By Ana Koperniku
25% of pharmaceuticals contain an amide bond and 55% contain an amine functionality (figure 1). Due to the prevalence of these functional groups, sustainable production methods of this class of molecules is necessary. There are already many chemical methodologies that produce these compounds. Nevertheless, there is always space for improvement, especially if sustainable production is a target.
Figure 1. Amide and amine functional groups
Ana’s research focuses on the development of methods to access amide libraries and series of branched amines in which the branch is installed via catalytic C-C bond formation. Below, she has shared with us the features and principles behind her methods for each cases. She explained what makes each unique in the context of sustainability.
1st part: Amide bond formation ~clean, green, generalizable
For the amide bond containing molecules, the derived amides are isolated in a pure form via filtration; the product is isolated in its purest form and the filtrate contains all the byproducts. No column chromatography is needed, rendering the amidation reaction as clean (Principle #1 of Green Chemistry). The bypass of column chromatography implies minimal use of solvents for purification which minimizes waste and makes the process green (Principle #1 of Green Chemistry). As the method can be applied to a series of nucleophilic amines with the same electrophile, the method can also be characterized as generalizable (Principle #3 of Green Chemistry). The more generalizable a method, the lower the cost and the safer.
2nd part: C-C bond formation ~green, atom economic
For the other part of her research, Ana is involved in catalytic reactions. Using unbranched amines as starting material, she moves to final branched amines via the use of catalytic amounts of metals. The use of catalytic instead of stoichiometric amounts of reagents makes a process greener (Principle #9 of Green Chemistry). With catalysis, it is anticipated all starting materials are incorporated into the final products. This means that the reaction has high atom economy (Principle #2 of Green Chemistry). After the C-C bond formation, the amines are isolated via organic solvent-aqueous work-up, and there is no need for column chromatography, which minimizes waste production (Principle #1 of Green Chemistry).
3rd part: Green is not always sustainable
The research descriptions in parts one and two illustrate distinct features of green chemistry. The more green principles are followed, the greener a process. While a clean process does not necessarily imply a green process, a green process is ideally a clean process as well. Equation 1 shows that it takes more than one feature of green chemistry to make a green process.
Clean ҂ Green ҂ Atom Economic equation 1
equation 1 ҂ Sustainable equation 2
Going further, equation 2 shows that a green process is not necessarily a sustainable process. Sustainability relates to the social, economic and environmental impact of the development of a process. Consequently, a sustainable process needs to provide multifaceted solutions.
Sustainability is the next step following the development of a green process. It is the desired evolution of a green process. A green process does not imply sustainability, but sustainability encompasses the term green (figure 2).
Figure 2. Using the principles and metrics of green chemistry allows us to develop a green process. Using green processes allows us to reach a sustainable future.
4th part: Qualitative vs quantitative evaluation
To follow the principles of Green Chemistry in the lab and in our everyday life shows consideration for our lives, the lives of others, and the lives of future generations. If you want to quantify how green you are, then have a look at the metrics: E factor and Process Mass Index.
~~ powered by Wikipedia: https://en.wikipedia.org/wiki/Green_chemistry_metrics
~~ powered by Wiley: Lapkin, Alexei and Constable, David (2008), Green Chemistry Metrics. Measuring and Monitoring Sustainable Processes, Wiley
~~ powered by Macmillan Publishers Limited: Tucker, John and Faul, Margaret (2016), Industrial research: Drug companies must adopt green chemistry, Nature, 534, 27-29