Novel 3-aryl-5-{4-[5-(2-hydroxyphenyl)-1-phenylpyrazolyl]}-2-pyrazolines 2a-g have been prepared by the treatment of 3-(3-aryl-3-oxopropenyl)chromen-4-ones

Hitherto unknown group of tricyclic fused pyrazolines have been synthesized by the reaction of 3-arylidenechromanones and 3-arylidene-1-thiochromanones with (4-carboxyphenyl) hydrazine in hot anhydrous pyridine solution. Structures of all new compounds have been elucidated by microanalyses, IR, H-1, C-13 NMR and mass spectrometric measurements.

Hitherto unknown tetracyclic 1,5-benzothiazepines 9-16 have been synthesized by an acidcatalyzed reaction of exocyclic α,β,γ,δ-unsaturated ketones 1-8 and 2-aminothiophenol.Structures of all new compounds have been elucidated by microanalyses, 1 H-, 13 C-NMR, IR and mass spectroscopic measurements.

Exocyclic (E,E)-cinnamylideneketones were oxidized by an excess of isolated dimethyldioxirane (DMDO, in acetone solution) at room temperature, providing diastereomeric mixtures of the α,β:γ,δ-diepoxides. In the case of derivatives bearing an ortho-nitrocinnamylidene moiety, α,β-monoepoxides were also isolated as minor products. The structures of all new compounds and the stereochemistry of the monoepoxides and diepoxide diastereomers were established by NMR studies.

Kalkonok, (3-kumarinil)-kalkonok, valamint dehidroecetsavbol nyert telitetlen ketonok es hidrazinok reakciojaval uj 2-pirazolinokat szintertizaltunk. E vizsgalatok koreben kiemelendők a (karboxi-fenil)-hidrazinok es ezen telitetlen ketonok erekakcionak vizsgalatai es karboxilcsoportot tartalmazo 2-pirazolinok szintezise. Izoflavonok, homoizoflavonok es 4-tioanalogonjaik es hidrazinok reakciojaval uj pirazolokat szintetizaltunk, amelyek tautomeria viszonyait NMR-spektroszkopiai meresekkel es kvantumkemiai szamitasokkal tanulmanyoztuk. Racionalis eljarast dolgoztunk ki uj, exociklusos (E,E)-cinnamiliden-ketonok előallitasara. E vegyuleteket kiindulasi anyagokkent hasznaltuk eddig ismeretlen sztiril-pirazolinok es tetraciklusos sztiril-1,5-benzotiazepinek előaalitasara. Resztesen tanulmanyztuk ezen telitetlen ketonok dimetildioxirannal tortenő epoxidalasat es az igy nyert epoxidik sztereokemiajat. | New 2-pyrazolines have been synthesized by the reaction of chalcones, (3-coumarinyl)-chalcones and unsaturated ketones derived from dehydroacetic acid with hydrazines. Reactions of these unsaturated ketones with (carboxyphenyl)hydrazines for the preapartion of hitherto unknown (carboxyphenyl)-2-pyrazolines should be emphesized. New types of pyrazoles have been prepared by the reaction of isoflavones, homoisoflavones and their 4-thio analogues with hydrazines. Tautomerism of these new substances have been elucidated by NMR spectrsocopy and quantumchemical calculations. Versatile procedures were worked out for the synthesis of new exocyclic (E,E)-cinnamylideneketones. These substances were utilized as starting materials for the synthesis of hitherto unknown styrylpyrazolines and tetracyclic styryl-1,5-benzothiazepines. Epoxidation of these (E,E)-cinnamylideneketones with dimethyldioxirane has been achieved.

New exocyclic alpha,beta,gamma,delta-unsaturated ketones have been synthesized by the base-catalyzed reaction of chromanone, flavanone, their 1-thio analogues and trans-cinnamaldehydes. These unsaturated ketones were reacted with diazomethane at ca. 4 degrees C to afford spiro-1-pyrazolines in regioselective and stereospecific reaction. Structure and stereochemistry of all these new compounds have been elucidated by combined utilization of various spectroscopic, mainly NMR techniques.

