Experimental Organic Chemistry E-Book

Philippa B. Cranwell

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1186

Veröffentlichungsjahr: 2017

Beschreibung

The definitive guide to the principles and practice of experimental organic chemistry — fully updated and now featuring more than 100 experiments

The latest edition of this popular guide to experimental organic chemistry takes students from their first day in the laboratory right through to complex research procedures. All sections have been updated to reflect new techniques, equipment and technologies, and the text has been revised with an even sharper focus on practical skills and procedures.

The first half of the book is devoted to safe laboratory practice as well as purification and analytical techniques; particularly spectroscopic analysis. The second half contains step-by-step experimental procedures, each one illustrating a basic principle, or important reaction type. Tried and tested over almost three decades, over 100 validated experiments are graded according to their complexity and all are chosen to highlight important chemical transformations and to teach key experimental skills.

New sections cover updated health and safety guidelines, additional spectroscopic techniques, electronic notebooks and record keeping, and techniques, such as semi-automated chromatography and enabling technologies such as the use of microwave and flow chemistry. New experiments include transition metal-catalysed cross-coupling, organocatalysis, asymmetric synthesis, flow chemistry, and microwave-assisted synthesis. Key aspects of this third edition include:

• Detailed descriptions of the correct use of common apparatus used in the organic laboratory
• Outlines of practical skills that all chemistry students must learn
• Highlights of aspects of health and safety in the laboratory, both in the first section and throughout the experimental procedures
• Four new sections reflecting advances in techniques and technologies, from electronic databases and information retrieval to semi-automated chromatography
• More than 100 validated experiments of graded complexity from introductory to research level
• A user-friendly experiment directory
• An instructor manual and PowerPoint slides of the figures in the book available on a companion website

A comprehensive guide to contemporary organic chemistry laboratory principles, procedures, protocols, tools and techniques, Experimental Organic Chemistry, Third Edition is both an essential laboratory textbook for students of chemistry at all levels, and a handy bench reference for experienced chemists.

Leseprobe

Experimental Organic Chemistry

Third Edition

Philippa B. Cranwell

MChem (Soton), PhD (Cantab), MRSC, FHEADepartment of Chemistry, University of Reading

Laurence M. Harwood

MA (Oxon), BSc, MSc, PhD (Manch), CSci, CChem, FRSC, AFIChemE

Department of Chemistry, University of Reading

Christopher J. Moody

BSc (Lond), PhD (L’pool), DSc (Lond), CChem, FRSC

School of Chemistry, University of Nottingham

This edition first published 2017 © 2017 by John Wiley & Sons Ltd© 1989, 1999 by Blackwell Science Ltd.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of Philippa B. Cranwell, Laurence M. Harwood and Christopher J. Moody to be identified as the authors of this work has been asserted in accordance with law.

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Library of Congress Cataloging‐in‐Publication Data

Names: Cranwell, Philippa B., 1985– | Harwood, Laurence M. | Moody, Christopher J.Title: Experimental organic chemistry.Description: Third edition / Philippa B. Cranwell, Laurence M. Harwood, Christopher J. Moody. | Hoboken, NJ : John Wiley & Sons, Inc., 2017. | Previous edition by Laurence M. Harwood, Christopher J. Moody, and Jonathan M. Percy. | Includes bibliographical references and index.Identifiers: LCCN 2017006552 (print) | LCCN 2017005557 (ebook) | ISBN 9781119952398 (cloth) | ISBN 9781119952381 (pbk.) | ISBN 9781118683415 (Adobe PDF) | ISBN 9781118683804 (ePub)Subjects: LCSH: Chemistry, Organic–Laboratory manuals.Classification: LCC QD261 .H265 2017 (ebook) | LCC QD261 (print) | DDC 547.0078–dc23LC record available at https://lccn.loc.gov/2017006552

Cover images: courtesy of Philippa Cranwell; background image © bluedogroom/GettyimagesCover design by Wiley

About the authors

Philippa B. Cranwell was born in Torquay, UK, and was educated at Torquay Girls’ Grammar School and the University of Southampton. She carried out her PhD research at the University of Cambridge under the guidance of Steven Ley, and then undertook postdoctoral research at the ETH in Zürich, working with Erick Carreira, before taking up the position of Teaching Fellow, then Lecturer, at the University of Reading. Her research interests are within the area of organic chemistry, particularly with regard to the development of new reactions suitable for undergraduate students.

