Green chemistry metrics describe aspects of a chemical process relating to the principles of green chemistry. The metrics serve to quantify the efficiency or environmental performance of chemical processes, and allow changes in performance to be measured. The motivation for using metrics is the expectation that quantifying technical and environmental improvements can make the benefits of new technologies more tangible, perceptible, or understandable. This, in turn, is likely to aid the communication of research and potentially facilitate the wider adoption of green chemistry technologies in industry.
For a non-chemist, an understandable method of describing the improvement might be a decrease of X unit cost per kilogram of compound Y. This, however, might be an over-simplification. For example, it would not allow a chemist to visualize the improvement made or to understand changes in material toxicity and process hazards. For yield improvements and selectivity increases, simple percentages are suitable, but this simplistic approach may not always be appropriate. For example, when a highly pyrophoric reagent is replaced by a benign one, a numerical value is difficult to assign but the improvement is obvious, if all other factors are similar.[1]
Numerous metrics have been formulated over time. A general problem is that the more accurate and universally applicable the metric devised, the more complex and unemployable it becomes. A good metric must be clearly defined, simple, measurable, objective rather than subjective and must ultimately drive the desired behavior.
Mass-based versus impact-based metrics
The fundamental purpose of metrics is to allow comparisons. If there are several economically viable ways to make a product, which one causes the least environmental harm (i.e. which is the greenest)? The metrics that have been developed to achieve that purpose fall into two groups: mass-based metrics and impact-based metrics.
The simplest metrics are based upon the mass of materials rather than their impact. Atom economy, E-factor, yield, reaction mass efficiency and effective mass efficiency are all metrics that compare the mass of desired product to the mass of waste. They do not differentiate between more harmful and less harmful wastes. A process that produces less waste may appear to be greener than the alternatives according to mass-based metrics but may in fact be less green if the waste produced is particularly harmful to the environment. This serious limitation means that mass-based metrics can not be used to determine which synthetic method is greener.[2] However, mass-based metrics have the great advantage of simplicity: they can be calculated from readily available data with few assumptions. For companies that produce thousands of products, mass-based metrics may be the only viable choice for monitoring company-wide reductions in environmental harm.
In contrast, impact-based metrics such as those used in life-cycle assessment evaluate environmental impact as well as mass, making them much more suitable for selecting the greenest of several options or synthetic pathways. Some of them, such as those for acidification, ozone depletion, and resource depletion, are just as easy to calculate as mass-based metrics but require emissions data that may not be readily available. Others, such as those for inhalation toxicity, ingestion toxicity, and various forms of aquatic eco toxicity, are more complex to calculate in addition to requiring emissions data.[3]
Atom economy was designed by Barry Trost as a framework by which organic chemists would pursue “greener” chemistry.[4][5] The atom economy number is how much of the reactants remain in the final product.
For a generic multi-stage reaction used for producing R:
A + B → P + X
P + C → Q + Y
Q + D → R + Z
The atom economy is calculated by
The conservation of mass principle dictates that the total mass of the reactants is the same as the total mass of the products. In the above example, the sum of molecular masses of A, B, C and D should be equal to that of R, X, Y and Z. As only R is the useful product, the atoms of X, Y and Z are said to be wasted as by-products. Economic and environmental costs of disposal of these waste make a reaction with low atom economy to be "less green".
A further simplified version of this is the carbon economy. It is how much carbon ends up in the useful product compared to how much carbon was used to create the product.
This metric is a good simplification for use in the pharmaceutical industry as it takes into account the stoichiometry of reactants and products. Furthermore, this metric is of interest to the pharmaceutical industry where development of carbon skeletons is key to their work.
The atom economy calculation is a simple representation of the “greenness” of a reaction as it can be carried out without the need for experimental results. Nevertheless, it can be useful in the process synthesis early stage design.
The drawback of this type of analysis is that assumptions have to be made. In an ideal chemical process, the amount of starting materials or reactants equals the amount of all products generated and no atom is lost. However, in most processes, some of the consumed reactant atoms do not become part of the products, but remain as unreacted reactants, or are lost in some side reactions. Besides, solvents and energy used for the reaction are ignored in this calculation, but they may have non-negligible impacts to the environment.
