VOGEL’s
`
`TEXTBIIOII OF
`
`PRACTICAL ORGANIC CHEMISTRY
`
`FIFTH EDITION
`
`Revised by former and current members of
`The School of Chemistry,
`Thames Polytechnic. London
`
`Brian S. Furniss
`
`Antony J. Hannaford
`
`Peter W. G. Smith
`
`Austin R. Tatchell
`
`
`
`pl»-I. Longman
`
`Scientific 8:
`IE: Technical
`Copublished in the United States with
`John Wiley 8: Sons, |nc., New York
`
`
`
`Petitioners‘ Exhibit 1012, Page 1 of 5
`
`Petitioners' Exhibit 1012, Page 1 of 5
`
`

`
`!l.‘tMl1'I\'\nnvI-
`
`Longman Scientific & Technical
`Longman Group UK Limited
`Longman House. Burnt Mill. Harlow
`Essex CMZO ZJE, England
`and Associated Companies throughout the worid
`
`Copubiished in the United States with
`John Wiley & Sons, Inc., 605 Third Avenue, New York, N Y 1058
`© Longman Group UK Limited 1989
`
`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 either the prior written permission of the Publishers, or a
`licence permitting restricted copying in the United Kingdom issued by
`the Copyright Licensing Agency Ltd, 33~34 Alfred Place, London. WCEE 7DP.
`First published I948
`New Impression with minor corrections, October 1948
`Second Edition 1'95!
`
`New impression with addition of Chapter XH on Semimirro Te('hr1t'que 1954
`Third Edition 1956
`
`New Impression with c'orrec!t'on5 and additions 1957
`New ]nipr'e.ssiort.s 1959. 1'96)’, 1962, I964. I965, 1967
`Fourth Edition 1978
`
`Reprinted. with minor corrections 1979. 1981. 1984. 1986. I987, 1988
`Fifth Edition 1989
`
`British Library Cataloguing in Publication Data
`Vogel, Arthur Israel
`Vogcl's textbook of practical organic chemistry —
`5th ed
`t. Organic chemistry. Laboratory techniques
`I. Title I. Furniss, B. S. (Brian Stanley), 1941 —
`547.0028
`
`ISBN O~582—46236—3
`
`Library of Congress Cataloging-in-Publication Data
`Vogel, Arthur Israel.
`Vogel's Textbook of practical organic chemistry — 5th ed. / rev.
`by Brian S. Furniss
`[et al.]
`p.
`cm.
`Fourth ed. published in [973 under title: Vogel‘s Textbook of
`practical organic chemistry, including qualitative organic analysis.
`Includes bibliographies and indexes.
`ISBN 0-410-21414-7
`1. Chemistry, Organic#Laboratory manuals. 2. Chemistry,
`Analytic—Qua]itative. I. Furniss, Brian S. (Brian Stanley], 1941-
`II. Vogel, Arthur Israel. Vogel's Textbook of practical organic
`chemistry, including qualitative organic analysis. III. Title.
`QD261.V63
`1989
`54’/'—dcl9
`
`S8-36786
`CIP
`
`Set in 10/11 pt. Lasercomp Times New Roman
`
`Filmset by Eta Services (Typesetters) Ltd. Beccles, Suffolk
`Printed in Great Britain
`
`‘°”“‘°B""‘ "““"“‘
`
`Petitioners‘ Exhibit 1012, Page 2 of 5
`
`Petitioners' Exhibit 1012, Page 2 of 5
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`

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`
`
`equired the ther-,
`side-arm using an
`at the start of the
`funnel and insert»
`n. On occasions it
`ttions in these set-
`nsers described in
`
`) is used for reac-
`
`EXPERIMENTM. TECHNIHIJES
`
`2.18
`
`SEPARATION OF LIQUIDS AND SOLIDS
`On occasions it is necessary to separate a liquid and a solid in an inert atmo-
`sphere. Ifthe liquid and solid separate easily and distinctly with the solid settling
`to the bottom of the flask, the process of separation can be accomplished by
`careful use of a syringe or cannula to remove the supernatant liquid. The liquid
`may be discarded, stored or transferred to another reaction set-up for further
`reaction as appropriate. The solid remaining in the flask can be washed if neces-
`sary by the addition and subsequent removal of further quantities of dry,
`oxygen—free solvent through the septum. If the solid is desired solvent—free,
`residual solvent can be removed by connecting the flask to the vacuum line and
`condensing the solvent in a suitable trap. If the solid and liquid do not separate
`easily and the solid remains in suspension, filtration will be necessary. The sim-
`plest way of achieving this is with the gas dispersion or filter tube with a sintered
`glass end (Fig. 2.59). The technique is simlar to that described in Section 2.20
`(Fig. 2.81) for recrystallisation at low temperature. The filter tube can be fitted to
`the flask at the start ofthe reaction or subsequently inserted (after thorough dry-
`ing) with a rapid stream of nitrogen flowing through the neck of the flask into
`which the tube is to be inserted. If the solid is required it remains in the flask
`after further washing. If the liquid is required for further reaction it can be led
`directly to a second reaction flask.
