KENNETH R. WEBERG
`
`Professor of Chemistry
`
`Um've1'sity of Was/3i72gt072
`
`McGRAW-HILL BOOK COMPANY, WC.
`
`1960
`
`New York
`
`Toronto
`
`London
`
`SteadyMed - Exhibit 1012 - Page 1
`
`SteadyMed - Exhibit 1012 - Page 1
`
`

`
`LABORATORY TECHNIQUE IN ORGANIC CHEMISTRY
`
`Inc‘. Printed
`Copyright © 1960 by the McGraw—Hill Book Company,
`in the United States of America. All rights reserved. This book, or
`para there0f,Inay not be reproduced in any forn1\vkhout pernfisfion
`of the publishers. Lz7b7'a7‘y of Congress Catalog Card Number 59-11950
`IV
`
`70095
`
`THE NIAPLE PRESS COMPANY, YORK, PA.
`
`SteadyMed - Exhibit 1012 - Page 2
`
`SteadyMed - Exhibit 1012 - Page 2
`
`

`
`
`
`Although there are a number of monographs available which deal
`with an aspect of the techniques required in dealing with organic com-
`pounds, there has for some time been no book which gives a brief de-
`scription of most of the important techniques. This book is written in
`an effort to fill this need and is directed mainly to the advanced un-
`dergraduate or beginning graduate student who is about to undertake
`a program of research work.
`Each of the three types of matter, liquids, solids and gases, is con-
`sidered with respect to both its properties and the methods of puri-
`fication. It
`is
`felt
`that an understanding of the properties of the
`substances adds materially to the appreciation of the methods of puri-
`fication. Methods which involve distribution between two phases are
`then considered. Finally, the reaction itself is examined in relation to
`the apparatus and techniques involved.
`the use of the proper
`In organic chemical
`laboratory technique,
`apparatus is important. A drawing of a commonly used piece of equip~
`ment has generally been provided to accompany the description of
`each method. These drawings are for the most part derived from the
`working drawings used in the shops at the University of VVashington,
`and in most cases all important dimensions are given in millimeters.
`In writing a book of this type, it is very diflicult to give credit to
`V
`
`PREFACE
`
`SteadyMed - Exhibit 1012 - Page 3
`
`

`
`amnomdwwna.
`
`5.33%m.S\2§.,m
`
`mmwmammnaamwmsmm5mEwanom£c:uEa:nom8$5camwdmaop.omm
`
`
`
`8255?.:53EacmEcoBSn.<£0?5cwmuannrnawmflv.ram
`
`
`233T691.5mfionmmfisa35EonrmnmmosmomBm:.<nmnrnwnwmsm.
`..:aon?ammo?am:288:39:85omms.5n:<E:w_an%858E.
`
`
`
`13198
`
`
`
`_u:¢.m_n>_.$02.55onTocfim
`
`
`
`n_§:£_.:n_s%.............
`
`fi..¢mcnm.................
`
`nozqmzqm
`
`SteadyMed - Exhibit 1012 - Page 4
`
`
`
`
`wozmamwowan.Umnmnfiwmuaoaom~<_o_mnEmn/<am_5.mmnnmom
`
`
`
`Unsmwnx.?5R._§Haamx.<5:wammmsmm.0223538om18
`mfldnncnaon«dowomanmomma.mmmnnomwaammcamas:5mommum
`
`
`
`
`
`wows.
`
`
`
`m.CEEo>dozomF553..........
`
`No
`
`
`
`wnmnammnflmnnmicanoUwmnEmQo:.m.:.:EaUmmnE»no:.Uwmazmmon
`
`
`
`
`
`
`
`
`
`aoummamOoFB:m.>nnmmmo...<mmcwwfinsn.maoaoaa935.
`
`
`
`
`
`
`
`
`
`E59.Wmmsonmwanmmcnn.mummies“:93:30:.Hvfimm9“3.3-
`
`
`
`
`
`
`
`
`
`_u§n1o..§_mnmnwwdm.Noam_SaE:m.
`
`
`
`
`
`4:
`
`
`
`
`
`m:Sc_:_O3.mSENmao:.waaanaoa.caaaaos.mczasaos.
`
`
`
`
`
`
`
`
`
`WmoJ.mSENwao:.HsacowsmC_..<mSENmmc:.fizflmacz.Ufiiam.
`
`
`
`
`
`Uaazfion.
`
`
`
`v:«.m_n>r903.3%ormoium...
`
`
`
`n_5_22~.mo_Em..............
`
`
`
`
`
`gofiammomma.xfirmnmgongommmmmamHrmnfioanmfl.Oofimoacnm.
`
`
`
`/NmvonHummmmcam.aaasm@058cmmomma.Uanaismumaosom
`
`
`
`
`
`
`
`.SmE:m;mo5mUmwnammmoz.Zwlammwoiaom33258.m.o_cUEn.<.
`
`
`
`
`
`
`
`
`
`?..§_.,E..:.Szonmorfim....‘.......
`
`om
`
`
`
`
`
`no:Siamw&%&wunmmmcam.EofinimnUmmmzmaos.mam»?
`
`
`
`
`
`
`
`SteadyMed - Exhibit 1012 - Page 4
`
`
`