Percentage yield is calculated by dividing the amount of the obtained desired product by the theoretical yield.[6] In a chemical process, the reaction is usually reversible, thus reactants are not completely converted into products; some reactants are also lost by undesired side reaction.[7][8] To evaluate these losses of chemicals, actual yield has to be measured experimentally.
As percentage yield is affected by chemical equilibrium, allowing one or more reactants to be in great excess can increase the yield. However, this may not be considered as a "greener" method, as it implies a greater amount of the excess reactant remain unreacted and therefore wasted. To evaluate the use of excess reactants, the excess reactant factor can be calculated.
If this value is far greater than 1, then the excess reactants may be a large waste of chemicals and costs. This can be a concern when raw materials have high economic costs or environmental costs in extraction.
In addition, increasing the temperature can also increase the yield of some endothermic reactions, but at the expense of consuming more energy. Hence this may not be attractive methods as well.
Reaction mass efficiency
The reaction mass efficiency is the percentage of actual mass of desire product to the mass of all reactants used. It takes into account both atom economy and chemical yield.
Reaction mass efficiency, together with all metrics mentioned above, shows the “greenness” of a reaction but not of a process. Neither metric takes into account all waste produced. For example, these metrics could present a rearrangement as “very green” but fail to address any solvent, work-up, and energy issues that make the process less attractive.
Effective mass efficiency
A metric similar to reaction mass efficiency is the effective mass efficiency, as suggested by Hudlicky et al.[9] It is defined as the percentage of the mass of the desired product relative to the mass of all non-benign reagents used in its synthesis. The reagents here may include any used reactant, solvent or catalyst.
Note that when most reagents are benign, the effective mass efficiency can be greater than 100%. This metric requires further definition of a benign substance. Hudlicky defines it as “those by-products, reagents or solvents that have no environmental risk associated with them, for example, water, low-concentration saline, dilute ethanol, autoclaved cell mass, etc.”. This definition leaves the metric open to criticism, as nothing is absolutely benign (which is a subjective term), and even the substances listed in the definition have some environmental impact associated with them. The formula also fails to address the level of toxicity associated with a process. Until all toxicology data is available for all chemicals and a term dealing with these levels of “benign” reagents is written into the formula, the effective mass efficiency is not the best metric for chemistry.
Environmental factor
The first general metric for green chemistry remains one of the most flexible and popular ones. Roger A. Sheldon’s environmental factor (E-factor) can be made as complex and thorough or as simple as desired and useful.[10]
The E-factor of a process is the ratio of the mass of waste per mass of product:
As examples, Sheldon calculated E-factors of various industries:
Table E-Factors across the chemical industry
Industry sector
Annual production (t)
E-factor
Waste produced (t)
Oil refining
106 – 108
Ca. 0.1
105 – 107
Bulk chemicals
104 – 106
< 1 – 5
104 – 5×106
Fine chemicals
102 – 104
5 – 50
5×102 – 5×105
Pharmaceuticals
10 – 103
25 – 100
2.5×102 – 105
It highlights the waste produced in the process as opposed to the reaction, thus helping those who try to fulfil one of the twelve principles of green chemistry to avoid waste production. E-factors can be combined to assess multi-step reactions step by step or in one calculation. E-factors ignore recyclable factors such as recycled solvents and re-used catalysts, which obviously increases the accuracy but ignores the energy involved in the recovery (these are often included theoretically by assuming 90% solvent recovery). The main difficulty with E-factors is the need to define system boundaries, for example, which stages of the production or product life-cycle to consider before calculations can be made.
This metric is simple to apply industrially, as a production facility can measure how much material enters the site and how much leaves as product and waste, thereby directly giving an accurate global E-factor for the site. Sheldon's analyses (see table) demonstrate that oil companies produce less waste than pharmaceuticals as a percentage of material processed. This reflects the fact that the profit margins in the oil industry require them to minimise waste and find uses for products which would normally be discarded as waste. By contrast the pharmaceutical sector is more focused on molecule manufacture and quality. The (currently) high profit margins within the sector mean that there is less concern about the comparatively large amounts of waste that are produced (especially considering the volumes used) although it has to be noted that, despite the percentage waste and E-factor being high, the pharmaceutical section produces much lower tonnage of waste than any other sector. This table encouraged a number of large pharmaceutical companies to commence “green” chemistry programs.
