Synthesis of Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.     

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 ).     

Synthesis of 3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles

Several 3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐1,3,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles have been synthesized and the structures of these compounds were established by elemental analysis, MS, IR and ¹H NMR spectral data.     

Synthesis and reactions of 2‐amino‐6‐(3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazolin‐4‐yl)‐4‐phenylpyridine‐3‐carbonitrile

2‐Amino‐6‐(3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazolin‐4‐yl)‐4‐phenylpyridine‐3‐carbonitrile (1) obtained by the reaction of 4‐(1‐iminoethyl)‐3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one with benzylidenemalononitrile, was reacted with triethyl orthoformate followed by hydrazine hydrate, acetic anhydride, acetyl chloride, alkyl halides, benzoyl chloride, sulphuric acid followed by formamide, phenyl isothiocyanate, carbon disulphide followed by ethyl iodide, formamide, trichloroacetonitrile, nitrous acid, giving new oxopyrazolinylpyridines ( 2,3,5,6,8,9,10 ) and related pyridopyrimidines ( 11‐17 ) and pyridotriazine ( 18 ).     

Synthesis of 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

Synthesis of 5‐(6‐Pyridazinone‐3‐yl)‐2‐Glycosylamino‐1,3,4‐Oxadiazoles

N‐Glycosyl‐2‐(1,4,5,6‐tetrahydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 3a‐3g and N‐glycosyl‐2‐(1,6‐dihydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 5a‐5g were prepared by the reaction of glycosyl isothiocyanates with the compounds 1,4,5,6‐tetrahydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 1 ) and 1,6‐dihydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 2 ). The terminal heterocyclic compounds 1,3,4‐oxadiazole derivatives were obtained from cyclization of compounds ( 3a‐3g ) and ( 5a‐5g ) by mercuric acetate. Their structures were confirmed by IR, ¹H NMR, MS and elemental analyses.     

An Efficient Synthesis of 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐6‐methyl‐4‐(2‐oxo‐2‐phenylethoxy)‐3,4‐dihydro‐2H‐pyran‐2‐one Derivatives via Multi‐Component Approach

An easy, highly efficient and a new convenient one‐pot, two‐step approach to the synthesis of 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐6‐methyl‐4‐(2‐oxo‐2‐phenylethoxy)‐3,4‐dihydro‐2H‐pyran‐2‐one is described. These compounds were synthesized from 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐4‐hydroxy‐6‐methyl‐3,4‐dihydro‐2H‐pyran‐2‐one and α‐bromoketones in good yields. The compounds 4 were synthesized by a multi‐component reaction between 1 , 2 , and 3 and the prominent features of this protocol are mild reaction conditions, operation simplicity, and good to high yields of products.     

The Synthesis of 2‐(Chromon‐2/3‐yl)‐3‐(5‐thione‐4‐hydro‐1,3,4‐thiadiazol‐2‐yl)‐4‐oxo‐thiazolidine

2‐Formylchromones and 3‐formylchromones as the first materials singly reacted with 2‐amino‐5‐mercapto‐1,3,4‐thiadiazole to give the corresponding Schiff bases, which on cyclocondensation with mercapto‐acetic acid in 1,4‐dioxane yielded target compounds named 4‐oxo‐thiazolidines. The structures of all the synthetic compounds were confirmed by elemental analysis and IR, ¹H NMR, LC‐MS (ESI) spectral data.     

Synthesis and Antibacterial Activities of 2‐(1‐Aryl‐5‐Methyl‐1,2,3‐triazol‐4‐yl)‐1,3,4‐Oxadiazole Derivatives

Eighteen novel 2‐(1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,3,4‐oxadiazole derivatives and two acylhydrazone intermediate compounds were synthesized by various pathways starting from 1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐formhydrazide ( 1 ). All products were identified by spectroscopic analysis, and 2‐(1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐5‐benzalthio‐1,3,4‐oxadiazole was further validated by X‐ray crystallography. Results from primary antibacterial activity tests indicated that most of the compounds were effective against E. coli, P. aeruginosa, B. subtilis and S. aureus.     

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₂₆H₂₇NOS, (I), and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₁₃H₁₇NOS, (II), are both characterized by a planar configuration around the heterocyclic N atom. In contrast with the chair conformation of the parent benzothiazepine, which has no substituents at the heterocyclic N atom, the seven‐membered ring adopts a boat conformation in (I) and a conformation intermediate between boat and twist‐boat in (II). The molecules lack a symmetry plane, indicating distortions from the perfect boat or twist‐boat conformations. The supramolecular architectures are significantly different, depending in (I) on C—H...O interactions and intermolecular S...S contacts, and in (II) on a single aromatic π–π stacking interaction.     