1-(2-Carboxyphenyl)- and 1-(4-carboxyphenyl)-2-pyrazolines have been synthesized by treatment of appropriate 3-aryl-1-(3-coumarinyl)propen-1-ones with (2-carboxyphenyl) hydrazine and (4-carboxyphenyl) hydrazine in hot acetic acid. The structures of all new 2-pyrazolines have been elucidated by microanalyses, IR, H-1- and C-13-NMR- spectroscopic measurements.

Hitherto unknown tetracyclic 1,5-benzothiazepines 9-16 have been synthesized by an acid-catalyzed reaction of exocyclic alpha,beta,gamma,delta-unsaturated ketones 1-8 and 2-aminothiophenol. Structures of all new compounds have been elucidated by microanalyses, H-1-, C-13-NMR, IR and mass spectroscopic measurements.

Diastereomeric mixtures of tricyclic 3‐styrylpyrazolines have been prepared by the reaction of 3‐cynnamylidenechroman‐4‐ones and their 1‐thio analogs with hydrazine in hot acetic acid or propionic acid solutions. The diastereomeric mixtures were separated by column chromatography to obtain the pure diastereomers. The elucidation of their structure and stereochemistry and complete 1H and 13C assignments have been performed by a combination of various one‐ and two‐dimensional NMR experiments. Copyright © 2008 John Wiley & Sons, Ltd.

This review describes synthetic procedures for the preparation of all the known benzocondensed derivatives of the 1,2-, 1,3- and 1,4-oxazepines. Examples for the most important chemical transformations of some benzoxazepine groups providing their useful derivatives have also been included. Owing to the huge number of papers in this field, it is not the aim of this review article to list and discuss all the papers published in the chemical literature.

3-(2-Aryl-2,3-dihydro-benzo[b][1,4]thiazepin-4-yl)chromen-2-ones (2a, e, f) and (Z)-3-(2,3-dihydro-2arylbenzo[b][1,4]thiazepin-4(5H)-ylidene)chroman-2-ones (3a-f) have been synthesized by the reaction of 3-aryl-1-(3-coumarinyl)propen-l-ones (la-f) with 2-aminothiophenol in a hot mixture of toluene and acetic acid. Structures of all new compounds and their complete H-1 and C-13 assignments were achieved applying different one- and two-dimensional nmr experiments in combination with various spectroscopic techniques.

The pathways of the ([M+H](+)) ions generated from electrosprayed solutions of nine 1,3,5-trisubstituted 2-pyrazoline derivatives were studied using energy-variable collision-induced dissociation (CID) and pseudo-MS(3) (in-source CID combined with MS/MS) methods. It was shown that under CID conditions several structurally important product ions such as the 2,4-substituted azete and 1,2-substituted aziridine ions were formed. The compositions of the product ions were unambiguously supported by accurate mass measurement (mass accuracy was within +/- 8 ppm). The fragmentation pathways of 1,3,5-trisubstituted 2-pyrazolines were established by means of pseudo-MS(3). It was found that a substituent at the N-1 position greatly affects the fragmentation pathways of the 2-pyrazoline derivatives. The 1-acetyl- and 1-propionyl-2-pyrazoline derivatives dissociate mainly through formation of a pyrazolium cation, while in the case of 1-phenyl-2-pyrazoline derivatives product ions arising from the consecutive fragmentation of 2,4-substituted azete and 1,2-substituted aziridine ions dominate. Another interesting finding is the formation of a radical cation from the 2,4-substituted azete by loss of a methyl radical. The fragmentation yield as a function of the collision energy for each of the 1,3,5-trisubstituted 2-pyrazolines was determined. Based on the fragmentation yield versus collision energy curves the relative fragmentation stabilities for the 1,3,5-trisubstituted 2-pyrazoline derivatives were also evaluated.

The reaction of dibenzylideneacetones or E,E-cinnamylidene- acetophenones and hydrazine hydrate provided 1-propionyl derivatives of 5-aryl-3-styryl-2-pyrazolines and 3-aryl-5-styryl-2-pyrazolines. These unsaturated ketones afforded 1-(2-carboxyphenyl) or 1-(4-carboxyphenyl) 5-aryl-3-styryl-2-pyrazolines and 1-(4-carboxyphenyl) derivatives of 3-aryl-5-styryl-2-pyrazolines on treatment with (2-carboxyphenyl)-hydrazine or (4-carboxyphenyl)hydrazine in hot acetic acid. Structures of all new 2-pyrazolines have been elucidated by microanalyses and a combined utilization of various spectroscopic methods.

