Isonicotinoylhydrazothiazoles and isonicotinoyl‐N4‐substituted thiosemicarbazides: Synthesis,characterization, and anti‐mycobacterial activity

Differently substituted isonicotinoylhydrazothiazoles and isonicotinoyl‐N⁴‐substituted thiosemi‐carbazides have been prepared and characterized by means of elemental analysis, ¹H‐NMR, ¹³C‐NMR, and Mass spectrometry. All the synthesised compounds have been screened in order to evaluate their antimycobacterial activity in vitro. Some of the new compounds showed activity towards M. tuberculosis H37R and M. Marinum in the millimolar range.     

Reactions of methyl 2‐(benzyloxycarbonyl)amino‐3‐dimethylaminopropenoate and related compounds with hydrazines. Regiospecific synthesis of 1‐substituted‐4‐amino‐substituted‐1H‐pyrazol‐5‐(2H)‐ones

In this paper the regiospecific transformations of methyl 2‐(benzyloxycarbonyl)amino‐3‐dimethylaminopropenoate ( 1 ) with hydrazine, alkyl‐, aryl‐ and heteroaryl‐substituted hydrazines via the corresponding hydrazones 12‐16 into pyrazoles 17‐25 are described. Heteroaryl‐substitued hydrazones 13‐16 afforded by oxidation with bromine or lead tetraacetate the corresponding substituted (1,2,4‐triazolo[4,3‐b]pyridazin‐3‐yl)glycinates 27‐30 . Alkyl 2‐(2,2‐disubstituted‐1‐ethenyl)amino‐3‐dimethylaminopropenoates 31‐33 gave with hydrazines alkyl 2‐[2,2‐(disubstituted)ethenyl]amino‐3‐heteroarylhydrazonopropanoates 40‐48 and 2‐alkyl 2,3‐bis((hetero)arylhydrazono)propanoates 51‐55 .     

Synthesis of 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic acid diethylamides as potential anti‐inflammatory agents

Fifteen novel 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydro‐ pyridine‐5‐carboxylic acid diethylamide ( 7, 15 ) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding 1‐(substituted phenylcarbonyl/ sulfonylimino)‐3‐diethylcarbamoyl pyridinium ylides ( 6, 14 ) in absolute ethanol.     

1,3‐Dipolar cycloadditions of 9‐diazofluorenes and diphenyldiazomethane to 2‐acyl‐2H‐1,2,3‐diazaphospholes

A series of 2‐acyl‐2H‐1,2,3‐diazaphospholes 3 underwent ready 1,3‐dipolar cycloaddition reactions with 9‐diazofluorenes as the 1,3‐dipole, yielding the respective bicyclic phosphiranes 5 or trimers 7 depending on the reaction conditions employed. The reaction is believed to proceed via the formation of the [3+2]‐cycloaddition adducts followed by elimination of nitrogen from the cyclic azo moiety. In the case of 3c , the phosphatetraazabicyclooctadiene compound 6 has been isolated with no loss of nitrogen. Likewise, the dipolar cycloaddition reaction of diphenyldiazomethane with the >C?P‐ moiety as the 1,3‐dipolarophile gave phosphadiazabicyclohexenes 8 in 32–68% yields.     

Synthesis of novel pyrazole‐linked norcantharidin derivatives of substituted aromatic amines with efficient 1,3‐dipolar cycloaddition

Highly efficient, practical and convient synthesis of fifteen compounds by the [3+2] 1,3‐dipolar cycloaddition reaction of norcantharidin derivatives of substituted aromatic amines with three hydrazines in the presence of Chloramine‐T.     

Synthesis and characterization of 4‐aryl‐5‐(1‐aryl‐2‐methyl‐2‐nitropropyl)‐1,2,3‐selenadiazoles

The synthesis of a new set of selenadiazoles, 4‐aryl‐5‐(1‐aryl‐2‐methyl‐2‐nitropropyl)‐1,2,3‐selenadiazoles ( 4 ) derived from 2‐[4‐methyl‐4‐nitro‐1,3‐diarylpentylidene]‐1‐hydrazinecarboxamide ( 3 ) has been reported. THF has been found to be the solvent of choice for this reaction. Structural features of 3 and 4 have been analyzed by NMR and X‐ray techniques.     

