of this study was to validate a method for the determination of valproic acid in serum, employing high performance liquid chromatography with diode array detection (HPLC-DAD), after derivatization with phenacyl bromide. The calibration curve (y=0.0133x-0.0025) presented good linearity with r2=0.9999. Accuracy (101-115%), intra-assay precision (4.53-8.15%) and inter-assay precision (3.15-6.77%) were acceptable. The quantification limit was 2.0 µg/mL. The method presented similar results to enzyme immunoassay.

The derivatization of saturated long-chain fatty acids (LCFA) with a UV chromophore, 1,4-dibromoacetophenone, using non-ionic micelles to facilitate the reaction is described. Synperonic NP-12 was used as a non-ionic surfactant and tetrakis(decyl)ammonium bromide as an ion-pair agent. The reaction was carried out in the dark at 60°C for 20 min. After adding 1 ml of chloroform to the reaction mixture and centrifugation for 30 s, the mixture was ready for high-performance liquid chromatographic analysis on an RP-18 column. The derivatization rate constant for LCFA was found to be in the range 6 · 10−4−9 · 10−4 s−1. The use of micelles overcomes solubility difficulties with highly lipophilic compounds such as LCFA and provides a simple derivatization procedure.

Preparation and Reactions of N-Phenacyl-N-tosylhydroxylamines and -hydrazines O-Alkyl-N-phenacyl-N-tosylhydroxylamines 3 were prepared in two steps from O-alkylhydroxylamines 1. In the presence of a base the N-tosylhydroxylamines 3 undergo rearrangement and cleavage to N-tosylphenacylamine (5) and aldehydes 6. N-Alkul-N′-phenacyl-N,N′-ditosylhydrazines 12 were obtained by stepwise treating of N,N′-ditosylhydrazine with alkyl halide and phenacyl bromide/potassium tert-butoxide/DMF.

Separation of prostaglandin E 3 (PGE 3 ) from prostaglandin E 2 (PGE 2 ) and prostaglandin E 1 (PGE 1 ) was achieved following derivatization with p-(9-anthroyloxy)phenacyl bromide (panacyl bromide). The eicosanoid esters were analysed by reverse phase high pressure liquid chromatography with fluometric detection (excitation 360nm and emission 470nm). Human, rat and mouse adherent cells were incubated overnight and the culture medium extracted, derivatized and analysed for PG production. PGE 2 was detected from biological samples of each species tested. PGE 2 synthesis was reduced when cells were incubated overnight with 5μM eicosapentaenoic acid. PGE 3 was not detectable under these experimental conditions. Studies were also undertaken using adherent cells from mice, rats and human subjects given dietary fish oil supplements rich in EPA. PGE 3 production by these cells was not detected although the dietary regimens yielded substantial incorporation of EPA into cell membranes and leukocyte LTB 5 production was demonstrable.

5-Cyano-4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine (I) reacts with P2S5 in pyridine to give pyrimidine-2,4-dithione (II). Further reaction of II with ethyl chloroacetate, chloroacetanilide, phenacyl bromide, bromoacetone and chloroacetonitrile gave the corresponding thieno[2,3-d]pyrimidine derivatives (III-VI). Interaction of compound IVa with hydrazine hydrate in ethanol or diluted ethanol gave the hydrazide and hydrazino derivatives (VII, IX), which reacted with aromatic aldehydes to give the corresponding hydrazones (VIIIa-c, Xa-c ). Alkaline hydrolysis of IV, using KOH gave the acid XI with extrusion of thioglycolic acid.

Several reagents and experimental conditions were tested to optimize the yield of the derivatization procedure for determining carboxylic acids in wines. Two techniques were applied for optimization: a modified sequential simplex method and a simultaneous modelling method. The results obtained were similar; advantages of the latter method are discussed. The optimized conditions (phenacyl bromide as reagent with 18-crown-6 as catalyst with a reaction time of 90 min at 90 ° C) were used to determine the main carboxylic acids in several varietal wines of the Tarragona region.

