M. Hammouda

A study on the doubleMannich reaction with 1,3-diphenylacetone

DoubleMannich reaction of the title compound1 with morpholine acetate in ethanol gave the symmetrical bis-base2, whereas such reaction in acetic acid afforded the vinyl-ketonic base3. Reactions of3 with morpholine, piperidine, thiophenol and dimethyl phosphite were investigated.Mannich reaction of2 with primary amines gave di-basically substituted γ-piperidones6a-b. Compound1 reacts with ethylenediamine and formaldehyde to give the diazatricyclic system7.ZusammenfassungDie Doppel-Mannichreaktion der Titelverbindung1 ergab mit Morpholinacetat in Ethanol die symmetrische Bis-Base2, in Essigsäure erhielt man jedoch die Vinyl-keton-base3. Die Reaktionen von3 mit Morpholin, Piperidin, Thiophenol und Dimethylphosphit wurden untersucht. DieMannich-Reaktion von2 mit primären Aminen ergab di-basisch substituierte γ-piperidone6a-b. Verbindung1 reagiert mit Ethylendiamin und Formaldehyd unter Ausbildung eines Diaza-tricyclischen Systems7.

new simple and one-pot synthetic routes to polyfunctionally substituted imidazo-[1,2-a]pyridines, pyrido[1,2-a]pyrimidines, pyrido-[1,2-a]-1,3-diazepines, and imidazo[1,2-a]pyrimidines

Reactions of arylidenemalononitriles with 2-nitromethylene-substituted imidazolidine, hexahydropyrimidine, and hexahydro-1,3-diazepine afforded the title derivatives. Reaction of 2-nitromethylenehexahydropyrimidine with benzylamine or n-butylamine and formalin in a molar ratio of 1:1:2 gave the hexahydro-1H-imidazo[1,2-c]pyrimidine derivatives. Treatment of 2-nitromethyleneimidazolidine and hexahydropyrimidine with secondary aliphatic amines and formalin in a molar ratio of 1:1:1 afforded the corresponding methylene bis-compounds.

Pictet-Spengler reactions of Tryptamine and tryptophan with cycloalkanones and ketonicMannich bases

APictet-Spengler reaction of Tryptamine (1) with cyclopentanone under physiological conditions gave 3-(cyclopentylideneaminoethyl)indole (3), which was cyclized to the 1-spirocyclic 1,2,3,4-tetrahydro-2-carboline (4). Treatment of (±)-tryptophan with cyclopentanone and cyclohexanone in acidic medium afforded the spirocyclic systems5 and6, respectively. ThePictet-Spengler reaction was extended further using ketonic bis-Mannich bases, to give compounds7 and8. The possibility of using other types of ketonic bases was investigated.ZusammenfassungDiePictet-Spengler-Reaktion von Tryptamin (1) mit Cyclopentanonen ergab unter physiologischen Bedingungen 30(Cyclopentylidenaminoethyl)indole (3), die zu den spirocyclischen Tetrahydro-2-carbolinen4 cyclisiert wurden. Die Behandlung von (±)-Tryptophan mit Cyclopentanon oder Cyclohexanon in saurem Milieu ergab die spirocyclischen Systeme5 oder6. DiePictet-Spengler-Reaktion wurde auch auf Keto-Bis-Mannich-Basen zur Synthese der Verbindungstypen7 und8 ausgeweitet. Die Möglichkeiten zur Nutzung anderer Keto-Basen wurde untersucht.

Recent developments in the chemistry of bicyclic 6-6 systems: Chemistry of pyrido[1,2-c]pyrimidines

ABSTRACT The present review provides a study on the structural features, reactions, and synthetic methodologies of pyrido[1,2-c]pyrimidines. The maximum deviation from the mean plane of the pyridopyrimidine skeleton of 4-(pyridin-2-yl)-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione indicated a reasonably planar system. The aim of this review is to give an overview of the diverse methodologies that have been reported on the chemistry of pyrido[1,2-c]pyrimidines. The different synthetic routes have been grouped according to the way the pyrido[1,2-c]pyrimidine moiety has been created. Thus, pyrido[1,2-c]pyrimidine compounds were obtained by the formation of one bond α to the bridgehead nitrogen atom [6+0(β)] and formation of two bonds from ([3+3], [4+2], and [5+1]) atom fragments. The mechanistic pathways of the reactions are discussed. GRAPHICAL ABSTRACT

