Synthesis of 1,3,3a,5‐tetraaryl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a] [1,5]benzodiazepines

A series of 3a,5‐diaryl‐1,3‐diphenyl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a][1,5]benzo‐diazepines was synthesized by the cycloaddition reactions of 2,4‐diaryl‐2,3‐dihydro‐1H‐1,5‐benzo‐diazepines and N‐phenylbenzonitrileimine generated from N‐phenylbenzenecarbohydrazonic chloride in the presence of triethylamine in anhydrous tetrahydrofuran. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:557–559, 2001     

New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine

The model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N⁴‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N⁴‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline ( 5 ) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine ( 8 ) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. ¹H nmr, ¹³C nmr, ir, mass spectroscopy and x‐ray identified compounds ( 4 ), ( 5 ) and ( 8 ).     

A simple synthesis of 5‐ethoxycarbonyl‐6‐phenyl‐1,3‐dioxin‐4‐ones and ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate

4‐Ethoxycarbonyl‐5‐phenyl‐2,3‐dihydrofuran‐2,3‐dione 1 reacts with aldehydes via the acylketene intermediate 2 giving the 1,3‐dioxin‐4‐ones 3a‐e and the 1,4‐bis(5‐ethoxycarbonyl‐4‐oxo‐6‐phenyl‐4H‐1,3‐dioxin‐2‐yl)benzene 4 , and a one step reaction between dibenzoylmethane and oxalylchloride gave 3,5‐dibenzoyl‐2,6‐diphenyl‐4‐pyrone 7 . The reaction of 1 with dibenzoylmethane, a dicarbonyl compound, provided ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate derivative 9 . Compound 9 was converted into the corresponding ethyl 3‐benzoyl‐4‐hydroxy‐2,6‐diphenylpyridine‐5‐carboxylate derivative 10 via its reaction with ammonium hydroxyde solution in 1 ‐butanol.     

Preparation of β2‐Amino Acid Derivatives (β2hThr, β2hTrp, β2hMet, β2hPro, β2hLys,Pyrrolidine‐3‐carboxylic Acid) by Using DIOZ as Chiral Auxiliary

The title compounds were prepared from valine‐derived N‐acylated oxazolidin‐2‐ones, 1 – 3, 7, 9 , by highly diastereoselective (≥ 90%) Mannich reaction (→ 4 – 6 ; Scheme 1) or aldol addition (→ 8 and 10 ; Scheme 2) of the corresponding Ti‐ or B‐enolates as the key step. The superiority of the ‘5,5‐diphenyl‐4‐isopropyl‐1,3‐oxazolidin‐2‐one’ (DIOZ) was demonstrated, once more, in these reactions and in subsequent transformations leading to various t‐Bu‐, Boc‐, Fmoc‐, and Cbz‐protected β²‐homoamino acid derivatives 11 – 23 (Schemes 3–6). The use of ω‐bromo‐acyl‐oxazolidinones 1 – 3 as starting materials turned out to open access to a variety of enantiomerically pure trifunctional and cyclic carboxylic‐acid derivatives.     

One Pot Photoredox Decarboxylation Reaction of N‐Cyano(α‐bromo‐α‐phenyl)methylanilines Leading to Synthesis of Four‐Membered Cyclic Carbamates

A new four‐membered cyclic carbamates have been synthesized through solar irradiation of N‐cyano(α‐bromo‐α‐phenyl)methylanilines in their aqueous methanolic solution using iodide salt in basic medium. These compounds have been characterized as 3,4‐diphenyl‐1,3oxazetidin‐2‐one through their elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral studies.     

