Talaat I. El-Emary

Facile synthesis of some new pyrazolo[3,4-b] pyrazines and their antifungal activity

The synthesis of new pyrazolo[3,4-b]pyrazines and related heterocycles has been reported. The key intermediate 1,6-diphenyl-3-methyl-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile 2 was obtained in one pot synthesis from the reaction of 5-amino-3-methyl-4-nitroso-1-phenylpyrazole 1 with benzoylacetonitrile. Modest antifungal activity was shown for some of the prepared compounds.

Synthesis and Antimicrobial Activity of Some New 1,3-Diphenylpyrazoles Bearing Pyrimidine, Pyrimidinethione, Thiazolopyrimidine, Triazolopyrimidine, Thio-and Alkylthiotriazolop-Yrimidinone Moieties at the 4-Position

1,3-diphenyl-1H-pyrazole-4-carboxaldehyde (1) reacted with ethyl cyanoacetate and thiourea to give the pyrimidinethione derivative 2. The reaction of 2 with some alkylating agents gave the corresponding thioethers 3a–e and 7. Thione 2 was cyclized to 5 and 6 upon a reaction with chloroacetic acid and with benzaldehyde, respectively. Thioether 3c was cyclized to 4 upon boiling with sodium acetate in ethanol, and 7 was cyclized to 8 upon boiling in an acetic anhydride-pyridine mixture. The hydrazino derivative 9 was prepared either by boiling 2 and/or 3a with hydrazine. The reaction of 9 with nitrous acid, acetylacetone, triethyl orthoformate, acetic anhydride, and carbon disulfide gave 10–14. The alkylation of 14 with ethyl iodide, phenacyl bromide, and ethyl chloroacetate afforded the alkythiotriazolo pyrimidinone derivatives 15a–c. The dialkyl derivative 16 was produced upon the treatment of 2 with two equivalents of ethyl iodide. Boiling 16 with hydrazine afforded the hydrazino 17. The reaction of 17 with nitrous acid, carbon disulfide, ethyl cyanoacetate, ethyl acetoacetae, and phenacyl bromide gave 18–22, respectively. Some of the newly obtained compounds were tested for their antibacterial and antifungal activities.

A Facile Synthesis of Some New Thiazolo[3, 2]pyridines Containing Pyrazolyl Moiety and Their Antimicrobial Activity

Abstract Condensation of 2-cyanomethyl-4-thiazolinone 1 with 1,3-diphenyl-pyrazole-4-carboxaldehyde 2 in ethanol containing a few drops of piperidine yielded the novel methylene derivative 3 . Compound 3 was refluxed with malononitrile to give the corresponding thiazolo[ [3] , [2] ]pyridine derivative 5 . Also, treatment of compound 3 with benzylidenemalononitriles gave the thiazolo[ [3] , [2] ]pyridine derivatives 6a–e . Refluxing of compound 6d with triethyl orthoformate furnished the ethoxymethylideneamino derivative 7 . Formic acid and malononitrile were reacted with compound 6d to produce thiazolo[ [3] , [2] ][ [1] , [8] ]naphthyridine derivative 8 and 11 , respectively. Condensation of 2 with cyanoacetohydrazide in ethanol containing piperidine as catalyst gave the hydrazone derivative 12 which, on treatment with salicyaldehyde and 2-cyano-3-(4-fluorophenyl)acrylic acid ethyl ester, yielded the novel chromene 13 and pyridinone 14 , respectively. Structures of the synthesized compounds have been established by elemental analysis and spectral data. Compounds 3 , 5 , 6a–d , 8 , 11 , 13 , and 14 have been screened for antimicrobial activities.

