Stefania Santeusanio

Synthesis of functionalized pyrroles via catalyst- and solvent-free sequential three-component enamine-azoene annulation.

A new and efficient synthesis of polysubstituted pyrroles by a sequential one-pot three-component reaction between primary aliphatic amines, active methylene compounds, and 1,2-diaza-1,3-dienes (DDs) is reported. The reactions were performed without catalyst and under solvent-free conditions with complete control of pathway selectivity. Notably, the ready availability of the starting materials and the high level of practicability of the reaction and work up make this approach an attractive complementary method for access to unknown polysubstituted pyrroles.

A Novel and Convenient Protocol for Synthesis of Pyridazines

A new flexible strategy for the synthesis of diversely functionalized pyridazines from 4-chloro-1,2-diaza-1,3-butadienes and active methylene compounds is reported. The high chemoselectivity of this approach offers access to structural precursors of GABA-A antagonist analogues.

2-Substituted 5-Acetyl-4-Thiazolyl Triflates as Useful Building Blocks for the Preparation of Functionalized Thiazoles

The readily available 2-substituted 5-acetyl-4-thiazolyl triflates 2are useful building blocks for the preparation of functionalised thiazoles by means of palladium-catalysed cross-coupling reactions with organometallic reagents and alkoxycarbonylation and deoxygenation reactions. The combination of palladium-catalysed coupling of 2 together with 1-alkynes/6-endo-dig annulation reactions in the presence of ammonia leads to functionalised pyrido[3,4-c]thiazoles in satisfactory yields. The utilisation of uncatalysed displacement reactions of the triflate group represents a very simple method for the synthesis of 4-N-,4-O-, and 4-S-substituted thiazoles.

Powerful approach to heterocyclic skeletal diversity by sequential three-component reaction of amines, isothiocyanates, and 1,2-diaza-1,3-dienes.

By highly efficient, one-pot, three-component reactions, combining one set of 1,2-diaza-1,3-dienes (DDs), primary amines, and isothiocyanates in a different sequential order of addition, heterocyclic skeletal diversity can be achieved. The key feature discriminating the different heterocyclic core formation is the availability of the N or S heteronucleophile to give the first Michael addition step affording regioselective substituted 2-thiohydantoins or 2-iminothiazolidinones. The hydrazone or enehydrazino side chain at the 5-position of both heterocycles represents a valuable functionality to reach novel 5-hydroxyethylidene derivatives difficult to obtain by other methods.

Tandem Aza-Wittig/Carbodiimide-Mediated Annulation Applicable to 1,2-Diaza-1,3-dienes for the One-Pot Synthesis of Fully Substituted 1,2-Diaminoimidazoles

One-pot sequential aza-Michael, Staudinger, and aza-Wittig reactions on 1,2-diaza-1,2-dienes (DDs) can afford fully substituted 1,2-diaminoimidazoles. A plausible mechanism for the imidazole core formation involving an intramolecular ring closure of the carbodiimide-derived phosphazene intermediate is given. The reported strategy has sufficient flexibility to allow substituted 1,2-diaminoimidazoles with orthogonal nitrogen-protective groups to be generated from a variety of heterocumulene moieties linked to the DDs skeleton.

A New Convenient Liquid- and Solid-Phase Synthesis of Quinoxalines from (E)-3-Diazenylbut-2-enes

3-{[(tert-Butoxy)carbonyl]diazenyl}but-2-enoates react in tetrahydrofuran at room temperature with aromatic 1,2-diamines to give 3-methylquinoxaline-2-carboxylates. These products were also obtained in solid-phase synthesis, by using polymer-bound 3-diazenylbut-2-enes.

Study of reactions between 1,2-diaza-1,3-butadienes and N,N′-diaryl- or N,N′-dialkylthioureas

1,2-Diaza-1,3-butadienes react with N,N′-diarylthioureas to give 2-(arylimino)-2,3-dihydrothiazole derivatives, whereas with N,N′-dialkylthioureas to afford 5,5-disubstituted 3-alkyl-2-(alkylimino)-thiazolidin-4-one derivatives. Under basic conditions, these last products surprisingly give rise to 2-thioxo-1,3,7-triazaspiro[4.4]non-8-en-4-one and 5-oxo-4-(4-substituted 5-oxo-2-thioxoimidazolidin-4-yl)-2,5-dihydro-1H-pyrazole derivatives. In acidic medium, 5,5-disubstituted 3-alkyl-2-(alkylimino)-thiazolidin-4-ones are converted into 2-(alkylimino)-1-thia-3,7-diazaspiro[4.4]non-8-en-4-ones. X-Ray crystal structures of two products were determined.

