Synthesis,Characterization, and Spectroscopic Properties of Hexa(4-Bromo-2-Formyl-Phenoxy)Cyclotriphosphazene and Hexa(4-Chloro-2-Formyl-Phenoxy)Cyclotriphosphazene and Fully Substituted Cyclotriphosphazene Derivatives Bearing a Schiff Base at Room Temperature

Abstract

Hexa(4-bromo-2-formyl-phenoxy)cyclotriphosphazene (2) and hexa(4-chloro-2- formyl-phenoxy)cyclotriphosphazene (3) were obtained from the reactions of hexachloro- cyclotriphosphazene (1) with 5-bromosalicylaldehyde and 5-chlorosalicylaldehyde in the presence of (C₂H₅)₃N and K₂CO₃ at room temperature, respectively. The new two organocyclotriphosphazenes bearing formyl groups were reacted with 4-cyano aniline, 2-phenyl aniline, 4-aceto aniline, 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, 2-(4-morpholino)ethyl amine, 4-carboxy aniline, 4-carbomoyl aniline, 2-mercapto aniline, and 5-amino isoquonoline to prepare cyclotriphosphazene derivatives containing a Schiff base at room temperature. However, fully phenoxy-substituted cyclotriphosphazenes containing a Schiff base were isolated from the reactions of the compound 2 and 3 with 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, and 2-(4-morpholino)ethyl amine. The structures of the synthesized compounds were characterized by elemental analysis, IR, and NMR (¹H, ¹³C, ³¹P) spectroscopy. According to the results of the analysis, all synthesized compounds were found to be fully substituted organocyclotriphosphazenes, such as hexa[4-bromo-2-(5-chloro-2-hydroxy-pheyliminomethyl)phenoxy]cyclotriphosphaze (2a). All cyclotriphosphazene derivatives synthesized gave fluorescence emission peaks in range between 300 nm and 410 nm.     

Synthesis,characterization, and photophysical properties of paraben substituted cyclotriphosphazenes with hydrophilic side groups

Abstract

In this study, five new paraben substituted cyclotriphosphazene compounds containing hydrophilic glycol groups were successfully synthesized. All synthesized cyclotriphosphazene compounds 1-10 were fully characterized via general spectroscopic techniques such as ¹H, ³¹P NMR and MALDI-TOF mass spectrometry. In addition, the investigations of the UV-vis absorption and fluorescence emission properties of the 1-10 carried out via absorption and fluorescence spectroscopies in different solvents. The absorbance bands of the all synthesized compounds 1-10 were observed at about 230–300?nm in all solvents studied. Furthermore, the highest fluorescence emission intensity of the compounds 1-10 was observed in tetrahydrofuran at about 312?nm and the lowest emission intensity was observed in chloroform. The synthesized molecules can be used as custom designed molecules to investigate the DNA binding properties in automatic biosensor device in our laboratories, since they carry hydrophilic glycol units for water solubility and paraben derivatives for DNA effecting properties.     

Synthesis of a series of triple-bridged cyclotriphosphazene hexa-alkoxy derivatives and investigation of their structural and mesomorphic properties

Triple diamino-bridged cyclotriphosphazene (1) was reacted in a 1:8 stoichiometry with the sodium derivatives of long-chain diols [1-octanol, 1-decanol, 1-dodecanol, 1-hexadecanol] tetrahydrofuran (THF) at room temperature to form hexa-substituted cyclotriphosphazene derivatives (2, 3, 4 and 5, respectively), whose mesomorphic behaviours were investigated for their possible applications as liquid crystals. The cylindrical-type cyclotriphosphazene derivatives (2–5) were characterised by mass and elemental analyses and by Fourier transform infrared spectroscopy (FT-IR), ¹H and ³¹P {¹H} NMR spectroscopies. The thermal and mesomorphic properties were investigated by differential scanning calorimetry and by polarising optical microscopy, respectively. It was found that liquid crystal materials could be obtained from compounds 3 and 4 with alkoxy chains rather than using aromatic ring(s) as mesogens as published previously.     

