Lidia De Luca

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.

Chlorination is a widely used strategy at the industrial level. Chlorinated products represent indispensable building blocks in synthetic chemistry. Here, we report the synthesis of benzyl chlorides and α-chloro alkyl arenes, mediated by visible light, starting from variously substituted toluenes and N,N-dichloroacetamide as a chlorinating reagent. This methodology is a valid alternative to the syntheses previously reported in the literature. It is a metal-free process and does not involve the use of additives or radical initiators.

Chlorination is a widely used strategy at industrial level. Chlorinated products represent indispensable building blocks in synthetic chemistry. For this reason, finding new and alternative methodologies of these compounds continues to be a challenge. Here we report the synthesis of benzyl chlorides and α-chloro alkyl arenes mediated by visible light. This methodology is a valid alternative to the syntheses previously reported in the literature. It is a metal-free process, without the use of additives and radical initiators.

Mechanochemistry, as an enabling technology, harnesses mechanical force to drive chemical reactions, presenting compelling advantages in organic synthesis within the principles of green chemistry. This review explores how its unique advantages and alignment with sustainable practices have been widely developed in different scientific fields in Italy. As a transformative strategy for organic synthesis, mechanochemistry has been portrayed in this review as a valuable synthetic alternative due to the various advantages, such as solvent reduction and new reaction pathways, that its use brings. Nonetheless, the improvements brought about by its use have also been crucial in other fields of chemistry described by Italian scientists. In this whole context, Italian researchers have analysed both already optimised processes and new feasible pathways, paving the way for new avenues previously hampered by all the limitations that belong to in‐solution chemistry.

Indole ring is widely represented in natural compounds, as well as in a great variety of drugs. In this paper, the synthesis of a 5-hydroxybenzoindole derivative carrying a pyridyl substituent on position 1 is reported. The method involved no chromatography for purification and used solvents and catalysts of very low toxicity.

The synthesis of a new tetracationic porphyrin derivative is described. Contrary to the best known derivatives in the literature, which are derived from 5,10,15,20-tetrakis-4-pyridylporphyrin (TPyP), in this procedure we start from 5,10,15,20-tetrakis-(4-carboxymethoxyphenyl)porphyrin (TPPCOOMe), obtained by the condensation reaction between pyrrole and 4-formylbenzoate. The reaction is carried out in refluxed xylene, avoiding the use of halogenated solvents. The final product, 5,10,15,20-tetrakis-(4-(3-carbamoyl-pyridyl)-methylphenyl)porphyrin bromide (P15p), exhibits four cationic portions that make it soluble in water and suitable for G4 stabilization. The choice to synthesize a derivative of TPPCOOMe is based on the idea of having a possible stabilizer that, unlike those obtained from TPyP, shows the cationic moieties farther from the porphyrin core and thus closer to the phosphate groups present on the G4 loops.

A synthesis of amides from aldehydes promoted by the photoactive complex of Fe₂SO₄ with 2‐picolinic acid, NaCl as a chlorine source, and Na₂S₂O₈ as a benign oxidant is reported. The reaction is mediated by visible light and is carried out at room temperature in the absence of additives. Fe₂SO₄ is a readily available earth‐abundant metal (EAMs) salt, which does not need to be prepared and is environmentally sustainable. Both aliphatic and aromatic aldehydes and mono‐ and disubstituted amines have been investigated for this transformation. This study opens intriguing perspectives for extending the application of photoactive complex iron salts toward halogenation processes as well as for C−H activation reactions and contributes to the field of earth‐abundant metal based catalysis.

Microwave-assisted organic synthesis (MAOS) has emerged as a transformative technique in organic chemistry, significantly enhancing the speed, efficiency, and selectivity of chemical reactions. In our research, we have employed microwave irradiation to expedite the synthesis of quinazolinones, using water as an eco-friendly solvent and thereby adhering to the principles of green chemistry. Notably, the purification of the product was achieved without the need for column chromatography, thus streamlining the process. A key innovation in our approach is using aldehyde bisulfite adducts (Bertagnini’s salts) as solid surrogates of aldehydes. Bertagnini’s salts offer several advantages over free aldehydes, including enhanced stability, easier purification, and improved reactivity. Green metrics and Eco-Scale score calculations confirmed the sustainability of this approach, indicating a reduction in waste generation and enhanced sustainability outcomes. This methodology facilitates the synthesis of a diverse array of compounds, offering substantial contributions to the field, with potential for widespread applications in pharmaceutical research and beyond.

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.

Ester is one of the most significant functional groups in organic chemistry and is enclosed in several valued molecules. Usually, esters are prepared through the acid-catalyzed esterification reaction of carboxylic acids with alcohols, transesterification of esters with alcohols, or via activation of carboxylic acids followed by the addition of alcohols. However, these procedures typically imply the excess use of reactants and harsh reaction conditions. Visible light-mediated photoreactions have been disclosed to display a safe, sustainable, and accessible alternative to traditional methods, and to lead new reactivity modes in organic procedures. In this context, we propose a transition metal-based and organic-based photocatalyst-free synthesis of esters from alcohols induced by visible light. The methodology can be carried out using sunlight or artificial visible light as a solar simulator or a blue LED source.