Juan C. Autino

Solvent-free catalytic preparation of 1,1-diacetates from aldehydes using a Wells–Dawson acid (H6P2W18O62·24H2O)

Aromatic and aliphatic aldehydes are transformed in 1,1-diacetates (acylals) in mild conditions, by a treatment with acetic anhydride and a Wells–Dawson acid (H6P2W18O62·24H2O). gem-Diacetylation proceeds in Ac2O with a little as 1% mol Wells–Dawson acid at room temperature and under solventless conditions, obtaining very good to excellent yields (88–98%) of 1,1-diacetates (19 examples). Neither 4-dimethylaminobenzaldehyde nor ketones react under the same conditions.

Efficient method for tetrahydropyranylation/depyranylation of phenols and alcohols using a solid acid catalyst with Wells–Dawson structure

Abstract A simple and efficient procedure to form 2-tetrahydropyranyl acetals of phenols and alcohols is reported. Wells–Dawson heteropolyacid catalyst is used both in bulk form or supported on silica, reaction conditions include room temperature and toluene as solvent. Fast deprotection of THP-acetals can be attained by mere change of the solvent using THF–1% MeOH. In both reactions the supported catalyst is easily recoverable and reusable, and the yields are good to excellent.

QSAR prediction of inhibition of aldose reductase for flavonoids

We performed a predictive analysis based on quantitative structure-activity relationships (QSAR) of an important property of flavonoids, which is the inhibition (IC(50)) of aldose reductase (AR). The importance of AR inhibition is that it prevents cataract formation in diabetic patients. The best linear model constructed from 55 molecular structures incorporated six molecular descriptors, selected from more than a thousand geometrical, topological, quantum-mechanical, and electronic types of descriptors. As a practical application, we used the obtained QSAR model to predict the AR inhibitory effect of newly synthesized flavonoids that present 2-, 7-substitutions in the benzopyrane backbone.

Quantitative Structure–Activity Relationships of Mosquito Larvicidal Chalcone Derivatives

The mosquito larvicidal activities of a series of chalcones and some derivatives were subjected to a quantitative structure-activity relationship (QSAR) study, using more than a thousand constitutional, topological, geometrical, and electronic molecular descriptors calculated with Dragon software. The larvicidal activity values for 28 active compounds of the series were predicted, showing in general a good approximation to the experimental values found in the literature. Chalcones having one or both electron-rich rings showed high toxicity. However, the activity of chalcones was reduced by electron-withdrawing groups, and this was roughly diminished by derivatization of the carbonyl group. A set of six chalcones being structurally similar to some of the active ones, with a still unknown larvicidal activity, were prepared. Their activity values were predicted by applying the developed QSAR models, showing that two chalcones of such set, both 32 and 34, were expected to be highly active.

Recent Applications of Heteropolyacids and Related Compounds in Heterocycles Synthesis

