Synthesis of some oxazolyl ‐ pyrazolyl; 1,4‐Dihydropyridinyl‐pyrazolyl and 1,2,3,4‐tetrahydro pyrimidinyl‐pyrazolyl coumarins

Various 3‐[1‐phenyl‐4‐(2‐substituted‐5‐oxo‐oxazol‐4‐ylidenemethyl) pyrazol‐3‐yl] coumarins 4a‐f ; 3‐[1‐phenyl‐4‐(2,6‐dimethyl‐3,5‐disubstituted‐1,4‐dihydropyridin‐4‐yl) pyrazol‐3‐yl] coumarins 5a‐f and 3‐[1‐phenyl‐4‐(6‐methyl‐5‐substituted‐2‐oxo‐1,2,3,4‐tetrahydropyrimidin‐4‐yl) pyrazol‐3‐yl] coumarins 6a‐f have been synthesized utilizing Erlenmyer‐Plochl reaction, Hantzsch reaction and Biginelli reaction respectively using 3‐(1‐phenyl‐4‐formyl‐pyrazol‐3‐yl) coumarins 3a‐c as a starting material.     

Synthesis of some new five membered heterocycles,a facile synthesis of oxazolidinones

The synthesis and structural properties of two kinds of thiosemicarbazide derivatives ( 2a‐c and 3a‐c ) and one kind of semicarbazide derivatives ( 4a, 4b ) have been described. These compounds were synthesized by treating 2‐(4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl)acetohydrazides ( 1a‐c ) with benzyl isothiocyanate, 3‐florophenyl isothiocyanate and benzylisocyanate, respectively. The synthesis of 4‐amino‐3‐alkyl‐1‐[(4‐alkyl‐5‐mercapto(or 5‐oxo)‐4H‐1,2,4‐triazol‐3‐yl)methyl]‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones ( 5a‐c, 6a‐c and 7 ) have been performed from the reaction with sodium hydroxide. On the other hand, the acidic treatment of compounds 2b, 3b and 4b has afforded 4‐amino‐3‐(4‐chlorobenzyl)‐1‐[(5‐alkylamino‐1,3,4‐thidazol(or 1,3,4‐oxazol)‐2‐yl)methyl]‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones ( 8, 9 and 10 ). The condensation of thiosemi(or semi)carbazide derivatives ( 2a‐c, 3c and 4b ) with 4‐chlorophenacylbromide have resulted in the formation of 2‐[4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl]‐N′‐(3,4‐dialkyl‐1,3‐thiazol(or oxazol)‐2(3H)‐yliden]acetohydrazides ( 11a‐c, 12, 13 ), while their condensation with chloroacetic acid has produced 2‐[4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl]‐N′‐[3‐(3‐alkyl)]‐4‐oxo‐1,3‐thiazolidin(or oxazolidin)‐2‐yliden}acetohydrazides ( 14, 15 and 16 ). The spectral data and elemental analyses have support the proposed structures.     

Azulene‐substituted pyridines and pyridinium salts. Synthesis and structure. 2. Azulene‐substituted pyridinium salts

4‐Azulen‐1‐yl substituted 2,6‐dimethyl‐and 2,6‐diphenyl‐pyridinium salts are obtained in yields between 50 % and 100 % in the reaction of corresponding 4‐azulen‐1‐yl‐pyranylim salts and various amines. The effects of amine structure and of substitution in the heterocycle or at azulene moieties on the synthesis have been investigated. The uv‐vis and NMR spectra of reaction products are examined and discussed in correlation with their structure.     

Synthesis and Optical Properties of 2‐(Benzo[b]thiophene‐3‐yl)pyrroles and a New BODIPY Fluorophore (BODIPY=4,4‐Difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene)

The light fantastic : Two new 2‐(benzo[b]thiophene‐3‐yl)pyrroles have been synthesized, and are shown to exhibit optical properties that are promising for optoelectronic materials and devices such as highly efficient fluorescent sensors (see scheme). In addition a new BODIPY fluorophore, derived from 2‐(benzo[b]thiophene‐3‐yl)pyrrole, was also isolated and shows good spectroscopic properties in solution which are fully preserved in the solid state.

     

Synthesis and characterization of a novel heterocycle: 1‐Substituted‐4‐arylazamethylene‐6‐arylpyrazolo[5,4‐d]‐1,3‐oxazine

A series of novel heterocycles 1‐aryl‐ or alkyl‐substituted‐4‐arylazamethylene‐6‐arylpyrazolo[5,4‐d]‐1,3‐oxazines were synthesized from the acylation of (5‐amino‐1‐substituted‐pyrazol‐4‐yl)‐N‐carboxamide in 63‐89% isolated yields at room temperature within 12 hours. The structure was confirmed by X‐ray crystal analysis.     