Synthesis,structural characterization,and cytotoxic activity of new spirocyclic octachlorocyclotetraphosphazenes

Octachlorocyclotetraphosphazene, N₄P₄Cl₈, (1) was reacted with N, N′-dibenzylethylenediamine to synthesize partially substituted monospiro- (2), dispiro- (5) and tetraspirocyclotetraphosphazene (8) derivatives. The reactions of 2 and 5 with excess pyrrolidine and morpholine produced fully substituted pyrrolidino (3 and 6) and morpholino (4 and 7) spirocyclotetraphosphazenes. The structures of the compounds were determined with 1D (¹H, ¹³C, ³¹P, and DEPT) NMR, 2D (HSQC) NMR, ESI-MS, FTIR, and elemental analysis. The solid-state structures of 6 and 7 were examined by X-ray crystallography. In 7, intramolecular C-H…O hydrogen bonds link the molecules into centrosymmetric dimmers. The cytotoxic activity of all the compounds against human cervix carcinoma cell lines (HeLa) was investigated. The study showed that these compounds exert limited cytotoxic, apoptotic and necrotic effects on HeLa cancer cell lines.     

Synthesis of new monodendrons,gallic acid derivatives,self- assembled in a columnar phase

This article describes the synthesis and liquid crystal properties of new compounds that are derived from gallic acid. All the compounds were characterised by ¹H and ¹³C nuclear magnetic resonance spectroscopy (¹H NMR and ¹³C NMR), Infrared spectroscopy (IR) and Elemental analysis (CHN). The mesophases of these compounds were characterised using polarising optical microscopy (POM), differential scanning calorimetry (DSC) and SAXS measurements. The morphology of the surface of the films was investigated using atomic force microscopy (AFM). Compounds 9 and 13, which remain in a supercooled state until room temperature, do not exhibit liquid crystalline behaviour. The other compounds (i.e., 5, 7 and 8) self-assemble into tubular supramolecular architectures generating hexagonal columnar (Col_h) mesophases, which was confirmed by SAXS measurements.     

Synthesis,Characterization, and Activity of Cyclotriphosphazene-Cyclene Conjugates

Abstract

Two novel cyclotriphosphazene derivatives were synthesized from hexachloro cyclotriphosphzene. Their structures were characterized by ¹H, ³¹P, and ¹³C NMR spectroscopy as well as by IR spectroscopy and electrospray ionization-mass spectrometry (ESI-MS). The Zn complex of 4d was effective in hydrolytic DNA cleavage reactions.     

Concise Synthesis and Cellular Evaluation of 3′-Formyl-4′,6′-dihydroxy-2′-methoxy-5′-methylchalcone (FMC) and Its Analogues

3′-Formyl-4′,6′-dihydroxy-2′-methoxy-5′-methylchalcone (FMC) was a natural product isolated from Cleistocalyx operculatus. A four-step synthetic strategy toward FMC and its four analogues (1b–1e) was first developed. All compounds were synthesized from commercially available 2,4,6-trihydroxyacetophenone; formylation at 3′ position under Vilsmeier–Haack conditions was followed by the introduction of a methyl group at 5′ position. The key step of selective methylation at 2′ position was achieved by trimethylsilyldiazomethane (TMSCHN₂). Then substituted aromatic aldehydes were condensed through Claisen–Schmidt reaction in the presence of potassium hydroxide. All structures were confirmed by ¹H NMR, ¹³C NMR, and high-resolution mass spectra. FMC and analogues were screened for their antiproliferative activity.     