Synthesis and Antimicrobial Activity of some New Heterocycles Based on 3-Methyl-1-Phenyl-5-Benzene Sulfonamido Pyrazole

Treatment of 3-methyl 1-phenyl-5-amino pyrazole 1 with 4-acetyl benzene sulfonyl chloride in pyridine gave the sulfonamide 2 . Condensation of 2 with aromatic aldehydes, semicarbazide, and thiosemicarbazide furnished the f , g -unsaturated ketones 3a-c , the semicarbazone 4a and the thiosemicarbazone 4b respectively. Reaction of 3a-c with hydrazine hydrate, phenyl hydrazine, hydroxylamine, thiourea afforded the pyrazoles 5a-f , isoxazoles 6a-c , and pyrimidinethiones 7a-c . Reaction of 3a-c with malononitrile in ethanol containing piperidine provided the pyran derivatives 8a-c , while, when the reaction was carried out in boiling acetic acid in presence of ammonium acetate, the pyridine derivatives 9a-c were formed. When 4a reacted with thionyl chloride and with selenium dioxide, 1,2,3-thiadiazole and 1,2,3-selenadiazole 10 , 11 were formed respectively. Allowing 4b to react with f -halocarbonyl compounds such as phenacyl bromide, chloroacetone, 2-bromomethyl propionate, chloroacetic acid, and bromo diethylmalonate afforded the thiazolines 12a , b and thiazolidinones 13a-c respectively.

Synthesis and characterization of new polyhydrazides based on 2,5-bis(mercapto-acetichydrazide)-1,3,4-thiadiazole moiety

Abstract New interesting class of novel polyhydrazides containing 1,3,4-thiadiazole moieties in the main chain was synthesized. A solution polycondensation technique was used in the synthesis of these polymers. The new monomer namely: 2,5-bis(mercapto-acetichydrazide)-1,3,4-thiadiazole III was synthesized from the nucleophilic replacement of 2,5-dimercapto-1,3,5-thiadiazole I with ethylchloroacetate, followed by hydrazinolysis. The model compound VII was synthesized from the monomer 2,5-bis(mercapto-acetichydrazide)-1,3,4-thiadiazole III with benzoyl chloride and characterized by 1H- NMR, IR, and elemental analyses. The polyhydrazides were synthesized from the polymerization of monomer III with 4,4′-biphenic, 3,3′-azodibenzoyl, 4,4′-azodibenzoyl dichlorides. These polymers were characterized by elemental and spectral analyses, viscometry and solubility. The thermal properties of these polymers were determined by thermal gravimetric analyses, and differential thermal analysis, and correlated with their structure. The crystallinity of some polymers was tested by X-ray analyses.

First synthesis and biological evaluation of indeno[2,1-e]pyrazolo[3,4-b]pyrazin-5-one and related derivatives

The synthesis of indeno[2,1-e]pyrazolo[3,4-b]pyrazin-5-one was achieved by intramolecular Friedel-Crafts reaction of the acid chloride 3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b] pyrazine-5-carboxylic acid chloride (4) using AlCl3 in boiling CS2. Compound 4 proved to be a versatile compound for the synthesis of several Indenopyrazolopyrazinone derivatives. The antibacterial and antifungal activities of selected derivatives were evaluated.

POLYCYCLIC PYRAZOLES : ROUTES TO NEW PYRAZOLOAZINES

A number of substituted pyrazolo[3,4-b]pyridines and pyrazolo[4′,3′:5,6]pyrido[2,3-d]-pyrimidinones and -1,2,3-triazinones have been made, starting from 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde.

New tetraaza macrocyclic complexes of palladium(II) and platinum(II) formed by the self-condensation of 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde in the presence of metal ions. α-Amino ether and carbinolamine derivatives of the macrocyclic Schiff base metal complex

The self-condensation of 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde (AMPC) in the presence of PdII and PtII ions yields the PdII and PtII complexes, [M(TAAP)]Cl2, of the fully cyclized tetradentate macrocyclic ligand tetrapyrazolo[1,5,9,13]tetraazacyclohexadecine, (TAAP). Metathetical displacement of the chloride has led to isolation a series of complexes of the type [M(TAAP)]X2, (X=I, ClO4 and BF4), the formulation of which is supported by elemental analysis, molar conductance and magnetic susceptibility measurements, and i.r. and u.v.–vis. spectra. Spectroscopic and other analytical results reveal that the complexes have square-planar stereochemistry with four donor nitrogen atoms coordinated to the metal ion in a planar array. The reaction which produces this new cyclic ligand is assumed to include the metal ion acting as a template for the condensation. Thus the probable mechanistic implications for the coordination template hypothesis are discussed to explain the formation of these new macrocyclic chelate compounds. Both PdII and PtII complexes appear to be sensitive to nucleophilic attack at the methine carbon, which is reversible upon acidification. The reaction of [Pt(TAAP)]2+ or [Pd(TAAP)]2+ with MeO- or EtO- ions results in the formation of partially solvolysed inner complexes containing two ionized α-amino ether functions, stabilized by the macrocyclic chelate ring. Attempts to prepare discrete α-carbinolamine derivatives were unsuccessful.