Diastereoselective Synthesis of (Z)‐6‐(2‐Oxo‐1,2‐dihydro‐3H‐indol‐3‐ylidene)‐3,3a,9,9a‐tetrahydroimidazo[4,5‐e]thiazolo[3,2‐b]‐1,2,4‐triazin‐2,7(1H,6H)‐diones

Two efficient and diastereoselective procedures for the synthesis of (Z)‐6‐(2‐oxo‐1,2‐dihydro‐3H‐indol‐3‐ylidene)‐3,3a,9,9a‐tetrahydroimidazo[4,5‐e]thiazolo[3,2‐b]‐1,2,4‐triazin‐2,7(1H,6H)‐diones by aldol‐crotonic condensation of 1,3‐dimethyl‐3a,9a‐diphenyl‐3,3a,9,9a‐tetrahydroimidazo[4,5‐e]thiazolo[3,2‐b]‐1,2,4‐triazin‐2,7(1H,6H)‐dione with isatins under acidic or basic catalysis are reported. Isomerization in (Z)‐7‐(1‐allyl‐2‐oxo‐1,2‐dihydro‐3H‐indol‐3‐ylidene)‐1,3‐dimethyl‐3a,9a‐diphenyl‐1,3a,4,9a‐tetrahydroimidazo[4,5‐e]thiazolo[2,3‐c]‐1,2,4‐triazin‐2,8(3H,7H)‐dione was observed under basic conditions.     

Synthesis and characterization of novel polyimide from bis‐(3‐aminophenyl)‐4‐(trifluoromethyl)phenyl phosphine oxide

A novel diamine, bis‐(3‐aminophenyl)‐4‐(trifluoromethyl)phenyl phosphine oxide (mDA3FPPO), containing phosphine oxide and fluorine moieties was prepared via the Grignard reaction from an intermediate, 4‐(trifluoromethyl)phenyl diphenyl phosphine oxide, that was synthesized from diphenylphosphinic chloride and 4‐(trifluoromethyl)bromobenzene, followed by nitration and reduction. The monomer was characterized by Fourier transform infrared (FTIR), ¹H NMR, ³¹P NMR, ¹⁹F NMR spectroscopies; elemental analysis; melting point measurements; and titration and was used to prepare polyimides with a number of dianhydrides such as pyromellitic dianhydride (PMDA), 5,5′‐[2,2,2‐trifluoro‐1‐(trifluoromethyl)ethyliden]‐bis‐1,3‐isobenzofuranedione (6FDA), 3,3′,4,4′‐benzophenone tetracarboxylic dianhydride (BTDA), and 4,4′‐oxydiphthalic dianhydride (ODPA). Polyimides were synthesized via a conventional two‐step route; preparation of polyamic acids, followed by solution imidization, and the molecular weight were controlled to 20,000 g/mol. Resulting polyimides were characterized by FTIR, NMR, DSC, and intrinsic viscosity measurements. Refractive‐index, dielectric constant, and adhesive properties were also determined. The properties of polyimides were compared with those of polyimides prepared from 1,1‐bis‐(4‐aminophenyl)‐1‐phenyl‐2,2,2‐trifluoroethane (3FDAm) and bis‐(3‐aminophenyl) phenyl phosphine oxide (mDAPPO). The polyimides prepared from mDA3FPPO provided high glass‐transition temperatures (248–311 °C), good thermal stability, excellent solubility, low birefringence (0.0030–0.0036), low dielectric constants (2.9–3.1), and excellent adhesive properties with Cu foils (107 g/mm). © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3335–3347, 2001     

Reaction of 2‐Alkoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one with different alcohols and elucidation of the products

Reaction of 2‐methoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one 1a with methanol was studied, and the product of the reaction was determined by spectroscopic data and X‐ray analysis. In addition, a series of (Z)‐alkyl 3‐(alkoxycarbonylamino)‐2,3‐diphenylacrylate 4 was synthesized and characterized. J. Heterocyclic Chem., (2012).     

