PRACTICAL ORGANIC CHEMISTRY by FREDERICK GEORGE MANN Sc-D. (Cantab.), D.Sc. (Lond.), F.R.I.C., F.R.S. FELLOW, TRINITY COLLEGE, CAMBRIDGE, UNIVERSITY EMERITUS READER IN ORGANIC CHEMISTRY and BERNARD CHARLES SAUNDERS C.B.E., M.A., Sc.D. (Cantab.), D.Sc. (Lond.), F.R.I.C., F.R.C. Path. LONGMAN London and New York LONGMAN GROUP LIMITED London Associated companies, branches and representatives throughout the world Published in the United States of America by Longman Inc., New York Fourth Edition © Frederick George Mann and Bernard Charles Saunders 1960 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, without the prior permission of the Copyright owner. First Published 1936 Second Edition 1938 New Impressions 1941,1942, 1943, I 944, X 94 6 , 1 947, T 949, *95 2 Third Edition 1952 New Impressions 1954, *955, I95 6 , I 957> J 95<? Fourth Edition 1960 New Impressions 1961, 1962, 1964, 1967, /970, /977 Neiv Impression with revisions 1974 New Impression KJ/5 Reprinted in paper covers, igj8 British Library Cataloguing in Publication Data XEW IMPRESSION, 1974 The last (4th) Edition of this book appeared in 1960, and has been followed by four New Impressions, the last in 1967. The rapid and ceaseless changing of the presentation of organic chemistry— both theoretical and practical—warranted an entirely new edition, but this would have entailed a massive task, for which neither Dr. B. C. Saunders nor I had time or opportunity to undertake. The publishers therefore suggested that a new impression should be prepared. This also proved a laborious task, partly because of the many minor changes in nomenclature and—more particularly—the presentation of names that the recommenda- tions of the LU.P.A.C. required, and partly because all correc- tions and additions were necessarily limited in length to the space which the original text had occupied. Several of my chemical colleagues have suggested that a new edition of 'M. and S.' should now deal also with the chief branches of modern spectroscopy. This would be an aim both excellent and impracticable. Students have their own mono- graphs on spectroscopy and their own teachers, whose exposition should clarify the branches of this subject more rapidly and easily than the printed text. An attempt to deal adequately with spectroscopy in this volume would greatly increase its size and probably fail in purpose—the fate of several books whose authors have attempted this ambitious programme. Wc are greatly indebted to Dr. D. K. C. Cooper, F.R.C.S., who has critically examined the section on First-Aid to ensure that it now harmonises with modern medical practice. F. G. Mann, University Chemical Laboratory, Cambridge. March 1973. PREFACE TO FOURTH EDITION IN the preparation of this revised and extended edition, we have had in mind two major factors. First, considerably greater emphasis has been placed on semi- micro techniques and their application to preparations, separa- tions, analysis and physical determinations such as those of molecular weight. We have therefore greatly expanded the section on Manipulation on a semi-micro scale which was in the Third Edition, and we have described many more preparations on this scale, some independent and others as alternatives to the larger-scale preparations which immediately precede them. Some 40 separate preparations on the semi-micro scale are described in detail, in addition to specific directions for the preparation of many classes of crystalline derivatives required for identification purposes. The equipment required for these small-scale reactions has been selected on a realistic basis, and care has been taken not to include the very curious pieces of apparatus sometimes suggested as necessary for working on the semi-micro scale. Secondly, whilst retaining undiminished the full and clear directions provided for students who are starting the study of practical organic chemistry, we have extended the scope of the work so that it covers most of the needs of students working for an Honours or Special Degree. To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf- Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. These preparations, with those noted in the Preface to the Third Edition, cover a considerable proportion of the standard synthetic reactions. Most of these preparations come towards the end of Part II (Preparations), and both elementary and advanced students should have no difficulty in selecting the preparative work they require. In earlier editions, Part III (Reactions and Identification of viii PREFACE TO FOURTH EDITION Organic Compounds) was designed to give students a thorough training in the general reactions of the simpler members of each of the main classes of organic compounds, and in the methods by which an unknown compound could be first allocated to its class and then identified. Clearly, more advanced students will meet a wider range of members of each class of compound, and the final identification must usually be based on the melting- points of crystalline derivatives. We have therefore inserted in the account of each class a note of the