4-Aryl-3(5)-2-(hydroxyphenyl)pyrazoles have been prepared by the reaction of isoflavones and their 4-thio analogues with hydrazine hydrate and phenylhydrazine in hot pyridine. The reaction mechanism for the formation of these pyrazoles is discussed. All the new compounds have been fully characterized by NMR spectroscopy. In [D6]DMSO, a 1H NMR study allows observation of the presence of both pyrazole annular tautomers, due to the presence of intramolecular hydrogen bonds in each tautomer (OH···N and NH···O). Theoretical calculations have been carried out on tautomers and conformers of compounds 20 (3(5)-(2-hydroxy-4-methoxyphenyl)-5(3)-methyl-4-phenylpyrazole) and 21 (3(5)-(2-hydroxy-4-methoxyphenyl)-4-(2-methoxyphenyl)-5(3)-methylpyrazole), including the absolute shieldings (GIAO/B3 LYP/6–311++G**) of 21.

(E,E)-Cinnamylideneacetophenones 3a-j were epoxidized under mild conditions with Jacobsen's catalyst 4 and hydrogen peroxide or iodosylbenzene as oxidants. gamma,delta-Monoepoxides and a diastereomeric mixture of alpha, beta:gamma,delta-diepoxides were obtained in each case, and only the alpha,beta-monoepoxide of 4-nitrocinnamylideneacetophenone (3d) was isolated. The presence of a methyl group in the vinylic moiety of substrates 3i,j allowed the formation of two gamma,delta-monoepoxide diastereomers. The epoxidation of (E,E)-2'-hydroxycinnamylideneacetophenones 3h,j led to the formation of the corresponding gamma,delta-monoepoxides as well as (E)-2,3-trans-3-hydroxy-2-styryl-4-chromanones, which originated from the in situ cyclisation of 2,3 -epoxy-1-(2-hydroxyphenyl)-5-phenyl-4-penten-1-ones. The structures of all new compounds and the stereochemistry of the mono- and diepoxide diastereomers were established by NMR studies. ((c) Wiley-VCH Verlag GmbH & Co.

The epoxidation of 2-styrylchromones 2a-h using Jacobsen's Mn(III)[salen] complex I as catalyst is reported for the first time. Several studies were performed using both hydrogen peroxide and iodosylbenzene as oxidants, in order to obtain the alpha,square-epoxy-2-styrylchromones 3a-h regioselectively. Due to the low reactivity of the substrates and the highly unstable character of the formed epoxides, reactions should be interrupted at lower conversions to obtain acceptable yields, especially when hydrogen peroxide is used.

The resistance to chemotherapy of cancer cells is mediated by the overexpression of P-glycoprotein, as an ATP-dependent membrane efflux pump. Two families of compounds have been screened, the cinnamylidenecycloalkanones and cinnamylidenebenzocycloalkanones, as promising multidrug resistance (MDR) reversal agents on mouse lymphoma and human colon cancer (COL0320) cell lines. The antiproliferative effects of the cinnamylidene derivatives were tested with the MTT method The MDR effect on drug accumulation was tested by flow cytometry. Combinations of resistance modifiers and cytostatics were tested on the two cell lines to obtain evidence for additive or synergistic interactions. Verapamil was applied as a resistance-modifying positive control. The best effects in the reversal of MDR in both cell lines were exhibited by the methoxy derivatives 2-(2-methaoxycinnamylidene)indan-1-one, 2-(2-methoxycinnamylidene)-3,4-dihydro-2H-naphthalen-1-one, 6-(2-methoxycinnamylidene)-6,7,8,9-tetrahydrocyclohepten-5-one), 2-cinnamylidene-3,4-dihydro-2H-naphthalen-1-one and 6-cinnamylidene-6,7,8,9-tetrahydrobenzocyclohepten-5-one. 2-(2-methoxycinnamylidene) indan-1-one and 2-(2-methoxy-cinnamylidene)-3,4-dihydro-2H-naphthalen-1-one were able to enhance the antiproliferative activity of doxorubicin in a synergistic way.