3,5-Dicyano-6-mercapto-4-phenylpyridin-2(1H)-one (1) was reacted with ethyl chloroacetate to give compound (II) which on reaction with hydrazine hydrate gave the corresponding hydrazide derivative (III). Acylation of (III) with acetic acid, phenylisocyanate, or phenylisothiocyanate gave different monoacyl derivatives (IV-VI). Condensation of III with aromatic aldehydes and acetylacetone gave compounds VIIa-c, VIII respectively. Compound I was reacted with chloroanilides, bromoacetone and phenacyl bromide to yield the IX-XI; these and compound II gave thieno[2,3-b]-pyridines (XU-XV) on treatment with sodium ethoxide solution. Reaction of XII with acetic anhydride gave the diacetyl derivative XVI. Hydrolysis of compound XII with sodium hydroxide gave the corresponding acid (XVII) which on treatment with acetic anhydride gave the oxazine derivative (XVIII). Reaction of oxazine compound XVIII with ammonium acetate and hydrazine hydrate gave pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidin-4.7-dione derivativ...

2-Aminothiazole and 2-iminothiazolidine derivatives were synthesized from the reaction of phenacyl bromide, thiourea, and its derivatives in aqueous media catalyzed by diammonium hydrogen phosphate (10%) and DABCO (10%) at room temperature in an efficient and simple procedure.

The triphenylarsine-catalyzed approach for the highly stereoselective synthesis of trans-2,3-dihydro-spiro[cyclopropane-1,2′-indan-1′,3′-dione] with alkenes and phenacyl bromide in organic solvent is described. The triphenylarsine-catalyzed cyclopropanation in water was investigated. The mixture of cis/trans isomers is provided with water as a solvent. The cis isomer is formed using water as a solvent. The reactivity of the reaction in water is higher than that in the organic solvent.

A series of novel 4-aryl/chloroalkyl-2-(2,3,5-trichlorophenyl)-1,3-thiazoles (5a-g and 7a-e) were synthesized by condensing 2,3,5-trichlorobenzenecarbothioamide with phenacyl bromide/dichloroacetone. 2,3,5-Trichlorobenzaldehyde thiosemicarbazone on treatment with phenacyl bromide afforded 4-aryl-2-(2,3,5-trichlorophenylidenehydrazino)-1,3-thiazoles (10a-g) in good yield. The newly synthesized compounds are characterized by IR, (1)H NMR and mass spectral studies. These compounds were also screened for their antibacterial and antifungal activities. Preliminary results reveal that some of the synthesized compounds are showing promising antimicrobial activity.

A novel and efficient approach to 2-pyrrolidinones and dihydropyrans via the ring transformation of 3-phenacylated tetrahydro-2-imino-3-furancarbonitriles in the presence of sodium iodide is described. The key feature in the ring transformation is that C-phenacylation of 2-amino-4,5-dihydro-3-furancarbonitriles using phenacyl bromides, e.g. phenacyl bromide, 4-chlorophenacyl bromide and 4-methoxyphenacyl bromide, proceeds smoothly and the ring-opening intermediate having leaving group such as iodide ion is produced.

Reaction of 1-hydroxycarbazole-2-carbaldehydes 1 with phenacyl bromide yielded 2-benzoyl-10 H -furo[2,3- a ]carbazoles 2 , whereas the reaction with ethyl bromoacetate yielded 1-oxo-1,2-dihydro[1,4]oxazino[2,3,4- jk ]carbazole-4-carbaldehyde ( 4 ). The reaction of 1 with ethyl acetoacetate and also with diethyl malonate yielded the pyranocarbazoles 6 and 7 , respectively. All the products were characterized by spectral and analytical means. Plausible mechanisms of product formation are proposed.

