Practical Organic Chemistry

Practical Organic Chemistry A student handbook of techniques

J. T. Sharp, I. Gosney University of Edinburgh

and

A. G. Rowley Consultant in analytical chemistry

London New York CHAPMAN AND HALL

First published in 1989 by Chapman and Hall Ltd 11 New Fetter Lane, London EC4P 4EE Published in the USA by Chapman and Hall 29 West 35th Street, New York NY 10001

© 1989 ]. T. Sharp, I. Gosney and A. G. Rowley

Typeset in 11/12 Sabon by Best-set Typesetter Ltd, Hong Kong

T. J. Press (Padstow) Ltd, Padstow, Cornwall

ISBN-13: 978-0-412-28230-0 e-ISBN-13: 978-94-009-0819-2 DOI: 10.10071 978-94-009-0819-2

The paperback edition is sold subject to the condition that is shall not, by way of trade or otherwise, be lent, resold, hired out, or otherwise circulated without the publisher's prior consent in any form of bin ding or cover other than that in which it is published and without a similar condition including this condition being imposed on the subsequent purchaser.

All rights reserved. No part of this book may be reprinted, or reproduced or utilized in any form or by any electronic, mechanical or other means, now known or hereafter invented, including photocopying and recording, or in any information storage and retrieval system, without permission in writing from the publisher.

British Library Cataloguing in Publication Data

Sharp,J. T. Oohn T.). 1939-Practical organic chemistry. 1. Organic chemistry. Laboratory techniques I. Tide II. Gosney, I. (lan), 1942-IlI. Rowley, A. G. (Alan G.), 1948-547'.0028

Library of Congress Catalo?ing in Publication Data

Sharp,]. T. Oohn Traquair), 1939-Practical organic chemistry: a student handbook of

techniques / J. T. Sharp, I. Gosney, and A. G. Rowley. p. cm.

Bibliography: p. lncludes index.

1. Chemistry, Organic- Technique. I. Gosney,l., 1942- . II. Rowley, A. G., 1948- . III. Tide. QD258.S57 1989 547 -dc19

Contents

Preface IX

Foreword Xl

Acknowledgements Xl11

Safety and supervision in the la bora tory xv

1 Introduction 1 1.1 The range of experimental techniques 1 1.2 Good laboratory practice 2 1.3 Safety in the laboratory 3

1.3.1 Chemical hazards 3 1.3.2 Fire hazard 5 1.3.3 Vacuum and pressure work 6

1.4 Keeping records 6 1.4.1 Recording experimental data 6 1.4.2 Final reports 6

1.5 Sampies and spectra 7

2 Carrying out reactions 8 2.1 Basic techniques 9

2.1.1 Apparatus 9 2.1.2 Addition of reactants 11 2.1.3 Stirring reaction mixtures 13 2.1.4 Temperature control 16 2.1.5 Reactions under anhydrous conditions and inert

atmospheres 22 2.2 Special techniques 32

2.2.1 The use of air- and water-sensitive reagents 32 2.2.2 Reactions in liquid ammonia 41 2.2.3 Catalytic hydrogenation 44 2.2.4 Photochemistry 48 2.2.5 Flash va cu um pyrolysis 51

Vi Contents

3 Isolation and purification of re action products 54 3.1 Primary work -up procedures 54

3.1.1 General considerations 54 3.1.2 Removal of solvent by rotary evaporator 55 3.1.3 Extraction procedures 57 3.1.4 Drying organic solutions 61 3.1.5 Separation of the target product(s) 63

3.2 Crystallization 64 3.2.1 General principles 64 3.2.2 Melting point as a criterion of purity 65 3.2.3 Methods of crystallization 66 3.2.4 Choosing the crystallization solvent 80 3.2.5 Special topics 84

3.3 Melting point 86 3.3.1 General principles 86 3.3.2 Determination of melting point 86 3.3.3 Other methods 88

3.4 Distillation 90 3.4.1 General considerations 90 3.4.2 Simple distillation 91 3.4.3 Fractional distillation 98 3.4.4 Small-scale distillation 102 3.4.5 Molecular distillation 106 3.4.6 Steam distillation 108 3.4.7 Sublimation of solids 109 3.4.8 Appendices 111

