Letters in Organic Chemistry - Volume 11, Issue 7, 2014

We describe herein a clean and efficient one-pot synthesis of 4H-benzo[b]pyran derivatives using dimedone, active methylene nitriles and aryl aldehyde via Knoevenagel condensation followed by Michael addition in the presence of Mg(NO3)2•6H2O as catalyst and water as a green solvent. The advantages of this method lie in its simplicity, low catalyst loading, cost effectiveness and easy handling. The present method also allows us to synthesize highly functionalized tetrahydrobenzo[b]pyran derivatives from simple and readily available starting materials.

Multifunctional chromenes have been efficiently synthesized in aqueous medium at room temperature using deep eutectic mixture of choline chloride:urea. In this one-pot synthesis, the benzylidenemalononitrile firstly formed by Knoevenagel condensation of aldehyde and malononitrile eventually underwent Michael addition-cyclization with dimedone and offered the chromenes in good to excellent yield.

Pyrimidine annulated sulfur heterocycles have been synthesized through tributyltin hydride-mediated radical reaction. This gave straight forward synthesis of tricyclic compound as well as spiro heterocyclic compounds. The reactions have been simple, straight forward and have been carried out in mild conditions.

We present experimental and computational studies on the pseudo-Michael reaction of (E)-1-aryl-2-hydrazinyl- 4,5-dihydro-1H-imidazoles with diethyl (ethoxymethylene)malonate (DEEM). The pseudo-Michael reaction leads to chain adducts, i.e. diethyl [[2-(1-aryl-4,5-dihydro-1H-imidazol-2-yl)hydrazinyl]methylene]propanedioates. This result is in contrast to our earlier studies on the pseudo-Michael reaction of DEEM with 1-aryl-4,5-dihydro-1H-imidazol-2-amines which results in imidazo[1,2-α]pyrimidine derivatives even at low temperature without the possibility of isolating chain intermediates. The structure of all the compounds is confirmed with experimental and computational spectroscopy (1H and 13C NMR, IR, MS). Furthermore, thermodynamics of the reaction and HOMO-LUMO of the reactants are studied by using of quantum chemical calculations.

The increasing resistance of bacteria and fungi to antimicrobial drugs has been a matter of concern in public health in the last decades. The continuing need for novel therapeutic compounds is still urgent regarding the number of new diseases and resistant strains of microorganisms. Chalcones are ketones α,β-unsaturated with one aromatic ring bonded to carbonyl and another aromatic ring bonded to an olefin function. Literature has already reported the antimicrobial potential of several chalcones against a wide range of fungal and bacterial strains, including resistant ones; clearly indicating that they are attractive target compounds for new antimicrobial drug development. Several studies have shown that the introduction of different functional groups is a strategy used to improve the biological activity of these compounds, moreover, the structure of chalcones can also be employed as an intermediate reaction, enabling different reactions and giving rise to new molecules. In this review, we describe recent advances on the synthesis of chalcones with antimicrobial activities.

This page isvestigated that bismuth triflate catalysed the nitration of a range of simple aromatic compounds in good to excellent yields at 0-30 ºC within 2 h using N2O5 has been investigated and the catalyst can be recycled without apparent loss of activity. Mechanistic insights demonstrate that triflic acid is generated and that, at least, two competing catalytic cycles are operating at the same time: a rapid one involving triflic acid and a slower one involving the bismuth triflate.

The synthesis of new 2-adamantyl-1,2,4-triazine derivatives is described utilizing both, conventional and microwave methods and were obtained in good yields. The proposed structures of the adamantyltriazines were characterized using MS, 1H NMR and 13C NMR spectral data and confirmed by determination of X-ray structure for 9c.

A new method for the synthesis of aryl nitriles has been developed by the cyanation of aryl bromides with K4Fe(CN)6 as a cyanide source in the presence of Cu(OAc)2.H2O as an inexpensive catalyst and a 1,3-phenylene-bis- (1H)-tetrazole ligand. This method has the advantages of high yield, simple methodology and easy work-up.

Organic reactions mediated by stoichiometric phosphines play a key role in modern organic synthesis as testified by the classic Wittig, Mitsunobu, Staudinger and Appel reactions. Mechanistically these reactions are usually driven by the strong oxophilicity of tertiary phosphines. As a result, the formation of phosphine oxide as a concomitant byproduct represents a drawback which impacts heavily on the atom economy and large-scale applicability of these reactions. To tackle the “phosphine-oxide” issue, considerable efforts have been recently engaged in how to convert a stoichiometric phosphine-mediated reaction into a catalytic one, which has stimulated much research interest in organic chemistry community. In this mini-review, recent developments on catalytic approaches to stoichiometric phosphine-mediated reactions primarily including in situ reduction and activation strategies are summarized.

Twenty-one new chalcones 9a-m (excluding 9e, 9j and 9l) and 10a-m (excluding 10j and 10l), containing nucleobases were synthesized from 2'-hydroxyacetophenone (1) by the reactions including chloromethylation, nucleophilic substitution with thymine and uracil, and Claisen-Schmidt reactions. These new chalcones were evaluated for in vitro cytotoxicity against five human cancer cell lines: SK-LU-1, Hep-G2, MCF7, SW480 and P388. The results showed that most of the tested chalcones exhibited inhibitory activity against five cancer cell lines except 10h, and 10i. Among the synthesized chalcones, compound 10c exhibited most potent cytotoxicity against MCF-7, SK-LU-1, SW480, HepG2 and P388 with IC50 values of 4.42, 4.81, 5.27, 3.67 and 4.11μg/mL, respectively.

The three-component reaction of malononitrile, aldehydes and thiourea/urea, is applied to the formation of pyrimidine derivatives. The reaction occurs at best in EtOH at reflux, in the presence of high surface area and nanosized MgO. This methodology is more convenient to compare with alternative ways because it needs shorter reaction times, allows straightforward product isolation, and provides higher yields.