4-Benzoyl-1-cyanoacetylthiosemicarbazide undergoes coupling reaction with aromatic diazonium chloride to afford (arylhydrazono)thiosemicarbazide, which was reacted with phenacyl bromide regioselectivity to afford the thiazoline. The (arylhydrazono)thiosemicarbazide could be transformed into the pyrazolo[1,5-a]triazine. Heterocyclization of 4-benzoyl-1-cyanoacetylthiosemicarbazide with α-haloketones (bromoacetone and phenacyl bromide), ethyl iodide, and ethyl bromoacetate furnished the pyrrylthiazoles, 1,2,4- triazole, and 1,3,4-thiadiazine. The latter was coupled with aromatic diazonium chloride to give the bis(arylhydrazono)‐thiadiazine. The mechanism for the formation of the title compounds was suggested and discussed.

Compounds incorporating 1,3-oxathiole moieties in their frameworks are biologically active. Active methylene ketones can be easily converted to the corresponding dithiocarboxylates by treatment with trithiocarbonate in the presence of sodium hydride. The reactions of aroyl dithiocarboxylates with α-haloketones such as phenacyl bromide or bromoacetone afford substituted 2-ylidene-1,3-oxathioles in good yields.

Two different 1 , 3-Distal thiacalix[4]arenas were prepared by the reaction of thiacalix[4]arene with phenacyl and/or p-nitro phenacyl bromide in acetone or acetonitrile in the presence of dry CsOH. The prepared 1, 3-distal disubstituted thiacalixarenes afforded two pairs of diastereomers upon brominating in chloroform. The obtained diastereomers were separated by fractional crystallization in a mixture dichloromethane-acetone.

The reaction of phenyl isothiocyanate with the active methylene reagents 1a–e gives the nonisolable 1:1 adducts 2a–e. The latter react with α-halogenated compounds, e.g. phenacyl bromide, bromoacetyl bromide, chloroacetone, chloroacetonitrile and some hydrazonoyl halides to give the corresponding polyfunctionally substituted 2,3-dihydrothiazoles or thiazolidinone ring systems.

Six novel series of substituted thiazoline (V, VI, VII and VIII) and thiazolidinone derivatives (IX and X) resulting from 2,3-dihydro-1, 5-dimethyl-3-oxo-2-phenyl-1H-pyrazole-4-carbaldehyde (I) and 1-phenyl-3-p-tolyl-1H-pyrazolc-4-carbaldehyde (II) were synthesized. The course of this synthesis included the preparation of two new scries of disubstituted thiosemicarbazone precursors (III and IV) which were cyclized with phenacyl bromide, ethyl 2-chloroacetoacetate as well as ethyl bromoacetatc to afford the target thiazolines and thiazolidinoncs. The antipyretic activity of some representative compounds was performed.

4-Cyano-5,6-diphenyl-2,3-dihydropyridazine-3-onc 1 reacts with phosphorous oxychloride to give 70% of the corresponding 3-chloro derivative 2. Treating 2 with anthranilic acid in butanol, 4-cyano-2,3-diphenyl-10H-pyridazino[6,1-b]quinoxaline-10-one, 3 was obtained. Compound 1 reacts with phosphorous pentasulphide to give 3-mercapto derivative 4, which was converted by acrylonitrile to S-(2-cyanoethyl)pyridazine derivative 5. Compound 4 reacts with ethyl bromoacetate and with phenacyl bromide gave the corresponding thieno[2,3-c] pyridazine derivatives 8, 9, Alkylation of 1 with ethyl chloroacetate afforded 3-0-carbethoxymethyl derivative 10. Compound 10 reacts with amines (aniline, hydrazine) to give the corresponding amide and acid hydrazide 13, 12 respectively. Hydrolysis of 10 with sodium hydroxide gave the corresponding acid derivative 11. Treating 1 with methyl iodide, 3-0-methyl derivative 14 was obtained, which was converted by ammonium acetate/acetic acid to 3-amino-4-cyano-5,6-diphenyl pyridazine 15. Compound 1 reacts with methyl magnesium iodide gave 4-acetyl derivative 16, which was reacted with hydrazine, phenyl hydrazine and with hydroxylamine to give the substituted I H pyrazolo [3,4-c] pyridazine 17 a,b and isoxazolo [5,4-c] pyridazine 18 derivatives respectively.