Efficient synthesis of methyl 4-chloro-6-fluoro-3-formyl-2H-chromene-2-carboxylate and its derivatives

Abstract  

Methyl 4-chloro-6-fluoro-3-formyl-2H-chromene-2-carboxylate was synthesized conveniently using Vilsmeier reagent. A series of new 2H-chromenes was prepared in high yields by introducing a corresponding β-halovinylaldehyde into condensation and cyclization reactions with active methylene compounds.     

Synthesis, reactions, and biological activity of 1,4-benzothiazine derivatives

Abstract  

6,7-Dimethoxy-2H-1,4-benzothiazin-3(4H)-one reacts with dimethylformamide dimethylacetal (DMF-DMA) to give the novel enaminone 2-(dimethylaminomethylene)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-one. The reaction of the latter with various active methylene compounds afforded pyrido[3,2-b][1,4]benzothiazines. Also, coupling of the enaminone with diazotized aniline derivatives gave 2-(arylhydrazono)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-ones. Spectral data indicated that the latter compounds exist predominantly in the hydrazone tautomeric form. In addition, coupling of the enaminone with diazotized heterocyclic amines afforded tetra- and pentaheterocyclic ring systems. The antitumor and antimicrobial activity of some of the synthesized compounds was screened.     

Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)-benzothiazolone derivatives

Abstract  

A simpler and efficient “green” method using solid sodium hydroxide in a solvent mixture of acetone/water was found to catalyze N-acylation of 2(3H)-benzoxazolones and 2(3H)-benzothiazolones for facile and rapid synthesis of N-acyl derivatives in excellent yields. This method was applied to the synthesis of a series of 132 compounds employing a variety of acyl chlorides.     

Synthesis, chemical properties, and antimicrobial activity of 2- and 2,3-substituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones

Abstract  

Mono- and disubstituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones were synthesized by the reaction of dihydro-1-(3-hydroxy- and 4-hydroxyphenyl)pyrimidine-2,4(1H,3H)-diones and their 5- and 6-methyl derivatives with 2,3-dichloro-1,4-naphthoquinone. Their stability in alkaline and acidic media was investigated. Four of the compounds exhibited good antimicrobial activity against Staphylococcus aureus, Mycobacterium luteum, Candida tenuis, and Aspergillus niger.     

Synthesis of alkaloid-like compounds via the bridging Ritter reaction

Abstract  

Alkaloid-like compounds containing a benzo[c]azepine core structure were successfully prepared in three steps from 5H-dibenzo[a,d]cyclohepten-5-ol via the bridging Ritter reaction. Biological studies of these compounds revealed that some of them are AChE inhibitors and antimalarial agents.     

Light-induced dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones

Abstract  

UV light irradiation of Biginelli 3,4-dihydropyrimidin-2(1H)-ones in chloroform in an argon atmosphere leads to dehydrogenation of these compounds to their corresponding pyrimidin-2(1H)-ones in excellent yields. Irradiation in the same solvent under an oxygen atmosphere generates, in addition, various hitherto unidentified products. A light-induced electron transfer from the substrate to the solvent is proposed as the initial event, supported by the detection of dichloromethane and hydrogen chloride in the photolysate.     

A facile and efficient method for synthesis of xanthone derivatives catalyzed by HBF4/SiO2 under solvent-free conditions

Abstract  

HBF₄/SiO₂ was used as an efficient, green, and inexpensive catalytic system for synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-one derivatives via a one-pot three-component reaction of aldehydes, 2-naphthol, and cyclic 1,3-dicarbonyl compounds. The reactions proceeded rapidly at 80 °C under solvent-free conditions and the desired products were obtained in good to excellent yields.     

Synthesis of novel 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones via azo coupling

Abstract  

6-(Substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones were prepared from β-aryl glutaconic acid, which, on fusion with aniline, results in 4-(4-ethoxyphenyl)-1-phenylpyridine-2,6(1H,5H)-dione. This, on further treatment with phosphorus oxychloride gave 6-chloro-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinone, and further treatment with secondary amines yielded 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones. These were subjected to azo coupling with different aryldiazonium chlorides furnishing two isomers, which were separated by column chromatography. All compounds were characterized by elemental analysis, and use of IR and NMR spectral data, and were evaluated for antimicrobial activity.     

