Mohamed Rifaat Hamza Elmoghayar

Chemistry of Pyrazolopyrimidines

Publisher Summary The interesting biological activities reported for pyrazolopyrimidines have stimulated chemists to develop the chemistry of this class of compounds. This chapter appears to be the first survey of the chemistry and biological activity of this class of compounds. Condensation of β-keto esters with 3( 5)-aminopyrazoles has been used extensively to synthesize pyrazolo[ 1,5-a]pyrimidines. Theoretically, two isomeric pyrazolo[ 1,5-a] pyrimidines can be produced. The parent pyrazolo pyrimidine has been synthesized via cyclocondensation of 1-unsubstituted 3(5)-aminopyrazoles (12) with malonodialdehyde tetramethylacetate. This approach was used to synthesize several substituted pyrazolo pyrimidines. 3- Oxoalkanonitriles and their functional derivatives condense readily with 12 to yield 7-aminopyrazolo. And benzoylacetonitrile and its p-chlorophenylazo and acetylbenzyl cyanide derivatives react with β-cyanoethylhydrazine (74) to yield pyrazolo pyrimidines formed via l-β-cyanoethyl-5-aminopyrazole intermediates. The chapter also discusses chemical properties of pyrazolo[ 1,5-a]pyrimidines and pyrazolo[3,4-d]pyrimldines and elaborates on theoretical methods, spectra, and tautomerism.

Reactions with β-cyanoethylhydrazine—II: Synthesis of some 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine derivatives

Abstract β-Cyanoethylhydrazine 1 reacts with benzoylacetonitrile 2 in refluxing ethanol to yield 5-amino-1-β-cyanoethyl-3-phenylpyrazole 4 ; in acetic acid acetyl-β-cyanoethylhydrazone 8 was obtained. Compounds 4 and 8 were readily cyclized into 2-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-5-one 5 by acetic acid-hydrochloric acid. 3-p-Chlorophenylazo-2-phenyl-4,5,6,4-tetrahydropyrazolo[1,5-a]pyrimidin-5-one 15 was synthesized by the action of 1 on the p-chlorophenylazo derivative of 2 and cyclization of the resulting aminopyrazole 12 by concentrated sulphuric acid. The arylidene derivative of benzoylacetonitrile 16 reacts with 1 in acetic acid to yield the correspondings β-cyanoethylhydrazones 17 . Cyclization of 17 with acetic acid-hydrochloric acid led to the formation of the pyrazolo (1,2-b) pyrazole derivative 19 . On the other hand, the 1-β-carboxyethylpyrazole derivative 20 was obtained by the action of 3% aqueous NaOH.

Structural Studies of Metal complexes with a Thiosemicarbazide Derivative

Abstract 1-Cyanoacety1-4-cinnamoylthiosemicarbazide and its complexes of the bivalent metal ions Cu(II), Ni(II), Co(II), Pb(II) and Hg(II) have been synthesised and characterized. Probable structures for the complex compounds have been proposed on the basis of elemental analyses, conductometric, spectral and magnetic susceptibility data. The acid dissociation constant of the ligand was determined potentiometrically.

Reactions with heterocyclic diazonium salts: novel synthesis of pyrazolo[4,3-c]pyridazines and of pyrazolo[4,3-c]pyrazoles

Diazotised 4-amino-1,5-dimethyl-2-phenylpyrazol-3(2H)-one (1) coupled with active methylene nitriles to yield the corresponding cyanohydrazones (3a–c) and (11). Compounds (3a–c) afforded the 4-(3-aminopyrazol-4-ylidenehydrazino)-1,5-dimethyl-2-phenylpyrazol-3(2H)-ones (5a–c) on treatment with hydrazine hydrate, and cyclised to give the pyrazolo[4,3-c]pyridazines (7a–c) on treatment with ethanolic hydrochloric acid. The hydrazone (11) cyclised to give the pyridazin-6-one derivative (12) when boiled under reflux in ethanol. Diazotised pyrazolone (1) coupled with 3-chloropentane-2,4-dione and with ethyl 2-chloro-3-oxobutanoate to yield the pyrazolo[4,3-c]pyrazole derivatives (9a and b).

