Encyclopedia of Sustainability Science and Technology

2012 Edition
| Editors: Robert A. Meyers

Green Chemistry Metrics: Material Efficiency and Strategic Synthesis Design

  • John Andraos
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0851-3_224

Definition of the Subject and Its Importance

Over the last 2 decades, the topic of “green metrics ” has grown rapidly in conjunction with the field of green chemistry. Green metrics promise to provide a rigorous, thorough, and quantitative understanding of material, energy, and cost efficiencies for individual chemical reactions and synthesis plans. Indeed, before the advent of green chemistry, good synthetic strategy and elegance were ill-defined, yet intuitive concepts couched less in quantitative terms and more by subjective ones. The quest for a reliable method of measuring material efficiency or “greenness” of a chemical reaction, synthesis, or process is of fundamental importance in the field of organic synthesis when various routes to a given target molecule are considered for selection. Such a method should be robust in its application to any kind of reaction or plan regardless of complexity. It should standardize the ranking of efficiencies of synthesis plans in an...

This is a preview of subscription content, log in to check access.


Primary Literature

  1. 1.
    Andraos J (2005) Unification of reaction metrics for green chemistry: applications to reaction analysis. Org Process Res Dev 9:149–163CrossRefGoogle Scholar
  2. 2.
    Andraos J (2005) Unification of reaction metrics for green chemistry II: evaluation of named organic reactions and application to reaction discovery. Org Process Res Dev 9:404–431CrossRefGoogle Scholar
  3. 3.
    Andraos J (2005) On using tree analysis to quantify the material, input energy, and cost throughput efficiencies of simple and complex synthesis plans and networks: towards a blueprint for quantitative total synthesis and green chemistry. Org Process Res Dev 10:212–240CrossRefGoogle Scholar
  4. 4.
    Andraos J, Izhakova J (2006) Perspectives on the application of green chemistry principles to total synthesis design. Chimica Oggi/The Int J Ind Chem 24(6, Suppl.):31–36Google Scholar
  5. 5.
    Andraos J, Sayed M (2007) On the use of “green” metrics in the undergraduate organic chemistry lecture and laboratory to assess the mass efficiency of organic reactions. J Chem Educ 84:1004–1010CrossRefGoogle Scholar
  6. 6.
    Andraos J (2007) Gauging material efficiency. Can Chem News 59(4):14–17Google Scholar
  7. 7.
    Trost BM (1991) The atom economy – a search for synthetic efficiency. Science 254:1471–1477CrossRefGoogle Scholar
  8. 8.
    Trost BM (2002) On inventing reactions for atom economy. Acc Chem Res 35:695–705CrossRefGoogle Scholar
  9. 9.
    Trost BM (1995) Atom economy. A challenge for organic synthesis - homogeneous catalysis leads the way. Angew Chem Int Ed 34:259–281CrossRefGoogle Scholar
  10. 10.
    Sheldon RA (1994) Consider the environmental quotient. Chem Tech 24(3):38–47Google Scholar
  11. 11.
    Sheldon RA (2000) Atom utilisation, E factors and the catalytic solution. CR Acad Sci Paris Sér IIc Chim 3:541–551Google Scholar
  12. 12.
    Sheldon RA (2001) Atom efficiency and catalysis in organic synthesis. Pure Appl Chem 72:1233–1246CrossRefGoogle Scholar
  13. 13.
    Curzons AD, Constable DJC, Mortimer DN, Cunningham VL (2001) So you think your process is green, how do you know? – using principles of sustainability to determine what is green - a corporate perspective. Green Chem 3:1–6CrossRefGoogle Scholar
  14. 14.