Laurence M. Harwood was born in Lincoln, UK, and was educated at the City Grammar School, then moving to Manchester University where he carried out his undergraduate studies and went on to carry out research under the supervision of Professor Hamish Sutherland, obtaining his PhD in 1978. After 2 years as a Royal Society Postdoctoral Fellow, working with Professor Marc Julia at the École Normale Supérieure in Paris, he returned to his first academic position at Manchester. In 1983, he was appointed to a lectureship at Oxford University and a fellowship at Merton College. In 1995 he moved to the Chair of Organic Chemistry at Reading. In 2001, he joined the team of Regional Editors for Synlett, in 2010 he was involved in the start‐up company TechnoPep Ltd, in 2015 he took on the additional role of Director of the University of Reading Chemical Analysis Facility, and in 2017 he became the Associate Editor of SynOpen. His research interests range from natural product synthesis, through synthetic methodology, to synthesizing metal‐selective ligands for use in nuclear waste treatment. His work has produced over 200 research publications and patents.

Christopher J. Moody was born in Manchester, UK, and was educated at Manchester Grammar School and King’s College, London. He carried out his PhD research at the University of Liverpool under the supervision of Charles Rees, and spent a postdoctoral year at the ETH in Zürich working with Albert Eschenmoser, before taking up a post in industry at Roche. In 1979, he was appointed to a lectureship at Imperial College, London, renewing a collaboration with Charles Rees in parallel with establishing an independent research career. In 1990, he moved to the Chair of Organic Chemistry at Loughborough University, and in 1996 he was appointed Professor of Organic Chemistry at Exeter. He took up his present post as the Sir Jesse Boot Professor of Chemistry in the University of Nottingham in August 2005. His research interests range across organic chemistry, with a focus on the synthesis of biologically active molecules, particularly heterocyclic compounds and quinones. His work is reported in over 420 publications and patents.

Preface to the third edition

In its first incarnation, this book grew out of the conviction that highly developed practical skills, as well as a thorough grasp of theory, are the hallmark of a true organic chemist and that chemistry is illustrated more vividly by experiment than from a book or lecture course, when the facts can seem abstract and sterile. The original aim, therefore, was to produce a book containing safe, interesting experiments of varying complexity, together with all the associated technical instruction, which could be used in a variety of courses from the elementary to the advanced. With the goal of enthusing budding and current organic chemists, experiments were chosen to be more than just recipes for preparing a particular compound, or manipulative exercises. Rather, each experiment was associated with some important reaction, an interesting mechanism, or an underlying principle, without forgetting the practical skills to be acquired along the way. Within the constant and overriding demands for safety, the range of experiments was chosen to illustrate as many techniques and to cover as much organic chemistry as possible, in order to link up with lecture courses, and provide depth and relevance to the whole teaching programme.

So that was in the years running up to 1989 when the first edition appeared, to be followed by a second edition in 1999. Time has moved on, and this third edition of Experimental Organic Chemistry, arguably long overdue, has been born out of the recognition that much has happened in the field of organic chemistry since 1999, although the original aims espoused in the first edition still remain central.

Such progress has been made since 1989 that reactions and techniques that were once the domain of the specialist research laboratory – or indeed not even discovered when the first edition appeared – have now become commonplace in both academic and industrial environments – metal‐catalysed cross‐coupling reactions, metathesis, organocatalysis, microwave and flow chemistry are all now represented in the third edition. To this end, a new member has joined the writing team and it is doubtless that, without the professional ability, enthusiasm, verve and sheer determination to see the job finished by Dr Philippa Cranwell, this project would probably have withered and petered out. She is a very welcome addition to the team.