Synthesis,characterization and α‐amylase and α‐glucosidase inhibition studies of novel vanadyl chalcone complexes

A series of chalcone ligands and their corresponding vanadyl complexes of composition [VO (L^I–IV)₂(H₂O)₂]SO₄ (where L^I = 1,3‐Diphenylprop‐2‐en‐1‐one, L^II = 3‐(2‐Hydroxy‐phenyl)‐1‐phenyl‐propenone, L^III = 3‐(3‐Nitro‐phenyl)‐1‐phenyl‐propenone, L^IV = 3‐(4‐Methoxy‐phenyl)‐1‐phenyl‐propenone) have been synthesized and characterized using various spectroscopic (Fourier‐transform infrared, electrospray ionization mass, nuclear magnetic resonance, electron paramagnetic resonance, thermogravimetric analysis, vibrating sample magnetometer) and physico‐analytic techniques. Antidiabetic activities of synthesized complexes along with chalcones were evaluated by performing in vitro and in silico α‐amylase and α‐glucosidase inhibition studies. The obtained results displayed moderate to significant inhibition activity against both the enzymes by vanadyl chalcone complexes. The most potent complexes were further investigated for the enzyme kinetic studies and displayed the mixed inhibition for both the enzymes. Further, antioxidant activity of vanadyl chalcone complexes was evaluated for their efficiency to release oxidative stress using 2,2‐diphenyl‐1‐picryl‐hydrazyl‐hydrate assay, and two complexes (Complexes 2 and 4 ) have demonstrated remarkable antioxidant activity. All the complexes were found to possess promising antidiabetic and antioxidant potential.     

Reactions of unsymmetrical α‐diazo‐β‐diketones with imines: Syntheses of 4H‐1,3‐oxazin‐4‐ones

Cycloaddition reactions of an unsymmetrical α‐diazo‐β‐diketone, 2‐diazo‐1‐phenyl‐1,3‐butanedione, with a series of imines having various substituents were studied. The results indicated that only cycloadducts derived from acetylphenylketene, which was generated by the thermal Wolff rearrangement of 2‐diazo‐1‐phenyl‐1,3‐butanedione with phenyl migration, and imines were obtained. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:165–168, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10015     

Synthesis and Antibacterial Activity of Some 3,5‐Diphenyl and 1,3,5‐Triphenyl‐2‐pyrazolines

Some new 3,5‐diphenyl and 1,3,5‐triphenyl‐2‐pyrazolines derivatives were synthesized by reacting 1,3‐diphenyl‐2‐propen‐1‐ones with hydrazine hydrates and phenyl hydrazine in ethanol. The structural elucidation of the compounds was performed by IR, ¹H NMR and elemental analysis. All examined compounds showed appreciable antibacterial activity.     

Catalytic Asymmetric 1,3‐Dipolar Cycloaddition of β‐Fluoroalkylated α,β‐Unsaturated 2‐Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and γ‐Amino Alcohols

2‐Pyridylsulfone‐ and fluoroalkylated group‐activated olefins underwent highly efficient diastereo‐ and enantioselective 1,3‐dipolar cycloadditions across various aromatic and aliphatic nitrones in the presence of a chiral Ni^II/bis(oxazoline) catalyst. The process was tuned by 4 Å molecular sieves, chiral bis(oxazoline) ligands, reaction solvents, and temperature. A wide array of optically pure fluoroalkylated isoxazolidines were obtained, thus facilitating the asymmetric synthesis of an enantioenriched α‐trifluoromethylated γ‐amino alcohol in gram‐scale and a trifluoromethylated derivative of 1,3‐oxazinan‐2‐one with potential pharmaceutical interest. A stereochemical model, based on the absolute configuration of one adduct and some control experiments, was postulated to account for the observed endo‐ and enantioselectivity.     

New class of cationic ring‐opening polymerizations of 2,2‐diphenyl‐1,3‐oxathiolanes accompanying quantitative elimination of benzophenone

Cationic polymerizations of three 2‐substituted 1,3‐oxathiolanes, 2,2‐diphenyl‐1,3‐oxathiolane ( 1a ), 5‐methyl‐2,2‐diphenyl‐1,3‐oxathiolane ( 1b ), and 4‐methyl‐2,2‐diphenyl‐1,3‐oxathiolane ( 1c ), were carried out with boron trifluoride etherate (BF₃ · OEt₂) in dichloromethane at 30 °C to obtain poly(alkylene sulfide)s accompanying the elimination of benzophenone. In the cationic polymerization of 1b and 1c , the consumption of the monomers and formation of benzophenone proceeded simultaneously. The obtained poly(propylene sulfide)s from 1b and 1c contain 41% head–head units, which is in good agreement with that of the polymer from methylthiirane with BF₃ · OEt₂. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2943–2949, 2004     

