Green metrics in Mechanochemistry

Abstract

The development of new green methodologies and their broader adoption for promoting sustainable development in chemistry laboratories and industry play a significant role in society, due to the economic importance of chemistry and its and widespread presence in everyday life. Therefore, a sustainable approach to chemistry contributes to the well-being of worldwide population and comply with the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal. The review highlights how mechanochemical methods in batch and in continuous are an eco-friendly approach for organic synthesis, with a lower environmental footprint in most cases, compared to solution-based procedures. The assessment is objectively based on the use of green metrics (e.g. atom and real atom economy, E-factor, Process Mass Intensity, Material Parameter Recovery, Eco-scale, Stoichiometric Factor, etc.) and indicators (e.g. DOZN tool and Life Cycle Assessment, LCA, studies) applied to organic transformations such as synthesis of amide bond, carbamates, heterocycles, Active Pharmaceutical Ingredients (APIs), porphyrins, Porous Organic Polymers (POPs), metal- or acid-catalysed processes, multicomponent and condensation reactions, rearrangements, etc. The generalized absence of bulk solvents, the precise control over the stoichiometry (i.e., using agents in a stoichiometrically rather than in excess), and the more selective reactions enabling simplified work-up procedures are the distinctive factors marking the superiority of mechanochemical processes over solution-based chemistry.

Mechanochemical-assisted decarboxylative sulfonylation of α,β-unsaturated carboxylic acids with sodium sulfinate salts

“…d KI (40 mol%). Various functional groups such as chloro, fluoro, bromo, nitro, and cyano functionalities at the ortho-, meta-, and para-positions smoothly reacted under this protocol to form the targeted products (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) in moderate to good yields. Moreover, the applicability of this method was demonstrated in the synthesis of some potent neuroprotective agents 32, 33 and 34 in 63-78% yields, with (E)-1-chloro-2-(2-( phenylsulfonyl)vinyl) benzene 33 being the most potent one.…”

Batch and continuous flow mechanochemical synthesis of organic compounds including APIs

“…In the recent literature, a few thoughts on future directions and challenges 72 on batch and continuous mechanochemistry have been reported. Some of these include mechanochemistry for carrying out the impossible reactions, 69 green metrics in mechanochemistry, 70 and mechanochemical rearrangement for organic synthesis with eco-friendly approach, especially for active pharmaceutical and complex natural products. 71 Recent reports on direct continuous mechanochemical solvent-free amidation 76,77 cover an important step toward solvent-free manufacturing.…”

The Role of Crystalline Intermediates in Mechanochemical Cyclorhodation Reactions Elucidated by in‐Situ X‐ray Powder Diffraction and Computation

“…Additionally, we obtained insight into the reactivity of both crystalline phases using the condensed dual Fukui indices, [50][51][52][53] for nucleophilicity and electrophilicity (see Figure 5b) calculated at all atomic positions as f (2) = f + À f À in the clusters. It is clear that in the 2Rc + 3BHQ clusters of 4 α one of the rhodium centers is an electrophile (f (2) = + 0.026) and the other one is a nucleophile (f (2) =-0.289), it is also seen that two of the terminal chloride centers are nucleophiles (f (2) =-0.468, À 0.033) while one more is an electrophile (f (2) = + 0.005) and the remaining terminal chloride is not activated. Comparing the Fukui indices for 4 α to the ones for the isolated [Cp*RhCl 2 ] 2 (Figure S22), it is evident that cocrystal 4 α is not well suited to undergo chemical reactions in which the rhodium centers act as electrophiles and the chloride centers act as nucleophiles.…”

“…Comparing the Fukui indices for 4 α to the ones for the isolated [Cp*RhCl 2 ] 2 (Figure S22), it is evident that cocrystal 4 α is not well suited to undergo chemical reactions in which the rhodium centers act as electrophiles and the chloride centers act as nucleophiles. Conversely, in the 4 β cluster, there are two active electrophile rhodium centers (f (2) = + 0.077 and + 0.080) and four active nucleophile terminal chloride centers (f (2) =-0.162, À 0.158, À 0.075, À 0.071). These numbers in conjunction with the above exposed fact that 4 α is more strongly bonded, help explaining why the [Cp*RhCl 2 ] 2 units within 4 β are the more reactive species by far.…”

“…for chemical synthesis has enabled the development of known and new transformations more sustainably. [1,2] Particularly interesting are the examples in which mechanochemistry has shown the ability to alter reaction mechanisms or to change product composition of well-established reactions. [3][4][5] There are various explanations as to why a reaction may proceed more effectively through mechanochemistry compared to in solution, as well as reasons for the eventual switch in reactivity by mechanochemistry.…”