However, the third edition is not simply about the addition of new subject matter, but the removal of other material in recognition of the technical advances that have been made since this book was last updated. The almost immeasurable increase in computational power during the lifetime of this book has rendered much of the initial discussions of data storage and retrieval obsolete, as the power of the Internet reigns supreme and will only continue to evolve and gather force at an ever‐increasing pace. As a result, most references to hardcopy data storage and retrieval have been removed, except for that last bastion of paper – the laboratory notebook – although it is recognized that, even here, its days are numbered.

If the Internet has changed for ever the way in which we obtain and exchange information, then technological advances combined with increased computing power have radically affected the way in which experimental data are measured and interpreted. This third edition contains expanded discussions of NMR and IR spectroscopic and mass spectrometric techniques that are now routine parts of the analytical arsenal of organic chemistry, while still retaining explanations of the fundamental principles of these techniques. UV spectroscopy is retained, even though it is recognized that this technique is rarely used in the research laboratory nowadays, except as a detection method in HPLC. So why have certain aspects of spectroscopic techniques been retained in the third edition? Quite simply, the more technology takes over, the more an analytical technique becomes a ‘black box’, so much so that the chemist may forget to question and challenge; accepting mutely, the data produced. Without a fundamental understanding and appreciation of a technique being used and its pitfalls and limitations, a scientist is treading on treacherous ground when carrying out spectroscopic analysis.

Nonetheless, some techniques described in the first edition and retained in the second have simply fallen out of practice and have been removed in recognition of standard practice in teaching and research laboratories at this time. However, it is not simply older practices that have been removed. In the second edition, microscale chemical techniques were included as, during that period, these were becoming popular in student teaching programmes in many universities. They now seem to have waned in popularity worldwide, so microscale methodology and experimental procedures pertaining to student experiments have been removed, although small‐scale protocols useful at the research level have been retained.

As in the previous two editions, the book is divided into two main sections – the first surveying aspects of safety, apparatus, purification and spectroscopic techniques, and the recording and retrieval of data, and the second containing the experimental procedures and appendices. As a result of the need to include examples of more recent synthetic methodologies, the experimental section has increased to 104 experimental procedures from the 86 contained in the second edition, almost back to the 105 contained in the first edition. More importantly, the range and choice of illustrative experiments more closely reflect the experimental environment in which today’s organic chemists operate, from the fundamental to the more esoteric. As before, the experimental procedures have been further subdivided into chapters covering ‘functional group interconversions’, ‘carbon–carbon bond‐forming reactions’ and ‘projects’, but an additional chapter covering ‘enabling technologies’ – microwave and flow chemistry – has been included. We are indebted to Associate Professor Nicholas Leadbeater of the University of Connecticut for providing procedures for the flow chemistry protocols contained in this chapter, and the Moody group at the University of Nottingham for the microwave chemistry protocols. Above all, we have continued to include examples of most of the important reaction types at varying levels of experimental difficulty, so that a concerted series of experiments might be designed that is tailored to the specific teaching needs of a class or an individual student.

Safety in the laboratory is, as always, the paramount consideration when choosing or retaining an experiment, and we have attempted to minimize potential hazards by avoiding toxic materials wherever possible and by highlighting in the text any possible hazards at appropriate points of the procedure. In addition, the scale of each standard experimental procedure has been kept as small as is commensurate with the level of difficulty, to minimize any adverse consequences of an accident, in addition to lessening disposal problems and cost. Nonetheless, health and safety regulations worldwide have become complex and sometimes contradictory, so the advice always is to assess the risk and validate all procedures with the local health and safety guidelines before commencing any experimental work.

Following feedback over the past 25 years or so, the experiments in this third edition have been included for their reproducibility and all have been independently assessed for such. Each experiment is preceded by a general discussion, outlining the aims and salient features of the investigation, and is followed by a series of problems designed to emphasize the points raised in the experiment. To emphasize safety aspects, make the greatest use of time available in the teaching laboratory and encourage forward planning, apparatus, instruments and chemicals required in the experiment are listed at the beginning of the procedure, together with an estimation of the amount of time necessary to complete the experiment. Extended periods of reflux or stirring have been avoided wherever possible and long experiments have been designed so that they have clear break points at roughly 3‐hour intervals, indicated in margin notes in the procedure. The indicative degree of difficulty of each experiment is as follows:

Introductory‐level experiments requiring little previous experience.