    Constable DJC, Curzons AD, Freitas dos Santos LM, Geen GR, Hannah RE, Hayler JD, Kitteringham J, McGuire MA, Richardson JE, Smith P, Webb RL, Yu M (2001) Green chemistry measures for process research and development. Green Chem 3:7–9CrossRefGoogle Scholar
  15. 15.
    Steinbach A, Winkenbach R (2000) Choose processes for their productivity. Chem Eng April: 94–104Google Scholar
  16. 16.
    Constable DJC, Curzons AD, Cunningham VL (2002) Metrics to “green” chemistry – which are the best? Green Chem 4:521–527CrossRefGoogle Scholar
  17. 17.
    Eissen M, Metzger JO (2002) Environmental performance metrics for daily use in synthetic chemistry. Chem Eur J 8:3580–3585CrossRefGoogle Scholar
  18. 18.
    Eissen M, Hungerbühler K, Dirks S, Metzger J (2003) Mass efficiency as metric for the effectiveness of catalysts. Green Chem 5:G25–G27CrossRefGoogle Scholar
  19. 19.
    Metzger JO, Eissen M (2004) Concepts on the contribution of chemistry to a sustainable development - renewable raw materials. CR Acad Sci Paris Sér IIc Chim 7:569–581Google Scholar
  20. 20.
    Eissen M, Mazur R, Quebbemann HG, Pennemann KH (2004) Atom economy and yield of synthesis sequences. Helv Chim Acta 87:524–535CrossRefGoogle Scholar
  21. 21.
    van Aken K, Strekowski L, Patiny L (2006) EcoScale, a semi-quantitative tool to select an organic preparation based on economical and ecological parameters. Beilstein J Org Chem 2. doi:10.1186/1860-5397-2-3Google Scholar
  22. 22.
    Andraos J (2009) Global green chemistry metrics analysis algorithm and spreadsheets: evaluation of the material efficiency performances of synthesis plans for oseltamivir phosphate (Tamiflu) as a test case. Org Process Res Dev 13:161–185CrossRefGoogle Scholar
  23. 23.
    Welch WM, Kraska AR, Sarges R, Koe BK (1984) Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetraline. J Med Chem 27:1508–1515CrossRefGoogle Scholar
  24. 24.
    Quallich GJ, Williams MT, Friedmann RC (1999) Friedel-Crafts synthesis of 4-(3, 4-dichlorophenyl)-3, 4-dihydro-1(2 H)-naphthalenone, a key intermediate in the preparation of the antidepressant sertraline. J Org Chem 55:4971–4973CrossRefGoogle Scholar
  25. 25.
    Lautens M, Rovis T (1999) Selective functionalization of 1, 2-dihydronaphthalenols leads to a concise, stereoselective synthesis of sertraline. Tetrahedron 55:8967–8976CrossRefGoogle Scholar
  26. 26.
    Yun J, Buchwald SL (2000) Efficient kinetic resolution in the asymmetric hydrosilylation of imines of 3-substituted indanones and 4-substituted tetralones. J Org Chem 65:767–774CrossRefGoogle Scholar
  27. 27.
    Vukics K, Fodor T, Fischer J, Fellegvári I, Lévai S (2002) Improved industrial synthesis of antidepressant sertraline. Org Process Res Dev 6:82–85CrossRefGoogle Scholar
  28. 28.
    Taber GP, Pfisterer DM, Colberg JC (2004) A new and simplified process for preparing N-[4-(3, 4-dichlorophenyl)-3, 4-dihydro-1(2 H)-naphthalenylidene]methanamine and a telescoped process for the synthesis of (1 S-cis)-4-(3, 4-dichlorophenol)-1, 2, 3, 4-tetrahydro-N-methyl-1-naphthalenamine mandelate: key intermediates in the synthesis of sertaline hydrochloride. Org Process Res Dev 8:385–388CrossRefGoogle Scholar
  29. 29.
    Wang G, Zheng C, Zhao G (2006) Asymmetric reduction of substituted indanones and tetralones catalyzed by chiral dendrimer and its application to the synthesis of (+)-sertraline. Tetrahedron Asymm 17:2074–2081CrossRefGoogle Scholar
  30. 30.
    Hendrickson JB (1971) A systematic characterization of structures and reactions for use in organic synthesis. J Am Chem Soc 93:6847–6854CrossRefGoogle Scholar

