It takes into account the yield, stoichiometry, solvent, and the reagents used in synthesis. Also, a few unified metrics has been developed which combine some of the above mentioned individual parameters and factors relevant for specific purposes. Intended primarily as a management tool for economic evaluation, it takes into account all important factors involved in large scale production.
These are process parameters, raw material cost, yield, throughput time, throughput volume, number of steps in synthetic sequence, special equipment requirements, reproducility, tolerance to abuse, linearity of sequence, environmental abuse potential, potential occupational health and safety hazards, raw material availability, susceptibility to regulatory changes and patent protection.
In this methodology, all stages of the life cycle of a chemical as well as environmental impacts of by-products and auxiliaries solvents, co-reagents, and technical facilities are considered.
It consists of three domains: the analysis of the starting material, the analysis of the impact, and the analysis of the improvements. The above analyses often show that the cost of waste, including effluent treatment, waste disposal, loss of raw materials, etc. Green Chemistry Program of the U. Environmental Protection Agency [ 18 ] and corporate initiatives to develop their own set of qualitative and semiquantitative green parameters.
For example, GlaxoSmithKline has published a set of metrics such as carbon efficiency CE and reaction mass efficiency RME which enables an assessment to be made of batch processes in terms of waste, energy usage, and chemistry efficiency. The development of a new reaction metric, the stoichoimetric factor SF , has been decribed which allows to take into account reactions run under nonstoichoimetric conditions.
As can be seen from the discussion above, the search and implementation of the appropriate metrics for evaluation of the quality of a chemical process can be complex, time-consuming, not straightforward unclear definitions or too focused on one topic waste, safety, etc. In particular, the lack of transparency of the life cycle analysis, the lack of objectivity in assigning the Q value for a reagent or the unclear definition of "non-benign" for the calculation of effective mass yield, can be noted.
To our knowledge, no tool for evaluation of chemical reaction conditions on laboratory scale has been developed. Herewith, we propose a unified algorithm, called EcoScale, to help select an acceptable organic preparation. A basic requirement for the design of the EcoScale is transparency and user-friendliness.
At the same time, it needs to cover the whole range of organic chemistry conditions and techniques. To combine all these goals, the following approach is used. Secondly, 6 general parameters which influence the quality of reaction conditions are analyzed Table 1.
Within each of these parameters, individual penalty points of various relative weights are assigned that take into account all possible situations when setting up an organic chemistry experiment.
The penalty points are cumulative for all components of the preparation. An ideal reaction has the EcoScale value of Although the choice of these 6 parameters will likely reach consensus among organic chemists, their relative weight and the assignments of the actual value of the penalties can raise a discussion. Specifically, it must be stressed that the relative weights of these parameters in the decision process fundamentally differ when the scale of the reaction is considered.
Basically, the focus shifts away from the overall time and convenience on a laboratory scale, to the overall cost in industry when all regulatory restrictions are considered. Similarly, reactions at room temperature are far more important on an industrial scale as no energy is needed for heating or cooling. Also, the waste issue is of a minor importance at a laboratory scale but can take up a significant cost of a production process. Therefore, it is important to stress that this EcoScale is specifically designed for laboratory scale conditions.
Even with the scale issue in mind, each weight of the parameters and each relative value of the penalty points are often only based on experience and intuition and not on "exact science".
The subjective basis of these values in EcoScale is explained in more detail below. In particular, the subjective assignment of particular weights to various penalty points can easily be modified, as some chemists may disagree with the proposed relative assignments. The EcoScale is designed to be a flexible tool. The yield is one of the most important factors. Indirectly, this parameter includes selectivity issues, as the quality of a reaction increases with increasing the functional group compatibility.
An independent selectivity parameter would make the analysis highly complicated. A high yield guarantees an optimal use of resources and usually results in an easy workup procedure as side-products are limited. The question remains which yield to take, before or after purification of the product?
Theoretically, the pre-purification yield is the best but is not practical to implement. First, this yield is often not determined and not mentioned in the literature.
In addition, the value of reaction conditions from which the end product cannot efficiently be purified is questionable. Therefore, points are calculated for the isolated yield. The EcoScale analysis can also be applied to the evaluation of non-racemic synthesis. In this case, only the chemical yield of the targeted enantiomer is considered.
