Quinolines and structurally related heterocycles as antimalarials

Recent Advances in the Friedländer Reaction

Metal-organic frameworks (MOFs) are finding increasing application as solid catalysts for liquid phase reactions leading to the synthesis of fine chemicals. In the present review we have focused on those reports describing the use of MOFs as catalysts for the synthesis of N-containing heterocycles that is a class of organic compounds with high added value due to their therapeutic use as drugs and their remarkable biological activities. After an introduction describing relevant structural features of MOFs and the nature of their active sites, this manuscript is organized according to the type of N-containing heterocycle synthesized employing MOFs as catalysts including pyrimidines, N-substituted piperidines, quinolines, indoles, N-substituted imidazoles, triazoles and heterocyclic amides. Special attention has been paid to the structural stability of MOFs under the reaction conditions, to the occurrence of metal leaching and reusability. The final section of this review provides some concluding remarks and future prospects for the field, with emphasis on showing the superiority of MOFs with respect to other solid catalysts for this type of liquid phase organic reactions and pointing out that the final goal in this research would be the use of these materials as catalysts in real industrial synthesis.

Metal–organic frameworks as solid catalysts for the synthesis of nitrogen-containing heterocycles

The development of metal–organic framework (MOF) materials starts with the use of supramolecular chemistry to yield porous coordination networks. Nowadays, MOFs are considered one of the most fascinating classes of materials due to their potential in areas such as optoelectronic devices and sensors, storage and separation of gases, medical imaging and drug delivery and more recently emerging as highly interesting catalytic materials. In this regard, MOFs can be rationally designed to assess structure–activity relationships. 7b] [Cu3(BTC)2] (BTC = benzene-1,3,5-tricarboxylate) is a 3D porous MOF with a zeolite-like structure, useful for the gas storage and the removal of sulfur odorant components from natural gas. Concerning its almost unexplored catalytic behavior, its use in the oxidation of p-benzoquinone, the cyanosilylation of aldehydes and a few catalytic test reaction for acidity, such as isomerization of a-pinene oxide, cyclization of citronellal, and rearrangement of ethylene ketal of 2-bromopropiophenone, have been reported. These reactions demonstrated that [Cu3(BTC)2] has a hard Lewis acid character. On this basis, this study concerns an important catalytic behavior of [Cu3(BTC)2] , highlighting its enormous potential as a promising acidic heterogeneous catalyst for the production of fine chemicals. We report herein that [Cu3(BTC)2] is an efficient and environmental-friendly catalyst for the Friedl nder reaction between 2-aminobenzophenones 1 and acetylacetone 2 under mild reaction conditions. The Friedl nder reaction is one of the most useful synthetic approaches for the synthesis of quinolines, nitrogen heterocyclic compounds with important pharmacological activities. The development of efficient catalysts for this transformation has recently the subject of many reports. 15] Herein we discuss the synthesis of the quinolines 3 catalyzed by [Cu3(BTC)2] . Compound 3 b is a simple substrate exhibiting antiparasitic activity (Scheme 1). In this study, we used [Cu3(BTC)2] , which is commercially available as Basolite C 300 (Sigma–Aldrich). This MOF had a particle size distribution of 15.96 mm (D50), a BET surface area of 1500–2100 m g, and a bulk density 0.35 g cm . We also determined the surface area of the catalyst under study by measurement of adsorption isotherms of nitrogen at 77 K by applying the BET method (Table 1).

[Cu3(BTC)2]: A Metal–Organic Framework Catalyst for the Friedländer Reaction

Friedlander condensation between 2-aminoaryl ketones and different carbonyl compounds, catalyzed by CuBTC was investigated by a combination of various experimental techniques and by density functional theory based modelling. CuBTC exhibiting hard Lewis acid character showed highly improved catalytic activity when compared with other molecular sieves showing high concentraion of Lewis acid sites, e.g. in BEA and (Al)SBA-15. Polysubstituted quinolines were synthesized via a Friedlander reaction catalyzed by CuBTC under the solvent-free conditions. High concentration of active sites in CuBTC together with the concerted effect of a pair of adjacent Cu2+ coordinatively unsaturated active sites are behind a very high quinoline yield reached within a short reaction time. Results reported here make CuBTC a promising catalyst for other Lewis acid-promoted condensations, including those leading to biologically active compounds with a particular relevance for the pharmaceutical industry. The mechanism of a catalyzed Friedlander reaction investigated computationally is also reported.

Mariela Bollini

Papers

Microwave-assisted Friedländer synthesis of quinolines derivatives as potential antiparasitic agents

New potent imidazoisoquinolinone derivatives as anti-Trypanosoma cruzi agents: biological evaluation and structure-activity relationships.

Microwave-assisted Döbner Synthesis of 2-Phenylquinoline-4-carboxylic Acids and their Antiparasitic Activities

Thalidomide analogues: Tumor necrosis factor-alpha inhibitors and their evaluation as anti-inflammatory agents.

Microwave‐Assisted Friedlaender Synthesis of Quinolines Derivatives as Potential Antiparasitic Agents.