Green methods and techniques

Catalysis

Catalysis is central to green synthetic chemistry, presenting an opportunity for substantial savings in materials, energy, and costs. Compared to reagents that are consumed in a reaction, catalyst molecules can perform multiple transformations and so can be used in lower quantities. Frequently the amount of catalyst needed is less than 1% of the reactants.

Types of catalyst include:

Homogeneous catalysts: Catalysts that are in the same phase as the reactants. For example, all the reaction components are dissolved in a solvent. Homogeneous catalysis is more common in fine chemical (including pharmaceutical) synthesis because it offers higher activity and selectivity. 

Heterogeneous catalysts: Catalysts present as a separate phase to the reactants. Heterogeneous catalysis is more prevalent in commodity chemical production where often gaseous reactants come into contact with a solid catalyst (Sheldon et al., 2007).

Immobilised catalysts: This refers to the process of converting homogeneous catalysts into heterogeneous forms by entrapping or grafting catalyst molecules onto solid supports such as silica (Fang et al., 2023). This approach can impart some of the benefits of heterogeneous catalysts to highly active homogeneous catalysts, providing ease of operational use and facile recycling.

Enzymes: Chemical catalysts often rely on rare and precious metals (see below). In contrast, biological catalysts, such as enzymes, often work under milder conditions with higher selectivity (Su et al., 2010).

Sustainable chemical catalysis

The pharmaceutical industry is highly dependent on catalysts made from scarce elements. For example, palladium is widely used to form the carbon-carbon bonds that are the basis of organic molecules. These reactions are fundamental to modern (small molecule) drug discovery (Rayadurgam et al., 2021). The chemical industry has made substantial efforts to address the challenges posed by the cost and scarcity of catalytic species based on precious metals, primarily by developing processes for reclaiming these metals. However, it would be preferable to use cheaper, more abundant metals in the first place. Promising examples include cobalt (Co), copper (Cu), nickel (Ni), and iron (Fe) (Chirik and Morris, 2015). Collectively, these are known as base metals. Base metals typically have a lower environmental impact than precious metals (Nuss and Eckelman, 2014).

Base metal catalysis represents a pivotal shift from the pursuit of purely performance-based catalyst design towards more sustainable alternatives in chemical manufacturing (Hutchings, 2007), offering a viable solution to the challenges posed by the scarcity and cost of precious metals (Maes et al., 2016). Recent advancements highlight the potential of base metals in driving reactions traditionally dominated by precious metals, marking a significant step forward in the development of more sustainable catalytic practices (Tamang and Findlater, 2019). This approach not only mitigates the reliance on limited precious metal resources but also opens up the possibility of new substances and reactions being discovered (Nair et al., 2019).

Ideally, new chemistry (and new catalysts) are developed and implemented early in the development of an active pharmaceutical ingredient (API). This avoids complete or partial redesign of large-scale processes and the associated regulatory hurdles. The design of robust, cheap catalysts without supply chain concerns requires substantial planning but ultimately solved issues related to precious metals' availability, cost, and sustainability (Bullock et al., 2020; Lopez and Padrón, 2022).