A convenient one‐pot synthesis of new 3‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐ones

Anhydrous zinc bromide catalysed reactions of arylidine‐3‐acetyl coumarins ( 1a‐c ) and 5,6‐benzoanalogs of arylidine 3‐acetyl coumarins ( 4a,4b ) with 1,3‐cyclohexanedione gives ‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2yl)‐2H‐chromen‐2‐ones ( 3a, 3c ) and 5,6‐benzoanalogs of 3‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2yl)‐2H‐chromen‐2‐one ( 5a,5b ). Under similar conditions arylidine‐3‐acetylcoumarins ( 1a, 1b,1d, 1e, 1f ) and 5,6‐benzoanalog of arylidine 3‐acetyl coumarin ( 4b ) react with 5,5‐dimethyl‐1,3‐cyclohexanedione (dimedone) yielding 3‐(4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐ones ( 3d‐3h ) and the 5,6‐benzoanalog of 3.(4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐one ( 5c ).     

FeCI3‐promoted [3+3] cycloaddition: Efficient preparation of 1,2‐dihydro‐2‐oxo‐3‐pyridinecarboxylate and 1,2‐dihydro‐2‐oxo‐3‐pyridinecarboxamide derivatives

A facile approach was developed on assembly of the 2‐pyridone nucleus by ferric chloride promoted [3+3] cycloaddition in propionic acid. The tandem process involves cyclization of Michael adduct followed by aromatization. Thus, different substituted 1,2‐dihydro‐2‐oxo‐3‐pyridinecarboxylate and 1,2‐dihydro‐2‐oxo‐3‐pyridinecarboxamide derivatives were prepared in good yields from various enones with malonamic ester and malonamide, respectively     

Synthesis and characterization of some novel 2‐{2‐[1‐(3‐substituted‐phenyl)‐1H‐1,2,3‐triazol‐4‐yl‐] ethyl}‐1‐substituted‐1H‐benzo [d] imidazole derivatives

Synthesis of some novel 2‐{2‐[1‐(3‐substitutedphenyl)‐1H‐1,2, 3‐triazol‐4‐yl‐]ethyl)‐1H‐benzo[d]‐imidazole derivatives, by the condensation of o‐phenylenediamine with 3‐(1‐(3‐substituted‐phenyl)‐1H‐1,2,3‐triazol‐4‐yl) propanoic acid and then subsequent reactions with different substituted alkyl halides as electrophiles are mentioned. The synthesized compounds were characterized by ¹H NMR, EI‐MS and IR spectroscopic techniques.     

Microwave assisted synthesis of thiazolo[3,2‐b][1,2,4]‐triazoles containing 1,8‐naphthyridine moiety

A simple and efficient protocol for the synthesis of 5‐aryl‐2‐(2‐substituted‐1,8‐naphthyridin‐3‐yl)‐thiazolo[3,2‐b][1,2,4]triazoles ( 4 ) is achieved by cyclocondensation of 3‐(2‐substituted‐1,8‐naphthyridin‐3‐yl)‐1,2,4‐triazoles ( 3 ) with α‐halogenoketones in anhyd. methanol under microwave irradiation. The products are obtained in good yields and in a state of high purity.     

Microwave induced efficient synthesis of (un)substituted benzaldehyde (5‐aryl‐1,3,4‐thiadiazol‐2‐yl)hydrazones using silica‐supported dichlorophosphate as a recoverable dehydrant

(Un)substituted benzaldehyde (5‐aryl‐1,3,4‐thiadiazol‐2‐yl)hydrazones were efficiently synthesized by reactions of (un)substituted benzaldehyde thiocarbohydrazones with aromatic carboxylic acids by using silica‐supported dichlorophosphate as a recoverable dehydrant under microwave irradiation. The protocol has advantages of short reaction time, high yield, easy work‐up procedure and no environmental pollution.     

Flash vacuum pyrolysis of 1‐azolyl‐1‐phenylhydrazono‐2‐propanones

Flash vacuum pyrolysis (FVP) of 1‐(2‐arylhydrazono)‐1‐(1H‐1,2,4‐triazol‐1‐yl)acetone 8a‐c at 650 °C and 2.67 Pa yielded 5‐substituted 1‐(1H‐indazol‐3‐yl)ethanone 14a‐c and 4,6‐disubstituted cinnoline 18a‐c . Similarly FVP of 1‐(1H‐benzo[d]imidazol‐1‐yl)‐1‐(2‐phenylhydrazono)acetone 9a‐c gave 8H‐benzo[4′,5′]imidazo[2′,1′:5,1]pyrrolo[2,3‐c]cinnoline derivatives 23a‐c . A plausible mechanism is suggested to account for their transformation based on the kinetics and products of reaction.     

Chemoselective reaction of formalin with 2‐(5‐substituted‐2‐hydroxybenzylamino)phenols: Synthesis of 6‐substituted 3‐(2‐hydroxyphenyl)‐3,4‐dihydro‐2H‐benzo[e][1,3]oxazines

Reaction of 2‐(5‐substituted‐2‐hydroxybenzylamino)phenols ( 2 ) with formalin in ethanol under reflux has chemoselectively led to 2‐(6‐substituted‐2H—benzo[e][1,3]oxazin‐3(4H)‐yl)phenols ( 3 ) in good yield involving the ring closure of the hydroxyl group of the C‐aryl ring and not that of the N‐aryl ring.     