Cyclocondensation reactions of heterocyclic carbonyl compounds XII. The double course of cyclization of 3‐(2‐aminobenzyl)‐1,2‐dihydro‐quinoxaline‐2‐one

The cyclocondensation reaction of compound 1 in boiling hydrochloric acid had an unexpected course. Instead of supposed 5,11‐dihydro‐quinoxalino[2,3‐b]quinoline 6a , 2‐(indol‐2‐yl)‐benzimidazole 4 was isolated as the major product.     

The reaction of aryl and heteroarylhydrazines with aryl‐trifluoromethyl β‐diketones

We report the results obtained when five aromatic or heteroaromatic hydrazines react with six β‐diketones bearing trifluoromethyl and aryl substituents. Forty‐two compounds have been isolated corresponding to two isomeric trifluoromethyl pyrazoles and the intermediate 5‐CF₃, 5‐OH pyrazolines. The results have provided useful information for establishing the mechanism of the synthesis of pyrazoles.     

Synthesis of 9‐[1‐benzyl‐5‐(alkylsulfonyl)‐1H‐2‐imidazolyl]perhydro‐1,8‐acridinediones

Tricyclic dihydropyridines like ZM244085 are potential K_ATP channel openers. In this study 3‐cyanophenyl ring of ZM244085 was replaced with imidazolyl ring. So, 9‐[1‐benzyl‐5‐(alkylsulfonyl)‐1H‐2‐imidazolyl]perhydro‐1,8‐acridinediones ( 5d‐f ) were synthesized from 2‐alkylsulfonyl‐1‐benzyl‐5‐formylimidazole ( 4d‐f ) and cyclohexane‐1,3‐dione according to classical Hantzch synthesis as potential potassium channel modulators.     

Rational Construction of 2D and 3D Borromean Arrayed Organic Crystals by Hydrogen‐Bond‐Directed Self‐Assembly

Borromean organic networks: The rigid and trigonal pyramidal molecule, 1,3,5‐tris(4‐carboxyphenyl)adamantane (TCA), self‐assembles into a 2D Borromean linked network by hydrogen bonds. Different linkers (methanol, phenazine, 4,4′‐bipyridine, and 4,4′‐azopyridine) result in more complex Borromean networks or a 3D polycatenation network.

     

The preparation of 3‐substituted 1,2‐benzisothiazole‐1,1‐dioxides from the condensation‐cyclization of dilithiated β‐ketoesters with methyl 2‐(aminosulfonyl)benzoate or 1,2‐benzisothiazol‐3(2H)‐one‐1,1‐dioxide

Several β‐ketoesters were dilithiated with an excess of lithium diisopropylamide, followed by condensation with methyl 2‐(aminosulfonyl)benzoate to give intermediates that were not isolated but cyclized to 3‐substituted 1,2‐benzisothiazole‐1,1‐dioxides. In most instances involving the ester‐sulfonamide, a single β‐ketoester tautomer is usually formed after recrystallization from ethanol. The same dilithiated β‐ketoesters generally condense less well with 1,2‐benzisothiazol‐3(2H)‐one‐1,1‐dioxide (saccharin) under the same conditions to afford the same products usually in the same or lower yields. The use of N,N,N',N'‐tetramethylethylenediamine during these syntheses has sometimes resulted in improved yields of products.     

The stereoselective synthesis of e‐1,2‐bis(3‐indolizinyl)ethylenes by the reactions of 3‐thioformylindolizines with n‐tributylphosphine

3‐Thioformylindolizines undergo novel reductive coupling reaction in the presence of tributylphosphine to give E‐1,2‐bis(3‐indolizinyl)ethylenes in high yield. These reactions proceed via (3‐indolizinyl)methylene carbene intermediate and provide a new, stereoselective synthesis of the bis(3‐indolizinyl)ethylene derivatives highly.     

