Mechanochemistry for Organic and Inorganic Synthesis

Abstract

In recent years, mechanochemistry has become an innovative and sustainable alternative to traditional solvent-based synthesis. Mechanochemistry rapidly expanded across a wide range of chemistry fields, including diverse organic compounds and active pharmaceutical ingredients, coordination compounds, organometallic complexes, main group frameworks, and technologically relevant materials. This Review aims to highlight recent advancements and accomplishments in mechanochemistry, underscoring its potential as a viable and eco-friendly alternative to conventional solution-based methods in the field of synthetic chemistry.

Figure 1

Mechanochemical tools commonly used for synthesis at different scales. Adapted with permission from ref (3). Copyright 2021 Elsevier.

Scheme 1. Mechanochemical Generation of LiBH₄, Its Use in Reducing Esters, and Comparison with a Representative Solution-Based Method

Scheme 2. Mechanochemical Preparation of K⁺[Li(N(SiMe₃)₂]e^–, Synthetic Applications, and Comparison with a Representative Solution-Based Method

Scheme 3. Mechanochemical Halide Metathesis of K[A’] CsI (a); Mechanochemical Reaction of K[A’] with BeCl₂ (b) and MgCl₂ (c); Comparison with a Representative Solution-Based Method

Scheme 4. Mechanochemical Preparation of Be(Indenyl)₂

Scheme 5. Example of the Mechanochemical Preparation and Synthetic Application of Fluoro-Based Grignard Reagent and Comparison with a Representative Solution-Based Method

Scheme 6. Mechanochemical Preparation of Highly Reactive Mg(I) Dimers (a); Solid State Preparation of CAAC Stabilized Mg(I) Compounds (b)

Scheme 7. Preparation of Grignard Reagents under Air and Broad Scope Reactivity (a); Preparation and Application of Heavier Ca-Based Grignard Reagent (b); Representative Solution-Based Method for Comparison

Scheme 8. Mechanochemical Reaction of K[A’] with CaI₂ and Representative Solution-Based Method for Comparison

Scheme 9. Preparation of Nonsolvated Al(A’)₃ by Mechanochemical Means and Comparison with Solution-Based Methods

Scheme 10. (a) Large-Scale Mechanochemical Preparation of Al and In Complexes Bearing Salen and Salophen Ligands; (b) Mechanochemical Preparation of Al and in Luminophores Based on Bulky Salen and Salophen Ligands; Representative Solution-Based Method

Scheme 11. Ar-BIAN Ligands and Indium(III) Complex Synthesis by Mechanochemistry; Representative Solution-Based Method

Scheme 12. Mechanochemical Purification of Ge(0) and GeO₂ via Catecholates Preparation and Comparison with a Representative Solution-Based Method

Scheme 13. Preparation of Nonsolvated SnA’₃K and SnA’₄ Mechanochemically and Comparison with a Representative Solution-Based Method

Scheme 14. Mechanochemical Preparation of Lappert’s Heavier Tetrylenes (a); Rheology of the Crude Reaction and Sublimed Products (Reproduced with Permission from ref (72). Copyright 2023 Royal Society of Chemistry) (b); and Comparison with Representative Solution-Based Reaction

Scheme 15. Mechanochemical Preparation of Wittig Reagents and Comparison with Representative Solution-Based Method

Scheme 16. (a) Comparison between Solution-Based and Mechanochemical Preparation of Cyclophoph(V/V)azanes; (b) Comparison between Previously Reported Approach (a) and Mechanochemical Preparation of Adamantoid Phosphazanes (b)

Scheme 17. Solid State Oxidation of Several Substituted Phosphines (Selected Examples) And Comparison with Representative Solution-Based Methods

Scheme 18. Mechanochemical Synthesis of Tris(allyl)scandium Complex and Comparison with a Representative Solution-Based Method

Scheme 19. Mechanochemical Synthesis of Vanadium Diketonates and Comparison with a Representative Solution-Based Method

Scheme 20. Mechanochemical Synthesis of Rhenium Complexes and Comparison with a Representative Solution-Based Method

Scheme 21. Mechanochemical Synthesis of Ferrocene and Comparison with a Representative Solution-Based Method

Scheme 22. (a) Mechanochemical Synthesis of Ru(biim)₃ complex; (b) Mechanochemical Preparation of Ru Complexes by Transmetallation and Comparison with a Representative Solution-Based Method

Scheme 23. Mechanochemical Preparation of Au and Pd Salts and Complexes from Their Elemental Metallic Form and Comparison with a Representative Solution-Based Method

Scheme 24. Mechanochemical Preparation of Pd Complexes via Oxidative Additions Of Aryl Halides And Comparison With A Comparative Solution-Based Method

Scheme 25. Mechanochemical Preparation of Short-Lived Cyclic Pd Dimer

Scheme 26. (a) Mechanochemical Preparation of Au, Cu, and Pd NHC Complexes; (b) Synthesis of Cu NHC Complexes Using Air As the Oxidising Agent; Comparison with a Representative Solution-Based Method

Scheme 27. Comparative Study (i.e., Mechanochemistry, Slow Reaction and Solution) of Zinc Organometallic Species with TEMPO and Representative Solution-Based Method for Comparison

Scheme 28. Mechanochemical Preparation Lanthanides Triscyclopentadienyl Complexes and Comparison with a Representative Solution-Based Method

