`
`
`
`PURIFICATION
`OF LABORATORY
`CHEMICALS
`
`FOURTH EDITION
`
`
`
`
`
`
` _Argentum EX1031 '
`
`
`
`
`
`Argentum EX1031
`
`Rage 1
`
`Page 1
`
`

`

`PURIFICATION
`0 F
`LABORATORY
`CHEMICALS
`
`Fourth Edition
`
`W.L.F Armarego
`I\
`Pteridine Biochemistry Laboratory
`Protein Biochemistry Group
`Division of Biochemistry & Molecular Biology
`The John Curtin School of Medical Research
`Australian National University, Canberra
`A.C.T
`
`And
`
`D.D Perrin
`Formerly of the Medical Chemistry Group
`Australian National University, Canberra
`A.C.T
`
`: UTTERWORTH
`EINEMANN
`
`Page 2
`
`

`

`Butterworth-Heinemann
`Linacre House, Jordan Hill, Oxford OX2 8DP
`A division of Reed Educational and Professional Publishing Ltd
`
`&A member of the Reed Elsevier pk group
`
`OXFORD BOSTON JOHANNESBURG
`_ fELBOURNE NEW DELHI SINGAPORE
`
`© First published 1996
`
`Reed Educational and Professional Publishing Ltd 1996
`
`All rights resereved. No part of this publication
`may be reproduced in any material form (including
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`and whether or not transiently or incidentally
`to some other use of this publication) without the
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`with the provisions of the Copyright, Designs and Patents Act 1988
`or under the terms of a licence issued by the Copyright Licensing
`Agency Ltd, 90 Tottenham Court Road, London, England WlP 9HE.
`Applications for the copyright holder's written permission
`to reproduce any part of this publication should be addressed
`io the publishers.
`
`British Library Cataloguing in Publication Data
`A catalogue record for this book is available from the British Library
`
`ISB1 0 7506 2839 1
`
`Library of Cong:l"e$ Cataloguing in Publication Data
`A catalogue record for this book is available from the Library of Congress
`
`B
`Printed and bound in Great Britain by The Bath p
`ress, ath
`
`t+-/ q+I ~
`
`Page 3
`
`

`

`-
`
`CONTENTS
`
`Preface to Fourth Edition ............................................................................................................... ix
`
`Preface to First Edition .................................................................................................................. x
`
`Preface to Second Edition ............................................................................................................... x
`
`Preface to the Third Edition ............................................................................................................ xi
`
`CHAPTER 1
`COMMON PHYSICAL TECHNIQUES USED IN PURIFICATION ................................... l
`
`GENERAL REMARKS ................................................................................................................ l
`Abbreviations ................................................................................................................ l
`Purity of Substances ....................................................................................................... 2
`Safety in the Chemical Laboratory ..................................................................................... 3
`Trace Impurities in Solvents ............................................................................................. 4
`Cleaning Apparatus ......................................................................................................... 4
`Sililation of Glassware and Plasticware ............................................................................... 5
`
`DISTILLATION ........................................................................................................................... 5
`Techniques .................................................................................................................... 6
`Distillation at Atmospheric Pressure .................................................................................. 7
`The distilling flask ....................................................................................... 7
`Types of columns and packings ...................................................................... 7
`Condensers ................................................................................................. 8
`
`VACUUM DISTILLATION .......................................................................................................... 9
`Kiigelrohr Distillation ................................................................................................... l 0
`Vacuum-lines, Schlenk and Glovebox Techniques ............................................................... 10
`Spinning-band Columns ................................................................................................ 10
`
`STEAM DISTILLATION ............................................................................................................ 10
`
`AZEOTROPIC DISTILLATION .................................................................................................. 11
`
`ISOPIESTIC OR ISOTHERMAL DISTILLATION ....................................................................... 11
`
`SUBLIMATION ......................................................................................................................... 12
`
`RECRYSTALLISATION ............................................................................................................. 12
`Techniques .................................................................................................................. 12
`Filtration .................................................................................................................... 13
`Choice of Solvents ....................................................................................................... 13
`Mixed Solvents ............................................................................................................ 14
`Recrystallisation from the Melt ....................................................................................... 14
`Zone Refining .............................................................................................................. 15
`V
`
`Page 4
`
`

