First synthesis of 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol from 1‐ and 2‐naphthol derivatives

Two new structurally isomeric, 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol ( 1 ) and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol ( 3 ) have been synthesized from 2‐acetyl‐1‐naphthol and ethyl‐3‐hydroxy‐2‐naphthoate, respectively, involving Grignard reaction, dehydration of the corresponding tertiary alcohols, and hetero Diels–Alder dimerization. The two benzochromenes ( 1 and 3 ) have been fully characterized by IR, NMR, and HRESIMS data. Their structures are further supported by crystallography of their corresponding acetates ( 2 and 4 ). J. Heterocyclic Chem., (2011).     

Synthesis and biological screening of 4‐(3,3‐dimethylspiro{bicyclo[2.2.1]heptan‐2,5′‐isoxazoline‐2}‐ 3′‐yl)‐2‐aryl‐2,3‐dihydro‐1H‐1,5‐benzodiazepines

A series of novel 4‐(3,3‐dimethylspiro{bicyclo[2.2.1]heptan‐2,5′‐isoxazoline‐2}‐3′‐yl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepines were synthesized. These molecules were screened in vitro for their antifungal and antibacterial activity, and none of the tested compounds showed promising antimicrobial or antifungal activity. J. Heterocyclic Chem., 2011.     

An efficient synthesis of 5‐aryl‐4,5‐dihydro‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(4‐phenylthiazol‐2‐yl)pyrazoles

Some new target products 5‐aryl‐4,5‐dihydro‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(4‐phenylthiazol‐2‐yl)pyrazoles 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j have been synthesized by reaction of 2‐bromo‐1‐phenylethanone and compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j which were prepared from the combination of thiosemicarbazide and (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j . All the structures were established by MS, IR, CHN, and ¹H NMR spectra data. Synthesis of structure diversity is applied. J. Heterocyclic Chem., (2011).     

Unanticipated products from reductive and oxidative cleavages of 1‐substituted 3,3‐diphenyl‐1′‐methylspiro[azetidine‐2,3′‐indoline]‐2′,4‐diones

Titled spiroazetidinones 1a , 1b undergo reductive cleavage on treatment with excess lithium aluminum hydride forming 3‐benzhydryl‐1‐methylindole as the main product together with a γ‐amino alcohol depending upon the substituent present on the azetidin‐2‐one ring. Treatment of 1a with Ce(IV) ammonium nitrate affords 2‐hydroxy‐N‐(4‐methoxyphenyl)‐2,2‐diphenylacetamide besides the anticipated N‐unsubstituted 2‐azetidinone, whereas a similar treatment of 1‐benzhydryl‐3,3‐diphenyl‐2‐azetidinone 1b affords the ring expansion product 1,3‐oxazolidin‐4‐one. The products have been characterized on the basis of satisfactory analytical and spectral (IR, ¹H and ¹³C‐NMR, DEPT, HMBC) data and their formation is discussed. J. Heterocyclic Chem., (2011).     

Synthesis of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas and their inhibition activity to acetylcholinesterase and butyrylcholinesterase

A series of novel 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas were synthesized by the condensation of (1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethanamine with substituted phenyl isocyanates under mild conditions. Their structures were confirmed ¹H, ¹³C, and ¹⁹F NMR spectra, and elemental analyses. The optical activities were confirmed by optical rotation measurements. The inhibition activity of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas to acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) was also tested. Preliminary bioassay indicated that the target ureas displayed excellent acetylcholinesterase and butyrylcholinesterase inhibition activity. J. Heterocyclic Chem., 2011.     

One‐pot synthesis and evaluation for 15‐lipoxygenase inhibition of 1‐ethoxy‐4‐cyano‐5‐ethoxycarbonyl‐3H‐azuleno[1,2‐c]pyran‐ 3‐imine

A method at room temperature, with one pot of 24 h reaction, to synthesize 1‐ethoxy‐4‐cyano‐5‐ethoxycarbonyl‐3H‐azuleno[1,2‐c]pyran‐3‐imine which showed inhibitory effect on 15‐lipoxygenase at IC₅₀ = 23.2 ± 1.3 mM. J. Heterocyclic Chem., 2011.     

