Green mass intensity

Yield and other mass-related metrics such as atom economy, reaction mass efficiency and mass intensity have been examined by Constable et al with regard to their significance concerning greenness and costs. The importance of using a (product) concentration term, which can be mass intensity or mass index, is additionally emphasized by Laird et al This is in compliance with Winterton, who in his twelve more green chemistry principles demands the establishment of full mass balances. 

The Green Chemistry Institute (GCl) Pharmaceutical Roundtable has used the Process Mass Intensity (PMl) [12], defined as the total mass used in a process divided by the mass of product (i.e. PMl = E factor -i- 1) to benchmark the environmental acceptability of processes used by its members (see the GCl website). The latter include several leading pharmaceutical companies (Eh Lilly, GlaxoSmithKline, Pfizer, Merck, AstraZeneca, Schering-Plow, and Johnson Johnson). The aim was to use this data to drive the greening of the pharmaceutical industry. We believe, however, that the E factor is to be preferred over the PMl since the ideal E factor of 0 is a better reflection of the goal of zero waste. 

Different variahons on E factor have been proposed and used in the pharma-ceuhcals industry (for example, mass intensity, mass productivity [6], and process mass intensity [21]). Each of these has the aim of greening pharmaceutical processes by highlighting the amount of material used in a process, either when... 

In the discussions around E factor/mass intensity and solvent selection, we have considered metrics that begin to address Green Chemistry Principle 1 (prevention) and 5 (use safer solvents). Green Chemistry Principle 7 considers the use of renewable resources. 

Quantitative evaluation of chemical processes in terms of environmental impact and eco-friendliness has gradually become a topic of great interest since the original introduction of the atom economy (AE) by Trost [1], and the E-factor by Sheldon [2]. Since then, other indexes have been proposed for the green metrics of chemical processes, such as effective mass yield (EMY) [3], reaction mass efficiency (RME) [4] and mass intensity (MI) [5], along with unification efforts [6, 7] and comparisons among these indexes [8]. 

Extensive statistical analysis of the mass intensity, yield, atom economy, and stoichiometry show that these data do not correlate with each other in any meaningful way. Because these metrics appear to be of discretely different types, following one metric in isolation from others may not drive the best behavior for greening reactions. This is illustrated in Table 2.2, which contains an example of three different chemistries of similar mass intensity that have generally different and conflicting data trends for the other metrics. 

With new technical processes, the determination of the process mass intensity (PMl = total mass in a process (kg)/mass of product (kg)) and considerations of possible adverse effects on the environment usually form part of the process evaluation (Green Chemistry). On grounds of modem environmental protection legislation, in many cases environmentally friendly procedures are reckoned better than older processes, which have a greater polluting effect on the environment (Fig. 1.8). [16,17]... 

Figure 15.6 Example output of the process mass intensity and life cycle assessment tool developed by the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable. The data presented in the columns provide the metrics for steps 1,2, 3, and the total of the synthesis. Some of the instructions in the tool are included as an illustration.

Cryst. M.p. 59-60°. B.p. 95°/9 mm. Sol. most org. solvents. Very volatile in steam and in air. Gives deep blue ppt. with I in cone. NaHCOs. Intense red pine splinter reaction. Fusion with oxalic acid —> green mass, sol. HjO. 

The difference in energy consumption between put-and-take distillation and the membrane setup is difficult to estimate. Both technologies result in waste streams that require further treatment. Moreover, the required pressure for the membrane setup is hard to define on the base of pilot-scale experiments. It is, however, clear that the membrane setup shows a much lower mass intensity than the distillation. Mass intensity is a commonly used concept in the context of green energy and is defined as the ratio of the total mass of the reactants and the mass of the reaction products (Curzons et al., 2001). Solvent exchange by distillation typically shows a mass intensity of 5-10 kg/kg, whereas the use of membrane technology results in a value of 2-3 kg/kg. Both values are vahd for a 95% exchange, which is often the required value in industrial apphcations. 

The various spectral and physical properties of the compounds prepared, including their elemental analysis, and IR, NMR, and mass spectra (which contained the appropriate ions, each of the intensity demanded by the isotopic composition of the ion), all fully supported the formulation of the species as reported. With two exceptions, all of the new compounds were found to be colorless liquids, typically having a relatively short liquid range, and they are usually very volatile for their molecular weight. The two exceptions are (CFsliTe, which is yellow-green, and (CFsljTez, which is red-brown (21). 

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