Sherief Moustafa

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

Summary The multicomponent reaction of 5-aminopyrazole derivatives with cyclic 1,3-dicarbonyl compounds and dimethylformamide dimethylacetal (DMFDMA) in DMF at 150 °C under controlled microwave heating afforded regioselectively 8,9-dihydropyrazolo[1,5-a]quinazolin-6(7H)-ones 6 rather than the corresponding dihydropyrazolo[5,1-b]quinazolin-8(5H)-ones 4.

Polyfunctional Nitriles in Organic Syntheses: A Novel Route to Aminopyrroles, Pyridazines and Pyrazolo[3,4-c]pyridazines

Phenacylmalononitrile 1 reacts with dimethylformamide dimethyl acetal to yield an enaminone which could be readily converted into a pyrrole or an aminopyridazine by treating with ammonium acetate and hydrazine hydrate, respectively. Compound 1 reacted with hydrazine hydrate in ethanol at room temperature to yield the dihydropyridazine 9 as a single product. In refluxing ethanol this product further reacted with hydrazine hydrate to yield the novel dihydropyrazolopyridazinamine 10.

Recent developments in utility of green multi-component reactions for the efficient synthesis of polysubstituted pyrans, thiopyrans, pyridines, and pyrazoles

Developments made since 2010 in the utilization of multi-component reactions as green efficient methodologies for the synthesis of polysubstituted pyrans, thiopyrans, pyridines, and pyrazoles are reviewed and the mechanisms of these processes are discussed. Reference is made to classical older synthetic methods developed earlier in our laboratories.Graphical Abstract

Studies with malononitrile derivatives: synthesis and reactivity of 4-benzylpyrazole-3,5-diamine, 4-benzylisoxazole-3,5-diamine and thiazolidin-3-phenylpropanenitrile

Benzylmalononitrile 6 reacts with hydrazines, and hydroxylamine hydrochloride to yield the 4-benzylpyrazole-3,5-diamines 7 and 4-benzylisoxazole-3,5-diamine 9, respectively. Pyrazole-3,5-diamines 7 could be readily reacted with α,β-unsaturated nitriles to yield pyrazolo[1,5-a]pyrimidines 20. Benzylmalononitrile, also reacted with thioglycolic acid to yield tautomeric mixture of 2-(4-hydroxythiazol-2-yl)-3-phenylpropanenitrile 29 and 2-(4-oxothiazolidin-2-yl)-3-phenylpropanenitrile 30 that coupled with benzene diazonium chloride to yield 2-(4-oxo-5-(phenylhydrazono)-thiazolidin-2-ylidene)-3-phenylpropanenitrile31.

Green methodologies in organic synthesis: recent developments in our laboratories

The results of the studies carried out in our laboratories during the last 15 years, aimed at developing green methodologies for the synthesis of polyfunctionalized heteroaromatic substances, are surveyed. The results of the investigations demonstrate that green methodologies are not only less hazard than classical preparative methods but they also are more efficient and economical. For example, short reaction times and higher yields are observed for reactions in which conventional heating is replaced by microwave or ultrasound irradiation. The implementation of multicomponent reactions in green preparative routes also reduces the cost of carrying out the reactions because multiple separation and crystallization steps are avoided. In general, by employing the new green methodologies we have been able to produce a large number of polyfunctional aromatic substances in a highly efficient manner.

Green synthetic approaches: solventless synthesis of polyfunctionally substituted aromatics as potential versatile building blocks in organic synthesis utilizing enaminones and enaminonitriles as precursors

Abstract A variety of 1,3,5-trisubstituted benzenes could be obtained upon heating enaminones in absence of solvent over montmorillonite-K-10. Heating mixtures of two different enaminones 2a–d have also afforded 1,3,5-trisubstituted benzenes 7b–d and 8b–d resulting from self-condensation of one enaminone with two molecules of the other enaminone. Heating enaminone 2b with ethyl propiolate afforded a mixture of triaroylbenzene 3b in addition to diaroylbenzoic acid esters 11 and 1,3,5-aroylbenzene dicarboxylate 12. On the other hand, reaction of enaminone derivative 2b with dimethyl acetylenedicarboxylate has afforded 2-oxopyran-4-carboxylic acid derivative 15. 2-Aminoprop-1-ene-1,1,3-tricarbonitrile 16 was reacted with enaminones to yield polysubstituted benzenes 19a–c. Likewise the reaction of 2-aminoprop-1-ene-1,1,3-tricarbonitrile 16 with benzylidenemalononitrile has afforded polysubstituted benzenes 24.

Unexpected Behavior of Enaminones: Interesting New Routes to 1,6-Naphthyridines, 2-Oxopyrrolidines and Pyrano[4,3,2-de][1,6]naphthyridines

Reaction of enaminones 1a–d with 2-aminoprop-1-ene-1,1,3-tricarbonitrile (2) in the presence of AcOH/NH4OAc afforded 7-amino-5-oxo-5,6-dihydro-1,6-naphthyridine-8-carbonitrile derivatives 9a–d. On the other hand, 2-aminopyrano[4,3,2-de][1,6]naphthyridine-3-carbonitriles 20a–c,e were the only obtained products from the reactions of 1a–d with 2 in the presence of AcOH/NaOAc, while 1d afforded [3,5-bis-(4-chloro-benzoyl)-phenyl]-(4-chloro-phenyl)-methanone 21 under the same condition. The reaction of 2 with diethyl acetylenedicarboxylate in the presence of AcOH/NH4OAc afforded (4-cyano-5-dicyanomethylene-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)-acetic acid ethyl ester 15B.

Recent Advances in the Synthesis of Polysubstituted Heterocycles

Abstract For over 50 years, we have continually searched achieving simple routes for syntheses of polyfunctional substituted heterocyclic compounds utilizing inexpensive readily obtainable starting materials. We had already achieved efficient syntheses of polyfunctional substituted pyrans, thiopyrans and their benzo, naphtho fused derivatives in high yields. In addition, a variety of syntheses for polyfunctional substituted azoles, azines azoloazines and their condensed derivatives could also be achieved. Recently, these applications of this methodology has attracted attention and plenty of efforts have been made by us and others to develop greener synthetic approaches as multicomponent and solventless reactions. Trials to replace homogeneous catalysis utilized in the past by ecofriendly heterogeneous ones has also been made and the results of these efforts are surveyed here. Trials to adapt upon conventional source for energy replacing conventional heating are also described. The trials of several novel unexpecting rearrangements are also reported and extensive utility of X-ray crystallography in recent work is also emphasizing upon. Finally, the biological significance of the product obtained over these years has been reviewed from patents literature as well as biological chemistry literature also been surveyed.

Scope and Limitations of a Novel Synthesis of 3-Arylazonicotinates

The reaction of 3-oxo-3-phenyl-2-phenylhydrazonal with functionally substituted and heteroaromatic substituted acetonitrile to yield arylazonicotinic acid derivatives and 5-arylsubstituted pyridines was established. In some cases the produced nicotinates could not be isolated as they underwent thermally induced 6π-electrocyclization yielding polynuclear pyridine derivatives.

Reassignment of the Structures of Products Produced by Reactions of the Product Believed To Be 2-(1-Phenyl-2-Thiocyanatoethylidene)-malononitrile with Electrophiles

The reactivity of the product believed to be 2-(1-phenyl-2-thiocyanato-ethylidene)malononitrile toward a variety of electrophilic and nucleophilic reagents is reported.