Regioselectivity of nitrilimines 1,3‐dipolar cycloaddition: Novel synthesis of spiro[4,4]nona‐2,8‐dien‐6‐one derivatives

Regioselective 1,3‐dipolar cycloaddition of nitrilimines (generated in situ from dehydrohalogenation of the corresponding hydrazonoyl halides by the action of triethylamine) with 4‐arylidene‐1‐aryl‐2‐phenyl‐1H‐imidazol‐5(4H)‐one 3 afforded the corresponding spiro[4,4]nona‐2,8‐dien‐6‐one 4 . The reaction was carried out in dry benzene under reflux temperature. Refluxing in acetic acid, 4a was converted to its respective N‐phenylpyrazole‐5‐carboxamide 8 . The structures of prepared compounds were established by elemental analyses and spectral data (IR, MS, ¹H, and ¹³C NMR). © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:131–136, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20666     

Utility of 3‐amino‐4,6‐dimethyl‐1H‐pyrazolo[3,4‐b]pyridine in heterocyclic synthesis

This review describe the synthesis and reactions of 3‐amino‐4,6‐dimethyl‐1H‐pyrazolo[3,4‐b]pyridine as building block for the synthesis of polyfunctionalized heterocyclic compounds with pharmacological interest. J. Heterocyclic Chem., 2011.     

Synthesis and antibacterial activity of novel series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline

A new series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline were synthesized from oxidative cyclization of N′‐((2‐(p‐tolyloxy)quinoline‐3‐yl)methylene)isonicotinohydrazide in DMSO/I₂ at reflux condition for 3–4 h. The structures of the new compounds were confirmed by elemental analyses as well as IR, ¹H‐NMR, and mass spectral data. All the synthesized compounds were screened for their antibacterial activities against various bacterial strains. Several of these compounds showed potential antibacterial activity. J. Heterocyclic Chem., (2011).     

Green synthesis and crystal structure of 4,7‐diaryl‐2‐oxo(thio)‐1,2,3,4,5,6,7,8‐octahydroquinazoline‐5‐one derivatives

A green and convenient approach to the synthesis of novel 4,7‐diaryl‐2‐oxo(thio)‐1,2,3,4,5,6,7,8‐octahydroquinazoline‐5‐one derivatives from appropriate aromatic aldehydes and 5‐aryl‐1,3‐cyclohexanedione with urea or thiourea in the presence of dilute HCl as catalyst in water is described. This method provides several advantages such as environmental friendliness, low cost, high yields, and simple workup procedure. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H NMR. The crystal and molecular structure of 4‐(4′‐chlorophenyl)‐7‐(4′‐methoxyphenyl)‐1,2,3,4,5,6,7,8‐octahydroquinazoline‐2,5‐dione 5m have been determined by single crystal X‐ray diffraction analysis. The crystal of compound 5m belongs to monoclinic with space group P‐2₁/c, a = 1.4353 (4) nm, b = 1.4011 (4) nm, c = 0.9248 (3) nm, α = 90.00°, β = 101.242 (6)°, γ = 90.00°, Z = 4, V = 1.8241 (9) nm³, R₁ = 0.0448, and wR₂ = 0.1022. J. Heterocyclic Chem., (2011).     

The formation of 3‐ferrocenylpyrazole‐4‐carboxylates and alkylhydrazine insertion products from α‐ferrocenylmethylidene‐β‐oxocarboxylates

The reactions of α‐ferrocenylmethylidene‐β‐oxocarboxylates ( 1 , 2 , 3a , and 3b ) with N‐methyl‐ and N‐(2‐hydroxyethyl)hydrazines ( 5a , 5b ) afford ethyl 1‐alkyl‐5‐aryl(methyl)‐3‐ferrocenylpyrazole‐4‐carboxylates ( 6a , 6b , 6c , 6d , 6e ) (～50%) and N‐alkylhydrazine insertion products, viz., ethyl (N′‐acyl‐N′‐alkylhydrazino)‐3‐ferrocenylpropanoates ( 7a , 7b , 7c , 7d , 7e ) (～20%) and 1‐acyl‐2‐(N′‐alkyl‐N′‐ethoxycarbonylhydrazino)‐2‐ferrocenylethanes ( 8a , 8b , 8c , 8d , 8e ) (～10%). The structures of the compounds obtained were established based on the spectroscopic data and X‐ray diffraction analysis (for pyrazoles 6a and 6b ). J. Heterocyclic Chem., (2011).     