`

`12
`
`Common Physical Techniques
`
`in Purification
`
`·
`t r 1·s sealed and left to stand at room temperature for
`. .
`.
`d
`·
`tor The es1cca o
`d
`the material to be punf1ed, m a esicca . · .
`th
`1 s between the two beakers whereas the non-volatile
`·1
`nts d1stnbute emse ve
`several days. The volau e compone
`.
`.
`h .
`has afforded metal-free pure solutions of ammonia,
`contaminants remain in the original beaker. This tee mque
`hydrochloric acid and hydrogen fluoride.
`
`SUBLIMATION
`
`. -
`·
`b
`use the vapour condenses to a solid instead of a liquid.
`.
`.
`"ff
`f
`d. ary d1su at10n eca
`11
`Subhmat10n d1 ers rom or m
`.
`. d.
`. ·shed by pumping and the vapour 1s condensed (after
`·
`th heated system 1s 1mm1
`'
`Usually, the pressure m
`e
`Id fi ger or some other cooled surface. 1bis technique, which is
`I u·
`.
`I hort distance) on to a co m
`travelling a re a ve Y s
`. .
`.
`.
`.
`al
`b
`sed with inorganic solids such as alummrnm chlonde,
`· bl
`amc sohds can
`so e u
`apphca e to many org
`In some cases passage of a stream of inert gas over the heated
`.d ' d . di
`ammonium chloride, arsenious ox1 e an 10 ne.
`,
`substance secures adequate vaporisation.
`
`RE CRY ST ALLISA TION
`
`Techniques
`The most common y use proce ure
`d
`d
`1
`involves the following steps:
`
`.
`· b
`all.
`·
`fr
`for the purification of a sohd matenal y recryst 1sat1on om a so uuon
`1 ·
`
`(a) The impure material is dissolved in a suitable solvent, by shaking or vigorous stirring, at or near the
`boiling point, to form a near-saturated solution.
`.
`.
`.
`.
`(b) The hot solution is filtered to remove any insoluble particles. To ?revent crystalhsat10n ~unng t~s
`filtration, a heated Uacketed) filter funnel can be used or the solution can be somewhat diluted with
`more of the solvent.
`(c) The solution is then allowed to cool so that the dissolved substance crystallises out.
`.
`(d) The crystals are separated from the mother liquor, either by centrifuging or by filtering, under suction,
`through a sintered glass, a Hirsch or a Buchner, funnel. Usually, centrifuging is much preferred
`because of the much greater ease and efficiency of separating crystals and mother liquor, and also
`because of the saving of time and effort, particularly when very small crystals are formed or when
`there is entrainment of solvent.
`(e) The crystals are washed free from mother liquor with a little fresh cold solvent, then dried.
`If the solution contains extraneous coloured material likely to contaminate the crystals, this can often be removed by
`adding some activated charcoal (decolorising carbon) to the hot, but not boiling, solution which is then shaken