The use of efficient chiral auxilaries can significantly raise the EcoScale higher yield of enantiomer , but the final score is strongly influenced by their amount, availability and safety profile. Every reaction component is taken into account, and the penalties are cumulative. We realize that by using this criterion, the EcoScale is time dependent.
A reaction component that is not commercially available today might appear in the catalogues next year and, as such, will rank higher on the EcoScale in the future. This is only fair because the evaluation process is also time dependent: we can refrain from using certain reagents today because we would need to synthesize them, but might use them in the future when they become commercially available. Reaction components present in over 10 equivalents in the reaction mixture are usually solvents and often are inexpensive.
The use of an expensive solvent e. In addition, two special cases can be noted. In a solvent-free reaction and when the solvent is used as the reagent, there is one reaction component less for which no extra penalties are deducted. An expensive but efficient catalyst e. It must be stressed that the real benefits of using catalysts usually are reflected in higher selectivity yield and lower energy requirements, which are accounted for in other parts of the EcoScale.
Safety is of paramount importance when carrying out organic chemistry experiments. Working with chemicals is never without a risk, and it is necessary to fully understand any potential hazard. Organic compounds can be carcinogenic, mutagenic, teratogenic, corrosive, lachrymatic, highly flammable or explosive, among other things.
In addition, the hazard can increase over time, and photooxidation of ether to generate explosive peroxides is a good example. It must also be emphasised that it takes a long time before the safety profiles of new products are fully characterized.
Finally, one should never forget that the combination of certain individual compounds can create a hazardous situation e. In order to avoid a complex calculation, the hazard warning symbols are taken as a reference.
A simple setup consisting of a regular flask, reflux condenser, and stirrer receives no penalty points. Finally, one should never forget that the combination of certain individual compounds can create a hazardous situation e.
In order to avoid a complex calculation, the hazard warning symbols are taken as a reference. A simple setup consisting of a regular flask, reflux condenser, and stirrer receives no penalty points.
Any extras including special glassware, equipment for controlled addition of chemicals, pressurized vessels, the application of unconventional techniques such as microwave irradiation, ultrasound or photochemistry, and the need for an inert atmosphere, especially in a glove box, downgrade the overall quality of the synthesis. The reaction temperature and time are closely related.
In an ideal situation, a reaction proceeds rapidly at room temperature. However, heating is often required to accomplish synthesis in an acceptable period of time. On the other hand, cooling is more difficult than heating. Above room temperature, the heating range is continuous while for cooling in a conventional way without the use of a cryostat only fixed temperatures e. These features are reflected in the relative penalty points.
The penalties are cumulative; if heating and cooling are required during the reaction, both must be accounted for.
The workup and purification of the end product can be a tedious process. In order to avoid a complex calculation e. As it makes no sense to use a chronometer in a laboratory workup procedure, standard purification techniques are ranked according to their execution time and convenience. Every workup step is taken into account in assigning the penalty points. The EcoScale evaluations of four important synthetic transformations taken from the recent literature are shown below.
Workup involves manipulations in the given order. The sum of all penalty points is 36 Table 2 , which gives total score of 64 on the EcoScale an acceptable synthesis. Scheme 1: Reduction of nitrobenzene to aniline [23]. Table 2: The penalty points for example 1. The sum of all penalty points is 22 Table 3 , which gives total score of 78 on the EcoScale an excellent synthesis.
Scheme 2: Oxidation of benzyl chloride to benzoic acid [24]. Table 3: The penalty points for example 2. The sum of all penalty points is 47 Table 4 , which gives total score of 53 on the EcoScale an acceptable synthesis.
Scheme 3: Synthesis of benzamide [25]. Table 4: The penalty points for example 3. In the introduction to the article, [25] the authors claim that this procedure for preparing primary amides starting from aryl halides is better than another procedure which uses hexamethyldisilazane HMDS.
The sum of all penalty points is 68 Table 5 , which gives total score of 32 on the EcoScale an inadequate synthesis. Table 5: The penalty points for example 4. This procedure receives a significantly lower score than the previous example largely due to its safety profile and the more tedious workup.
By using EcoScale, the two analyses 3 and 4 illustrate a rapid selection of the better preparation 3. In general, the EcoScale favours high-yielding, low-cost and safe reaction conditions and an easy purification.
The analysis 1 is straightforward it takes into account all important parameters , 2 is transparent it is clear how the final score is obtained , 3 is fast it can be calculated in less than 5 min [27] , 4 does not take a general standpoint but takes into account advantages and disadvantages of specific methodologies or auxiliary reagents, 5 offers a general overview of the reaction conditions, and the areas for improvement are clearly indicated.