New Hydrazides and Thiosemicarbazides Derived from Ethylenedioxythiophene as Potential Anticonvulsants

A series of ethyl 7-({2-[(substituted)carbonyl]hydrazino}carbonyl)-2,3-dihydrothieno [3,4-b][1,4]dioxine-5-carboxylates (5–13) and ethyl 7-{[({2-[(substituted)carbonyl]hydra-zino}carbonothioyl)amino]carbonyl}-2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carboxy-lates (15–20) were synthesized in good yield by condensing ethyl-7-(chlorocarbonyl)-2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carboxylate (4) with suitable hydrazides. The newly synthesized compounds were characterized using FTIR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analyses. The anticonvulsant activity of all the title compounds was investigated against maximal electroshock-induced seizures (MES) and pentylenetetrazole (PTZ)-induced convulsion models. None of the compounds showed toxicity at the maximum dose of 2000 mg/kg. Almost all the compounds showed protection in flexion and extension stage against induced convulsion. Among them, naphthyloxy-substituted derivatives exhibited very good response against induced seizures.

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.     

The synthesis,structural characterization and biological evaluation of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives as potential anticancer agents

A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i and 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of ¹H NMR, ¹³C NMR, ¹⁹F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, ¹H–¹H correlation spectroscopy (COSY) and ¹H–¹³C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g , 4i , 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide ( 5h ) was the most active compound, with an IC₅₀ value of 2.84 μm . Compounds 4i , 5h and 5i had lower IC₅₀ values than that found for the clinically employed anticancer drug cisplatin (IC₅₀ = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and Biological Study of Some 4-oxo-Thiazolidine Derivatives of 2-Aminothiazole

Conventional and microwave assisted synthesis of new series of N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐5‐(substituted benzylidene)‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 5a–5m have been developed. The cycloaddition reaction of thioglycolic acid with N‐{2‐(substituted benzylidenehydrazino)‐ethyl}‐2‐aminothiazole 3a–3m in the presence of anhydrous ZnCl₂ afforded new heterocyclic compounds N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 4a–4m . The later product on treatment with several selected substituted aromatic aldehydes in the presence of C₂H₅ONa undergoes Knoevenagel reaction to yield 5a–5m . The structures of compounds 1 , 2 , 3a–3m , 4a–4m and 5a–5m were confirmed by IR, ¹H NMR, ¹³C NMR, FAB‐Mass and chemical analysis. All above compounds were screened for their antimicrobial activities against some selected bacteria and fungi and antituberculosis study against M. tuberculosis.     

New peripherally tetra-[trans-3,7-dimethyl-2,6-octadien-1-ol] substituted metallophthalocyanines: synthesis,characterization and catalytic activity studies on the oxidation of phenolic compounds

In this paper, we elucidated the synthesis, characterization, and investigation of catalytic activity studies of new metallophthalocyanines 4 and 5 as the catalyst for phenolic compounds oxidation by trying different types of oxygen sources. The structural characterization of the products was made by a combination of elemental analysis, FT-IR, LC-MS/MS (for phthalonitrile derivative 3), MALDI-TOF mass spectral data (for metallophthalocyanines 4–7), UV–vis spectroscopy (for metallophthalocyanines 4–7), ¹H NMR and ¹³C NMR spectroscopies (for compounds 3 and 6). The synthetic routes for the (trans-3,7-dimethyl-2,6-octadien-1-ol) substituted phthalonitrile derivative 3 and corresponding metallophthalocyanines 4–7 are outlined in Scheme 1. The MPc complexes 4–7 were synthesized via cyclotetramerization of compound 3 in the presence of the corresponding anhydrous metal salts (CoCl₂ for 4, CuCl₂ for 5, Zn(CH₃COO)₂ for 6 and MnCl₂ for 7) in dry n-pentanol as solvent and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as strong base at reflux temperature under nitrogen gas. Phthalocyanines and their metal complexes, in general, display poor solubility in most of the organic solvents, however, the synthesized metallophthalocyanine complexes 4–7 were highly soluble in common organic solvents because of the introduction of the methyl groups on alkyl chains of peripheral arms. The catalytic activity of compounds 4 and 5 was evaluated for the oxidation of phenolic compounds such as 4-nitrophenol, o-chlorophenol, 2,3-dichlorophenol, and p-methoxyphenol. CoPc 4 displayed good catalytic performance with a full oxidation of 4-nitrophenol into the corresponding benzoquinone and hydroquinone with the highest TON and TOF values within 3 h.     