4 Separation of organic mixtures by chromatography 114 4.1 Analytical methods 114

4.1.1 Thin-Iayer chromatography 114 General description 115 TLC plates and adsorbents 116 Application of the sampie 116 Running (developing) the chromatogram 117 Examining the chromatogram 117 The use of TLC for qualitative analysis 118 Choosing the developing solvent 119

4.1.2 Gas-liquid chromatography 119 General description 120 The instrument 120 Injecting the sampie 122 Running the chromatogram 123 Identification by GLC 125

Contents Vll

Quantitative analysis 125 Recording GLC data 129 Selection of the stationary phase and other operating parameters 129 Setting up the instrument, some general points 134

4.1.3 High-performance liquid chromatography 135 General description 135 Equipment 136 Operation of the equipment 140 Qualitative and quantitative analysis 142 Retention and resolution - basics 142 Optimizing the separation 144 Selection of the chromatographic mode 145 Liquid - solid (adsorption) chromatography (LSC) 146 Liquid -liquid chromatography (LLC) on bonded phases 150

4.2 Preparative methods 152 4.2.1 Preparative thin-Iayer chromatography 152 4.2.2 Column chromatography 153

General description 154 Choosing the method 155 Flash chromatography 156 Dry-column flash chromatography 160 Medium-pressure liquid chromatography 163 Gravity-elution chromatography 167

4.3 Appendices 170 4.3.1 General principles of chromatographic separation 170 4.3.2 Control of adsorbent activity 175 4.3.3 Preparation ofTLC plates 176

5 Preparation of sampIes for spectroscopy 178 5.1 Infra-red 178 5.2 N uclear magnetic resonance 182 5.3 Mass spectrometry 185 5.4 Ultraviolet 186

6 Finding chemical information 188 6.1 Physicalproperties 189 6.2 Spectroscopic properties 190 6.3 Beilstein's Handbuch 191 6.4 Chemical Abstracts 194

Index 197

Preface

One of the very best things about organic chemistry is actually doing experimental work at the beneh. This applies not only at the profes­sionallevel but also from the earliest stages of apprenticeship to the craft as a student. The fascination sterns from the nature of the sub­ject itself, with its vast array of different types of reaction and its al­most infinite variety of different chemical compounds. Each reaction and each new compound pose their own particular problems to chal­lenge the skill and ingenuity of the chemist, whether working in a first-year teaching la bora tory or at the frontiers of research.

This book is intended to provide basic guidance in the essential experimental techniques used in a typical undergraduate course. It gives concise coverage of the range of practical skills required, from first-year level when students may have no previous experience, up to final-year level when students are usually involved in more complex and dem an ding experimental work in supervised research projects.

Our objective was to produce a handbook of techniques that could be used with a variety of practical courses throughout a student's whole period of study. Those who run practical courses generally have strong feelings about what particular experiments or exercises are appropriate for their own students, and it is rare that a book of experiments suitable for one department is acceptable to another. However, there is a common body of techniques applicable to all courses, and we hope that this book will provide a useful source of information on the range of techniques that are an essential part of current chemical practice. We have included not only the classical and timeless methods, for example the purification of compounds by crystallization and distillation, but also more modern techniques, such as those required for working with air- and water-sensitive re­agents, without which most recent advances in organic chemistry would not have been possible. Also included are the modern methods of preparative chromatography, such as the 'flash' and 'medium-pres­sure' techniques, and the instrumental forms of chromatography,

x Preface

gas-liquid chromatography (GLC) and high-performance liquid chromatography (HPLC), which play such a vital role in the monitor­ing and analysis of reactions.

A book of this length cannot be comprehensive, and, as with all practical teaching, some techniques are better demonstrated than described. To this end the advice and guidance of experienced instruc­tors are essential in the application of the techniques described to particular compounds or reactions under study.