Abstract: Heteropolyacids (HPAs) and related compounds have received considerable attention as solid acids in recent years. HPAs pos-sess unique physicochemical properties, with their structural mobility and multifunctionality being the most important for catalysis. They possess a very strong Bronsted acidity and appropriate redox properties that make them excellent catalysts in substoichiometric quanti-ties. This review will focus on describing new developments in the application of HPAs in the organic synthesis of heterocycles. Hetero-cycles that will be covered include coumarins, flavones, chromones, quinazolidones, dihydropyrimidinones, imidazoles, isoxazoles, pyrimidines, tetrazines, pyrazoles, dihydropyridines, and others. Keywords: Heteropolyacids, Catalysis, Heterocycles, Green Chemistry. It is well known that the use of conventional liquid and Lewis acids such as H 2 SO 4 , HCl, HF, AlCl 3 , BF 3 and ZnCl 2 poses risks in handling, containment, disposal and regeneration due to their corro-sive and toxic nature. There is an urgent need to eliminate the ag-gressive mineral acid-catalyzed processes [1]. There are numerous acid-catalyzed organic reactions and the use of solid acid catalysts is very important in several industrial and environmental processes [2]. The use of solid (heterogeneous) cata-lysts in organic synthesis and in the industrial manufacture of chemicals is increasingly important since they provide green alter-natives to homogeneous catalysts [3]. In recent times, inorganic solid-catalyzed organic transforma-tions are gaining much importance due to the proven advantage of heterogeneous catalysts, such as simplified product isolation, mild reaction conditions, high selectivities, easy recovery and catalyst reuse, and reduction in generation of waste byproducts [1,4-6]. Heterogeneous catalysts are used extensively in protec-tion/deprotection process in organic synthesis [7]. Catalysis by heteropolyacids (HPAs) and related compounds is a field of increasing importance worldwide. Numerous develop-ments are being carried out in basic research as well as in fine chemistry processes [8]. HPAs possess, on the one hand, a very strong acidity and, on the other hand, appropriate redox properties, which can be changed by varying the chemical composition of het-eropolyanion. The reactions catalyzed by both heterogeneous and homogeneous systems have been reviewed by many researchers [9-17]. The reactions in which they can be used, from dehydration, cyclization or esterification up to amine oxidation or olefin epoxi-dation, may find wide applications in fine chemical production, such as fragrances, pharmaceutical and food [18,19]. Although there are many structural types of HPAs, the majority of the catalytic applications use the most common Keggin-type HPAs [20], especially for acid catalysts, owing to their availability and chemical stability. Other catalysts such as Wells-Dawson and Preyssler heteropolyacids have began to be used [21,22]. Heteropolycompounds are known as condensates of different oxoacids. The heteropolycompounds with Keggin-type primary structure are polynuclear complexes principally constituted by mo-lybdenum, tungsten or vanadium as polyatoms (M), and phospho-rus, silicon or germanium as central atom or heteroatom (X). The

Solvent‐Free Approach to 3,4‐Dihydropyrimidin‐2(1H)‐(thio)ones: Biginelli Reaction Catalyzed by a Wells–Dawson Reusable Heteropolyacid

Abstract The Biginelli reaction is performed in an efficient, simple, solvent‐free procedure, using a small amount of H6P2W18O62 · 24H2O, a reusable heteropolyacid catalyst with Wells–Dawson structure. Both aromatic and aliphatic aldehydes, and different β‐dicarbonyl compounds and urea or thiourea, were used as starting materials. Seventeen examples of dihydropyrimidinones and dihydropyrimidinethiones were prepared by heating the reactants either in refluxing acetonitrile or in the absence of solvent. Operational simplicity, the use of a noncorrosive, reusable catalyst in solventless conditions, short reaction times, and very good to excellent yields in most of the selected examples are the main advantages of the method.

Efficient Microwave Solvent-Free Synthesis of Flavones, Chromones, Coumarins and Dihydrocoumarins

Simple, clean, environmentally friendly procedures for the solvent-free preparation of coumarins, dihydrocou- marins, flavones and chromones under microwave heating are described. Silica-supported Wells-Dawson heteropolyacid (H6P2W18O62·24 H2O) was employed as catalyst. High selectivity, very good yields and short reaction times were ob- tained. The results are compared with those of the reactions performed under conventional heating.

Sustainable synthesis of flavonoid derivatives, QSAR study and insecticidal activity against the fall armyworm, Spodoptera frugiperda (Lep.: Noctuidae).

A simple, clean, solvent-free preparation of flavones by the use of a silica-supported Preyssler heteropolyacid as reusable catalyst is described. High selectivity and very good yields (87-94%) were obtained in short reaction times (7-13 min). Bioassays for insecticidal activity against Spodoptera frugiperda were carried out with a set of flavones. Bioassays showed that some of the flavones had moderate insecticidal activity. Quantitative structure-activity relationships were established on the available data with the purpose of predicting the insecticidal activity of a number of structurally related flavones. A relationship between the molecular structure and biological activity is proposed.

Efficient deprotection of phenol methoxymethyl ethers using a solid acid catalyst with Wells-Dawson structure

Deprotection of various phenols from their respective methoxymethyl ethers using an heteropolyacid catalyst was studied. The catalyst was the Wells-Dawson heteropolyacid, used both in bulk or supported on silica. Yields were high to quantitative after less than one hour reaction time and the catalyst was easily recoverable and reusable.

QSAR analysis on Spodoptera litura antifeedant activities for flavone derivatives.

We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED(50) feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure-Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds. After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure-activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-(alpha-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED(50)=1.162.