A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Synthesis of Novel 2-(4-Oxo-3,4- Dihydroquinazolin-2-Ylsulfinylmethyl)-3H-Quinazolin-4-One

Abstract

Condensation of 2-mercapto-3H-quinazolin-4-one (1) with chloroacetic acid gave 4-oxo-3,4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid (2) that with anthranilamide (3) gave 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-quinazolin-4-one (4). Oxidation of 4 with sodium hypochlorite in alkaline medium gave the novel product, 2-(4-oxo-3,4- dihydroquinazolin-2-ylsulfinyl methyl)-3H -quinazolin-4-one) (5). The entire sequences of reactions in this work have been carried out using eco-friendly solvents and green conditions.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应, 合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m. 化合物结构经元素分析, ¹H NMR, IR和MS进行了表征. 抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

Prins-Reaktionen mit Arylaldehyden, 4. Mitt.: 2,4-Diphenylhexahydro-4H-1,3-benzodioxine

The four diastereomeric 2-(hydroxyphenylmethyl)cyclohexanols2a-2d are prepared. By reaction with benzaldehyde each2a-2c gives stereospecifically only one of the two possible configurationally correlated 2,4-diphenylhexahydro-4H-1,3-benzodioxins3a-3c. However, from (1RS, 2SR)-2 [(SR)-hydroxyphenylmethyl]cyclohexanol (2d) both dioxins3d and3e are obtained. The configurational assignments are based on¹H-NMR spectroscopy and synthetic correlations. Conformational aspects are discussed. As is shown by chromatography, inPrins reactions of cyclohexene with benzaldehyde only one dioxin3c is formed.     

Synthesis and Spectral Characterization of Some New 4-(2,6-Diarylpyridin-4-yl)-2H-chromen-2-ones

Some new 4-(2,6-diarylpyridin-4-yl)-2H-chromen-2-one derivatives 5a–l have been synthesized by reacting 4-(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-ones 3a–c with appropriate 1-(2-oxo-2-arylethyl)pyridinium bromide salt 4a–d in the presence of ammonium acetate in refluxing glacial acetic acid. The newly synthesized compounds have been characterized by elemental and spectral analysis.     

Synthesis and antimicrobial activity of new 2-((1-furan-2-yl)ethylidene)hydrazono)-4-phenylthiazol-3(2H)-amine derivatives and their schiff bases with 4-nitrobenzaldehyde

Abstract

A new series of 2-((1-furan-2-yl)ethylidene)hydrazono)-4-substitutedphenylthiazol-3(2H)-amines (2a–2o) and their Schiff bases (3a–3o) from 4-nitrobenzaldehyde were synthesized. The chemical structures of all the synthesized compounds were confirmed by their IR, ¹H-NMR, ¹³C-NMR spectroscopy and mass spectrometry. They were screened for their antimicrobial and antifungal activities. Additionally, in vitro cytotoxic acivity of the most active antifungal compound (3o) and ketoconazole was determined in NIH/3T3 cells by MTT assay. Compound 2i (4-{3-Amino-2-[(1-(furan-2-yl)ethylidene)hydrazono]-2,3-dihydrothiazol-4-yl}phenol) showed the greatest antifungal activity among the newly synthesized derivatives. Schiff bases (3c-3n) displayed an undeniable fungicidal action against Candida parapsilosis ATCC 22019 as intense as the reference ketoconazole. In addition, the most active Schiff base 3o (2-[(1-(Furan-2-yl)ethylidene)hydrazono]-N-(4-nitrobenzylidene)-4-(2,3,4-trichloro phenyl)thiazol-3(2H)-amine) showed the highest antifungal activity against both Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019, and was as potent as ketoconazole. Moreover, compound 3o was found to be non-cytotoxic against NIH/3T3 cells.     

Synthesis, spectroscopic properties and crystal structure determination of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives

Substituted 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives 2, 3 and 6 were synthesized. 2-(2-Pyridin-4-yl-vinyl)-1H-benzimidazole 2 and 6-methyl-2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 3 were prepared by condensation reaction from 3-pyridin-4-yl-acrylic acid and corresponding 1,2-phenylenediamines in polyphosporic acid (PPA). 2,7,11-b-Triaza-benzo[c]fluorene 4 was prepared by photochemical dehydrocyclization reaction of ethanolic solution of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2. 2-(2-Pyridin-4-yl-vinyl)-3H-benzimidazole-6-carbonitrile 6 was prepared by condensation reaction from 3-pyridin-4-yl-propenal and 4-cyano-1,2-phenylenediamine using p-benzoquinone as oxidants. The structure of novel benzimidazole derivatives has been studied by ¹H and ¹³C NMR, IR, MS, UV/Vis and fluorescence spectroscopy. The structure of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2 was confirmed by X-ray single crystal structure analysis. The conformation of the molecule is E in regard to substituents position around vinyl double C=C bond. The non-planar molecules are mutually connected via the N–H···N and C–H···N type of intermolecular hydrogen bonds into infinite chains spreading along y axis.     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

