The Algebra of Organic Synthesis: Green Metrics, Design Strategy, Route Selection, and Optimization, 1st Edition (Paperback) book cover

The Algebra of Organic Synthesis

Green Metrics, Design Strategy, Route Selection, and Optimization, 1st Edition

By John Andraos

CRC Press

1,221 pages | 2455 B/W Illus.

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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 CD-ROM 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.

Table of Contents

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


About the Author

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 ( 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.

Subject Categories

BISAC Subject Codes/Headings:
SCIENCE / Chemistry / General
SCIENCE / Chemistry / Organic
SCIENCE / Chemistry / Industrial & Technical