1st Edition

The Algebra of Organic Synthesis Green Metrics, Design Strategy, Route Selection, and Optimization

By John Andraos Copyright 2012
    1222 Pages 2455 B/W Illustrations
    by CRC Press

    1222 Pages 2455 B/W Illustrations
    by CRC Press

    The Algebra of Organic Synthesis combines the aims, philosophies, and efforts involved in organic synthesis, reaction optimization, and green chemistry with techniques for determining quantitatively just how "green" synthesis plans are. It provides the first complete quantitative description of synthesis strategy analysis in the context of green chemistry and reaction optimization.

    Providing what is perhaps the first complete description of synthesis strategy analysis, this book:

    • Explores quantitative material efficiency for synthesizing molecules, including 1,000+ worked out synthesis plans to important target molecules
    • Explains, in simple language, the most useful ideas in graph theory that have direct application in organic synthesis
    • Reinforces the value of simple mathematical analysis in organic synthesis to help any synthetics or process chemist understand presented ideas and apply them to their own work
    • Illustrates concepts with example target plans to classical targets that are considered milestones in synthetic chemistry, from pharmaceuticals, industrial commodity chemicals, dyestuffs, agrichemicals, flavorings, natural products, and molecules of theoretical interest

    The accompanying download includes a reproduction of the tables in the book, with direct electronic links to files for all plans. Files contain a list of references for each plan, including secondary references for the synthesis of starting materials if applicable. Ancillary materials also include a complete synthesis scheme with fully balanced chemical equations, a synthesis tree, a summary of green metrics parameters, a target bond map and list of reagents that end up in the target molecule, and a series of graphs that offer a visual depiction of the plan performance.

    Aims and Scope
    What Does This Book Offer?
    Chapter Descriptions
    Synthesis Plan Database
    How to Use Synthesis Database Compilation

    General Comments on Organic Chemistry and Green Chemistry
    Getting Our House in Order
    Research Trends in Organic Synthesis
    Research Trends in Green Chemistry Trends
    Green Chemistry Trends in Industry

    Problems with Literature Reporting of Synthesis Plans
    Missing Information in Plans
    Mistakes in Reported Yields and Amounts of Materials Used
    Mismatches in Reported Reaction Yields
    Tactics to Artificially Amplify Reaction Performance
    Reporting of Classical Resolutions
    Exaggerated Claims of Efficiency
    Good "Greening" Progression But Little Detail to Substantiate Claim
    "Readily Available Starting Materials"
    Biotransformations Not Revealing Reaction Yields in Usual Way
    Papers Describing Reactions Using Microwave Irradiation
    Reviewing of Scientific Papers

    Problems and Challenges in Synthesis and Green Chemistry
    Philosophy and Practice of Chemistry
    Chemistry Literature
    Reaction Performance Improvements
    Synthesis Performance
    Reaction Mechanism

    Overview of Green Metrics
    Advantages of Using Green Metrics
    Material Efficiency Metrics and Visuals
    Strategy Efficiency Metrics and Visuals
    Hypsicity (Oxidation Level) Analysis
    Instructions on Using PENTAGON, LINEAR, and CONVERGENT Spreadsheets
    Mathematical Derivations and Analysis
    Complete Worked Out Examples

    Worked-Out Radial Pentagon Examples
    Radial Hexagon Analysis
    Connectivity Analysis
    Probability Analysis
    An Eight-Component Coupling

    Named Organic Reaction Database
    Categorization of Named C–C Coupling/Addition/Cyclization Reactions
    Categorization of Named Condensation Reactions
    Categorization of Named Elimination/Fragmentation Reactions
    Categorization of Multicomponent Reactions
    Categorization of Named Non-C–C Coupling/Addition/Cyclization Reactions
    Categorization of Named Oxidation Reactions (with Respect to Substrate of Interest)
    Categorization of Named Rearrangement Reactions
    Categorization of Named Reduction Reactions (with Respect to Substrate of Interest)
    Categorization of Named Sequences
    Categorization of Named Substitution Reactions
    Summary of Trends in Named Organic Reaction Database

    Example Transformations Illustrating Sacrificial Reagents
    Single-Step Reactions
    Two-Step Reactions
    Sacrificial Reactions from Synthesis Database

    Synthesis Strategies
    Brainstorming Exercises
    Direct Syntheses
    Indirect Syntheses

    Choice of Starting Materials for Synthesis
    Comparison of Total Synthesis versus Semisynthesis
    Bio-Inspired Strategies
    Chemoselectivity versus Classical Resolution Comparison
    Mismatch between Strategy and Waste Production
    Route Selection and Reaction Networks
    What Can Go Wrong with Computer-Assisted Synthesis Software

    Ring Construction Strategies
    Ring Construction Strategies in Synthesis Database.
    Ring Contractions in Named Organic Reaction Database.
    Ring Expansions in Named Organic Reaction Database
    Bicyclic Formation Reactions in Named Organic Reaction Database
    Sacrificial Rings
    Use of the Furan Ring
    Wender [x + y + z] Ring Construction Strategies
    Spectacular Ring Construction Strategies
    Proposal for a Computer-Searchable Ring Construction Database

    Example Highlights from Database
    Which Plan to Choose for Scale-Up?.
    Sparse Target Bond Making Profiles
    Recycling Options
    Improvement in Waste Reduction
    Spectacular Examples of Synergy between Strategy and Material Efficiency Metrics
    Microchannel and Flow Technique Strategies
    Ring Construction Novelty
    Wrong Starting Materials Used
    Plan with No Target Bonds Made
    Old Reactions Using One of 12 Principles of Green Chemistry
    Telescoping Steps
    Extreme Convergence in Plans
    Use of a Hub Common Intermediate
    Compromise between Strategy and Material Efficiencies
    Inclusion of Syntheses of Catalysts and Ligands for Complete Analysis
    Synthesis Plans Tracing Back to Common Starting Materials for Fairest Comparisons
    Most Challenging Molecule to Synthesize: Colchicine
    Target Compound Where Fundamental Named Organic Reactions Were Discovered
    Contrast between Classical and Modern Chemical Routes
    Resolution with Lipase

    Summary of Overall Trends in Synthesis Database
    Overall Atom Economy Trends
    Overall Yield Trends
    Kernel Overall Reaction Mass Efficiency Trends
    Degrees of Convergence and Asymmetry Trends
    Target Bond Forming Profile Parameters
    Sacrificial Reagents and Sacrificial Reaction Trends
    Hypsicity Trends

    Compounds with Multiple Plans

    Appendix A
    Appendix B



    John Andraos earned a Ph.D. in 1992 from the University of Toronto in physical organic chemistry. Since his appointment as Lecturer and Course Director at York University, he launched the first industrial and "green" chemistry course in the history of the Department of Chemistry. He has done consulting assignments with the pharmaceutical industry on various aspects of synthesis optimization and green chemistry education. His research spans several disciplines in organic chemistry which utilize mathematical analysis including reaction kinetics, retrosynthesis and synthesis planning, and the creation of reaction and ring construction databases. He is the author of 50 scientific papers in refereed journals and 6 book chapters on the subject of green chemistry metrics and education. In 2000 he launched the CareerChem website (http://www.careerchem.com/MainFrame.html) which is an in-depth resource for tracking and cataloguing all named things in chemistry and physics, chronicling the development of chemistry through scientific genealogies, and supplying career information to young researchers and students for placement in academic and industrial positions worldwide.