Longer experiments with the emphasis on developing basic experimental techniques.

Experiments using more complex techniques and spectroscopic analysis.

Research level.

Data on yields and melting points, useful hints and checkers’ comments for each experiment, and guidelines for answers to all of the problems are available at the companion website: www.wiley.com/go/cranwell/EOC. Of course, almost all necessary data can be obtained from the Internet with a few clicks of a mouse or a few swipes of the finger. Nonetheless, some data tables are presented in appendices at the end of this book as we felt that these were likely to be of greatest use both to students working for their first degree and also to research workers.

In addition to those already mentioned, we would like to acknowledge others whose help has been fundamental in the production of this third edition. In alphabetical order, thanks go to Professor Matthew Almond (University of Reading), Professor Chris Braddock (Imperial College), Dr Geoff Brown (University of Reading), Professor Rainer Cramer (University of Reading), Dr Rob Haigh (University of Reading) and Associate Professor John Mckendrick (University of Reading). In addition, we reiterate our gratitude to all those individuals who gave their time, expertise and advice to assist with the production of the two preceding editions.

On the book production side, we would like to thank the Wiley team, in particular Jenny Cossham for her support, hard work and patience in making this third edition a reality, and Sarah Keegan for her dedication to seeing the project to completion.

Philippa B. CranwellDepartment of Chemistry, University of Reading, Whiteknights, Reading, UK

Laurence M. HarwoodDepartment of Chemistry, University of Reading, Whiteknights, Reading, UK

Christopher J. MoodySchool of Chemistry, University of Nottingham, University Park, Nottingham, UK

September 2016

About the companion website

This book is accompanied by a companion website:

www.wiley.com/go/cranwell/EOC

The website includes:

PowerPoint files of all images in the book for downloading

Instructor’s Manual

Part 1Laboratory practice

1 Safety in the chemical laboratory

2 Glassware and equipment in the laboratory

3 Organic reactions: From starting materials to pure organic product

4 Qualitative analysis of organic compounds

5 Spectroscopic analysis of organic compounds

6 Keeping records: The laboratory notebook and chemical literature

1Safety in the chemical laboratory

The chemistry laboratory is a dangerous environment in which to work. The dangers are often unavoidable, since chemists regularly have to use hazardous materials. However, with sensible precautions, the laboratory is probably no more dangerous than your home, be it house or apartment, which, if you stop to think about it, also abounds with hazardous materials and equipment – household bleach, pharmaceutical products, herbicides and insecticides, natural or bottled gas, kitchen knives, diverse electrical equipment, the list goes on and on – all of which are taken for granted. In the same way that you learn to cope with the hazards of everyday life, so you learn good laboratory practice, which goes a long way to help minimize the dangers of organic chemistry.

The experiments in this book have been carefully chosen to exclude or restrict the use of exceptionally hazardous materials, while still highlighting and exemplifying the major reactions and transformations of organic chemistry. However, most chemicals are harmful in some respect, and the particular hazards associated with the materials should not be ignored. Unfortunately, it has not been possible to exclude totally the use of some chemicals, such as chloroform and dichloromethane, which are described as ‘cancer suspect agents’, but if handled correctly with proper regard for the potential hazard, there is no reason why such compounds cannot be used in the organic chemistry laboratory. Ultimately, laboratory safety lies with the individual; you are responsible for carrying out the experiment in a safe manner without endangering yourself or other people, and therefore it is your responsibility to learn and observe the essential safety rules of the chemical laboratory.

Prior to starting any experiment, a risk assessment should be prepared to identify the hazards, the likelihood of harm and any steps you can undertake to reduce the level of risk. The material safety data sheets (MSDSs) for any chemicals you are planning to use will provide valuable information. The risk assessment should also consider the end product and any intermediates that may be produced, as these may have hazardous properties.