`frequently for several minutes before being filtered. (The large active surface of the carbon makes it a good adsorbent
`for this purpose.) In general, the cooling and crystallisation step should be rapid so as to give small crystals which
`occlude less of the mother liquor. This is usually satisfactory with inorganic material, so that commonly the filtrate is
`cooled in an ice-water bath while being vigorously stirred. In many cases, however, organic molecules crystallise
`much more slowly, so that the filtrate must be set aside to cool to room temperature or left in the refrigerator. It is
`often desirable to subject material that is very impure to preliminary purification, such as steam distillation, Soxhlet
`extraction, or sublimation, before recrystallising it. A greater degree of purity is also to be expected if the
`crystallisation process is repeated several times, especially if different solvents are used. The advantage of several
`cry~tallisations_ '.rom different solvents lies in the fact that the material sought, and its impurities, are unlikely to have
`s1trular solub1ht1es as solvents and temperatures are varied.
`For the final separation_ of solid material, _sintered-glass discs are preferable to filter paper. Sintered glass is unaffected
`?Y strong_ly acid solut10ns or by ox1d1smg agents. Also, with filter paper, cellulose fibres are likely to become
`mcluded m _the sample, The sintere_d-glass discs or funnels can be readily cleaned by washing in freshly prepar_ed
`chr~m1c acid cleaning mlXture. This mixture 1s made by adding 100ml of concentrated sulphuric acid slowly with
`stJmng to _a solu~10n of ~g of s~dium dichromate in 5ml of water. (The mixture warms to about 700).
`For matenals with meltmg pomts below 70° it is sometimes convenient to use dilute solutions in acetone, methanol,
`pentane, ethyl ether or CHClrCC14. The solutions are cooled to -780 in Dry-ice, to give a filtrable slurry which is
`filter~d off through a precooled Buchner funnel. Experimental details, as applied to the purification of nitromethane,
`are given by Parrett and Sun [J Chem Educ 54 448 1977].
`W~ere substances vary little in solubility with temperature, isothermal crystallisation may sometimes be employed.
`This usually takes the form of a partial eva
`pora ion ° a saturated solution at room temperature by leavmg 11 un er
`t·
`f
`·
`.
`.
`·
`·
`d
`reduced pressure m a desiccator.
`Howevl er,hin rare_ cases, crystall!sation is not a satisfactory method of purification especially if the impurity forms
`crysta s t at are 1somorphous with the materi I b ·
`·f·
`'
`a emg pun 1ed. In fact, the impurity content may even be greater m
`·
`
`Page 5
`
`