Cyclization of 4‐Phenylthiosemicarbazide with Phenacylbromide Revisited. Formation of 1,3,4‐Thiadiazines and of Isomeric 1,3‐Thiazoles

The cyclization of 4‐phenylthiosemicarbazide with phenacylbromide, carried out in refluxing ethanol, afforded 1,3,4‐thiadiazine 1 as the major product. In contrast to a previous report, 2‐phenylimino‐4‐phenyl‐2,3‐dihydro‐1,3‐thiazol‐3‐amine ( 2 ) and not 2‐hydrazono‐3,4‐diphenyl‐2,3‐dihydro‐1,3‐thiazole ( 8 ) was formed as a side‐product. This product is the main product when the reaction is carried out in concentrated hydrochloric acid. Our findings were independently confirmed by independent syntheses of the isomeric products and by a thorough study of their reactivity. It is important to note that the product distribution of the cyclization of thiosemicarbazides with haloketones strongly depends on the substitution pattern and on the reaction conditions.     

Reaction of 6‐Methyl‐2‐Thiouracil and 6‐Phenyl‐2‐Thiouracil with Chloro‐β‐Dicarbonyl and Bromo‐β‐Dicarbonyl Compounds and Their Nitrile Analogs

Derivatives of 2‐methylidene‐1,3‐dihydropyrimidin‐4‐ones 2a , 2b , 2c , 2d , 2e , 2f , 2g were synthesized by interaction of 6‐methyl‐2‐thiouracil and 6‐phenyl‐2‐thiouracil 1a , 1b with some activated halogenides: diethyl bromomalonate, ethyl 2‐chloro‐3‐oxobutanoate, ethyl 2‐bromocyanoacetate, 2‐bromo‐5,5‐dimethylcyclohexan‐1,3‐dione, and bromomalononitrile. The boiling of 1a with ethyl 2‐bromocyanoacetate in mixture of ethanol and EtONa results in intramolecular cyclization and formation of thiazolo[3,2‐a]pyrimidin‐5‐one 3 . Interaction of 1a with 3‐chloropentane‐2,4‐dione and 2‐bromo‐1,3‐diphenylpropane‐1,3‐dione yielded corresponding S‐substituted thiopyrimidines 4a , 4b . In general, the products of 1b S‐alkylation are less prone to sulfur extrusion. Reaction of 1b with diethyl bromomalonate in the absence of EtONa stops at the S‐alkylation step, while in the presence of EtONa in ethanol or PPh₃ in dioxane 2‐(ethoxycarbonylmethyl)thio‐6‐phenyl‐1,3‐dihydropyrimidin‐4(1H)‐one 6 is formed exclusively. Molecular structure and crystal structure of 2‐(1,1‐diethoxycarbonylmethyliden)‐6‐methyl‐1,3‐dihydropyrimidin‐4(1H)‐one 2a are discussed.     

A Novel Synthesis and Antioxidant Evaluation of Functionalized [1,3]‐Oxazoles Using Fe3O4‐Magnetic Nanoparticles

In this research, green procedure was employed for biosynthesis of magnetic nanoparticles of iron oxide (Fe₃O₄‐MNPs) by reduction of ferric chloride solution with Orange peel water extract. Also, dihydro‐2H‐cyclopenta[d][1,3]oxazole was generated through multicomponent reaction of 1,3‐oxazole‐2(3H)‐thione, dialkyl acetylenedicarboxylates, α‐haloketones, and Fe₃O₄‐MNPs as catalyst at ambient temperature in good yield. Initially, 1,3‐oxazole‐2(3H)‐thione derivatives as one of the precursors are produced through the reaction of alkyl bromides, isothiocyanate, sodium hydride, and Fe₃O₄‐MNPs as catalyst water at ambient temperature in 83–95% yields. Also, diphenyl‐picrylhydrazine radical trapping and ferric reduction activity potential assays are used for evaluation of antioxidant activity of some synthesized compounds. Among investigated compounds, 4b has good power for radical trapping activity and 4d has good reduction power to butylated hydroxytoluene and 2‐tert‐butylhydroquinone.     