Legislation varies between the United Kingdom, Europe and the United States, therefore the references given in this section are generally for the UK only. Further information for a UK laboratory can be found at the following websites:

http://www.hse.gov.uk/coshh/basics/assessment.htm

http://www.hse.gov.uk/risk/controlling‐risks.htm

1.1 Essential rules for laboratory safety

The essential rules for laboratory safety can be expressed under two simple headings: ALWAYS and NEVER.

Most of these rules are common sense and need no further explanation. Indeed, if asked to name the single most important factor that contributes towards safety in the laboratory, the answer is simple: common sense.

ALWAYS

familiarize yourself with the laboratory safety procedures

wear eye protection and a laboratory coat

dress sensibly

wash your hands before leaving the laboratory

read the instructions carefully before starting any experiment

check that the apparatus is assembled correctly

handle all chemicals with great care

keep your working area tidy

attend to spills immediately

ask your instructor if in doubt

carry out a risk assessment

NEVER

eat or drink in the laboratory

smoke in the laboratory

apply makeup in the laboratory

inhale, taste or sniff chemicals

fool around or distract your neighbours

run in the laboratory

work alone

carry out unauthorized experiments

1.1.1 Laboratory safety procedures

Your laboratory will have certain safety procedures with which you must be familiar. Some of these procedures are legal requirements; others will have been laid down by the department. Make sure you know:

where all the exits to the laboratory are, in the event of an evacuation because of fire or other incident;

the precise location of fire extinguishers, fire blankets, sand buckets, safety showers and eye‐wash stations;

what type the fire extinguishers are and how to operate them, especially how to remove the safety pin.

If you are unsure of which type of extinguisher to use then do not attempt to fight the fire; the use of an incorrect type can, and probably will, make things worse.

1.1.2 Eye protection

You must wear eye protection at all times in the laboratory. Even if you are just writing in your notebook, your neighbour may be handling hazardous materials. The use of corrosive chemicals is not the only hazard for eyes, as many solvents are just as painful and irritating. Eyes are particularly vulnerable to damage from sharp objects such as broken glass and from chemicals, and therefore must always be protected to prevent permanent damage. Protection should be in the form of approved safety goggles or safety glasses (http://www.hse.gov.uk/foi/internalops/oms/2009/03/om200903app3.pdf). Ordinary prescription glasses do not provide adequate protection, since they do not have side shields and may not have shatter‐proof lenses. If you are going to do a lot of laboratory work, it is probably worth obtaining a pair of safety glasses fitted with prescription lenses. Alternatively, wear goggles over your normal glasses for full protection. Contact lenses are often forbidden in chemical laboratories, because in the event of an accident, chemicals can get under the lens and damage the eye before the lens can be removed. Even if contact lenses are permitted, then you must wear well‐fitting goggles for protection. Inform your instructor, the laboratory staff and your neighbours that you are wearing contact lenses so that they know what to do in case of accident. Although no experiments in this book require them, full face shields should be worn for particularly hazardous operations. If a chemical does get into the eye, you must take swift action. The appropriate action is discussed in Section 1.4.5.

Contact lenses

1.1.3 Dress

Dress sensibly in the laboratory. The laboratory is no place to wear your best clothes, since however careful you are, small splashes of chemicals or acids are inevitable. For this reason, shorts or short skirts are unsuitable for laboratory work and are forbidden in many institutions. A laboratory coat should always be worn, and loose‐fitting sleeves that might catch on flasks and other equipment should be rolled back. Long hair is an additional hazard, and should always be tied back. Proper shoes should be worn; there may be pieces of broken glass on the laboratory floor, and sandals do not provide adequate protection from glass or from chemical spills.

1.1.4 Equipment and apparatus

Never attempt to use any equipment or apparatus unless you fully understand its function. This is particularly true of items such as vacuum pumps, rotary evaporators and cylinders of compressed gas, where misuse can lead to the damage of expensive equipment, your experiment being ruined or, most serious of all, an accident. Remember the golden rule:

If in doubt, ask.

Before assembling the apparatus for your experiment, check that the glassware is clean and free from cracks or imperfections. Always check that the apparatus is properly clamped, supported and correctly assembled before adding any chemicals. Again, if in any doubt as to how to assemble the apparatus, ask.

1.1.5 Handling chemicals