`

`Common Physical Techniques in Purification
`
`13
`
`such recrystallised ~aterial. F~r this rea~on, it still remains necessary to test for impurities and to remove or
`adequately lower their concentrations by suitable chemical manipulation prior to recrystallisation.
`
`Filtration
`Filtration removes particulate impurities rapidly from liquids and is also used to collect insoluble or crystalline
`solids which separate or crystallise from solution. The usual technique is to pass the solution, cold or hot,
`through a fluted filter paper in a conical glass funnel (see Vogel's Textbook of Practical Organic Chemistry, p
`46).
`
`If a solution is hot and needs to be filtered rapidly a Buchner funnel and flask are used and filtration is performed under a
`slight vacuum (water pump), the filter medium being a circular cellulose filter paper wet with solvent. If filtration is
`slow, even under high vacuum, a pile of about twenty filter papers, wet as before, are placed in the Buchner funnel and,
`as the flow of solution slows down, the upper layers of the filter paper are progressively removed. Alternatively, a
`filter aid, e.g. Celite, Florisil or Hyflo-supercel, is placed on top of a filter paper in the funnel. When the flow of the
`solution (under suction) slows down the upper surface of the filter aid is scratched gently. Filter papers with various
`pore sizes are available covering a range of filtration rates. Hardened filter papers are slow filtering but they can
`withstand acidic and alkaline solutions without appreciable hydrolysis of the cellulose (see Table 3). When using
`strong acids it is preferable to use glass micro fibre filters which are commercially available (see Table 3).
`Freeing a solution from extremely small particles (e.g. for ORD or CD measurements) requires filters with very small
`pore size. Commercially available (Millipore, Gelman, Nucleopore) filters other than cellulose or glass include nylon,
`Teflon, and polyvinyl chloride, and the pore diameter may be as small as 0.01 micron (see Table 4). Special containers
`are used to hold the filters, through which the solution is pressed by applying pressure, e.g. from a syringe. Some of
`these filters can be used to clear strong sulphuric acid solutions .
`As an alternative to the Buchner funnel for collecting crystalline solids, a funnel with a sintered glass-plate under
`suction may be used. Sintered-glass funnels with various porosities are commercially available and can easily cleaned
`with warm chromic or nitric acid (see above).
`
`When the solid particles are too fine to be collected on a filter funnel because filtration is extremely slow,
`separation by centrifugation should be used. Bench type centrifuges are most convenient for this purpose.
`The solid is placed in the centrifuge tube, the tubes containing the solutions on opposite sides of the rotor
`should be balanced accurately (at least within 0.05 to O. lg), and the solutions are spun at maximum speed for as
`long as it takes to settle the solid (usually ca 3-5 minutes). The solid is washed with cold solvent by
`centrifugation, and finally twice with a pure volatile solvent in which the solid is insoluble, also by
`centrifugation. After decanting the supernatant the residue is dried in a vacuum, at elevated temperatures if
`necessary. In order to avoid "spitting" and contamination with dust while the solid in the centrifuge tube is
`dried, the mouth of the tube is covered with silver paper and held fast with a tight rubber band near the lip. The
`flat surface of the silver paper is then perforated in several places with a pin.
`
`Choice of Solvents
`The best solvents for recrystallisation have the following properties:
`(a) The material is much more soluble at higher temperatures than it is at room temperature or below.
`(b) Well-formed (but not large) crystals are produced.
`(c) Impurities are either very soluble or only sparingly soluble.
`(d) The solvent must be readily removed from the purified material.
`(e) There must be no reaction between the solvent and the substance being purified.
`(f) The solvent must not be inconveniently volatile or too highly flammable. (These are reasons why
`ethyl ether and carbon disulphide are not commonly used in this way.)
`
`The following generalisations provide a rough guide to the selection of a suitable solvent:
`(a) Substances usually dissolve best in solvents to which they are most closely related in chemical and
`physical characteristics. Thus, hydroxylic compounds are likely to be most soluble in water,
`methanol, ethanol, acetic acid or acetone. Similarly, petroleum ether might be used with water(cid:173)
`insoluble substances. However, if the resemblance is too close, solubilities may become excessive.
`(b) Higher members of homologous series approximate more and more closely to their parent
`hydrocarbon.
`(c) Polar substances are more soluble in polar, than in non-polar, solvents.
`
`Page 6
`
`