The EcoScale
The EcoScale metric was proposed in an article in the Beilstein Journal of Organic Chemistry in 2006 for evaluation of the effectiveness of a synthetic reaction.[11] It is characterized by simplicity and general applicability. Like the yield-based scale, the EcoScale gives a score from 0 to 100, but also takes into account cost, safety, technical set-up, energy and purification aspects. It is obtained by assigning a value of 100 to an ideal reaction defined as "Compound A (substrate) undergoes a reaction with (or in the presence of)inexpensive compound(s) B to give the desired compound C in 100% yield at room temperature with a minimal risk for the operator and a minimal impact on the environment", and then subtracting penalty points for non-ideal conditions. These penalty points take into account both the advantages and disadvantages of specific reagents, set-ups and technologies.
Related Research Articles
In a chemical reaction, chemical equilibrium is the state in which both the reactants and products are present in concentrations which have no further tendency to change with time, so that there is no observable change in the properties of the system. This state results when the forward reaction proceeds at the same rate as the reverse reaction. The reaction rates of the forward and backward reactions are generally not zero, but they are equal. Thus, there are no net changes in the concentrations of the reactants and products. Such a state is known as dynamic equilibrium.
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking of chemical bonds between atoms, with no change to the nuclei, and can often be described by a chemical equation. Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive elements where both electronic and nuclear changes can occur.
Stoichiometry is the relationship between the weights of reactants and products before, during, and following chemical reactions.
In chemistry and thermodynamics, the standard enthalpy of formation or standard heat of formation of a compound is the change of enthalpy during the formation of 1 mole of the substance from its constituent elements in their reference state, with all substances in their standard states. The standard pressure value p⦵ = 105 Pa(= 100 kPa = 1 bar) is recommended by IUPAC, although prior to 1982 the value 1.00 atm (101.325 kPa) was used. There is no standard temperature. Its symbol is ΔfH⦵. The superscript Plimsoll on this symbol indicates that the process has occurred under standard conditions at the specified temperature (usually 25 °C or 298.15 K).
In chemistry, chemical synthesis is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses, the process is reproducible and reliable.
In chemistry, the law of mass action is the proposition that the rate of the chemical reaction is directly proportional to the product of the activities or concentrations of the reactants. It explains and predicts behaviors of solutions in dynamic equilibrium. Specifically, it implies that for a chemical reaction mixture that is in equilibrium, the ratio between the concentration of reactants and products is constant.
Chemical kinetics, also known as reaction kinetics, is the branch of physical chemistry that is concerned with understanding the rates of chemical reactions. It is different from chemical thermodynamics, which deals with the direction in which a reaction occurs but in itself tells nothing about its rate. Chemical kinetics includes investigations of how experimental conditions influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition states, as well as the construction of mathematical models that also can describe the characteristics of a chemical reaction.
In chemistry, reactivity is the impulse for which a chemical substance undergoes a chemical reaction, either by itself or with other materials, with an overall release of energy.
Fischer esterification or Fischer–Speier esterification is a special type of esterification by refluxing a carboxylic acid and an alcohol in the presence of an acid catalyst. The reaction was first described by Emil Fischer and Arthur Speier in 1895. Most carboxylic acids are suitable for the reaction, but the alcohol should generally be primary or secondary. Tertiary alcohols are prone to elimination. Contrary to common misconception found in organic chemistry textbooks, phenols can also be esterified to give good to near quantitative yield of products. Commonly used catalysts for a Fischer esterification include sulfuric acid, p-toluenesulfonic acid, and Lewis acids such as scandium(III) triflate. For more valuable or sensitive substrates other, milder procedures such as Steglich esterification are used. The reaction is often carried out without a solvent or in a non-polar solvent to facilitate the Dean-Stark method. Typical reaction times vary from 1–10 hours at temperatures of 60-110 °C.