A facile regioselective synthesis of (5‐amino‐4‐cyano‐1h‐imidazol‐1‐yl) benzoic acids

A simple and efficient method was developped for the synthesis of 3‐(5‐amino‐4‐cyano‐1H‐imidazol‐1‐yl)‐4‐substituted benzoic acids 3 . These compounds were isolated by intramolecular cyclisation of the corresponding 3‐{[(Z)‐2‐amino‐1,2‐dicyano‐vinyl]amino}methyleneaminobenzoic acids in the presence of base.     

Nitropyridyl isocyanates in 1,3‐dipolar cycloaddition reactions

The reactivity of 3‐nitro‐4‐pyridyl isocyanate ( 7 ) and 5‐nitropyridin‐2‐yl isocyanate ( 9 ) in 1,3‐dipolar cycloaddition reactions with azides and pyridine N‐oxides has been investigated. 1,3‐Dipolar cycloaddition to trimethylsilylazide (TMSA) afforded the respective tetrazolinones, 1‐(3‐nitropyridin‐4‐yl)‐1H‐tetrazol‐5(4H)one ( 8 , 50 %) and 1‐(5‐nitropyridin‐2‐yl)‐1H‐tetrazol‐5(4H)one ( 11 , 64 %). Respectively, 1,3‐dipolar cycloaddition of nitropyridyl isocyanates 7 and 9 to 3,5‐dimethylpyridine N‐oxide ( 14 ), 3‐methylpyridine N‐oxide ( 21 ) and pyridine N‐oxide ( 22 ) gave the substituted amines, 3,5‐dimethyl‐N‐(3‐nitropyridin‐4‐yl)pyridin‐2‐amine ( 17 ), 3,5‐dimethyl‐N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 20 ), N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 24 ), 5‐methyl‐N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 23 ) and 3‐methyl‐N‐(5‐nitropyridin‐2‐yl)pyridin‐2‐amine ( 25 ) in 65 ‐ 80 % yield, obtained by cycloaddition, rearrangement and decarboxylation. The results demonstrate that the nitropyridyl isocyanates ( 7,9 ) readily undergo 1,3‐dipolar cyloaddition reactions similar to phenyl isocyanates.     

Reactions of some pyrrole‐2,3‐diones with hydrazine hydrate and o‐phenylenediamine

2,3‐Dihydro‐1H‐pyrrole‐2,3‐diones 1a‐d react with hydrazine hydrate 2 and o‐phenylenediamine 4 under different conditions to yield the pyrazole‐3‐carboxamide derivatives 3a‐d , the pyrrol‐2‐ones 5a‐d and the quinoxaline‐2‐one derivatives 6a‐d , respectively. Hydrolysis of the quinoxaline‐2‐one derivatives 6a‐d gave a substituted furo[2,3‐b]quinoxaline 7 . The structures of the synthesized compounds were assigned on the basis of analytical results as well as spectroscopic data.     

A Highly Sensitive Fluorescence Probe for Fast Thiol‐Quantification Assay of Glutathione Reductase

Fast detection of cellular thiols in aqueous medium was achieved using a newly developed fluorescence probe (see picture). Based on this probe, a high‐throughput fluorescence assay for glutathione reductase was developed.

     

Synthesis of condensed pyridones by using a new ring switching reaction

A new ring‐switching reaction of enaminoesters behaving as bisnucleophiles towards other enaminoesters behaving as biselectrophiles is described. By starting from pyroglutamic derivatives, this reaction provided easy access to methyl 5‐oxo‐1,2,3,5‐tetrahydro‐3‐indolizinecarboxylates substituted by an aminoester side chain in position 6.     

Disubstituted Azidotetrazoles as Energetic Compounds

Base‐catalyzed activation of the C? F bond in the trifluoromethylazo‐substituted cyclic and acyclic alkanes provides a route to disubstituted azidotetrazoles. For example, the reaction of 1,2‐bis(trifluoromethylazo)ethane with four equivalents of NaN₃ gave the alkyl‐bridged bis(5‐azido‐1H‐tetrazol‐1‐yl)‐1,2‐dimine, N,N′‐bis(5‐azido‐1H‐tetrazol‐1‐yl)‐1,2‐diiminoethane, in 75 % yield (see scheme).

     

Utility of 2‐[4‐(3‐oxobenzo[f]‐2H‐chromen‐2‐yl)‐1,3‐thiazol‐2‐yl]ethanenitrile in heterocyclic synthesis

Pyrazolo[4,3‐d]pyrimidines, pyrazolo[4,3‐d]triazolino[4,3‐a]pyrimidines, 3‐(2‐thiazolyl)thiophenes, thiazolo[3,2‐a]pyridine and pyrazolo[1,5‐a]pyrimidines were synthesized from 2‐[4‐(3‐oxobenzo[f]‐2H‐chromen‐2‐yl)‐1,3‐thiazol‐2‐yl]ethanenitrile. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation and alternative synthesis route whenever possible.