Advanced Practical Organic Chemistry

Citation

Leonard, J., Lygo, B., & Procter, G. (2013). Advanced Practical Organic Chemistry (3rd ed.). CRC Press.

Chapter Summary

The third edition has 356 pages and follows the order in which a synthetic chemist works: preparation and safety, equipment and materials, running the reaction, working it up, purifying and characterising the product, and finding information. According to the publisher, the book is written for advanced undergraduate and graduate students and for industrial organic chemists, particularly in pharmaceutical, agrochemical and other fine-chemical research, and it gives the often hard-to-find information on reagent properties needed to carry out general techniques. The text was fully updated for this edition and the figures were newly drawn.

General Introduction; Safety

The opening chapters set out the principle that safety is the chemist's own primary responsibility, followed by safe working practice, safety risk assessments, common hazards, and accident and emergency procedures.

Keeping Records of Laboratory Work

This chapter covers the laboratory notebook, keeping records of data, and some tips on preparing reports and theses.

Equipping the Laboratory and the Bench

It covers setting up the laboratory, general laboratory equipment, the individual bench, and equipment for parallel experiments and for controlled experimentation.

Purification and Drying of Solvents; Reagents: Preparation, Purification, and Handling

The solvent chapter covers purification of solvents, drying agents and the drying of solvents. The reagents chapter classifies reagents for handling, describes techniques for obtaining pure and dry reagents and for handling and measuring them, and includes the preparation and titration of simple organometallic reagents and lithium amide bases and the preparation of diazomethane.

Gases; Vacuum Pumps

The gases chapter covers gas cylinders, handling and measuring gases, inert gases and reagent gases. The vacuum chapter runs from house vacuum systems to medium and high vacuum pumps, with pressure measurement and regulation.

Carrying Out the Reaction

This chapter addresses reactions with air-sensitive reagents, reaction monitoring, reactions at other than room temperature, driving equilibria, agitation, and controlled reactor systems.

Working Up the Reaction; Purification

Work-up covers quenching, isolating the crude product, and the data to collect on the crude product before purification. The purification chapter covers crystallization, distillation, sublimation, flash chromatography, dry-column flash chromatography, preparative TLC, medium-pressure and prepacked chromatography systems, and preparative HPLC.

Small-Scale Reactions; Large-Scale Reactions

The small-scale chapter treats reactions at or below and above room temperature, reactions in NMR tubes, and purification of small quantities. The large-scale chapter covers carrying out the reaction, work-up and product isolation, and purification of products.

Special Procedures

A chapter on catalytic hydrogenation, photolysis, ozonolysis, flash vacuum pyrolysis, liquid ammonia reactions and microwave reactions.

Characterization; Troubleshooting

The characterization chapter covers NMR, IR and UV spectroscopy, mass spectrometry, melting and boiling points, optical rotation, microanalysis and keeping the data. A further chapter is devoted to what to do when things do not work.

The Chemical Literature; Appendices

The literature chapter describes the structure of the chemical literature, important paper-based and electronic sources, how to find chemical information and how to keep up to date. The appendices tabulate properties of common solvents and gases, approximate pKa values of common reagents against common bases, and common Brønsted acids, Lewis acids, reducing reagents and oxidizing reagents.

Key Concepts

Preparation (safety to reagents)

• Risk assessment: assessing hazards before work begins, in the safety chapter.
• Laboratory records: the notebook and data records as part of method.
• Pure and dry reagents and solvents: purification, drying and handling.

Running reactions

• Air-sensitive reagents: techniques for handling them, in the chapter on carrying out the reaction.
• Reaction scale: small-scale and large-scale reactions as separate chapters.
• Special procedures: hydrogenation, photolysis, ozonolysis, flash vacuum pyrolysis, liquid ammonia and microwave reactions.

Isolation and information

• Work-up and purification: quenching, crystallization, distillation, sublimation and chromatography.
• Characterization: the spectroscopic and physical data used to identify a product.
• Chemical literature: finding information efficiently.

Critical Analysis

Strengths

• Organised by the workflow of a synthesis. The sequence of chapters follows the life of an experiment, so a reader can find the relevant section at the stage of work they have reached.
• Detail on reagents and equipment. The publisher says the book supplies hard-to-find information on reagent properties and guidance on protocols and precautions, and the contents show dedicated chapters on gases, vacuum and reagent handling.
• Range of scale. Small-scale and large-scale reactions each have their own chapter, as do special procedures such as ozonolysis and microwave reactions.
• Safety and records first. Safety and record keeping come before any technique, and a troubleshooting chapter follows the characterization material.
• Reference tables. The appendices tabulate solvent and gas properties, pKa values and common acids and oxidizing and reducing reagents.
• Reception. Reviews of earlier editions are quoted by the publisher: Synthesis (June 1995) called it concise and highly readable and recommended it to new research students, and Chemistry & Industry (July 1995) said it should be present in every organic chemistry research laboratory.

Limitations

• Techniques, not reactions. The book is about how to carry out and purify reactions and not about which reactions to choose, so it must be used with a textbook or synthesis reference.
• Reviews date from earlier editions. The reviews the publisher quotes are from 1995 and concern previous editions.
• No stated problems or exercises. The table of contents lists no exercises, so the book works as a manual and not as a course text.
• Characterization is one chapter. NMR, IR, UV and mass spectrometry share a single chapter, so interpreting spectra needs a dedicated text.

Where It Fits in the Course

Among the laboratory-practice books, Hill and Finster's Laboratory Safety for Chemistry Students and the National Research Council's Prudent Practices in the Laboratory are dedicated safety references, the first graded by year of study and the second a committee reference on safety culture, risk assessment and waste. Leonard, Lygo and Procter treat safety in one chapter and then move to technique, so they assume safety training is in hand.

Practical Skills in Chemistry is a one-volume guide to the practical, analytical and data-handling skills needed throughout a degree and is the earlier step: read it first, and then use Leonard for research-level synthesis. Shriver and Drezdzon's The Manipulation of Air-Sensitive Compounds is a specialist monograph on inert-atmosphere equipment and procedures; Leonard's chapters on gases, vacuum and air-sensitive reactions are the general introduction to the same area, and Shriver and Drezdzon are the deeper follow-up.

How to Use This Book

The book suits students moving from teaching laboratories to research, and organic chemists in industry starting in synthesis, who have completed undergraduate organic chemistry and basic laboratory safety training.

• Before the first experiment: read the chapters on safety, records and equipping the bench.
• While planning an experiment: go to the chapters on solvents, reagents, gases and carrying out the reaction that match the conditions you need.
• After the reaction: use the work-up, purification and characterization chapters in turn, and the troubleshooting chapter when something fails.
• As a reference: keep the appendices to hand for solvent properties, pKa values and reagent choices, and use the literature chapter when planning a new route.