`
`ISOLATION AND PUR|FlCATl0N TECHNIQUES
`
`2.18 GENERAL CONSIDERATIONS
`
`At the conclusion ofa reaction the pure product must be isolated from the reac-
`tion mixture by a sequence of operations collectively termed the ‘work-up‘. As
`well as the required product the reaction mixture may contain, for cxampie, sol-
`vent which has been used as the reaction medium, excess reactants or reagents,
`unwanted reaction products (by—products) arising from alternative reaction
`pathways and so on. The planning ofthe isolation operations and application to
`such complex mixtures is therefore an exacting test of the expertise of the
`chemist. Frequently a student fails to bring a successful reaction to a fruitful con-
`clusion by using an ill-considered work-up procedure, which results in loss ofthe
`required product either by decomposition during attempted isolation, or from a
`premature discard of product because of lack of appreciation of its physical or
`chemical properties. It should be emphasised that even when a detailed pub-
`lished procedure is being followed it is unwise to discard any liquid or solid frac-
`tions separated during work-up until the final product has been isolated and
`adequately characterised.
`Because of the length of time that a complete isolation process often takes, it
`is wise practice, particularly with new syntheses carried out for the first time, to
`monitor the progress of the reaction. Thus the disappearance from a reaction
`mixture of one of the reactants or the build—up of the reaction product, measured
`on small aliquot portions removed at convenient time intervals from the bulk
`reaction mixture, can yield valuable information on the progress of a reaction.
`Usually the former is to be preferred since the physical properties (e.g. spectro-
`scopic information, Chapter 3), chemical reactivity (e.g. characteristic tests of
`functional groups, Section 9.5) and chromatographic behaviour (Section 2.31) of
`
`Petitioners‘ Exhibit 1012, Page 3 of 5
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`Hi
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`Petitioners' Exhibit 1012, Page 3 of 5
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`

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`2.18
`
`PMETIEAL EIHGANIB CHEMISTRY
`
`the reactant, and the influence of solvents or other reactants on the reliability of
`the chosen monitoring processes may be readily checked before the reaction is
`commenced.
`The adoption ofa particular isolation procedure will depend to a large extent
`upon the physical and chemical properties of the product. Some guidelines for
`useful general approaches may however be given with regard to the physical
`state at ambient temperature of the crude mixture resulting from the reaction,
`i.e. whether it is a one-phase (either solid or liquid) or a two-phase (solid/liquid or
`liquid,/liquid‘) system.
`In the case of the one~phase solid system if the organic product is neutral and
`insoluble in water, washing with water may be used to remove soluble impurities
`such as inorganic salts. Alternatively the crude solid may be extracted with a
`suitable organic solvent (Section 2.22), filtered, and the extract washed with
`water. Further washing successively with dilute aqueous acid and dilute
`aqueous alkali removes basic and acidic impurities. Removal of solvent after
`drying (Sections 2.23 and 2.24) leads to the recovery of the purified solid for
`recrystallisation from a suitable solvent (Section 2.20). Continuous extraction of
`the solid (eg. in a Soxhlet apparatus) may be necessary ifthe required product is
`only sparingly soluble in convenient organic solvents.