Synthesis and anticancer activity of some 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines

Abstract  

The deregulation of cell cycle components in cancer cells has provided a rationale for the development of small molecule inhibitors of cyclin-dependent kinases as novel anticancer drugs. A series of 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines was synthesized and their kinase inhibitory activity and cytotoxicity against several cancer cell lines has been evaluated. Some of the compounds of the series exhibited induction of caspase-dependent cell death and inhibition of cyclin-dependent kinase 2 (CDK2).     

Structural effects on the solid-state photodimerization of 5-chloro and 5-nitro-2(1<Emphasis Type="Italic">H</Emphasis>)-pyridone in molecular compounds

Abstract  

The preparation and crystal structure of six molecular compounds consist of light-stable host molecules [(1-cyclohexyl-4-hydroxybenzene, 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol, 4-((10-[4-(ethoxycarbonyl)phenoxy]decyl)oxy)benzene, 1,2,4,5-benzenetetracarboxylic acid, resorcinol] and light-sensitive guest molecules [(5-chloro-2(1H)-pyridone or 5-nitro-2(1H)-pyridone] are described in light of their failure to undergo [4 + 4] photodimerization in the solid-state upon irradiation with UV light. Unlike in many cases were pyridone and its derivatives undergo such dimerization in the solid-state due to the packing arrangement in the crystalline form in which the geometric requirement for photodimerization meet, the compounds described here failed to pack in ways to enable such photodimerization. The distances between the potentially reactive atoms ranged from 4.620 to 8.408 ? which are too long to react.     

The synthesis of azole derivatives from 3-[(4-methylphenyl)amino]propanehydrazide and its N′-phenylcarbamoyl derivatives, and their antibacterial activity

Abstract  

5-[2-[(4-Methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-thione, 5-[2-[(4-methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-one, N-(2,5-dimethyl-1H-pyrrol-1-yl)-3-[(4-methylphenyl)amino]propanamide, and a series of N-[(phenylcarbamoyl)amino]-3-[(4-methylphenyl)amino]propanamides and 3-[(4-methylphenyl)(phenylcarbamoyl)amino]-N-[(phenylcarbamoyl)amino]propanamides, and their thio analogues were synthesized from 3-[(4-methylphenyl)amino]propanehydrazide. 1,3,4-Oxadiazole-2(3H)-thione was converted to 4-amino-2,4-dihydro-5-[2-[(4-methylphenyl)amino]ethyl]-3H-1,2,4-triazole-3-thione, whereas cyclization of N′-phenylcarbamoyl derivatives provided thiazole, oxadiazoles, and thiadiazole, as well as triazole derivatives. Two of the synthesized compounds exhibited good antibacterial activity against Rhizobium radiobacter.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones

Abstract  

The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species.     

Facile microwave-assisted synthesis of bis-pyrazol pyrimidine derivatives via an <Emphasis Type="Italic">N</Emphasis>-alkylation reaction

Abstract  

We present herein a new and efficient method for synthesis of bis-pyrazol pyrimidine derivatives by N-alkylation using a microwave-assisted synthetic process. Two new compounds, N-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl nicotinonitrile and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-4-methyl nicotinonitrile, were synthesized by the N-alkylation reaction. The novel compounds were characterized by Fourier transform infrared spectrometry, ultraviolet spectroscopy, elemental analysis, and nuclear magnetic resonance spectroscopy, etc. The microwave-assisted procedures have noteworthy advantages in terms of thermal efficiency over those carried out by conventional heating methods.     

Synthesis and biological activity of novel 4- and 6-(1-alkyl/aryl-1H-benzimidazol-2-yl)benzene-1,3-diols

Abstract  

A one-pot synthesis of new biologically active 4- and 6-(1-alkyl/aryl-1H-benzimidazol-2-yl)benzene-1,3-diols has been developed. The compounds were obtained by the reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione] with N-substituted benzene-1,2-diamines. Elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectral data were used to elucidate their structures. The developed method offers short reaction times, easy and quick isolation of the products, and good yields. The antiproliferative properties of the synthesized compounds were investigated against a panel of human cancer cell lines. Some of the tested compounds showed significant cytotoxic activity.     