Effect of Hydrogenated Cardanol on the Structure of Model Membranes Studied by EPR and NMR

Hydrogenated cardanol (HC) is known to act as an antiobesity, promising antioxidant, and eco-friendly brominating agent. In this respect, it is important to find the way to transport and protect HC into the body; a micellar structure works as the simplest membrane model and may be considered a suitable biocarrier for HC. Therefore, it is useful to analyze the impact of HC in the micellar structure and properties. This study reports a computer aided electron paramagnetic resonance (EPR) and (1)H NMR investigation of structural variations of cetyltrimetylammonium bromide (CTAB) micelles upon insertion of HC at different concentrations and pH variations. Surfactant spin probes inserted in the micelles allowed us to get information on the structure and dynamics of the micelles and the interactions between HC and CTAB. The formation of highly packed HC-CTAB mixed micelles were favored by the occurrence of both hydrophobic (chain-chain) and hydrophilic (between the polar and charged lipid heads) interactions. These interactions were enhanced by neutralization of the acidic HC heads. Different HC localizations into the micelles and micellar structures were identified by changing HC/CTAB relative concentrations and pH. The increase in HC concentration generated mixed micelles characterized by an increased surfactant packing. These results suggested a rod-like shape of the mixed micelles. The increase in pH promoted the insertion of deprotonated HC into less packed micelles, favored by the electrostatic head-head interactions between CTAB and deprotonated-HC surfactants.

Regioselective role of the hydrazide moiety in the formation of complex pyrrole–pyrazole systems

Abstract The treatment of alkyl 2-chloroacetoacetate with ethyl 3-hydrazino-3-oxopropionate, (4-chlorobenzenesulphonyl)acetic acid hydrazide, 4-nitrophenylacetic acid hydrazide, phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide leads to the corresponding hydrazone derivatives. In the presence of sodium carbonate, these compounds react at room temperature with acetoacetanilide or 2,4-pentanedione to give the corresponding 1-aminopyrrole rings through the relevant 1,2-diaza-1,3-butadiene intermediates. In the presence of sodium methoxide, the activated methylene group present on the 1-amino side chain of the heterocycles obtained from ethyl 3-hydrazino-3-oxopropionate or 4-nitrophenylacetic acid hydrazide attacks at room temperature 1,2-diaza-1,3-butadienes affording the respective hydrazonic 1,4-adducts. Under basic conditions, these adducts cyclise at room temperature providing NH CO CH-bridged pyrrole–pyrazole systems. In the case of (4-chlorobenzenesulphonyl)acetic acid hydrazide, the corresponding 1-aminopyrrole does not add a further molecule of 1,2-diaza-1,3-butadiene giving rise to 1 H -pyrrole and 2-oxohydrazone derivatives as identified compounds. Under the same reaction conditions, the NH group of 1-aminopyrroles derived from phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide adds at room temperature 1,2-diaza-1,3-butadienes producing another type of hydrazonic 1,4-adduct. Under basic conditions, these adducts cyclise at room temperature giving rise to different N-bonded pyrrole–pyrazole systems.

Conjugated azoalkenes. Part XVI. Reaction of some conjugated azoalkenes with β-nitrocarbonyl derivatives.

Abstract Unknown 2-hydroxy-3-nitro-2,3-dihydro-1-aminopyrrole derivatives were directly obtained by easy reaction of conjugated azoalkenes with 2-nitro-1,3-indanedione. The treatment of the same reagents with benzoylnitromethane or β-nitroesters gave α,β-olefinated-γ-carbonyl- or α,β-olefinated-γ-alkoxycarbonylhydrazone derivatives, respectively. New asymmetric α-azinohydrazones were isolated from the reaction of the above-mentioned materials with some β-nitroketone tosylhydrazones.