Scheme 29. (a) First Reported Mechanochemical Pinacol Rearrangement Finalised to the Preparation Phenytoin (API); Mechanochemical Beckmann Rearrangement for the Synthesis of (b) ε-Caprolactame and (c) Paracetamol; Comparison with a Representative Solution-Based Method

Scheme 30. Solvent-Free Protocol for the Achmatowicz Rearrangement Using Al₂O₃ and Representative Solution-Based Method (a) for Comparison

Scheme 31. Mechanochemical Protocol for the Loosen Rearrangement and Comparison with Representative Derivatives in Solution-Based Methods^,

Scheme 32. Coupling Reaction of Tetrahydroisoquinolines with Nitroalkanes, Indoles, and Alkynes by Ball Milling Mechanochemistry and Comparison with Representative Example (a) in a Solution-Based Method^,

Scheme 33. Mechanochemical Preparation of Organozinc Reagents and Their Use in Negishi Reactions and Comparison with Representative Examples in the Literature

Scheme 34. Solid State Enantioselective Aldol Reaction Catalyzed by (S)-Proline and Comparison with Solution Based-Methods

Scheme 35. Mechanochemical Catalytic Reactions for Cross Metathesis (a) and Ring-Closing Metathesis (b) and Comparison with Solution-Based Method for (a)

Scheme 36. Mechanochemical Alkynylations of Indoles Using Rh and Au Catalysts and Comparison with Solution-Based Method

Scheme 37. Mechanochemical Pd-Catalyzed Heck Reaction and Comparison with Solution-Based Methods

Scheme 38. Mechanochemical Pd-Catalyzed Oxidative Heck Reaction (Left), Buchwald-Hartwig Reaction (Right), and Representative Solution-Based Reaction

Scheme 39. Mechanochemical Cu Catalyzed Preparation of N-Sulfonylguanidines and Comparative Solution-Based Method

Scheme 40. Mechanochemical C–N Coupling of Amides and Isocyanates and Comparison with Solution-Based Method

Scheme 41. Mechanochemical CuAAC Reaction and Comparison with a Representative Solution-Based Method^,

Scheme 42. Mechanochemical C–H Amidation of Arenes and Comparison with Solution-Based Methods^,

Scheme 43. Mechanochemical CuAAC Reaction and Comparison with a Solution-Based Representative Method

Scheme 44. Mechanochemical Palladium-Based Oxidative Addition Complexes Air-Sensitive Pd(0) Intermediates and Comparison with a Solution-Based Method

Scheme 45. Mechanochemical C–C Bond Formation with Oximes and Anilides and Solution-Based Method for Comparison for (a)

Scheme 46. Mechanochemical Suzuki Polymerization of 4-Bromophenylboronic Acid

Scheme 47. Copper Ball Catalyzed Cross Dehydrogenative Coupling Reactions and Representative Solution-Based Method for Comparison

Scheme 48. One-Pot Mechanochemical Sonogashira Coupling/Cyclopropenation and Comparison with a Solution-Based Method^,

Scheme 49. Mechanochemical Enzymatic Resolution of Secondary Alcohols

Scheme 50. General Reaction Scheme of the Mechanoenzymatic Hydrolysis of PET using HiC (Novozym 51032) by Ball-Milling and Comparison with Other Enzymatic-Based Method

Scheme 51. Enantioselective (S)-Proline-Catalyzed Aldol Reaction under Ball-Milling Conditions and Representative Solution-Based Method for Comparison

Scheme 52. Squaramide Catalyzed Michael Addition of Aldehydes to Nitroalkenes by Ball-Milling and Representative Solution-Based Method for Comparison

Conducted by authors of mechanochemical study.

Scheme 53. Tertiary Amine (DABCO)-Catalyzed MBH Reaction by Mechanochemistry and Representative Solution-Based Method for Comparison

Scheme 54. First Example of Photomechanochemical Catalysis and Representative Solution-Based Method for Comparison

Scheme 55. Supramolecular Solid-State Photodimerization and Mechanochemical Depolymerization Steps

Scheme 56. Mechanoredox Reduction of Azonium Salts Mediated by Piezoelectric Materials and Comparison with a Representative Solution-Based Method

Scheme 57. Solid State Reduction of Umemoto′s Reagent for Radical Trifluoromethylation Reactions and Comparison with a Solution-Based Method

Scheme 58. Mechanoredox Generation of Catalytically Active Cu(I) Species

Scheme 59. Mechanoredox Addition of Sulfoximidoyl Chlorides to Allenes

Scheme 60. Mechanoredox Preparation of 1,2-Diketoindolizine and Comparison with a Representative Solution-Based Method

Scheme 61. ILAG Procedure for the Encapsulation of C60 Fullerene into Cavities of ZIF-8

Scheme 62. Mechanochemical Synthesis of HE-ZIF (Adapted with Permission from Ref (337). Copyright 2019 Wiley)

Scheme 63. Mechanochemical Preparation of FA-MHPs Together with Their Crystal Structure Diagram, Underlining the [PbX_xX′_6–x]^4– Octahedral Configuration and the Normalized Reflectance Spectra for FAPbX₃ and MHPs Performed by Hand Grinding (HG-FAPb(Cl_0.5Br_0.5)₃) and Ball Milling (BM-FAPb(Br_0.5I_0.5)₃

Figure 2

Representative luminescence photographs of MAPbX₃ perovskite solutions under a 365 nm UV lamp irradiation. Reproduced with permission from ref (368). Copyright 2019 ACS.