`

`1
`
`p
`
`icaJ Techniques in Purification
`
`-
`
`0 e oh·ent and too insoluble in another, for either to be used for
`·ded the are miscible) to use them as a mixed solvent. (In general,
`e eo sol e t if this is practicable.) Table 6 contains many of the common
`a mixed solvent is as follows:
`hich it is the more soluble, then the other solvent (heated to near
`·on until a slight turbidity persists or crystallisation begins. This is
`t solvent, and the solution is allowed to cool and crystallise in the
`I; 0 precipitate the material in a microcrystalline f~rrn from s_olutio~ in
`,
`addi g a little more of the second solvent, filtering this off, ad~1~g ~ httle
`rcpeaung the process. This ensures, at least in the first or last prec1p1tatJon, a
`e as {Xl'SSi le of the impurities which may also be precipitated in this way. With
`at.er, and the second solvent is alcohol or acetone.
`
`e . 1elt
`its te perature is raised sufficiently for the thermal agitation of its molecules or
`re
`· posed y the crystal lattice. Usually, impurities weaken crystal structures,
`el · g po· ts of solids (or the freezing points of liquids). If an impure material is melted
`if necessary, of a trace of solid material near the freezing point to avoid
`o
`e firs ens
`- that form will usually contain less of the impurity, so that fractional
`partial freeri:ig can be used as a purification process for solids with melting points lying in a
`temperature ra.::ige (or more readily frozen liquids). In some cases, impurities form higher melting
`be
`"fied, so that the first material to solidify is less pure than the melt. For this
`le to discard the first crystals and also the final portions of the melt. Substances
`· g similar bot g
`· ts ofte differ much more m melting points, so that fractional solidification can offer
`real adv
`tages, especially here ultrapurity is sought
`The tee
`e of rCCI) stallis o
`ro
`e melt as a means of purification dates back from its use by Schwab and
`J Res 'a1 Bw Stand 25 - ~,, J "0 to punfy benzoic acid. It works best if material is already nearly pure, and
`to be a fi
`·fica o step. A simple apparatus for purifying organic compounds by progressive
`freezing 1s described
`·as
`Coggeshall AC 31 1124 1959). In principle, the molten substance is cooled
`sl
`I_ y progressi e o eri g of e tube containing it into a suitable bath. For temperatures between 0° and 100°,
`are co eme .
`aterl, •
`'here lo er temperatures are required, the cooling baths given in Table 7 can be used.
`Coo · g is stopped hen pan of lhe melt has solidified, and the liquid phase is drained off. Column crystallisation has
`bee used to p..rify s earyl alco ol, ceryl alcohol, myristic acid; fluorene, phenanthrene, biphenyl, terphenyls,
`dibenzyI: p enol, 2-:iap t ol; be zop enone and 2,4-dinitrotoluene; and many other organic (and inorganic)
`co,u,,....,""'""-
`[See, for ex p e, Devdopmmts in Separation Science
`. .Lee (ed), CRC Press, Cleveland, Ohio,
`/972]. Th • an increase ·
`·ry from 99.80 to 99.98 mole% was obtained when acetarnide was slowly crystallised in
`an
`ated r
`botto
`fl
`· half the material had solidified and the solid phase was then recrystallised from
`benzene {Sc
`and
`icbers J Res at Bur Stand 32 253 1944].
`Fracuonal solidificatio and its applications to obtammg ultrapure chemical substances has been treated in detail in
`Fractional Solidification
`LZief and R.Wilcox eds, Edward Arnold Inc Lond~n )967 and Purification of
`Inorganic and ~rg~ic Materials . Y • tZief, Marcel Dekker Inc, ew York /969. These m~nographs should be
`c
`lted for di~s10_ of the basic pnnciples of s~lid-liquid processes such as zone melting, progressive freezing
`and colu
`crystzlhsano
`laboratory apparatus and industrial scale equipment, and examples of applications. These
`incl de lhe remo al of cyclobexane from benzene, and the purification of aromatic amines, dienes and naphthalene,
`
`Page 7
`
`