Synthesis of derivatives of 1,3,2‐diazaphospholidin‐4‐ones and the corresponding 2‐sulfides

Aromatic‐substituted derivatives of 1,3,2‐diazaphospholidin‐4‐ones 2a–g were readily prepared from 1,3‐diaryl glycinamides 1 by the reaction with hexaethylphosphoric triamide. Their chemical transformation was selectively effected with different thionation reagents to afford thionated products at the phosphorus atom to give 3a–g and at the carbonyl group to give 4a . An oxidation reaction at phosphorus to produce 5a was effected with 10% hydrogen peroxide. Preliminary bioassays revealed that some of the title compounds, 2a–g and 3a–g possess selective herbicidal activity against rape. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:497–500, 2001     

Trapping of Tricarbonyl(η1,η2‐homoallyl)iron and Tricarbonyl(η3‐allyl)iron Anion Intermediates with 2‐(Phenylsulfonyl)‐3‐phenyloxaziridine

The addition of reactive carbanions to (η⁴‐1,3‐diene)Fe(CO)₃ complexes at ?78 °C and 25 °C produced putative homoallyl and allyl anion complexes, respectively. Reaction of the reactive intermediates with 2‐(phenylsulfonyl)‐3‐phenyloxaziridine afforded nucleophilic substituted (η⁴‐1,3‐diene)Fe(CO)₃ complexes.     

(1,3‐Diphenyl‐1H‐Pyrazol‐4‐yl)‐Methylamine Analogues as Inhibitors of Dipeptidyl Peptidases

A number of pyrazole compounds reported in literatures elicit anti‐hyperglycemic effects. By modifying the side chain of the heterocyclic skeleton, a new chemical class of DPP‐IV inhibitors structurally derived from the (pyrazol‐4‐yl)‐methylamine scaffold have been discovered and evaluated the biological activities of these inhibitors against DPP‐IV, DPP8, DPP‐II and FAP. The SAR studies showed the (1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐methylamines with 2,4‐dichloro substituents at the 3‐phenyl ring selectively preferred as DPP‐IV inhibitors, whereas with difluoro substituents at the 3‐phenyl ring selectively preferred as DPP8 inhibitors. The binding mode of representative compound 15h at the active site of DPP‐IV was predicted by computer model. In additional, 15h exhibited the ability to significantly decrease the glucose excursion in mice.     

Calix[4]arenes bearing α‐amino‐ or α‐hydroxyphosphonic acid fragments at the upper rim

By the reaction of para‐formylcalix[4]arenes 1–6 with trialkyl phosphites in the presence of dry hydrogen chloride, calix[4]arenes 7–13 possessing dialkylphosphoryl‐hydroxymethyl groupings at the upper rim were synthesized. Calix[4]arenes 18–23 functionalized with dialkylphosphoryl‐alkyl(aryl)aminomethyl groups were obtained by sodium‐promoted addition of dialkyl phosphites to C=N bonds of para‐iminocalix[4]arenes 14–17 . The consecutive treatment of α‐hydroxy‐ or α‐aminophosphonic acid dialkyl esters of calix[4]arenes 7, 10, 18 , and 21 with bromotrimethylsilane and methanol gave dihydroxyphosphoryl derivatives of calix[4]arenes 24–27 . It was shown that calix[4]arenes bearing at the macrocyclic upper rim hydroxymethylphosphonic fragments, as well as bis‐hydroxymethyl(aminomethyl)phosphonic fragments, are able to undergo self‐assembly with formation of dimeric OH···O=P hydrogen bonded associates. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:58–67, 2001