Recently, mechanical milling using a mixer mill or planetary mill has been fruitfully utilized in organic synthesis under solvent-free conditions This review article provides a comprehensive overview of various solvent-free mechanochemical organic reactions, including metal-mediated or -catalyzed reactions, condensation reactions, nucleophilic additions, cascade reactions, Diels–Alder reactions, oxidations, reductions, halogenation/aminohalogenation, etc The ball milling technique has also been applied to the synthesis of calixarenes, rotaxanes and cage compounds, asymmetric synthesis as well as the transformation of biologically active compounds

Mechanochemical organic synthesis

During the last decade numerous protocols have been published using the method of ball milling for synthesis all over the field of organic chemistry. However, compared to other methods leaving their marks on the road to sustainable synthesis (e.g. microwave, ultrasound, ionic liquids) chemistry in ball mills is rather underrepresented in the knowledge of organic chemists. Especially, in the last three years the interest in this technique raised continuously, culminating in several high-quality synthetic procedures covering the whole range of organic synthesis. Thus, the present tutorial review will be focused on the highlights using this method of energy transfer and energy dissipation. The central aim is to motivate researchers to take notice of ball mills as chemical reactors, implementing this technique in everyday laboratory use and thus, pave the ground for future activities in this interdisciplinary field of research.

Ball milling in organic synthesis: solutions and challenges.

Azobenzenes are ubiquitous motifs very important in many areas of science. Azo compounds display crucial properties for important applications, mainly for the chemical industry. Because of their discovery, the main application of aromatic azo compounds has been their use as dyes. These compounds are excellent candidates to function as molecular switches because of their efficient cis–transisomerization in the presence of appropriate radiation. The classical methods for the synthesis of azo compounds are the azo coupling reaction (coupling of diazonium salts with activated aromatic compounds), the Mills reaction (reaction between aromatic nitroso derivatives and anilines) and the Wallach reaction (transformation of azoxybenzenes into 4-hydroxy substituted azoderivatives in acid media). More recently, other preparative methods have been reported. This critical review covers the various synthetic methods reported on azo compounds with special emphasis on the more recent ones and their mechanistic aspects (170 references).

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Organicka%20chemia%20II/Prednaska%202_Aminy_Reakcie/Doplnkove%20studijne%20materialy/Azobenzenes/Synthesis%20of%20azobenzenes%20-%20the%20coloured%20pieces%20of%20molecular%20materials.pdf

Synthesis of azobenzenes: the coloured pieces of molecular materials

Mechanochemistry means mechanical breakage of intramolecular bonds by external force and must be differentiated from molecular solid-state chemistry, where contacts between micronized molecular solids are created by the mechanical action for mutual approach of the reacting centers. After an outline of the mechanistic differences, the varied mechanochemistry is discussed. Grinding, milling, shearing, scratching, polishing, and rapid friction (for polymers also cutting, kneading, extruding) provide the mechanical impact for mechanochemistry, while sonication and shock waving for intramolecular bond breaking are generally described as thermal processes. The various types of mechanophysics (e.g., mechanoelectricity, conformational changes, thixotropy, rheopexy, stirring of Newtonian liquids or suspensions, etc.) are not treated here. Mechanochemistry covers solid-state reactions of infinitely covalent crystals, brittle metals, polymers, molecular solids with weak covalent bonds, strong intramolecular bond breakage in shearing Bridgman's anvil or by friction at lubrication of rapidly moving cold contacting surfaces, and single bond breaking or cutting. The diverse wealth of practical applications of mechanochemistry is outlined with typical examples for ceramics, mechanical alloying, hydrogen storage, organic syntheses, waste remediation, leachings, surface plasmas, radical formation, explosives, nanotube formation, nanoparticles grafting, polymer technology, radical initiation, scratch-less polishing, wear protection, lubrication, mechanochromism, nano-dissection, and many more.

http://webpages.iust.ac.ir/naimi/Lectures/Current%20Topics%20in%20Synthetic%20Organic,%20PhD/Kaupp,%20MechanochemistryReprint.pdf

Mechanochemistry: the varied applications of mechanical bond-breaking

Ball milling has been applied in numerous solvent-free carbon-carbon bond formations. In many cases, these transformations proved superior to the analogous reactions performed in solution. The reaction scope involves purely organic addition and coupling reactions, transformations involving metals (in stoichiometric and catalytic amounts) as well as asymmetric organocatalyses.

Solvent-Free Carbon-Carbon Bond Formations in Ball Mills

Calcite and fluorite as catalyst for the Knövenagel condensation of malononitrile and methyl cyanoacetate under solvent-free conditions

When milled together with bismuth shots, nitroarenes are readily converted to azoxy- and/or azoarenes depending on substrates and conditions employed. Simple extraction with organic solvent followed by evaporation of the resulting dark pasty solid gave the product in good yield.

The newborn surface of dull metals in organic synthesis. Bismuth-mediated solvent-free one-step conversion of nitroarenes to azoxy- and azoarenes.

When milled together with bismuth shot in the presence of allyl halide, aromatic aldehydes readily underwent a Barbier-type allylation to afford the corresponding homoallyl alcohols in good yield. In contrast to the failure in solution reaction, aromatic ketones also underwent allylic carbonyl addition under solvent-free conditions to give the expected tertiary homoallyl alcohols in moderate to good yield.

Noticeable facilitation of the bismuth-mediated Barbier-type allylation of aromatic carbonyl compounds under solvent-free conditions

S,S-Acetals are smoothly deprotected with air in the presence of a catalytic amount of Bi(NO3)3⋅5 H2O (1–50 mol %) under ambient conditions to regenerate the original carbonyl compounds in good to excellent yield. This mild, simple, and environmentally benign system is successfully applied to the deprotection of S,O- and O,O-acetals and is compatible with various functional groups. From the mechanistic study of the reaction, the catalytic cycle is considered to be composed of the following four steps: (1) the nitrososulfonium ion of the S,S-acetal is formed by attack of nitrosonium ion (NO +) generated from Bi(NO3)3⋅5 H2O through the equilibrium with NO2, (2) the nitrososulfonium ion is hydrolyzed to afford the hemithioacetal and thionitrite, (3) the hemithioacetal collapses to the original carbonyl compound and thiol, which is oxidized by NO + to give disulfide and NO via thionitrite, and (4) the NO captures molecular oxygen from air to regenerate NO2.

Shinobu Wada

Papers

Calcite and fluorite as catalyst for the Knövenagel condensation of malononitrile and methyl cyanoacetate under solvent-free conditions

The newborn surface of dull metals in organic synthesis. Bismuth-mediated solvent-free one-step conversion of nitroarenes to azoxy- and azoarenes.

Noticeable facilitation of the bismuth-mediated Barbier-type allylation of aromatic carbonyl compounds under solvent-free conditions

A Catalytic Deprotection of S,S‐, S,O‐ and O,O‐Acetals Using Bi(NO3)3⋅5 H2O under Air

A novel dry route to ortho-functionalized triarylbismuthanes that are difficult to access by conventional wet routes