types of crystalline deriva- tives which can be most rapidly and reliably prepared, with full experimental details. Our Tables of Melting-points of deriva- tives, given at the end of the book, have been very considerably extended, so that the advanced student, who, like the elementary student, must first allocate his unknown compound to its class, can now prepare one or more crystalline derivatives, and com- plete the identification by reference to these tables. The pre- paration of these crystalline derivatives gives the student a further and very valuable exercise in semi-micro preparations. It should be emphasised that in Sections 10-27 °f ^ ai "t HI, i.e., the sections which are each devoted to one class of com- pound, the simpler or more common members are still clearly specified, and their reactions discussed, so that again the less advanced student can readily discern the range of the material which is his immediate concern. For the more advanced student, we have extended the section on Quantitative Semi-micro Analysis, and we have included a section dealing with Special Techniques in Separation and Purification, namely Adsorption Chromatography, Paper Chro- matography, and Ion-Exchange Processes. The use of more complex or more costly articles of equipment, such as catalytic hydrogenation apparatus, autoclaves, polari- meters, ultraviolet absorption spectrometers, etc., has not been described, because the type of such apparatus employed in different laboratories varies considerably, and students must be taught the use of their own laboratory equipment. In the First Edition of this book, we included a short section to illustrate some of the more simple or the more clearly defined reactions which are promoted by enz\mes. It was hoped that this section might stimulate the interest of younger chemists in the preparative value oi such T cactioris, but organic chemists still largely ignore this branch oi preparative work. We have now deleted certain portions of this section, and emphasised other portions having greater current interest. PREFACE TO FOURTH EDITION ix Throughout this edition the nomenclature adopted is in general that recommended by the International Union of Pure and Applied Chemistry, and by the Chemical Society (1959). In the preparation of this edition, we are indebted for much help to many of our colleagues, and in particular to Dr. P. Sykes, Dr. F. B. Kipping, Dr. P. Maitland, Dr. J. Harley-Mason and Dr. R. E. D. Clark. We have maintained the standard which was self-imposed \vhen this book was first written, namely, that all the experiments in the book had been critically examined, and then performed either by the authors, or under their super- vision. The heavy load of work \vhich this has involved would have been impossible without the willing, patient, and very considerable help of AIr. F. C. Baker and Mr. F. E. G. Smith. F. G. M. Cambridge, 1960 B.C.S. PREFACE TO THIRD EDITION FOR the production of this edition, we have made a thorough and critical revision of the whole contents of the book, based on our experience of its use in the laboratory and on the general advance in organic chemical practice. In addition to this general revision. however, we have extended the book in three main directions. The book as originally planned was intended to meet the needs primarily of pupils'in the senior forms at schools and of under- graduates up to the level of a Pass Degree. We have extended Parts II and III dealing with Preparations and with the Reactions and Identification of Organic Compounds so that the book should now cater fully for the needs of students working for Honours Degrees. In particular, the Preparations now include examples of most of the more simple standard reactions: for this pur- pose we have now added, for example, preparations illustrating the Benzidine Transformation, the Ullmann Condensation, the Benzilic Acid Rearrangement, the Reformatsky Reaction, the Clemmensen Reduction, the Fischer Indolisation Reaction, the Mannich Reaction, and the Diels-Alder Reaction. It is probable that preparative work on a much smaller scale than has hitherto been customary in teaching laboratories will become more common in future. To meet this need, we have added a short section to Part I, describing the design and use of apparatus for this purpose, and we have also included some examples of these small-scale preparations as alternatives to the larger preparations in Part II. In Part III, dealing with the Reactions and Identification of Organic Compounds, greater emphasis has now been placed on the preparation of suitable crystalline derivatives. Quite apart from the importance of these derivatives for purposes of identi- fication, encouragement is thereby given to the student to gain experience in small-scale preparative work. We have also added an entirely new section dealing with semi- microanalysis. In our original Introduction (p. ix) we justified the retention of macro-methods of quantitative analysis on the grounds that they formed an excellent introduction to micro- methods and also afforded a valuable