CeCl3·7H2O Catalyzed,Microwave-Assisted High-Yield Synthesis of α-Aminophosphonates and their Biological Studies

Abstract

A new class of diethyl(3,5-dibromo-4-hydroxyphenylamino) (substituted phenyl/heterocyclic) methylphosphonates 4(a–j) has been synthesized by one-pot three component simultaneous reaction (Kabachnik–Fields) of 4-amino-2,6-dibromophenol 1, substituted heterocyclic/phenyl aldehydes 2(a–j), and diethylphosphite 3 using a Lewis acid catalyst, CeCl₃·7H₂O (5 mol%) under microwave irradiation as well as conventional conditions. It was observed that microwave irradiation method is more facile, efficient, and advantageous with respect to reaction time and yields. The structures of all the synthesized compounds were supported by analyzing IR, ¹H/¹³C/³¹P NMR, and mass spectral data. The synthesized compounds were screened for their in vitro antimicrobial and antioxidant activities.     

4-(取代嘧啶-2-基)-1-芳磺酰基氨基脲化合物的合成与表征

以取代的苯磺酰肼与(取代嘧啶-2-基)-氨基甲酸苯酯在非亲核性碱存在下合成了12个4-(取代嘧啶-2-基)-1-芳磺酰基氨基脲化合物5和3个5与碱形成的有机盐5as, 5bs和5cs. 所有合成化合物均经过元素分析和¹H NMR的结构确证. ¹H NMR数据证明, 在5as～5cs中, 磺酰氨基脲起到提供质子的作用.     

Synthesis,characterization, crystal structure,and antibacterial evaluation of Ni (II) complex with new dithiophosphorus compound

The reaction of 2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson^’s reagent) with phenylethylamine produced [H₃NCH₂CH₂C₆H₅]⁺ [(C₆H₅CH₂CH₂NH)(p C₆H₄OMe)PS₂]^? (1). Furthermore, reaction of 1 with NiCl₂ in dry methanol led to the novel complex 2. The compounds were characterized by ¹H and ³¹P NMR, IR spectroscopy, and elemental analysis. A single crystal X-ray structure of complex 2 showed that the nickel complex is square planar. The complex formed a supramolecular structure via intermolecular S1…H7B and O1…H2N2 hydrogen bonds. The X-ray crystallography of complex showed [R²₂](18) and R⁴₄(18) motifs in the monomers were connected to each other via S1…H7B, O1…H2N2 hydrogen bonds with donor–acceptor distance of 2.89 and 2.51 Å, respectively. The new compounds were additionally tested in view of their antibacterial properties.     

Synthesis,antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles

In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB) with MIC 12.5?μg/mL. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity.     

Synthesis and spectroscopic studies of diorganotin(IV) adducts based on cyclotriphosphazene scaffolds with exocyclic pyrazolyl substituents

Functionalized cyclotriphosphazenes with four pyrazolyl substituents have been employed for the synthesis of two new organotin complexes. These new compounds have been characterized by elemental analysis and IR, ¹H, ³¹P and ¹¹⁹Sn NMR spectroscopy. On the basis of these data, pyrazolylcyclotriphosphazene is bis-bidentate neutral ligand coordinating to two SnMe₂Cl₂ molecules in the resulting adducts. Coordination occurs only via the pyrazolyl nitrogens; cyclotriphosphazene ring nitrogens are not involved in coordination. The ¹¹⁹Sn NMR data are consistent with increasing of coordination number of tin(IV) in solution.     