Since the book is intended for use at different levels, the various chapters are structured so that the early parts of each section con­centrate on learning how to handle the equipment and on the basic aspects of the technique. The later parts are concerned with more advanced aspects, such as the optimization of operating conditions or parameters. Basic theory, of chromatography for example, is dealt with only at the level needed for effective practical work.

While intended mainly for undergraduates, it is our hope that this book will also be of value to more advanced students as a guide to basic experimental methods onto which they can graft the refine­ments, modifications and extensions necessary for particular areas of research.

We thank our many colleagues (past and present), research students and undergraduates for their invaluable advice as to what is good, effective and safe laboratory practice at the present time. In particu­lar, we thank Dr David Reid (of the University of Edinburgh NMR Service) for his advice on the section on the preparation of sampies for nudear magnetic resonance (NMR) spectroscopy. Finally, we express the hope that many of you, about to come to grips with the challenges of practical organic chemistry for the first time, will get as much pleasure and satisfaction from it as we have.

Edinburgh October 1988 J. T. S., I. G. and A. G. R.

Foreword

There were two aspects of the teaching of organic chemistry which first attracted me to the subject. First, the application of the concepts of reaction mechanism to the rationalization of experimental observation and, secondly and most importantly, the enjoyment and fascination in performing synthetic reactions leading to pure products.

Although the methods now used in the characterization of these products are largely instrumental, the overwhelming requirement of an organic chemist is still for the undertaking of experiments to make compounds, and to isolate them in pure form. In order to enjoy this aspect of the subject the chemist must become skilIed in the art of practical organic chemistry. Sadly, with the decrease in practical content of many undergraduate courses, the necessary skills are harder to acquire. This book gives an excellent grounding in the experimental techniques required for practical organic chemistry from first year level up to Honours level and beyond, and does so with due reference to essential modern safety practice. There are several excellent books which emphasize a range of interesting pre­parations and reactions. However, they lack any in-depth treatment of the basic practical requirements for the efficient performance of reactions and the isolation of pure materials, both crucial aspects of study for beginners to master. The authors have produced a text which should find wide appeal as it can be used in combination with books dealing with standard preparations. Although sophisticated computer programmes are being developed for mapping out the reaction paths to be followed in synthesis, it must be remembered that the vast number of products sold by the chemical and pharmaceutical industries are pure compounds and not computer print-outs. Producing these compounds demands a high degree of skill from the professional chemist.

Thus a text such as this volume, which guides young chemists through the correct practical procedures, has an important role to

Xll Foreword

play in training people in experimental methods and deserves a place alongside them on the laboratory beneh.

R. Ramage Forbes Professor of Chemistry University of Edinburgh October 1988

Acknowledgements

We thank J. Bibby Science Products Ltd for permission to use some of their product drawings of 'Quickfit®' standard taper glassware, 'Bibby' plastic joint clips and 'Rotaflo®' stopcocks in our dia grams of apparatus assemblies. We also thank the American Chemical Society, Marcel Dekker 1nc., Aldrich Chemical Company Ltd, and John Wiley and Sons 1nc. for permission to use various copyright items of text, diagrams or tables as indicated in the text.

Safety and supervision in the laboratory

KEY SAFETY PRECAUTIONS

1. Work in the laboratory only during approved hours when super­vision is available.

2. Wear safety spectacles (or a face shield) AT ALL TIMES. (Those who wear contact lenses, read Section 1.3.1.)

3. Do not eat, drink or smoke in the laboratory. 4. If you are in any doubt about experimental procedure or safe

practice, then consult your instructor before proceeding.

More detailed safety precautions are given in Section 1.3; these must be read before starting experimental work.

SUPERVISION

The techniques described in this book represent accepted experi­mental practice. However, it must be emphasized that they are general descriptions, and their application to a particular chemical reaction or to particular chemical compounds may require modifica­tions, either to make them effective for that particular ca se or for reasons of safety. For this reason it is essential that undergraduates and other inexperienced workers carry out practical work ONL Y under the supervision of qualified personnel with due regard to safety considerations ':- and legislation.

" See Guide to Safe Practices in Chemical Laboratories published by the Royal Society of Chemistry, London.