In environmental chemistry, the chemical oxygen demand (COD) is an indicative measure of the amount of oxygen that can be consumed by reactions in a measured solution. It is commonly expressed in mass of oxygen consumed over volume of solution which in SI units is milligrams per litre (mg/L). A COD test can be used to easily quantify the amount of organics in water. The most common application of COD is in quantifying the amount of oxidizable pollutants found in surface water or wastewater. COD is useful in terms of water quality by providing a metric to determine the effect an effluent will have on the receiving body, much like biochemical oxygen demand (BOD).
A reversible reaction is a reaction in which the conversion of reactants to products and the conversion of products to reactants occur simultaneously.
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In physical organic chemistry, a kinetic isotope effect (KIE) is the change in the reaction rate of a chemical reaction when one of the atoms in the reactants is replaced by one of its isotopes. Formally, it is the ratio of rate constants for the reactions involving the light (kL) and the heavy (kH) isotopically substituted reactants (isotopologues):
A chemical reactor is an enclosed volume in which a chemical reaction takes place. In chemical engineering, it is generally understood to be a process vessel used to carry out a chemical reaction, which is one of the classic unit operations in chemical process analysis. The design of a chemical reactor deals with multiple aspects of chemical engineering. Chemical engineers design reactors to maximize net present value for the given reaction. Designers ensure that the reaction proceeds with the highest efficiency towards the desired output product, producing the highest yield of product while requiring the least amount of money to purchase and operate. Normal operating expenses include energy input, energy removal, raw material costs, labor, etc. Energy changes can come in the form of heating or cooling, pumping to increase pressure, frictional pressure loss or agitation.
In chemistry, yield, also referred to as reaction yield, is a measure of the quantity of moles of a product formed in relation to the reactant consumed, obtained in a chemical reaction, usually expressed as a percentage. Yield is one of the primary factors that scientists must consider in organic and inorganic chemical synthesis processes. In chemical reaction engineering, "yield", "conversion" and "selectivity" are terms used to describe ratios of how much of a reactant was consumed (conversion), how much desired product was formed (yield) in relation to the undesired product (selectivity), represented as X, Y, and S.
The limiting reagent in a chemical reaction is a reactant that is totally consumed when the chemical reaction is completed. The amount of product formed is limited by this reagent, since the reaction cannot continue without it. If one or more other reagents are present in excess of the quantities required to react with the limiting reagent, they are described as excess reagents or excess reactants, or to be in abundance.
Conversion and its related terms yield and selectivity are important terms in chemical reaction engineering. They are described as ratios of how much of a reactant has reacted (X — conversion, normally between zero and one), how much of a desired product was formed (Y — yield, normally also between zero and one) and how much desired product was formed in ratio to the undesired product(s) (S — selectivity).
Atom economy is the conversion efficiency of a chemical process in terms of all atoms involved and the desired products produced. The simplest definition was introduced by Barry Trost in 1991 and is equal to the ratio between the mass of desired product to the total mass of products, expressed as a percentage. The concept of atom economy (AE) and the idea of making it a primary criterion for improvement in chemistry, is a part of the green chemistry movement that was championed by Paul Anastas from the early 1990s. Atom economy is an important concept of green chemistry philosophy, and one of the most widely used metrics for measuring the "greenness" of a process or synthesis.
In physics, a mass balance, also called a material balance, is an application of conservation of mass to the analysis of physical systems. By accounting for material entering and leaving a system, mass flows can be identified which might have been unknown, or difficult to measure without this technique. The exact conservation law used in the analysis of the system depends on the context of the problem, but all revolve around mass conservation, i.e., that matter cannot disappear or be created spontaneously.
Process chemistry is the arm of pharmaceutical chemistry concerned with the development and optimization of a synthetic scheme and pilot plant procedure to manufacture compounds for the drug development phase. Process chemistry is distinguished from medicinal chemistry, which is the arm of pharmaceutical chemistry tasked with designing and synthesizing molecules on small scale in the early drug discovery phase.
References
↑ Lapkin, Alexei and Constable, David (2008), Green Chemistry Metrics. Measuring and Monitoring Sustainable Processes, Wiley
↑ Hudlicky, Tomas (1996). "Design Constraints in Practical Syntheses of Complex Molecules: Current Status, Case Studies with Carbohydrates and Alkaloids, and Future Perspectives". American Chemical Society. 96 (1): 3–30. doi:10.1021/cr950012g. PMID11848742.
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