Utilization of 2-substituted 3, 1-benzoxazin-4-ones in synthesis of some quinazoline annulated derivatives

Abstract

In this study, a new series of quinazoline and their annulated derivatives have been synthesized. A number of quiazolinone derivatives substituted at position-3 were prepared from 3, 1-benzoxazinone by the treatment of 3,1-benzoxazinone with different nitrogen nucleophiles such as, hydrazine hydrate, phenylhydrazine, ethanolamine, and cyano acetohydrazide afforded the quinazolinone derivatives 7–11. The reaction of hydrazide derivative 5 with aromatic aldehydes gave the Schiff’s bases derivative 16a–c. Some of the synthesized compounds were tested against the breast cancer cell line (MCF-7). The structures of all the newly synthesized compounds were established based on IR, ¹H, ¹³C NMR, mass spectral data, and elemental analyses.     

Ketene dithioacetal mediated synthesis of 1,3,4,5-tetrasubstituted pyrazole derivatives and their biological evaluation

Abstract

Ketene dithioacetal mediated chemo- and regioselective synthesis of a series of novel 1,3,4,5-tetrasubstituted pyrazole derivatives (4a-l) integrated with a bioactive indole nucleus was achieved by reacting substituted 2-(1-methyl-1H-indole-3-carbonyl)-3,3-bis-(methylthio)-acrylonitrile (2) and substituted phenyl hydrazine hydrochloride (3) in the presence of a catalytic amount of anhydrous K₂CO₃ under reflux conditions. The structures were ascertained by ¹H NMR, NOESY, ¹³C NMR, FT-IR, and HRMS data. In vitro cytotoxicity evaluation of the synthesized compounds against MCF 7 (breast carcinoma) and normal Vero (monkey kidney) cell lines revealed that the compound 5-(5-Bromo-1-methyl-1H-indol-3-yl)-1-(4-cyano-phenyl)-3-methylsulfanyl-1H-pyrazole-4-carbonitrile (4k) showed significant cytotoxicity against MCF 7 (GI₅₀ = 15.6 µM) with low cytotoxicity against normal Vero cell line. Most of the synthesized compounds were also found to possess excellent anti-inflammatory and antioxidant (DPPH, NO, H₂O₂ and SOR) potential.     

Synthesis of spirooxindoles promoted by the deep eutectic solvent,ZnCl2+urea via the pseudo four-component reaction: anticancer,antioxidant, and molecular docking studies

Abstract

Various spirooxindoles (7a–c, 8a–c, 9a–c, and 10a–c) were efficiently synthesized using deep eutectic solvent ZnCl₂+urea and well characterized using IR, ¹H NMR, and ¹³C NMR spectroscopic techniques. The biological screening results showed that the compound 9a exhibited potent anticancer activity against MCF7 and HeLa cell lines with IC₅₀ values 6.47?±?0.01 and 9.14?±?0.32?µM, respectively. The compound 7c exhibited potent activity against the HeLa cell line with IC₅₀ value 6.81?±?0.01?µM. The compound 9a exhibited a potent antioxidant activity with IC₅₀ value 7.34?±?0.17?µM. The comparative molecular docking study against the cancer proteins EGFR and HER2 revealed that the EGFR was the best target protein receptor for the target compounds. Among all the compounds, the compound 9a exhibited the least binding energy ?10.72?kcal/mol against the protein EGFR (PDB ID: 4HJO).     

Novel and Efficient Synthesis of 4-Indazolyl-1,3,4-trisubstituted Pyrazole Derivatives

In the present study, 1-(4,5-dihydro-3,6-dimethyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)-3aH-indazol-5-yl)methanone derivatives (9–12) and isoxazoleyl (13–16) have been synthesized by the condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1–4) with acetyl acetone via Knoevenagel/Michael/aldol reactions in a sequential manner to yield intermediate cyclohexanone (5–8). The intermediates (5–8) treated with NH₂NH₂ · H₂O/NH₂OH · HCl afforded 4-indazolyl-1,3,4-trisubstituted pyrazole and isoxazoleyl derivatives. All of these compounds are reported for the first time, and the structures of these compounds were confirmed by means of infrared, ¹H NMR, ¹³C NMR, and mass spectroscopy.