Synthesis of 1‐H‐1,5‐benzodiazepines derivatives using SiO2/ZnCl2

A general and easy method for the synthesis of several 1‐H‐1,5‐benzodiazepines using SiO₂/ZnCl₂ under solvent‐free conditions is described. This efficient and improved method furnishes selectively and in good yields the corresponding 1‐H‐1,5‐benzodiazepines derivatives starting from o‐phenylenediamine and cyclic or acyclic ketones. The catalytic system was reused up four times, and the use of focused microwaves accelerates the reaction. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:180–185, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20674     

Synthesis and chemistry of new spiro‐Δ1‐pyrazoline

In explorations of syntheses and chemistry of spiroheterocycles, we found that the reaction of 2‐diazopropane with (E)‐α‐arylidenepyrrolin‐2‐one, (E)‐α‐arylidene‐γ‐butyrolactone, and (E)‐arylidene‐N‐arylsuccinimide derivatives produced spiro‐Δ¹‐pyrazolines. The photolysis of Δ¹‐pyrazolines has led to cyclopropanes. The structures of the obtained adducts have been assigned by means of spectroscopic measurements. J. Heterocyclic Chem., (2011).     

New synthesis and reactivity of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with binucleophilic amines

3‐(Bromoacetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one was synthesized by the reaction of dehydroacetic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized from the reaction of bromo‐DHAA with alkanediamines, phenylhydrazines, ortho‐phenylenediamines, and ortho‐aminobenzenethiol. The obtained new products 3‐(2‐N‐substituted‐acetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐ones, 4‐hydroxy‐3‐[1‐hydroxy‐2‐(2‐phenylhydrazinyl)vinyl]‐6‐methyl‐2H‐pyran‐2‐one, 1‐(2,4‐dinitrophenyl)‐7‐methyl‐2,3‐dihydro‐1H‐pyrano[4,3‐c]pyridazine‐4,5‐dione, 3‐(3,4‐dihydroquinoxalin‐2‐yl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one/3‐(3,4‐dihydroquinoxalin‐2‐yl)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione, 6‐methyl‐3‐(3,4‐dihydroquinoxalin‐2‐yl)‐2H‐pyran‐2,4(3H)‐dione, and (E)‐3‐(2H‐benzo[b][1,4]thiazin‐3(4H)‐ylidene)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione were fully characterized by IR, ¹H and ¹³C NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

Asymmetric anionic polymerizations of 7‐cyano‐7‐alkoxycarbonyl‐1,4‐benzoquinone methides

Asymmetric anionic polymerizations of 7‐cyano‐7‐alkoxycarbonyl‐1,4‐benzoquinone methides ( 1 ) with various alkoxy groups were performed using chiral initiators such as lithium isopropylphenoxide (ⁱPrPhOLi)/(S)‐(–)‐2,2′‐isopropylidene‐bis(4‐phenyl‐2‐oxazoline) ((–)‐PhBox) and lithium isopropylphenoxide (ⁱPrPhOLi)/(–)‐sparteine ((–)‐Sp) to investigate the effect of the alkoxy groups of alkoxycarbonyl substituent in the monomers 1 and chiral ligands of chiral initiators on the control of chiral center in the formation of polymers. Molar optical rotation values of the polymers were significantly dependent upon alkoxy groups, and the polymers with higher molar optical rotation were obtained in monomers with primary alkoxy groups. The asymmetric anionic oligomerizations of the quinone methides having methoxy( 1a ), ethoxy( 1b ), and n‐propoxy( 1c ) groups with chiral initiators were carried out. Both 1‐mers and 2‐mers were isolated and their optical resolutions were performed to determine the extent of stereocontrol. High stereoselectivity was observed at the propagation reaction, but not at the initiation reaction. The effect of the counterion on the control of chiral center in the formation of the polymer was investigated in the asymmetric anionic polymerizations of 1b with ⁱPrPhOM(M = Li, Na, K)/(–)‐Sp and ⁱPrPhOM(M = Li, Na, K)/(–)‐PhBox initiators and discussed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