`if the crude solid product contains the required product in the form of a salt
`(eg. the alkali metal salt ofa phenol) and is therefore water soluble, acidification
`of the aqueous solution (or basification in the case, for example, of amine salts)
`liberates the free acidic compound (or base) which may be recovered by filtra-
`tion or solvent extraction as appropriate.
`The nimpliase liquid system is more frequently encountered since many
`organic reactions are carried out in solution. Direct fractional distillation may
`separate the product, if it is a liquid, from the solvent and other liquid reagents,
`or concentration or cooling may lead to direct crystallisation of the product if
`this is a solid. However,
`it
`is often more appropriate, whether the required
`product is a liquid or solid, to subject the solution to the acid/base extraction
`procedure outlined above and considered in detail on p. 162. This acid/base
`extraction procedure can be done directly if the product is in solution in a water-
`immiscible solvent. A knowledge of the acid—base nature of the product and ofits
`water solubility is necessary to ensure that the appropriate fraction is retained
`for product recovery. In those cases where the reaction solvent is water miscible
`(e.g. methanol, ethanol, dimethylsulphoxide, etc.) it is necessary to remove all or
`most of the solvent by distillation and to dissolve the residue in an excess of a
`water-immiscible solvent before commencing the extraction procedure. The re-
`moval of solvent from fractions obtained by these extraction procedures is these
`days readily effected by the use of a rotary evaporator (p. 185) and this obviates
`the tedium of removal of large volumes of solvent by conventional distillation.
`A crude reaction mixture consisting of two phases is very common. In the case
`of a solid/liquid system, it will of course be necessary to make certain in which
`phase the required product resides. A simple example is where the product may
`have crystallised out from the reaction solvent; the mixture therefore only re-
`quires to be cooled and filtered for the bulk of the product to be isolated. The
`filtrate should then routinely be subjected to suitable concentration or extrac-
`tion procedures to obtain the maximum yield of product.
`Direct filtration would also be employed when the solid consists of unwanted
`reaction products, in which case the filtrate would be treated as the sirigle—phase
`
`132
`
`liquid system above. W.
`admixed with contamint
`mixture is reheated and
`
`Liquirlfliquid two-pita
`suit from the frequent pr
`solvent by pouring it on
`liquid system arises fror
`liminary isolation proce
`relatively high—boiling l
`taminants, involatile ta
`presents no additional r
`and can be treated in at
`
`ties of the required pror
`All
`these prelirninarj
`rarely of high purity; thi
`and spectroscopic methc
`by recrystallisation or St
`distillation under atmos
`solids (Sections 2.26 at
`(Section 2.28). In those C
`yield product of adequa
`graphic procedures (p.
`haviour obtained from
`valuable.
`The final assessment
`
`its physical constants ('5
`those cited in the literat=
`assessed and the structu
`
`and spectroscopic meth
`
`2.19 FILTRATION TI
`
`Filtration of a mixture
`either to isolate a solid i
`impurities or reactants,
`this section the filtratior
`tions is considered in S
`When substantial qu
`liquid, a Buchner funne
`funnel (Fig. 2.43(a)) co.
`flat, perforated porcelai
`cone or fiat rubber rir
`termed a filter flask, Bu
`nected by means of thin
`similar flask or safety
`tubing to a filter pump;
`water pressure may rest
`filtrate. The use of sucti
`more complete rernova
`
`Petitioners‘ Exhibit 1012, Page 4 of 5
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`Petitioners' Exhibit 1012, Page 4 of 5
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`

`
`
`
`in the reliability of
`ore the reaction is
`
`id to a large extent
`ime guidelines for
`rd to the physical
`from the reaction,
`ase (solid/liquid or
`
`luct is neutral and
`soluble impurities
`: extracted with a
`tact washed with
`acid and dilute
`al of solvent after
`
`purified solid for
`uous extraction of
`
`equired product is
`
`the form of a salt
`luble, acidification
`ale, of amine salts)
`:covered by filtra-
`
`tered since many
`ii distillation may
`er liquid reagents,
`i of the product if
`ther the required
`id/base extraction
`32. This acid/base
`)lution in a water-
`product and ofits
`‘action is retained
`t is water miscible
`‘y to remove all or
`3 in an excess of a
`nrocedure. The re-
`arocedures is these
`) and this obviates
`itional distillation.