The synthesis of 3,3‐dimethyl‐2‐(1‐aryl‐1h‐pyrazol‐4‐yl)‐3h‐indoles

2,3,3‐Trimethylindolenine and 5‐chloro‐2,3,3‐trimethylindolenine were converted into β‐diformyl compounds by the action of the Vilsmeier reagent at 50°C. The dialdehydes reacted with various arylhydrazines and 2‐pyridylhydrazine to produce mono‐hydrazones as mixtures of cis and trans isomers. Heating the hydrazones in refluxing ethanol produced 3,3‐dimethyl‐2‐(1‐aryl‐1H‐pyrazol‐4‐yl)‐3H‐indoles in excellent yields. Reaction of the β‐diformyl compounds with hydrazine itself led directly to 3,3‐dimethyl‐2‐(pyrazol‐4‐yl)‐3H‐indoles.     

Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters

A diastereoselective synthesis of 1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters has been developed using a tandem reduction‐double reductive amination reaction. The nitro dicarbonyl cyclization substrates were synthesized by alkylation of methyl (2‐nitrophenyl)acetate with 2‐bromomethyl‐1,5‐hexadiene derivatives, followed by ozonolysis. Catalytic hydrogenation of each substrate gave the target heterocycle, along with a deacylated product and an adduct resulting from capture of the intermediate hydroxylamine by the side chain carbonyls. The product ratio varied dramatically with the catalyst and the hydrogen pressure. Cyclization to the title compounds was highly diastereoselective, producing each hexahydropyrrolo[1,2‐a]‐quinoline as a single stereoisomer with the all‐cis geometry. The competing processes have not been observed in previous heterocyclization studies but can be attributed to greater strain in the system, which slows the final ring closure.     

Dual‐Responsive Supramolecular Hydrogels from Water‐Soluble PEG‐Grafted Copolymers and Cyclodextrin

Novel temperature and pH dual‐responsive hydrogels were constructed by inclusion of poly(PEGMA)‐co‐poly(DMA) with α‐cyclodextrin in aqueous solution. The temperature‐ or pH‐induced sol/gel transition in the hydrogels was completely reversible. Studies on structure/property relationships show that chain uniformity, graft density and copolymer concentration affect the hydrogel behavior. A dual‐responsive mechanism is proposed. The in vitro release of a model drug from this hydrogel was studied. It was found that the release kinetics were greatly accelerated at higher temperature and at acidic pH conditions, indicating potential applications in controlled drug delivery.

     

Synthesis of some new 4‐substituted‐3, 5‐bis(2‐pyridyl)‐1h‐pyrazole

Several 4‐substituted‐3, 5‐bis(2‐pyridyl)‐1H‐pyrazoles, where the substituent is chloro, bromo, iodo, nitro, diazo, were synthesized under mild reaction conditions in high yields. The structures of the products were characterized by ¹H NMR, ¹³C NMR, ESI‐MS, IR and elemental analyses.     

Ring closure reactions of 5‐azidopyrido[2,3‐d]pyrimidinetriones to isoxazolo‐ and oxadiazolopyrido[2,3‐d]pyrimidinetriones

Thermal decomposition of 5‐azidopyrido[2,3‐d]pyrimidines 2 and 7 having reactive ortho‐substituents such as a formyl or a nitro group yielded isoxazolo[3′,4′:4,5]pyrido[2,3‐d]pyrimidines 3 or oxadiazolo‐[3′,4′:4,5]pyrido[2,3‐d]pyrimidines 9. The reaction conditions of the azide decomposition were studied by differential scanning calorimetry (DSC). In addition, desoxygenation of N‐oxides 9 to oxadiazoles 10 and regioselective reduction of azides 7 to amines 8 were studied.     

Alpha vinylation of haloquinoline‐5,8‐diones with methyl acrylate and methyl vinyl ketone under baylis‐hillman reaction conditions

A synthesis of mono‐ and di‐vinylquinolinediones based on substitution of the halogens in 6,7‐dihaloquinoline‐5,8‐diones by DABCO‐assisted enolate ion is described. Divinylquinolines undergo 6π‐electrocyclization by thermally to give the benzo[g]quinoline derivatives.     

Synthetic study for two 2H‐chromenic acids, 8‐chlorocannabiorcichromenic acid and mycochromenic acid

Two 2H‐chromenes having a fully substituted benzene ring, 8‐chlorocannabiorcichromene ( 1 ) and mycochromenic acid ( 2 ), were synthesized by a condensation of salicylaldehydes with isopropylidenemalonate or the thermal cyclization of corresponding propargyl ethers.     

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.