training in exact manipula- tion generally. By now, however, the macro-estimation par- ticularly of carbon and hydrogen and of nitrogen has disappeared entirely from most laboratories. On the other hand, the micro- PREFACE TO THIRD EDITION xi methods developed so largely by Pregl, and which usually require no more than 5 mgm. of material, necessitate prolonged training and an impeccable experimental technique, and give consistently reliable results only in the hands of full-time analysts. They are consequently unsuitable for students. The semi-micro methods of analysis, which usually require 20-50 mgm. of material, form an ideal compromise for student-training, for the necessary technique can be acquired after only a few attempts. These methods moreover provide the student with very valuable manipulative exercise, and serve as an introduction to the hand- ling of even smaller quantities of material which may arise in his post-graduate work. This section on Semi-microanalysis has been designed and written by Dr. P. Sykes, and is based on his experience of teaching such methods in the Cambridge labora- tories. We wish to thank him sincerely for a valuable contribution to this work. In the original planning of this book we were at pains to ensure that the preparations in particular were designed to afford a minimum expenditure of time, materials and heating. We hope that the economy thus introduced will be especially appreciated in view of the recent heavily increased cost of chemicals, fuel and laboratory service. This increased cost, incidentally, must necessarily increase the attraction of the small-scale preparations referred to above. We are grateful to our colleagues for many valuable discussions and suggestions: in particular we would mention Dr. F. B. Kipping, Dr. P. Maitland, Dr. G. W. Kenner and Mr. J. Harley- Mason. We should also like to express once again our sincere thanks for the considerable help we have received from our laboratory assistants, Mr. F. C. Baker and Mr. F. E. Smith. F.G.M. B.C.S. PREFACE TO SECOND EDITION THE two chief additions which have now been made are the Sodium Carbonate-Zinc Method as an alternative to Lassaigne's Sodium Fusion Method for detecting elements in organic com- pounds, and the Tables of Physical Constants which have been included in the Appendix. These Tables have been compiled to cover a very much wider scope of organic compounds than those described in this book. In addition to the general utility of these Tables, we hope that they will be of value to students wishing to extend their practice in the identification of organic compounds beyond the range given in Part III of this book. This range has been deliberately limited in order to enable students to obtain a firm grasp of the methods of identifying simple compounds, and these methods have therefore been based almost entirely on chemical reactions alone. When the range of organic compounds to be identified is extended, and particularly when higher homologues are being investigated, identification by the physical properties of derivatives becomes increasingly necessary, and the Tables of Physical Constants should con- siderably facilitate this extension. We wish to express our gratitude to the chemists who have made suggestions with regard to the subject-matter of this book: many of these suggestions have now been incorporated in this edition. W r e would warmly welcome further suggestions for improving its contents. F.G.M. B.C.S. INTRODUCTION THIS laboratory manual of organic chemistry has been compiled primarily to cover the work required for Part I of the Natural Sciences Tripos at Cambridge University, the General B.Sc. course at London University, and the Pass Degree courses at other universities. At the same time, however, it has been carefully arranged to cover adequately the needs of students pro- ceeding to the M.B. examinations in organic chemistry at the various universities. Moreover, since the introductory work has been given in considerable detail, the book is suitable for senior pupils at schools (more particularly for Higher Certificate and University Entrance Scholarship candidates), and should therefore be sufficient to cover both their school and university needs. This work is based largely on the authors' experience with the teaching of practical organic chemistry to very large classes of students at Cambridge University. For such classes experimental directions involving the utmost economy in chemicals and apparatus, and also in the students' time, are obviously required. Therefore the whole of the experimental work described in this book has been repeatedly checked by the authors themselves (and for the most part by their classes also) in order to obtain the desired results with a minimum expenditure of materials and time. In the section on Organic Preparations in particular, this detailed investigation of each preparation has frequently enabled unexpected simplifications and economies to be introduced, more particularly as many text-books still contain experimental direc- tions which have frequently remained unchanged since their original publication in chemical journals many years ago, and in which, moreover, occasional errors both in fact and in tran- scription have thus remained uncorrected. It is almost uni- versally found that departments of organic chemistry are more costly to maintain than other science departments, primarily because of the heavy consumption of organic reagents and sol- vents, and the economies which have now been effected will, we think, be appreciated by most teachers of practical organic chemistry. Teachers of chemistry (and of the sciences generally) will have found that many students appear to dissociate their practical work sharply in their minds from their theoretical knowledge. Many xiii [...]