3-Pyrrolidinones: Michael Addition and Schmidt Rearrangement Reactions

Abstract Various spiro-pyrano[3,2-b]pyrrolo-2-oxoindolines 3a–d and dicyano-pyrano[3,2-b]pyrroles 5a–e have been synthesized in the present study by Michael addition of 3-pyrrolidinones 1 to isatin-3-ylidenes 2 and arylidenemalononitrile 4. Hexahydro-4-oxo-1-aryl-pyrimidine-5-carboxylic acids 7a,b were synthesized from 1 by Schmidt rearrangement.

Synthesis of 2-Acetoacetyl- and 2-OxaIoacetyl-1,3-indandiones and Related Compounds

Abstract Claisen condensation of 2-acetyl-1,3-indandione (1) with ethyl acetate afforded the 2-acetoacetyl-1,3-indandione (2) which upon treatment with benzylamine and paraformaldehyde in a molar ratio of (1:1:2) and (1:2:4) afforded the piperidinone and the diazabicyclic derivative (4) and (5) respectively. On the other hand, Claisen condensation of 1 with diethyl oxalate yielded two products (6) and (9). The behaviour of 6 towards phenyl hydrazine, and of 9 towards selenium dioxide and double Mannich reaction were also investigated.

Cesium carbonate as a mediated inorganic base in some organic transformations

Cesium carbonate is a type of alkali carbonate salt having a remarkable number of applications and has been demonstrated to be a mild inorganic base in organic synthesis. It has received much attention for its utility in C, N, O alkylation and arylation reactions. Cesium carbonate not only promotes successful carbonylation of alcohols and carbamination of amines, but also suppresses common side reactions traditionally encountered with other protocols. It is used also in six-membered annulation, intramolecular and intermolecular cyclizations, Suzuki coupling, aza-Henry, nucleophilic substitution, cross coupling and different cycloaddition reactions.

Recent progress in the chemistry of bicyclic 6–6 systems: chemistry of pyrido[1,2-a]pyrimidines

AbstractThe present review provides a study on the structural features, reactions, and synthetic methodologies of pyrido[1,2-a]pyrimidines. Thus, the synthetic procedures and organic reactions since 2000 are described. The aim of this review is to give an overview of the diverse methodologies that have been reported on the chemistry of pyrido[1,2-a]pyrimidines. The tautomeric forms of 2-methyl-3-chloro-9-hydroxypyrido[1,2-a]pyrimidin-4-one are discussed, as well as, the biological importance and mechanistic pathways.Graphical abstract

Synthesis and antioxidant activity of 2-indolinone bis(Mannich bases) and related compounds

Mannich bases attracted the interest of chemists and biologists due to their reactivity as a synthetic intermediate and their wide spectrum of biological activities. Based on the potent antioxidant, cytotoxic, and other biological properties of Mannich bases, there is a strong motivation for the continued synthesis of novel Mannich bases containing 2-indolinone core. In the present study 3-(phenacylidene)-1-(piperidin-1-ylmethyl)indolin-2-one, 3-(2-oxo-2-phenylethylidene)indolin-2-one, and 1,3-di(2-oxoindolin-3-ylidene)acetone were synthesized and used as a key intermediate in the synthesis of new 2-indolinone derivatives. All the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectra, and elemental analysis. The synthesized compounds were tested for their antioxidant activity in vitro using ABTS and bleomycin-dependent DNA damage assays.Graphical abstract

Synthesis and some reactions of functionalized 11,12-dihydro-5H-dibenzo[b,g]azonines

Abstract Dihydro-5H-dibenzo[b,g]azonine-6,13-dione (2) has been used as a precursor in the synthesis of the indolo[2,3-e]dibenzo[b,g]azonine and tribenzo[b,g,j][1,6]diazacyclododecine ring systems 6 and 7 respectively via a Fischer indolization/periodate oxidation sequence. Fischer indolization of the (1,4-phenylenedihydrazono) derivative 8 gave the polycyclic system 9. The Schmidt reaction of 2 led to the formation of the benzimidazo[1,2-b] [2]benzazepine ring system 11. The Mannich reaction of 2 led to the spirocyclic system 15. The reactions of 2 with aldimines and aromatic aldehydes were also investigated.