A Greener Approach

The reduction in the number of equivalents of NaH and (R)-quinuclidin-3-ol (31) during the synthesis offers many advantages over the original approach, for example, (i) it is catalytic, (ii) the yield is increased from 50 to 87%, and, last but not least, (iii) it has a 50% cost advantage. Thus, the eventual synthesis was designed to be low waste producing. 

---

In order to extend the scope of the reaction, and with the aim of designing a greener approach to the above set of reactions, we preformed the acylation of the same substrates with different acylation agents, such as maleic anhydride, p-methoxybenzoic acid and acetic acid (Scheme 48.4). Table 48.3 shows the results for acylation of benzenesulfonamide. 

Enantiomers often have very different properties when interacting with biological enzymes that are chiral. As we just discussed, sometimes we use a resolution to convert an enantiomeric mixture to a set of diastereomers in order to separate them. This technique of resolving one enantiomer from another is a practical approach, but it is not necessarily good for the environment. Additional steps are needed to prepare and to separate the diastereomers, and then the enantiomers need to be regenerated as discussed in Section 5.12. Each of these steps would need solvents and, of course, would generate some waste. A greener approach is to prepare the desired enantiomer in its pure form and without formation of the undesired enantiomer. 

Farina V, Shu C, Zeng X, et al. Second-Generation Process for the HCV Protease Inhibitor BILN 2061 A Greener Approach to Ru-Catalyzed Ring-dosing Metathesis. 

Visible light photocatalysis as a greener approach to photochemical synthesis. Nat Chem.,... 

Hoyos, P, Pace, V., and Alcantara, A. R. (2013). Biocatalyzed on water synthesis of chiral building blocks for the preparation of anti-cancer drugs A greener approach. Curr. Org. Chem., 17,1132-1157. 

The Future s Green an Integrated Approach to a Greener Chemical Industry... 

A fast and efficient molybdenum-catalyzed asymmetric allylic alkylation under noninert conditions has been reported using MW-accelerated reaction [178]. Inter-molecular hydroacylation of 1-alkenes with aldehydes has been presented as a greener alternative to classical approach using a homogeneous catalyst in toluene. 

A mild and greener approach to the synthesis of 1,2,4-triazoles by the dipolar cycloaddition of nitrilimines with nitriles has been reported. The nitrilium intermediates were generated in situ from hydrazonyl chlorides 120 and reacted with the nitriles in a one-pot process. Yields of the 1,3,5-trisubstituted products 121a-o were good in the majority of cases (Equation 37 and Table 20) <2005H(65)1183>. 

The power of this statement is that even if we do not know the toxicity of the currently used chemical for which we are seeking a greener alternative, we can make an educated prediction that the proposed replacement will be less or more toxic. This rule restates ideas already published by Anastas and co-workers [2], but describes a practical approach to using this type of information. Before delving into details on how to implement the principle, we need to define terms briefly, although these will be familiar to many readers. 

Hopefully these approaches pioneered by companies like AZ and Pfizer will have a rapid take-up in the pharmaceutical industry over the next few years leading to a greener drug discovery process. 

Kirchhoff, M. Ryan, M. A., Eds Greener Approaches to Undergraduate Chemistry Experiments, American Chemical Society Washington, 2002. (The following experiments are all authored by John C. Warner) ... 

The American Chemical Society (ACS) offers a number of resources that supplement the curriculum. ACS collaborated with the Royal Society of Chemistry and the Gesellschaft Deutscher Chemiker to produce Introduction to Green Chemistry (18 a collection of six units that present key concepts in green chemistry. High-school students are the target audience for this resource, whose units incorporate hands-on activities such as a Vitamin C clock reaction. The ACS lab manual Greener Approaches to Undergraduate Chemistry Experiments (13) is available in both Spanish and Chinese. 

Once a synthetic route for preparing a complex has been designed, the stoichiometry of the reaction will help to determine the minimum amount of reagents needed. Often, excess reagents are used to maximize the yield of a desired product, in compliance with Le Chatelier s principle. A move towards greener approaches, however, asks chemists to think of a new definition of maximizing yield, one in terms of total atoms rather than just the desired product. This new approach asks synthetic chemists to adhere as closely as possible to the stoichiometric amounts. 

---