Ugo Azzena

Beta‐enaminoketones and beta‐enaminoesters are valuable as drug candidates and intermediates in the synthesis of nitrogen heterocycles and multidentate ligands. These compounds were obtained by the addition of aliphatic or aromatic amines to beta‐diketo‐derivatives, catalyzed by either ammonium chloride or glycine hydrochloride, both inexpensive and nontoxic catalysts. The reactions were conducted under neat conditions allowing efficient work‐up, catalyst recovery and the possibility for reaction telescoping. The process yielded beta‐enaminoketones and beta‐enaminoesters in high to excellent yields with a mechanism involving the formation of key intermediates that facilitate the condensation.

Aryl and heteroaryl iodides have been efficiently converted into the corresponding thioacetates in cyclopentyl methyl ether (CPME), a green solvent, under Cu catalysis. The chemoselectivity of the reaction is mainly controlled by electronic factors, enabling the conversion of both electron-rich and electron-deficient substrates into the corresponding thioacetates in good to excellent yields. The products can be easily deprotected to the corresponding thiolates to carry out additional synthetic transformations in situ. Surprisingly, despite CPME’s relatively low dielectric constant, the reaction rate significantly increased when conducted under microwave irradiation conditions. This synthetic methodology exhibits a remarkable tolerance to functional groups, mild reaction conditions, and a wide substrate scope, utilizing a safe and inexpensive CuI pre-catalyst in the green solvent CPME. A non-aqueous workup allowing for the complete recovery of both catalyst and solvent makes this approach an environmentally sustainable protocol for C(sp²) sulfur functionalization. Additionally, the reaction shows selective cross-coupling with iodides in competition with chlorides and bromides, allowing its use in multistep syntheses. To demonstrate the potential of this methodology, it was applied to the high-yield synthesis of a photochromic dithienylethene, where a selective synthesis had not been reported before.

Reaction of glycerol with aldehydes and ketones is a strategy widely studied in literature to valorize this bioproduct. A Brønsted or Lewis acid is normally used to activate the carbonyl function and various strategies adopted to drive the equilibrium to the products. In this study ammonium salts as catalysts, and removal of water by azeotropic distillation of cyclopentyl methyl ether, permit the conversion of glycerol into acetals obtained as mixture of dioxanes and dioxolanes determined by ¹ H‐NMR. Under the optimized conditions, the products could be obtained in excellent yield without using excess of reactants and the solvent was recycled efficiently.

Disposing of residual cooking oil is a major environmental concern, so its conversion into commercial products is a desirable goal. To design the chemical modification of a domestic waste oil into valuable biochemicals other than biodiesel, we analyzed a series of its samples, collected over a period of three years, using quantitative ¹H-NMR. This analysis, allowing a quick determination of its main chemical characteristics, has rendered the image of a vegetable oil with an almost constant composition over time and with a relative low content of saturated fatty acids. To make this collection protocol more economical, we projected its chemical transformation into esters and epoxidized esters of long chain and branched alcohols, which could find employment as biolubricants and/or bioplasticizers. The one-pot transesterification of the waste cooking oil into esters of commercially available and biodegradable Guerbet alcohols was obtained under environmentally friendly conditions by employing commercial CaO as a catalyst. Additionally, microwave irradiation of this reaction allowed to optimize the energy expenditure by significantly reducing the reaction time as compared with reactions run under conventional heating. To improve their oxidation stabilities, the resulting esters were epoxidized under conditions useful to minimize side-reactions. An investigation of their main rheological properties shows that some of the resulting products display characteristics that make their use as biolubricants or bioplasticizers predictable. The entire process represents a virtuous example of circular economy. Graphical Abstract

In this work, mild Lewis acids and low environmental impact solvents were investigated for Nenitzescu synthesis. Cyclopentyl methyl ether can be used at room temperature in substitution of halogenated solvents with zinc, iron and magnesium salts as homogeneous catalysts to give 5‐hydroxyindoles in fair to good yields. The reaction features a straightforward workup and excellent solvent recycle.

Cyclopentyl methyl ether and 2-methyltetrahydrofuran, low impact ethereal solvents forming a positive azeotrope with water, were successfully employed as solvents in the synthesis of a variety of acetals carried out under Dean–Stark conditions in the presence of heterogeneous acidic catalysts. Under these conditions, ammonium salts, either as such or supported on SiO₂, performed better or equally well than widely employed homogeneous and heterogeneous acidic catalysts such as p-toluenesulfonic acid, Amberlyst 15^®, or Montmorillonite K10. Several examples highlight the advantage of tuning the relative acidities of ammonium salts by appropriately selecting the counterion. Within one of these examples, our protocol clearly outweighs the classic p-toluenesulfonic acid/toluene protocol in terms of chemoselectivity. Silica-supported catalysts were characterized by SEM, TEM, and FTIR spectroscopies, as well as by N₂ physisorption. Such a characterization reveals an even distribution of ammonium salts on silica, thus confirming the formation of expected catalytic supports.

Solvents represent one of the major contributions to the environmental impact of fine‐chemical synthesis. As a result, the use of environmentally friendly solvents in widely employed reactions is a challenge of vast real interest in contemporary organic chemistry. Within this Review, a great variety of examples showing how cyclopentyl methyl ether has been established as particularly useful for this purpose are reported. Indeed, its low toxicity, high boiling point, low melting point, hydrophobicity, chemical stability towards a wide range of conditions, exceptional stability towards the abstraction of hydrogen atoms, relatively low latent heat of vaporization, and the ease with which it can be recovered and recycled enable its successful employment as a solvent in a wide range of synthetic applications, including organometallic chemistry, catalysis, biphasic reactions, oxidations, and radical reactions.

The application of heterogeneous catalysis and green solvents to the set up of widely employed reactions is a challenge in contemporary organic chemistry. We applied such an approach to the synthesis and further conversion of tetrahydropyranyl ethers, an important class of compounds widely employed in multistep syntheses. Several alcohols and phenols were almost quantitatively converted into the corresponding tetrahydropyranyl ethers in cyclopentyl methyl ether or 2-methyltetrahydrofuran employing NH₄HSO₄ supported on SiO₂ as a recyclable acidic catalyst. Easy work up of the reaction mixtures and the versatility of the solvents allowed further conversion of the reaction products under one-pot reaction conditions.