Syntheses of 1‐(4‐methylsulfonylphenyl)‐5‐aryl‐1,2,3‐triazoles and ‐(4‐aminosulfonylphenyl)‐5‐aryl‐1,2,3‐triazoles

Condensation of 4‐methylsulfonylaniline with aryl aldehyde in ethanol‐tetrahydrofuran afforded the imino compound 3 . 1,3‐Cycloaddtion of diazomethane with compound 3 followed by oxidazation of the triazoline 4 with potassium permanganate gave 1‐(4‐methylsulfonylphenyl)‐5‐aryl‐1,2,3‐triazoles 5 . Similarly, condensation of 4‐(N,N‐dibenzylaminosulfonyl)aniline with aryl aldehyde followed by 1,3‐cycloaddition of diazomethane with the imino compound 11 and the subsequent oxidation of triazoline 12 with potassium permanganate yielded the triazole 13 . Debenzylation of compound 13 with sulfuric acid gave the desired compound 1‐(4‐aminosulfonylphenyl)5‐aryl‐1,2,3‐triazoles 14 .     

Preparation of 2‐phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline and 2‐methyl‐4‐oxo‐3,4‐dihydroquinazoline derivatives formation

The cyclization of phenacyl anthranilate has been studied with the aim to develop the synthesis of 2‐(2′‐aminophenyl)‐4‐phenyloxazole. However, a different course of the reaction than expected was observed. 2‐Phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 3a ) was formed by the reaction of phenacyl anthranilate ( 2 ) with ammonium acetate under various conditions. 3‐Hydroxy‐2‐phenyl‐4(1H)‐quinolinone ( 4 ) arose by heating compound 3a in acetic acid. The same compound was obtained by melting compound 3a , but the yield was lower. Different types of products resulted in the reaction of compound 3a with acetic anhydride. Under mild conditions acetylated products 2‐acetoxymethyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 7a ) and 2‐acetoxymethyl‐3‐acetyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 8 ) were prepared. If the reaction was carried out under reflux of the reaction mixture, molecular rearrangement took place to give cis and trans 2‐methyl‐4‐oxo‐3‐(1‐phenyl‐2‐acetoxy)vinyl‐3,4‐dihydroquinazolines ( 9a and 9b ). All prepared compounds have been characterised by their ¹H, ¹³C and ¹⁵N NMR spectra, IR spectra and MS.     

Synthesis and Antifungal Activities of ω‐[4‐Aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenones

New 4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thiones 3 have been synthesized by the intramolecular cyclization of 4‐aryl‐1‐(1‐phenyl‐5‐methyl‐1,2,4‐triazol‐4‐formyl)thiosemicarbazides 2 with an 8% NaOH solution, and then 3 reacted with ω‐bromo‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenone to afford ω‐[4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)‐acetophenones 4 . The preliminary biological test showed that the representative compounds possess some anti fungal activities.     

Synthesis and Fluorescent Properties of 2‐Arylamino‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐Yl)‐1,3,4‐Thiadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐thiadiazole derivatives ( 6a‐6d, 7a‐7d, 8a‐8d ) were prepared by cyclization of the intermediate 3‐aryl‐l‐phenyl‐pyrazol‐4‐ylformaldehyde 4′‐phenylthiosemicarbazones with 0.5 M ferric chloride solution. The structures of the new compounds were confirmed by IR, ¹H NMR and elemental analysis. Simultaneously, the compounds were detected by fluorescence spectrophotometer and had preferable fluorescence activity.     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

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).     

Synthesis of 3‐(Pyridin‐4‐Ylmethyl)‐4‐Substituted‐1,2,4‐Triazoline‐5‐Thione

The reaction of the hydrazide of pyridine‐4‐acetic acid with isothiocyanate gave thiosemicarbazide derivatives respectively. Further cyclization with 2% NaOH led to the formation of 4‐substituted 3‐(pyridin‐4‐ylmethyl)‐1,2,4‐triazoline‐5‐thione and 3‐(pyridin‐4‐ylmethyl)‐1,2,4‐triazoline‐5‐thione. The structures of all new products were confirmed by analytical and spectroscopic methods.     

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).     

Polymorphism of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐ and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐ones

This study of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐2H‐chromen‐2‐one, C₁₇H₁₀N₂O₃, 1 , and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐one, C₁₆H₉N₃O₃, 2 , was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the `head‐to‐head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar‐layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.     

Synthesis of 3‐aroyl‐4‐(3‐chromonyl)‐2‐pyrazolines

New 3‐aroyl‐4‐(3‐chromonyl)‐2‐pyrazolines have been synthesized by the reaction of 3‐(3‐aryl‐3‐oxo‐propenyl)chromen‐4‐ones and diazomethane. Some of these 2‐pyrazolines have also been N‐acylated with a mixture of anhydrous pyridine and acetic anhydride or propionic anhydride. Structures of all new compounds have been elucidated by elemental analyses, mass spectrometry, ir and nmr spectroscopic measurements.