Crystal structures of 4-(oxiran-2-ylmethoxy) benzoic acid and 4-acetoxybenzoic acid

Compounds 4-(oxiran-2-ylmethoxy)benzoic acid (2) and 4-acetoxybenzoic acid (4) are synthesized by a new synthetic route and studied by X-ray crystallography. Compound 2 crystallizes in the monoclinic system, P2₁/n space group, a = 5.1209(2) ?, b = 30.3429(16) ?, c = 5.9153(3) ?, β = 96.725(3)°, V = 912.81(8) ?³, Z = 4. Compound 4 crystallizes in the triclinic system, P-1 space group, a = 7.3400(4) ?, b = 8.0819(3) ?, c = 15.6548(9) ?, α = 85.754(3)°, β = 84.268(2)°, γ = 70.023(3)°, V = 867.63(8) ?³, Z = 4. The crystal structure of 2 comprises two crystallographically independent molecules of the compound. In the crystal structures of 2 and 4, pairs of molecules form carboxyl dimers.     

2-(2-Hydroxy-4-methoxybenzoyl)benzoic acid derivatives of Group 4 metal alkoxides

Continued exploration of the coordination behavior of derivatives of 2-benzophenone-based ligands with metal alkoxides ([M(OR)₄]) was undertaken from the reaction of 2-(2-hydroxy-4-methoxybenzoyl)benzoic acid (H₂-OBzA) with a series of Group 4 precursors. The products of these reactions were identified as: [(OR)₂Ti(μ-(c,c-OBzA))]₂ (OR?=?OCHMe₂ (OPrⁱ; 1 ?2tol); OCMe₃ (OBu^t; 2 ?THF); OCH₂CMe₃ (ONep; 3)), [[(OPrⁱ)₃Ti(μ-OPrⁱ)Ti(OPrⁱ)₂]₂(μ-(μ_c,μ-OBzA))₂]₂ (4), [(ONep)₃Zr(μ-ONep)₂Zr(ONep)₂]₂(μ-(c,μ-OBzA)₂) (5 ?tol), [(py)(OBu^t)₃Zr]₂(μ-(c,c-OBzA)) (6), [(OBu^t)₂Hf(μ-OBu^t)]₂(μ-(c,η¹-OBzA)) (7) where ‘c’?=?chelating or η²; ‘μ’?=?bridging or η¹,η¹(O,O’); and μ_c?=?bridging chelating or η¹,η¹(O,O’); η^2?:?η¹. The metal centers for each of these compounds adopt a pseudo-octahedral geometry employing the OBzA ligand in numerous binding modes. The different functional oxygens (carboxylate, hydroxyl, and carbonyl) were employed in a variety of coordination modes for 1–7. The complexity of these OBzA-modified compounds is driven by a combination of the coordination behavior of the OBzA moieties, the size of the metal cation, and the pendant chain of the OR ligand. Solution NMR indicates a complex structure exists in solution that was considered to be consistent with the solid-state structure.     

Synthese von 4H-Pyrano[2,3-d]pyrimidinen

Summary Good yields of substituted 5-(5R-2-furyl)-4H-pyrano[2,3-d]pyrimidines4 were obtained in the reaction of 2-ethoxymethyleneamino-3-cyano-4H-pyranes2 with ammonia. Compounds2 were prepared by the condensation of the starting 2-amino-5-acetyl-3-cyano-6-methyl-4H-pyranes1 with ethyl orthoformate. Spectral properties of the bicyclic system4 in relation to compounds3 are discussed.

     

Synthesis of 2-acetyl-3-methyl-4H-1,4-benzothiazine and its derivatives

Summary 2-Aminothiophenol (1) reacts with 3-chloro-2,4-pentanedione (2) in the presence of pyridine to form 2-acetyl-3-methyl-4H-1,4-benzothiazine (3) in high yields. Reaction of3 with hydrazine gives 4-(2-aminophenylthio)-3,5-dimethylpyrazole (5). Condensation of3 with 4-nitrobenzaldehyde yields the corresponding Schiff base7. Hydroxylamine with benzothiazine3 affords 3,9a-dimethyl-3a, 9a-dihydro-9H-isoxazolo[4,5-b][1,4]benzothiazine (8).