`

`Common Physical Techniques in Purification
`
`15
`
`and inorganic _species such_ as the alkali iodides, potassium chloride, indium antimonide and gallium trichloride. The
`authors also discuss analytical methods for assessing the purity of the final material.
`Zone Refining
`Zone refining ( or zone melting) is a particular development for fractional solidification and is applicable to all
`crystalline substances that show differences in soluble impurity concentration in liquid and solid states at
`solidification. The apparatus used in this technique consists essentially of a device by which a narrow molten
`zone moves slowly down a long tube filled with the material to be purified. The machine can be set to recycle
`repeatedly. At its advancing side, the zone has a melting interface with the impure material whereas on the
`upper surface of the zone there is a constantly growing face of higher-melting, resolidified material. This leads
`to a progressive increase in impurity in the liquid phase which, at the end of the run, is discarded. Also, because
`of the progressive increase in impurity in the liquid phase, the resolidified material becomes correspondingly less
`further purified. For this reason, it is usually necessary to make several zone-melting runs before a sample is
`satisfactorily purified. This is also why the method works most successfully if the material is already fairly
`pure. In all these operations the zone must travel slowly enough to enable impurities to diffuse or be convected
`away from the area where resolidification is occurring.
`The technique finds commercial application in the production of metals of extremely high purity (impurities down to
`l o-9 ppm), in purifying refractory oxides, and in purifying organic compounds, using commercially available
`equipment. Criteria for indicating that definite purification is achieved include elevation of melting point, removal of
`colour, fluorescence or smell, and a lowering of electrical conductivity. Difficulties likely to be met with in organic
`compounds, especially those of low melting points and low rates of crystallisation, are supercooling and, because of
`surface tension and contraction, the tendency of the molten zone to seep back into the recrystallised areas. The method
`is likely to be useful in cases where fractional distillation is not practicable, either because of unfavourable vapour
`pressures or ease of decomposition, or where super-pure materials are required. It has been used for the latter purpose
`with anthracene, benzoic acid, chrysene, morphine and pyrene.
`(See references on p. 47).
`
`DRYING
`
`Removal of Solvents
`Where substances are sufficiently stable, removal of solvent from recrystallised materials presents no problems. The
`crystals, after filtering at the pump (and perhaps air-drying by suction), are heated in an oven above the boiling point
`of the solvent (but below their melting point), followed by cooling in a desiccator. Where this treatment is
`inadvisable, it is still often possible to heat to a lower temperature under reduced pressure, for example in an
`Abderhalden pistol. This device consists of a small chamber which is heated externally by the vapour of a boiling
`solvent. Inside this chamber, which can be evacuated by a water pump or some other vacuum pump, is placed a small
`boat containing the sample to be dried and also a receptacle with a suitable drying agent. Convenient liquids for use as
`boiling liquids in an Abderhalden pistol, and their temperatures, are given in Table 9. In cases where heating above
`room temperature cannot be used, drying must be carried out in a vacuum desiccator containing suitable absorbants.
`For example, hydrocarbons, such as benzene, cyclohexane and petroleum ether, can be removed by using shredded
`paraffin wax, and acetic acid and other acids can be absorbed by pellets of sodium, or potassium, hydroxide. However,
`in general, solvent removal is less of a problem than ensuring that the water content of solids and liquids is reduced
`below an acceptable level.
`
`Removal of Water
`Methods for removing water from solids depends on the thermal stability of the solids or the time available. The safest
`way is to dry in a vacuum desiccator over concentrated sulphuric acid, phosphorus pentoxide, silica gel, calcium
`chloride, or some other desiccant. Where substances are stable in air and melt above l 00° drying in an air oven may be
`adequate. In other cases, use of an Abderhalden pistol may be satisfactory.
`Often, in drying inorganic salts, the final material that is required is a hydrate. In such cases, the purified substance is
`left in a desiccator to equilibrate above an aqueous solution having a suitable water-vapour pressure. A convenient
`range of solutions used in this way is given in Table 10.
`.
`.
`The choice of desiccants for drying liquids is more restricted because of the need to avoid all substances hkely to react
`with the liquids themselves. In some cases, direct distillation of an organic liquid i~ a suitable method f~r drying both
`solids and liquids, especially if low-boiling azeotropes are formed. Examples mclu_de acetone, amhne, benzene,
`chloroform, carbon tetrachloride, ethylene dichloride, heptane, hexane, methanol, mtrobenzene, petroleum ether,
`toluene and xylene. Addition of benzene can be used for drying ethan_ol by distillation. In_ c_arrying ?ut distill~tions
`intended to yield anhydrous products, the apparatus should be fitted with guard-tubes co~tam!ng_ calcium chlon~e or
`silica gel to prevent entry of moist air into the system.
`(Many anhydrous organic hqu1ds are appreciably
`hygroscopic).
`
`Page 8
`
`