Books and Reviews

  1. Abdel-Magid FA (2004) Chemical process research: the art of practical organic synthesis. American Chemical Society, WashingtonGoogle Scholar
  2. Anastas PT, Warner JC (1998) Green chemistry: theory and practice. Oxford University Press, OxfordGoogle Scholar
  3. Anderson NG (2000) Practical process research and development. Academic, San DiegoGoogle Scholar
  4. Baran PS, Maimone TJ, Richter JM (2007) Total synthesis of marine natural products without using protecting groups. Nature 446:404–408CrossRefGoogle Scholar
  5. Bertz SH, Sommer TJ (1993) Applications of graph theory to synthesis planning: complexity, reflexivity, and vulnerability. In: Hudlicky T (ed) Organic synthesis: theory and applications, vol 2, JAI Press. Greenwich, CT, pp 67–92Google Scholar
  6. Burns NZ, Baran PS, Hoffmann RW (2009) Redox economy in organic synthesis. Angew Chem Int Ed 48:2854–2867CrossRefGoogle Scholar
  7. Calvo-Flores FG (2009) Sustainable chemistry metrics. ChemSusChem 2:905–919CrossRefGoogle Scholar
  8. Carey JS, Laffan D, Thomson C, Williams MT (2006) Analysis of the reactions used for the preparation of drug candidate molecules. Org Biomol Chem 4:2337–2347CrossRefGoogle Scholar
  9. Carlson R (1992) Design and optimization in organic synthesis. Elsevier, AmsterdamGoogle Scholar
  10. Cornforth JW (1993) The trouble with synthesis. Aust J Chem 46:157–170CrossRefGoogle Scholar
  11. Eissen M (2001) Bewertung der Umweltverträglichkeit organisch-chemischer Synthesen. PhD thesis, Universität OldenburgGoogle Scholar
  12. Fuchs PL (2001) Increase in intricacy – a tool for evaluating organic synthesis. Tetrahedron 57:6855–6875CrossRefGoogle Scholar
  13. Hendrickson JB (1977) Systematic synthesis design. 6. Yield analysis and convergency. J Am Chem Soc 99:5439–5450CrossRefGoogle Scholar
  14. Hoffmann RW (2006) Protecting-group-free synthesis. Synlett 3531–3541Google Scholar
  15. Lapkin A, Constable DJC (2008) Green chemistry metrics: measuring and monitoring sustainable processes. Wiley, ChichesterCrossRefGoogle Scholar
  16. Lee S, Robinson G (1995) Process development: fine chemicals from grams to kilograms. Oxford University Press, OxfordGoogle Scholar
  17. Newhouse T, Baran PS, Hoffmann RW (2009) The economies of synthesis. Chem Soc Rev 38:3010–3021CrossRefGoogle Scholar
  18. Nicolaou KC, Vourloumis D, Winssinger N, Baran PS (2000) The art and science of total synthesis at the dawn of the twenty-first century. Angew Chem Int Ed 39:44–122CrossRefGoogle Scholar
  19. Nicolaou KC (2003) Perspectives in total synthesis: a personal account. Tetrahedron 59:6683–6738CrossRefGoogle Scholar
  20. Nicolaou KC, Snyder SA (2004) The essence of total synthesis. Proc Nat Acad Sci USA 101:11929–11936CrossRefGoogle Scholar
  21. Nicolaou KC, Edmonds DJ, Bulger PG (2006) Cascade reactions in total synthesis. Angew Chem Int Ed 45:7134–7186CrossRefGoogle Scholar
  22. Orru RVA, de Greef M (2003) Recent advances in solution-phase multicomponent methodology for the synthesis of heterocyclic compounds. Synthesis 1471–1499Google Scholar
  23. Posner GH (1986) Multicomponent one-pot annulations forming three to six bonds. Chem Rev 86:831–844CrossRefGoogle Scholar
  24. Qiu F (2008) Strategic efficiency – the new thrust for synthetic organic chemists. Can J Chem 86:903–906CrossRefGoogle Scholar
  25. Seebach D (1990) Organic synthesis –where now? Angew Chem Int Ed 29:1320–1367CrossRefGoogle Scholar
  26. Serratosa F (1990) Organic chemistry in action: the design of organic synthesis. Elsevier, AmsterdamGoogle Scholar
  27. Sheldon RA (1997) The E factor: fifteen years on. Green Chem 9:1273–1283CrossRefGoogle Scholar
  28. Sheldon RA (2008) E factors, green chemistry and catalysis: an odyssey. Chem Commun 3352–3365Google Scholar
  29. Smit WA, Bochkov AF, Caple R (1998) Organic synthesis: the science behind the art. Royal Society of Chemistry, CambridgeGoogle Scholar
  30. Snieckus V (1999) Optimization in organic synthesis. Med Res Rev 19:342–347CrossRefGoogle Scholar
  31. Tietze LF (1996) Domino reactions in organic synthesis. Chem Rev 96:115–136CrossRefGoogle Scholar
  32. Tietze LF, Modi A (2000) Multicomponent domino reactions for the synthesis of biologically active natural products and drugs. Med Chem Rev 20:304–322Google Scholar
  33. Ugi I, Dömling A, Hörl W (1994) Multicomponent reactions in organic chemistry. Endeavour New Ser 18(3):115–122CrossRefGoogle Scholar
  34. Ugi I, Dömling A, Werner B (2000) Since 1995 the new chemistry of multicomponent reactions and their libraries, including their heterocyclic chemistry. J Heterocycl Chem 37:647–658CrossRefGoogle Scholar
  35. Ugi I (2001) Recent progress in the chemistry of multicomponent reactions. Pure Appl Chem 73:187–191CrossRefGoogle Scholar
  36. Weber L, Illgen K, Almstetter M (1999) Discovery of new multi-component reactions with combinatorial methods. Synlett 366–374Google Scholar
  37. Weber L (2002) Multi-component reactions and evolutionary chemistry. Drug Discov Today 7:143–147Google Scholar
  38. Weber L (2002) The application of multi-component reactions in drug discovery. Curr Med Chem 9:1241–1253CrossRefGoogle Scholar
  39. Wender P, Miller BL (1993) Toward the ideal synthesis: connectivity analysis and multibond-forming processes. In: Hudlicky T (ed) Organic synthesis: theory and applications, vol 2, JAI Press. Greenwich, Connecticut, pp 27–65Google Scholar
  40. Zhang TY (2006) Process chemistry: the science, business, logic, and logistics. Chem Rev 106:2583–2595CrossRefGoogle Scholar
  41. Zhu J, Bienyamé H (2005) Multicomponent reactions. Wiley, WeinheimCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of ChemistryYork UniversityTorontoCanada