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Synthese von 2-Acetyl-3-methyl-4H-1, 4-benzothiazin und seinen Derivaten

Zusammenfassung 2-Aminothiophenol (1) reagiert mit 3-Chlor-2,4-pentandion (2) in Anwesenheit von Pyridin unter Bildung von 2-Acetyl-3-methyl-4H-1,4-benzothiazin (3) in sehr hoher Ausbeute. Benzothiazin3 kondensiert mit Hydrazin zu 4-(2-Aminophenylthio)-3,5-dimethylpyrazol (5), dessen Aminogruppe reagiert mit 4-Nitrobenzaldehyd zu einer Schiffschen Base (7), die spektroskopisch charakterisiert wurde. Benzothiazin3 mit Hydroxylamin ergibt 3,9a-Dimethyl-3a,9a-dihydro-9H-isoxazolo[4,5-b][1,4]benzothiazin (8). Die Stereochemie der letztgenannten Verbindung wurde ermittelt.

     

The substituent effect on mesomorphic properties of 4-octyloxyphenyl 4-(4-R-3-nitrobenzoyloxy)benzoates and 4-(4-octyloxybenzoyloxy)phenyl 4-R-3-nitrobenzoates

Abstract

The thermal properties of 4-octyloxyphenyl 4-(4-R-3-nitrobenzoyloxy) benzo-ates (1) and 4-(4-octyloxybenzoyloxy)phenyl 4-R-3-nitrobenzoates (2) have been examined, where R = hydrogen, halogens, alkyl and alkoxy groups. The derivatives of compound 1 incorporating hydrogen, halogens, methoxy and nitro groups show a smectic A phase having a bilayer arrangement, and the others with a long alkoxy group show the S_A phase with the monolayer arrangement. The derivatives of compound 2 incorporating halogens, and the nitro group show the S_A phase with the monolayer arrangement. The alkoxy derivatives show a smectic C phase as well as the nematic phase. The nitro group at the lateral position tends to increase the ratio of the S_A-N transition temperature to the N-I. The effect of the nitro group on the smectic properties has been discussed in terms of the structural and electrostatic nature of the nitro group.     

Synthetic Studies on Sialoglycoconjugates 44: Synthesis of KDN-Gangliosides Gm4 and GM3

Abstract

Ganglioside GM₄ and GM₃ analogs, containing 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid (KDN) in place of N-acetylneuraminic acid, have been synthesized. KDN, prepared by the condensation of oxalacetic acid with D-mannose, was converted into methyl (phenyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate (2) via methyl esterification, O-acetylation and replacement of the anomeric acetoxy group with phenyl thio. Glycosylation of 2 with 2-(trimethylsilyl)ethyl 6-O-benzoyl-β-D-galactopyranoside (3) or 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-2,6-di-O-benzoyl-β-D-glucopyranoside (4) was performed, using N-iodosuccinimide-trimethylsilyl trifluoromethanesulfonate as the glycosyl promoter, to give 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-6-O-benzoyl-β-D-galacto-pyranoside (5) and 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-(6-O-benzoyl-β-D-galactopyrano-syl)-(l→4)-(2,6-di-O-benzoyl-β-D-glucopyranoside (9), respectively. Compounds 5 and 9 were converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the corresponding trichloroacetimidates 8 and 12, respectively. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (13) with 8 and 12 in the presence of boron trifluoride etherate afforded the expected β-glycosides 14 and 17, which were transformed via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation and de-esterification, into the target gangliosides 16 and 19 in high yields.     

Synthesis and biological evaluation of 5-methyl-4-phenyl thiazole derivatives as anticancer agents

Abstract

New N-(5-methyl-4-phenylthiazol-2-yl)-2-(substituted thio)acetamides were synthesized and studied for their anticancer activity. The title compounds were procured by reacting 2-chloro-N-(5-methyl-4-phenylthiazol-2-yl)acetamide with some mercapto derivatives. The structural elucidation of the compounds was performed by ¹H-NMR, ¹³C-NMR and LC-MS/MS spectral data and elemental analyses. The synthesized compounds were investigated for their antitumor activities against A549 human lung adenocarcinoma cells and NIH/3T3 mouse embryoblast cell line for determining their selective cytotoxicity. 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N-(5-methyl-4-phenylthiazol-2-yl)acetamide (4c) showed high selectivity, and whose IC₅₀ value was determined as 23.30?±?0.35?µM and >1000?µM against A549 human lung adenocarcinoma cells and NIH/3T3 mouse embryoblast cell lines, respectively. 2-[(1-Methyl-1H-imidazol-2-yl)thio]-N-(5-methyl-4-phenyl thiazol-2-yl)acetamide (4a) and 2-[(1-Methyl-1H-tetrazol-5-yl)thio]-N-(5-methyl-4-phenyl thiazol-2-yl)acetamide (4c) exhibited the highest apoptosis percentage among those tested, but not as high as the standard, cisplatin.     

Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

Zur Synthese der 4-Dialkylamino-5,6-dihydro-2(1H)-pyridinthione sowie entsprechender 4-Alkylamino- bzw. 4-Arylaminoverbindungen

The rearrangement of 1-alkyl- and 1-aryldihydro-6-methyl-2(1H)-pyrimidinethiones (1 a) or-ones (1 b) and of methylene compounds (2a, 2b) resp., to 4-alkylamino- and 4-arylaminodihydro-2(1H)-pyridinethiones (4 a) or-ones (4 b) takes place via the corresponding 3-alkylamino- and 3-aryl-amino-3-butenylisothiocyanates (3 a) or-isocyanates (3 b). Dialkylamino-dihydro-2(1H)-pyridinethiones (10) are formed by heating dihydro-6-methyl-2(1H)-pyrimidinethiones (6 a) and 3,4-dihydro-6-methyl-1,3-thiazin-2-thiones (6 b) with dialkylformamides and by the reaction of secondary amines with tetrahydro-6-hydroxy-6-methyl-1,3-thiazin-2-thiones (5 a), with N,N-dialkyl-N-(3-oxobutyl)-thioureas (7) and 3-oxobutyl isothiocyanates (8). A general method for the preparation of10 is the reaction of dialkylammoniumrhodanides12, N,N-dialkylthioureas13 and dialkylammonium chlorides and KCNS, resp., with 3-alken-2-ones14 and 4-hydroxy-2-alkanones15, resp. Methyl ketones such as acetone, which readily undergo the aldol condensation, behave analogously. The reactions described take place via the intermediate aminoalkenyl isothiocyanates (9).     

Conformationally Restricted Analogues of Tryptophan: Synthesis of Chiral 3-Amino-4-indolyl-2-piperidones

Abstract

The {Trp-phenylglycinol} pseudodipeptide (αR,3R?,4R?)-N-(2-acetoxy-1-phenylethyl)-3-amino-4-indolyl-2-piperidone 33 has been synthezised by condensation of the 3-amino-substituted anhydride 30 with (R)-(-)-phenylglycinol followed by reduction of the resulting imide.     

Synthesis and anticancer activity evaluation of 3-(4-oxo-2-thioxothiazolidin-5-yl)-1H-indole-carboxylic acids derivatives

Abstract

A mild and efficient method for the synthesis of 1-oxo-9H-thiopyrano[3,4-b]indole-3-carboxylic acids and dimerized 3-(4-carboxy-1H-3-indolyl)-2-propenoic acids via alkaline hydrolysis of 3-(rhodanin-5-yl)-1H-indole-2-carboxylic acids derivatives was elaborated. Anticancer activity screening in NCI60-cell lines assay allowed identification of 5-fluoro-3-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-1H-indole-2-carboxylic acid methyl ester 2a with significant antimitotic activity at micromolar and submicromolar concentrations.     

杂金属杯[4]配位聚合物的合成与表征

合成了4个杂金属杯[4]配位聚合物{[Cd（L）（tpa）]·3H₂O}_n（1）,{[Zn2（L）₂（tpa）₂]·3H₂O}_n（2）,{[Co（L）（oba）]·2DMA·0.5H₂O}_n（3）和{[Zn（L）（oba）]·DMA}_n（4）（L=2-（1H-咪唑基-甲基）-6-（3-（1H-咪唑基-甲基）-5-叔丁基-2-羟基）苄基-4-叔丁基苯酚,H₂tpa=对苯二甲酸,H₂oba=4,4''-二苯醚二甲酸）,并通过元素分析、热重、红外光谱、固态紫外、单晶X射线衍射和粉末X射线衍射对其进行了表征。单晶结构分析表明晶体1是单斜晶系,P2₁/n空间群,而晶体2,3和4均为三斜晶系,P1空间群。化合物1,2,3和4是由0维[M（N₄O₂C₂₉H₃₆）]（M=Zn,Co,Cd）的杂金属杯[4]与配体对苯二甲酸和4,4''-二苯醚二甲酸形成的一维配位聚合物。