`

`Common Physical Techniques in Purification
`
`35
`
`TABLE 5.
`
`COMMON SOLVENTS USED IN RECRYSTALLISATION
`(and their boiling points)
`
`Acetic acid ( 118°)
`*Acetone (56°)
`Acetylacetone (139°)
`*Benzene (800)
`Benzyl alcohol (93°110mm)
`n-Butanol (118°)
`Butyl acetate (126.5°)
`n-Butyl ether (142°)
`y-Butyrolactone (206°)
`Carbon tetrachloride (77°)
`Cellosolve ( 135°)
`Chlorobenzene (132°)
`Chloroform (61°)
`
`*Cyclohexane (81 °)
`Methyl cyanide (82°)
`Diethyl cellosolve (121°)
`Methylene chloride (41°)
`*Diethyl ether (34.5°)
`*Methyl ethyl ketone (80°)
`Dimethyl forrnamide (76°139mm)
`Methyl isobutyl ketone (116°)
`*Dioxane (101 °)
`Nitrobenzene (210°)
`*Ethanol (78°)
`Nitromethane (101 °)
`*Ethyl acetate (78°)
`*Petroleum ether (various)
`Ethyl benzoate (98°119mm)
`Pyridine (115.5°)
`Ethylene glycol (68°14mm)
`Pyridine trihydrate (93°)
`Forrnamide (110°110mm)
`*Tetrahydrofuran (64-66°)
`Glycerol (126°/l Imm)
`Toluene (1100)
`Isoamyl alcohol (131 °)
`Trimethylene glycol (59°/11mm)
`*Methanol (64.5°)
`Water(lOOO)
`*Highly flammable, should be heated or evaporated on steam or electrically heated water
`baths only (preferably in a nitrogen atmosphere).
`
`TABLE 6.
`
`PAIRS OF MISCIBLE SOLVENTS
`
`Acetic acid: with chloroform, ethanol, ethyl acetate, methyl cyanide, petroleum ether, or water.
`Acetone: with benzene, butyl acetate, butyl alcohol, carbon tetrachloride, chloroform, cyclohexane, ethanol,
`ethyl acetate, methyl acetate, methyl cyanide, petroleum ether or water.
`Ammonia: with ethanol, methanol, pyridine.
`Aniline: with acetone, benzene, carbon tetrachloride, ethyl ether, n-heptane, methanol, methyl cyanide or
`ni trobenzene.
`Benzene: with acetone, butyl alcohol, carbon tetrachloride, chloroform, cyclohexane, ethanol, methyl
`cyanide, petroleum ether or pyridine.
`Butyl alcohol: with acetone or ethyl acetate.
`Carbon disulphide: with petroleum ether.
`Carbon tetrachloride: with cyclohexane.
`Chloroform: with acetic acid, acetone, benzene, ethanol, ethyl acetate, hexane, methanol or pyridine.
`Cyclohexane: with acetone, benzene, carbon tetrachloride, ethanol or ethyl ether.
`Dimethyl formamide: with benzene, ethanol or ether.
`Dimethyl sulphoxide: with acetone, benzene, chloroform, ethanol, ethyl ether or water.
`Dioxane: with benzene, carbon tetrachloride, chloroform, ethanol, ethyl ether, pet. ether, pyridine or water.
`Ethanol: with acetic acid, acetone, benzene, chloroform, cyclohexane, dioxane, ethyl ether, pentane,
`toluene, water or xylene.
`Ethyl acetate: with acetic acid, acetone, butyl alcohol, chloroform, or methanol.
`Ethyl ether: with acetone, cyclohexane, ethanol, methanol, methylal, methyl cyanide, pentane or pet.ether.
`Glycerol: with ethanol, methanol or water.
`Hexane: with benzene, chloroform or ethanol.
`Methanol: with chloroform, ethyl ether, glycerol or water.
`Methylal: with ethyl ether.
`Methyl ethyl ketone: with acetic acid, benzene, ethanol or methanol.
`Nitrobenzene: with aniline, methanol or methyl cyanide.
`Pentane: with ethanol or ethyl ether.
`Petroleum ether: with acetic acid, acetone, benzene, carbon disulphide or ethyl ether.
`Phenol: with carbon tetrachloride, ethanol, ethyl ether or xylene.
`Pyridine: with acetone, ammonia, benzene, chloroform, dioxane, petroleum ether, toluene or water.
`Toluene: with ethanol, ethyl ether or pyridine.
`Water: with acetic acid, acetone, ethanol, methanol, or pyridine.
`Xylene: with ethanol or phenol.
`
`Page 9
`
`