An experimental NMR and computational study of 4-quinolones and related compounds

Abstract  

We report the synthesis and structural study of eight compounds, either quinolin-4(1H)-ones or quinolines. Tautomerism as well as (E) → (Z) and rotational isomerism were studied both experimentally (¹H and ¹³C NMR) and theoretically [B3LYP/6-311++G(d,p)].     

Benzenedicarboxylate-modulated zinc(II)-3,5-bis(3-pyridyl)-1H-1,2,4-triazole frameworks: syntheses, structures and luminescent properties

Abstract  

Based on the polydentate ligand 3,5-bis(3-pyridyl)-1H-1,2,4-triazole (3,3′-Hbpt), three coordination compounds [Zn(3,3′-Hbpt)(ip)]·2H₂O (1), [Zn(3,3′-Hbpt)(5-NO₂-ip)]·H₂O (2), and [Zn(3,3′-Hbpt)₂(H₂pm)(H₂O)₂]·2H₂O (3) have been hydrothermally constructed with H₂ip, 5-NO₂-H₂ip and H₄pm as auxiliary ligands (H₂ip = isophthalic acid, 5-NO₂-H₂ip = 5-NO₂-isophthalic acid, H₄pm = pyromellitic acid). Structural analysis reveals that Zn(II) ions serve as four-coordinated, five-coordinated, and six-coordinated connectors in 1–3, respectively, while 3,3′-Hbpt adopts μ-N_py and N_py coordination modes in two typical conformations in these target coordination compounds. Dependently the applied ligand, compounds 1–3 exhibit either 1D channel, cage or chain structures, respectively. In addition, the luminescence properties of 1–3 have been investigated in the solid state at room temperature.     

Synthesis of imidazo[4,5-a]acridones and imidazo[4,5-a]acridines as potential antibacterial agents

Abstract  

New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug.     

A facile and expeditious approach for the synthesis of 2-azetidinone derivatives via a multicomponent reaction

Abstract  

New organic reactions allow chemical transformations which were previously unknown. Therefore, new reactions are important contributions to progress in the field of organic synthesis. Herein, we are reporting a simple, one-pot, efficient three-component synthesis of novel 3-chloro-4-[4-(2-oxo-2H-chromen-4-ylmethoxy)phenyl]-1-phenylazetidin-2-one derivatives using 4-(2-oxo-2H-chromen-4-ylmethoxy)benzaldehydes, anilines, and chloroacetyl chloride in the presence of triethyl amine as a catalyst under different conditions. Taking into account environmental and economic considerations, the protocol presented here has the merits of simple operation, convenient work-up, being environmentally benign, and providing good yields. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis.     

Aldimines of 5-aminouracil as reagents in 1,3-dipolar cycloaddition reaction

Abstract  

The condensation of 5-aminouracil with aromatic aldehydes gave the appropriate C-arylimines, which were used in [2+3] cycloaddition with nitrile oxides derived from 4-substituted benzaldoximes. As a result of the dipolar cycloaddition reaction several hitherto unknown 5-(3,5-diphenyl-1,2,4-oxadiazol-4(5H)-yl)pyrimidine-2,4(1H,3H)-diones have been obtained in satisfactory yields.     

Derivatives of 5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione: design, synthesis, and biological activity

Abstract  

A series of mono and bis-2-(2-(dimethylamino)-ethyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-diones with different amino side chains, a novel family of antitumor agents, has been designed and synthesized. Their antitumor activity was evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8, and A375 cancer cell lines in vitro. Preliminary results showed that most of the derivatives had antitumor activity comparable with that of mitonafide, with IC ₅₀ values of 10⁻⁶–10⁻⁵ M. More importantly, the derivatives had distinct antitumor selectivity against different cancer cell lines. This work provided a novel class of mitonafide-based lead compounds with improved antitumor selectivity against cancer cell lines for further optimization.