This study thoroughly examines the role of mechanochemistry in organic synthesis by analysing the factors affecting the mechanochemical reduction process of unsaturated and oxidized compounds.

This concept review describes the recent achievements on the Heyns rearrangement appeared in literature over the last decade and aims to provide the reader with a general overview of the fundamental synthetic advances in this research area.

The [3 + 2] annulation reaction between a thiourea, an ambident dinucleophile, and a 2-(phenacylethylidene)cyclobutanone, containing a novel pull-pull alkene system, could in principle proceed with several chemo- and regioselectivity profiles. Here we describe a convenient synthesis of the functionalized cyclobutanone substrates and show that they react with thioureas in a manner that is rationalized mechanistically in terms of the steric and electronic effects at play. The [3 + 2] annulation proceeds in mild, additive-free conditions to provide access to previously unknown cyclobutane-fused imidazolidine-2-thione and thiazolidine-2-imine derivatives in good yields.

The tangible environmental concerns of the last few decades are prompting science to a new sustainable paradigm for chemical reactions and a circular economy. In the present manuscript, complying with this dichotomy, Sardinian wool is presented as a promising material for organic synthesis. Aldol and nitro-aldol additions, and Knoevenagel reactions were demonstrated with high efficiency under wool-promoted and solvent-free conditions, paving the way to novel approaches for converting wool biomass waste into value-added products for C-C bond formation.

An expedient, solvent-free, mild base catalyzed intermolecular cyclization reaction has been developed to enable the one-pot synthesis of fourteen examples of cyclobutane-fused oxazolidine-2-thiones in good to high yields. Bicyclic structures of this type have not previously been described in the literature; they have a cis ring junction with both rings deviating slightly from planarity.

Our research has demonstrated that mechanochemical activation is more effective with solid reagents. We have showcased the practicality of Bertagnini's salts, also called aldehyde‐bisulfite adducts, which are crystalline, simplifying preparation and storage. These salts are stable substitutes for liquid aldehydes and ketones that have been employed in reductive amination, synthesizing aza‐heterocycles and hydrazones within mechanochemistry. The technique‘s effectiveness broadens the substrate scopes, simplifies purification, reduces reaction times, and yields the desired products ranging from 38–91%. Additionally, the thermal stability of the bisulfite adducts has been confirmed through TGA (Thermogravimetric analysis) analysis.

Herein, we demonstrate a solvent-free mechanochemical approach involving a one-pot-double-step procedure mediated by solid sodium hypochlorite (NaOCl5H(2)O) for the synthesis of sulfonamides. The protocol entails a tandem oxidation-chlorination reaction on disulfides in the presence of a catalytic solid acidic species, followed by an amination prompted by a Lewis acid-base solid inorganic reagent. The methodology works smoothly with aromatic and aliphatic disulfides and amines. The purification process pays due attention to environmental concerns and avoids harsh conditions to obtain pure sulfonamide products. Some relevant biologically active compounds have been prepared with this procedure.

Nitroso derivatives with unique characteristics have been extensively studied in various fields, including biology and clinical research. Although there has been substantial investigation of "nitrosable" components in many drugs and commonly consumed nutrients, there is still a need for a higher awareness about their formation and characterization. This study demonstrates how these derivatives can be produced through a mechanochemical procedure under solid-state conditions. The results include synthesizing previously unknown compounds with potential biological and pharmaceutical applications, such as a nitrosamine derived from a Diclofenac-like structure.

The synthesis of nitrogen-based heterocycles has always been considered essential in developing pharmaceuticals in medicine and agriculture. This explains why various synthetic approaches have been proposed in recent decades. However performing as methods, they often imply harsh conditions or the employment of toxic solvents and dangerous reagents. Mechanochemistry is undoubtedly one of the most promising technologies currently used for reducing any possible environmental impact, addressing the worldwide interest in counteracting environmental pollution. Following this line, we propose a new mechanochemical protocol for synthesizing various heterocyclic classes by exploiting thiourea dioxide (TDO)'s reducing proprieties and electrophilic nature. Simultaneously exploiting the low cost of a component of the textile industry such as TDO and all the advantages brought by a green technique such as mechanochemistry, we plot a route towards a more sustainable and eco-friendly methodology for preparing heterocyclic moieties.