A convenient synthesis of pyrrolo‐annelated 1,3‐diselenole‐2‐thione and 1,3‐diselenol‐2‐one derivatives via dipyrrolo‐annelated 1,2,5,6‐tetraselenocine derivatives

The reaction of 2,5‐dimethyl‐3,4‐diselenocyanato‐1H‐pyrrole by NaBH₄ or NaOCH₃ led to tetraselenide 7 in quantitative yield. Treatment of protected tetraselenide 8 with LiAlH₄ afforded the aluminum complex intermediate that was converted into pyrrole‐annelated 1,3‐diselenolo‐2‐thione 9 in excellent yield. Similarly, treatment of tetraselenide 8 with LiAlH₄ followed by TFA afforded 1,2‐diselenol intermediate that was converted into pyrrole‐annelated 1,3‐diselenolo‐2‐one 10 upon treatment of diimidazole carbonate. J. Heterocyclic Chem., (2011).     

An intramolecular N‐arylation approach to 3‐functionalized 4,9‐dihydropyrrolo[2,1‐b]quinazolines

A series of 4,9‐dihydropyrrolo[2,1‐b]quinazolines containing electron withdrawing groups at the 3‐position have been prepared by the palladium‐catalyzed intramolecular N‐arylation of some 2‐aminopyrroles having a 2‐bromobenzyl group at the N‐1 position. Important for success of the reaction is the use of X‐phos, a biphenyl mono‐phosphine ligand, instead of xantphos, a more standard diphosphine ligand, and the use of t‐BuOH as reaction solvent. J. Heterocyclic Chem., (2011).     

An efficient one‐pot synthesis of 2‐benzylpyrroles and 3‐benzylindoles

One‐pot regioselective benzylation of pyrroles and indoles using zirconium tetrachloride is discussed. This has been achieved by in‐situ generation of di(1H‐pyrrol‐1‐yl)zirconium(IV) chloride and di(1H‐indol‐1‐yl)zirconium(IV) chloride. It was observed that benzylation reactions of these complexes using n‐BuLi occurred at C‐2 position for pyrrole and C‐3 for indole. Copyright © 2011 John Wiley & Sons, Ltd.     

An experimental and theoretical approach to the molecular structure of 3‐{[4‐(3‐Methyl‐3‐phenyl‐cyclobutyl)‐thiazol‐2‐yl]‐hydrazono}‐1,3‐dihydro‐ indol‐2‐one

The title molecule, 3‐{[4‐(3‐methyl‐3‐phenyl‐cyclobutyl)‐thiazol‐2‐yl]‐hydrazono}‐1,3‐dihydro‐indol‐2‐one (C₂₂H₂₀N₄O₁S₁), was prepared and characterized by ¹H NMR, ¹³C NMR, IR, UV–visible, and single‐crystal X‐ray diffraction. The compound crystallizes in the monoclinic space group P21 with a = 8.3401(5), b = 5.6976(3), c = 20.8155(14) Å, and β = 95.144(5)°. Molecular geometry from X‐ray experiment and vibrational frequencies of the title compound in the ground state has been calculated using the Hartree–Fock with 6‐31G(d, p) and density functional method (B3LYP) with 6‐31G(d, p) and 6‐311G(d, p) basis sets, and compared with the experimental data. The calculated results show that optimized geometries can well reproduce the crystal structural parameters, and the theoretical vibrational frequencies values show good agreement with experimental data. Density functional theory calculations of the title compound and thermodynamic properties were performed at B3LYP/6‐31G(d, p) level of theory. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

New succinyl‐spaced pyrazoles: Regioselective synthesis of 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones

The facile and convenient access by a conventional procedure in ethanol as solvent to a new series of succinyl‐spaced pyrazoles including 1,4‐bis[5‐(trichloromethyl)‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones (64–82%) and the respective dehydrated derivatives as 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones in 57–82% yields, from the regioselective cyclocondensation reactions of 4‐substituted 4‐methoxy‐1,1,1‐trichloroalk‐3‐en‐2‐ones with succinic acid dihydrazide, where the 4‐substituents are Me, Ph, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐NO₂C₆H₄, 2‐furyl, and 2‐thienyl, is reported. J. Heterocyclic Chem., 2011.