`-mmon. In the case
`.e certain in which
`
`e the product may
`therefore only re
`.0 be isolated. The
`itration or extrac-
`
`nsists of unwanted
`
`as the single-phase
`
`
`
`EXPEflIMHl'I'll TEEIIHIIIIJES 2.19
`
`liquid system above. Where it is evident that the product has crystallised out
`admixed with contaminating solid material a separation might be effected if the
`mixture is reheated and filtered hot (p. 139).
`Liquid/liquid two—phase systems are often encountered; for example, they re-
`sult from the frequent practice ofquenching a reaction carried out in an organic
`solvent by pouring it on to ice or into dilute acid. A further instance ofa liquid]
`liquid system arises from the use of steam distillation (Section 2.25) as a pre-
`liminary isolation procedure. This is particulalry suitable for the separation of
`relatively high—boiling liquids and steam volatile solids from inorganic con-
`taminants, involatile tars, etc. The subsequent work-up procedure normally
`presents no additional problems since the phases are usually readily separable
`and can be treated in a manner appropriate to the chemical or physical proper-
`ties of the required product by procedures already outlined.
`All
`these preliminary procedures give solid or liquid products which are
`rareiy of high purity; the degree of purity may be checked by chromatographic
`and spectroscopic methods. Purification may often be successfully accomplished
`by recrystallisation or sublimation for solids (Sections 2.20 and 2.21); fractional
`distillation under atmospheric or reduced pressure for liquids or low melting
`solids (Sections 2.26 and 2.27); molecular distiltation for high»boiling liquids
`(Section 2.28). In those cases where the use ofthese traditional methods does not
`yield product of adequate purity, resort must be made to preparative chromato-
`graphic procedures (p. 199). Here a knowledge of the chromatographic be-
`haviour obtained from small-scale trial experiments will be particularly
`valuable.
`
`The final assessment of the purity ofa known product is made on the basis of
`its physical constants (Sections 2.33 to 2.37 and Chapter 3) in comparison with
`those cited in the literature. In the case of a new compound the purity should be
`assessed and the structural identity established by appropriate chromatographic
`and spectroscopic methods.
`
`2.1!!
`
`FILTRATION TECHNIIIUES
`
`Filtration of a mixture after completion of a reaction will often be necessary
`either to isolate a solid product which has separated out or to remove insoluble
`impurities or reactants, in which case the desired product remains in solution. In
`this section the filtration of cold solutions is described; the filtration of hot solu-
`tions is considered in Section 2.20.
`
`When substantial quantities of a solid are to be filtered from suspension in a
`liquid, a Buchner funnel of convenient size is employed. The ordinary Buchner
`funnel (Fig. 2.43(a)) consists of a cylindrical porcelain funnel carrying a fixed,
`fiat, perforated porcelain plate. It is fitted by means of a rubber stopper, rubber
`cone or flat rubber ring into the neck of a thick—walled filtering flask (also
`termed a filter flask, Buchner flask or suction flask) (Fig. 2.43(c)), which is con-
`nected by means of thick-walled rubber tubing (rubber ‘pressure’ tubing) to a
`similar flask or safety bottle, and the latter is attached by rubber ‘pressure’
`tubing to a filter pump; the safety bottle or trap is essential since a sudden fall in
`water pressure may result in the water being sucked back and contaminating the
`filtrate. The use of suction renders rapid filtration possible and also results in a
`more complete removal of the mother-liquor than filtration under atmospheric
`
`Petitioners‘ Exhibit 1012, Page 5 of 5
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`133
`
`Petitioners' Exhibit 1012, Page 5 of 5