In this way, it can be used as a convenient tool in education students learn to analyze a reaction protocol , and is valuable in research as an effective way to compare different sets of preparations of the same product. John Andraos. Christoph P. Twitter: BeilsteinInst. How to cite this article: Van Aken, K.
Toggle navigation. Please enable Javascript and Cookies to allow this site to work correctly! EcoScale, a semi-quantitative tool to select an organic preparation based on economical and ecological parameters Koen Van Aken 1 , Lucjan Strekowski 2 and Luc Patiny 3. Koen Van Aken. Lucjan Strekowski. Luc Patiny. Graphical Abstract.
Atom economy [3,4] This parameter is the ratio of the molecular weight of the target molecule to the sum total of the molecular weights of all the substances produced in the stoichiometric equation for the reaction involved. Environmental factor E-factor [] This factor is the ratio of the weight of generated waste to the total weight of the end product.
Environmental quotient EQ [10] The value of the E-factor is limited as it does not take into account the nature and environmental impact of the generated waste.
Effective mass yield [12] This parameter is defined as the percentage of the mass of desired product relative to the mass of all non-benign materials used in the synthesis. Mass intensity [13] The mass intensity is defined as the ratio of the total mass used in a process step and the mass of the end product. The process profile [14] Intended primarily as a management tool for economic evaluation, it takes into account all important factors involved in large scale production.
Life cycle analysis LCA [15,16] In this methodology, all stages of the life cycle of a chemical as well as environmental impacts of by-products and auxiliaries solvents, co-reagents, and technical facilities are considered.
Proprietary metrics The above analyses often show that the cost of waste, including effluent treatment, waste disposal, loss of raw materials, etc.
Unification of reaction metrics for green chemistry The development of a new reaction metric, the stoichoimetric factor SF , has been decribed which allows to take into account reactions run under nonstoichoimetric conditions. Design of the EcoScale. Starting principles A basic requirement for the design of the EcoScale is transparency and user-friendliness. Parameter Penalty points 1. Yield The yield is one of the most important factors. Price of reaction components Every reaction component is taken into account, and the penalties are cumulative.
Safety Safety is of paramount importance when carrying out organic chemistry experiments. Technical setup A simple setup consisting of a regular flask, reflux condenser, and stirrer receives no penalty points. Workup and purification The workup and purification of the end product can be a tedious process. Examples of calculations The EcoScale evaluations of four important synthetic transformations taken from the recent literature are shown below. Scheme 1: Reduction of nitrobenzene to aniline [23] Scheme 1: Reduction of nitrobenzene to aniline [23].
Jump to Scheme 1. Scheme 2: Oxidation of benzyl chloride to benzoic acid [24] Scheme 2: Oxidation of benzyl chloride to benzoic acid [24]. Jump to Scheme 2. Scheme 3: Synthesis of benzamide [25] Scheme 3: Synthesis of benzamide [25]. Jump to Scheme 3. Jump to Scheme 4. Anastasas, P. Return to citation in text: [ 1 ] Constable, D. Green Chem. Science , , Return to citation in text: [ 1 ] Trost, B. London , — Return to citation in text: [ 1 ] Sheldon, R. CO; Return to citation in text: [ 1 ] Sheldon, R.
London , 12— Return to citation in text: [ 1 ] Dunn, P. Return to citation in text: [ 1 ] Hudlicky, T. Return to citation in text: [ 1 ] Anastasas, P. Pure Appl. Return to citation in text: [ 1 ] Green Chemistry Program of the U.
Environmental Protection Agency. Process Res. Return to citation in text: [ 1 ] Gowda, D. Return to citation in text: [ 1 ] Shi, M. Tetrahedron Lett. I think that the fact that inspector goole has such an effect on mr birling is because he believes the inspector to be powerful in the law and although when he. Buy personal narrative essay and buy essay, aspect of how to ability to strong narrative market is skills for shopping essay starting point of.
This essay looks at some of the effects of drug use on society, and suggests some drug abuse causes multiple problems for countries and communities. Essay on paper an automated phylogenetic tree-based small subunit rrna it is still the longest, the happiest and the most exciting christmas day i have had.
Share this: Twitter Facebook. Like this: Like Loading
0コメント