The results reported in this study provide a practical protocol for the construction, in one single step of synthetically important γ-lactones in good yields starting from α‐hydroxy cyclobutanone, H2O2 and several stabilized phosphonium ylides. Our synthetic strategy relies on a tandem Baeyer–Villiger oxidation/Wittig reaction/oxa-Michael addition.

The design and use of organic, inorganic, and metal‐based catalysts is critical to academic and industrial laboratories all around the world. In this framework, ammonia production embodies the most iconic use of catalysis. This review aims to describe the most recent and exciting developments in the mechanocatalytic preparation of ammonia.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

A stereoselective one-pot double derivatization of cyclobutene-1-carboxylic acid via a mild organic base catalyzed amidation/aza-Michael addition of benzo[d]oxazol-2(3H)-ones has been developed. This unprecedented tandem reaction provides access to novel beta-N-heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans-beta-N-heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures.

Mechanochemical transformations have made chemists enter unknown territories, forcing a different chemistry perspective. While questioning or revisiting familiar concepts belonging to solution chemistry, mechanochemistry has broken new ground, especially in the panorama of organic synthesis. Not only does it foster new "thinking outside the box", but it also has opened new reaction paths, allowing to overcome the weaknesses of traditional chemistry exactly where the use of well-established solution-based methodologies rules out progress. In this Review, the reader is introduced to an intriguing research subject not yet fully explored and waiting for improved understanding. Indeed, the study is mainly focused on organic transformations that, although impossible in solution, become possible under mechanochemical processing conditions, simultaneously entailing innovation and expanding the chemical space.

The acylation of amines has always attracted a deep interest as a synthetic route due to its high versatility in organic chemistry and biochemical processes. The purpose of this article is to present a mechanochemical acylation procedure based on the use of acyl-saccharin derivatives, namely N-formylsaccharin, N-acetylsaccharin, and N-propionylsaccharin. This protocol furnishes a valuable solvent-free alternative to the existing processes and aims to be highly beneficial in multi-step procedures due to its rapid and user-friendly workup.

Isocyanides are hardly produced, dramatically sensitive to purification processes, and complex to handle as synthetic tools. Notwithstanding, they represent one of the most refined and valuable compounds for accessing sophisticated and elegant synthetic routes. A unique interest has always been addressed to their production, though their synthetic pathways usually involve employing strong conditions and toxic reagents. The current paper intends to provide a conceptually innovative synthetic protocol for mechanochemical isocyanide preparation, simultaneously lowering the related reagents' toxicity and improving their purification in a straightforward procedure.

In just a few years, chemists have significantly changed their approach to the synthesis of organic molecules in the laboratory and industry. Researchers are encouraged to approach “greener” reagents, solvents, and methodologies, to go hand in hand with the world’s environmental matter, such as water, soil, and air pollution. The employment of plant and animal derivates that are commonly regarded as “waste material” has paved the way for the development of new green strategies. In this review, the most important innovations in this field have been highlighted, paying due attention to those materials that have played a crucial role in organic reactions: wool, silk, and feather. Moreover, we decided to focus on the other most important supports and catalysts in green syntheses, such as proteins and their derivates. Different materials have shown prominent activity in the adsorption of metals and organic dyes, which has constituted a relevant scope in the last two decades. We intend to furnish a complete screening of the application given to these materials and contribute to their potential future utilization.

We developed an environmentally friendly mechanochemical protocol to induce an effective Fischer indolisation to synthesize indoles and indolines taking advantage of oxalic acid and dimethylurea. The solvent-free procedure shows versatility and wide scope; it applies to a broad range of arylhydrazines and carbonyl compounds, leading to variously decorated indoles and indolenines. Upon suitable modification, the methodology can also allow preparing compounds of pharmaceutical interest.

AbstractA novel Brønsted acid promoted condensation reaction between a primary aniline and 2-hydroxycyclobutanone provides access to diverse tryptamine derivatives in moderate to good yields. The proposed mechanism involves an α-iminol rearrangement, ring expansion, ring closure, and a depart-and-return rearrangement process.

We have developed one-step protocols for the preparation of a large selection of alpha-aminocyclopropyl ketones or benzo[d]imidazoles, by reacting 2-substituted-2-hydroxycyclobutanones with aryl amines oro-phenylenediamines, respectively. In most case the reactions proceed at room temperature and are catalyst-free. The formation of benzo[d]imidazoles is rationalized in terms of an unusual ring-closure/ring-fission process followed by aromatization.