... these methods and of their comparative practical value This combination of theory and practice will, it is hoped, both simplify and elucidate the practical study of organic chemistry, and enable the student to visualise his practical work as an orderly whole and not as a vast number of isolated and unrelated experiments Part III, on the Reactions and Identification of Organic Compounds, has been strictly... Simple Enzyme Reactions, is rather a new departure in practical books of this type The importance of INTRODUCTION xv this section to medical students, biochemists, physiologists, etc., is obvious We consider, however, that students of chemistry who are not reading any biological subject should have some practical knowledge of a branch of organic chemistry which is of the greatest scientific importance,... describe here the general methods of filtration The two principal occasions in organic chemistry when filtration is necessary are: * A simpler \\ater-condenser having both ends comically ground (cf (B), p 45), and a thin-walled inner tube, is lighter and more efficient than those illustrated above io PRACTICAL ORGANIC CHEMISTRY (A) A solid substance has crystallised from a solution, and it is necessary... simple distillation from their practical inorganic chemistry Other students should determine the boiling-point of acetone (56°), using a water-bath and water-condenser, or of benzene (81°), using a sand-bath and water-condenser, and finally of either aniline (184°) or nitrobenzene (210°), using for both these liquids a sand-bath and aircondenser Filtration Before discussing the practical details of the purification... essentially from the practical standpoint The student should always acquaint himself with the theoretical basis of these operations, for which he should consult any standard text-book of physical chemistry: this applies particularly to such processes as the distillation of constant boiling-point mixtures, steam-distillation, ether extraction, etc The experimental operations in organic chemistry which occur... liquids, unless otherwise stated, is given at i5°C The experiments described in Part I have been numbered, as they form a graded series to illustrate the chief manipulative processes employed in practical organic chemistry The experiments in Parts 11-V have not been numbered, as in general a selection must be made from them In each part of the book, the experiments have been arranged as far as possible... not necessarily the order of increasing difficulty XlX PART I METHODS AND MANIPULATION IN this part of the book, a brief account is given of the chief manipulative processes which are used in practical organic chemistry Most of these processes are those which students are likely to use repeatedly in their work The remainder are not of such frequent occurrence, but are processes with which more advanced... simple programme given in Part III before proceeding to wider and more detailed systems for the identification of organic compounds The comparatively wide prevalence of micro-methods of quantitative organic analysis, applied more particularly to the estimation of the constituent elements in an organic compound, may cause the advisability of including the macro-methods in Part IV to be questioned Quite... chemically pure This is almost invariably the cause of a sharp melting-point (2) Substance is a eutectic mixture of two or more compounds The chance of a given mixture containing two compounds 2 PRACTICAL ORGANIC CHEMISTRY in just the proportion to give a sharp-melting eutectic mixture is so remote that this possibility may be neglected [Occasionally arbitrary mixtures of two substances which (usually)... possesses the following very suitable properties: (a) it has a low specific heat and therefore the temperature can be easily increased using only a small (B) flame, (b) even when hot it FIG i 4 PRACTICAL ORGANIC CHEMISTRY is almost non-inflammable, and therefore should the flask break whilst still over the flame, the oil seldom ignites, (c) the oil is non-corrosive, and owing to its low specific heat . will, we think, be appreciated by most teachers of practical organic chemistry. Teachers of chemistry (and of the sciences generally) will have found . practical value. This combination of theory and practice will, it is hoped, both simplify and elucidate the practical study of organic chemistry,