Reactions with Heterocyclic Diazonium Salts, II Synthesis of Some New Pyrazolo[1,5-c]-as-triazines and 1,2,4-Triazolo[1,5-c] -as-triazines

3-Phenylpyrazole-5-diazonium chloride (2) couples with benzoylacetonitrile and with phenacylthiocyanate to yield the corresponding hydrazone derivatives 3 a, b. Whereas 3 a cyclised into the pyrazolo[1,5-c]-as-triazine derivative (4a) upon treatment with concentrated sulphuric acid via elimination of water, treatment of 3 b with the same reagent under the same conditions has resulted in elimination of thiocyanic acid and the formation of the pyrazolo[1,5-c]-as-triazine derivative (4b). Treatment of 2 with aqueous sodium acetate has afforded the corresponding 3-phenyl-5-diazopyrazole (6). The latter reacted readily with dipolarophiles to yield pyrazolo- [1,5-c]-as-triazine derivatives. Pyrazolo[1,5-c]-as-triazines has also been formed upon treatment of 6 with active methylene compounds. The mechanism of reaction of 2 and 6 with active methylene compounds is discussed. Diazotization of 5-amino-3-ethyl-1,2,4-triazole nitrate (7) has afforded the corresponding diazonium derivative which coupled with benzoylacetonitrile and with acetoacetanilide to yield the corresponding hydrazones 9 a, b. The latter could be cyclised into 1,2,4-triazolo[1,5-c]-as-triazines by the action of concentrated sulphuric acid

Electroreduction of the activated olefinic double bond in some 2-aryl-1(2-acetylamino-1,3,4-thiadiazol-5-yl)-propionitrile derivatives

The electrochemical reduction of a series of the title compounds has been investigated in alcoholic buffered media at the DME. A mechanism for the reduction process has been proposed and confirmed through spectrophotometric and potentiometricpKa determinations and identification of CPE products. A trial to calculate the kinetic parameterkf,ho by different methods is included.ZusammenfassungEs wurde die elektrochemische Reduktion einer Serie der Titelverbindungen in alkoholischer, gepufferter Lösung an der tropfenden Quecksilberelektrode untersucht. Ein Mechanismus für den Reduktionsprozeß wird vorgeschlagen, der auf Befunde spektrophotometrischer und potentiometrischerpKa-Messungen und die Identifizierung von Produkten der kontrollierten Potentialelektrolyse (CPE) gestützt ist. Ein Versuch zur Ermittlung der kinetischen Parameterkf,ho mit verschiedenen Methoden wurde unternommen.

Activated Nitriles in Heterocyclic Syntheses, I Novel Synthesis of Pyrrolones and 1,2,4-Triazol-3-oyl nitriles

Abstract Heterocyclic Synthesis, Pyrrolones The behaviour of 4-benzylidene-2-oxazolin-5-one (2) and of 4-phenylazo-2-oxazolin-5-one (3) toward a variety of active methylene reagents is reported. Cleavage of the oxazolin-5-one ring was observed in most cases. A variety of new, otherwise, difficult accessible, azolyl derivatives could be prepared.

Studies on 3,5-Diamino Pyrazoles: Chemical Behavior of 4-Phenylazo-3,5-diaminopyrazoles

The behaviour of 3,5-diamino-4-phenylazopyrazole (1) toward isothiocyanates, acrylonitrile and ethyl ethoxymethylenecyanoacetate is investigated. An improved synthesis of 4-unsubstituted-3,5-diaminopyrazoles by an arylazo removal reaction is also reported.

Electroreduction of a series of 2-benzoylamino-5-(1-cyano-2-arylvinyl)-1,3,4-thiadiazoles

The electrochemical reduction of a series of 1,3,4-thiadiazoles in alcoholic buffered media has been investigated. The mechanism of the electrode processes is suggested and discussed. A cyclopentene carboxylic acid product is formed through a Ziegler–Throp reaction; the thiadiazole ring is inactive. Confirmation of the mechanism via c.p.e., spectrophotometric analyses, and the study of Hammetts relations is presented.