`

`•
`
`60
`
`Chemical Methods used in Purification
`
`. I Th
`h
`I .
`overed by acidification of the aqueous phase with 20% sulphuric acid, and either extracted
`ct· 1·11 t
`e P eno ts rec
`matena
`d f
`·
`h
`t
`f
`·
`.
`·
`ct· -11 d I th second case the phenol 1s extracte
`rom t e s earn
`ts 1 a e a ter saturatmg it with
`with ether or steam 1st1 e · n e
`·
`·
`h
`I
`· fi d Th
`h
`I ·
`sodium chloride. A solvent is necessary when large quantities of hqmd P_ eno s are p~n-ie_ .
`~ p _eno ts f~actionated
`b distillation under reduced pressure, preferably in an a_tmosphere of mtrogen to mm1m1ze ox1d~t1on. Sohd phenols
`11- d f
`y b
`toluene petroleum ether or a mixture of these solvents, and can be subhmed under vacuum
`can e crysta 1se
`rom
`,
`.
`.
`·
`F
`f h
`·fi
`·
`·
`Purification can also be effected by fractional crystalhsat10n or zone refinmg.
`or urt er pun 1cat10n of phenols via
`their acetyl or benzoyl derivatives, see p. 53.
`
`Polypeptides and proteins . See Chapter 5.
`
`Quinones. These are neutral compounds which are usually col?ured. They ca? be sepaz:ated fr~m acidic or basic
`impurities by extraction of their solutions in organic solvents with aqueous basic or a~1d1c solut10n_s, respectively.
`Their colour is a useful property in their purification by chromatography. thro~gh an ~Iumm~ column with, e.g. toluene
`as eluent. They are volatile enough for vacuum sublimation, although w1t_h h1gh-meltmg qumones a very high vacuum
`is necessary. p-Quinones are stable compounds and can be recrystalhsed from wat~r, et~a~ol, aqueous ethanol,
`toluene, petroleum ether or glacial acetic acid. a-Quinones, on the other hand, are readily ox1d1sed. They should be
`handled in an inert atmosphere, preferably in the absence of light.
`
`Salts (organic).
`(a) With metal ions: Water-soluble salts are best purified by preparing a concentrated
`aqueous solution to which, after decolorising with charcoal and filtering, ethanol or acetone is added so that the salts
`crystallise. They are collected, washed with aqueous ethanol or aqueous acetone, and dried. In some cases. water(cid:173)
`soluble salts can be recystallised satisfactorily from alcohols. Water-insoluble salts are purified by Soxhlet
`extraction, first with organic solvents and then with water, to remove soluble contaminants. The purified salt is
`recovered from the thimble.
`
`(b) With organic ions: Organic salts (e.g. trimethylammonium benzoate) are usually purified by
`recrystallisation from polar solvents (e.g. water, ethanol or dimethyl formamide). If the salt is too soluble in a polar
`solvent, its concentrated solution should be treated dropwise with a miscible nonpolar solvent (see p. 14) until
`crystallisation begins.
`
`(c) Sodium alkane disulphonates: Purified from sulphites by boiling with aq HBr. Purified from
`sulphates by adding BaBr2. Sodium alkane disulphonates are finally pptd by addition of MeOH. [Pethybridge and Taba
`JCSFT 118 1331 1982] .
`
`Sulphur _compom_ids.
`(a) Disulphides can be purified by extracting acidic and basic impurities with aqueous
`base or acid, respecuv_ely. However, they are somewhat sensitive to strong alkali which slowly cleaves the disulphide
`bond. The lower-meltmg members can be fractionally distilled under vacuum. The hi