Studies on the Synthesis of Some New Cyanopyridine-Thione and Thieno[2,3-b]pyridine Derivatives

The work included in this article involves the synthesis of new cyanopyridinethiones as good synthons for new thieno[2,3-b]pyridines with anticipated biological activities. Thus, the reaction of β–aryl-α-thiocarbamoylacrylonitrile ( 1a–c ) with (2-thenoyl)-ω,ω,ω-trifluoroacetone led to an unexpected formation of 4-aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thiones ( 4a–c ). In contrast, the reaction of 1a,b with ethyl acetoacetate produced 4-aryl-3-cyano-5-ethoxycarbonyl-6-methylpyridine-2(1H)-thiones ( 12a,b ). The reaction of compound 4a with methyl iodide gave 2-methylthio derivative 6 , which upon treatment with hydrazine hydrate furnished pyrazolopyridine 7 . Treatment of 4a–c with chloroacetaimde, in the presence of sodium ethoxide, led to the formation of 3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamides ( 8a–c ). The reactions of 8a with some aromatic aldehydes and/or cycloalkanones were carried out and their products were identified. Compounds 12a,b were reacted with chloro-N-arylacetamides to give ethyl 4-aryl-2-(N-aryl)carbamoylmethylthio-3-cyano-6-methylpyridine-5-carboxylates ( 13a–j ). Upon treatment of compounds 13a–j with sodium alkoxide in alcohol, they underwent an intramolecular Thorpe-Ziegler cyclization to furnish ethyl 3-amino-4-aryl-2-(N-aryl)carbamoyl-6-methylthieno[2,3-b]pyridine-5-carboxylates ( 14a–j ). Compounds 14a–j , in turn, were reacted with triethyl orthoformate and/or carbon disulfide to give corresponding pyridothienopyrimidinone derivatives 15a–j and 18 . Pyridothienotriazinone analogs 17a–j were synthesized via diazotisation of compounds 14a–j .

Synthesis of Thiazolo[5,4-d]pyrimidine, Thiazolo[5,4-b]pyridine, Thiazolo[4,5-b]pyrrolizine and Thiazolo[5,4-d]thiazaphosphinine

5-amino-2-methylsulfanyl-thiazole-4-carboxylic acid ethyl ester 1 reacted with malononitrile, benzoylisothiocyanate, and 2-(methylsulfanyl-phenylaminomethylene)malononitrile to furnish the thiazolopyrimidine-2-one derivatives 2–4, respectively. 1 reacted with the dipotassium salt of the 2-dimercaptomethylene-malononitrile prepared by the reaction of malononitrile and CS 2 and KOH in the presence of TBAB under solid–liquid phase transfer catalysis to give 5. Reacting 1 with triethyl orthoformate, chloroacetyl chloride, and 2,5 dimethoxy tetrahydrofuran afforded 6–8. The reaction of 1 with Lawessons reagent gave 9. The reaction of 1 with benzylidinemalononitrile gave 10. The reaction of hydrazine hydrate with 1 and/or 6 afforded 11 and 12, respectively. 7 reacted with malononitrile to give 13. The cyclization of 8 by the action of PPA gave 14. Thiazole-4-carbohydrazide 11 reacted with acetic anhydride/acetic acid mixture and with formic acid to yield 15 and 16, respectively. 11 reacted with p-chloro benzaldehyde to give 17. The treatment of compound 17 and/or 11 with triethyl orthoformate afforded 18 and 19, respectively. The reaction of 11 with CS2 and with 2-(bismethylsulfanyl-methylene)malononitrile gave 20 and 21, respectively.