`
`
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`Vacuum Lines. Pumping System. Vacuum Manifold. Toepler
`Pump. Stopcoclts
`and Lubricants. Simple Distillation. Frac-
`tional
`l)istillation. Diffusion. Purification of Gases by Chemical
`Methods.
`
`Chapter 4. Adsorption and Extraction
`Ansoru>T1oN
`.
`.
`.
`.
`.
`.
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`149
`149
`
`Distribution between Liquid and Solid Phases. Adsorbents.
`Standardization of Adsorbents. Effect of the Structure of the
`
`Solute on the Degree of Adsorption. Batchwise Adsorption and
`l)ecolori7.ation. Chromatography. Advantages and Limitations
`of Chromatography. Partition Chromatography and Paper
`Chromatography. Vapor-phase Chromatography.
`Ion Exchange.
`l£x'rRAc'rzoN.................179
`
`Simple Extraction. Continuous Liquid—Liquid Extraction. Con-
`tinuous Solid-Liquid Extraction. Multiple~contact Pseudoc0unter~
`current Extraction. Countercurrent Extraction.
`
`191
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`Chapter 5. The Reaction
`APPARA'I‘US..................l9l
`
`
`
`Flasks. Condensers. Stirrers and Stirring Motors. Addition of
`Liquids. Addition of Solids. Addition of Gases. Heating and
`Cooling Baths. Vi/ater Separators. Apparatus for Conducting Re-
`actions at High Dilution. Reactions Effecrcd in an Inert Atmos-
`phere. Semimicro Scale Preparations. Thermostats. Hydrogena-
`tion Apparatus. Ultraviolet Light Sources.
`PURIFICATION or SOLVENTS.
`.
`.
`.
`.
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`240
`
`Chapter 6. Literature of Synthetic Organic Chemistry .
`
`.
`
`.
`
`.
`
`.
`
`253
`
`index
`
`Page 5
`
`viii
`
`Contents
`
`.
`.
`.
`.
`Chapter 3. Gases .
`PHYSICAL PROPERTIES or GAsi.-is.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`.
`.
`
`1220
`120
`
`Pressure. Vapor Density. Heat Capacity and Thermal C0n~
`tluctivity.
`Pt'Rnr1t:AT1oN or Gases .
`
`.
`
`.
`
`129
`
`SteadyMed - Exhibit 1012 - Page 5
`
`

`
`Lcxborcxiory Technique in Organic Chemistry
`l l 2
`ing homogeneity, particularly of natural products. If the material is
`fractionally crystallized, giving perhaps 8 to 10 fractions from the
`head fraction to the tail fraction (8 to 10 layers), and if these fractions
`are compared and found to be identical, it is reasonable to assume that
`the material ishomogeneous.
`’
`The alembic shown in Fig. 2-21 is particularly useful in fractional
`crystallization, since it permits convenient adjustment of the amount
`of- solvent and prevents loss of solvent during the prolonged refluxing
`sometimes required to bring the material into solution.
`
`Precipitation
`
`In some cases, the most convenient method for the purification of a
`solid consists in precipitating it from a solution in which it is con-
`tained as a derivative. A typical example is the purification of a water:
`insoluble solid carboxylic acid by dissolving it in sodium hydroxide
`solution, filtering, and precipitating the compound by the addition of
`acid. A similar procedure may be used with amines: dissolve the com-
`pound in acid and precipitate it with a base. These procedures usually
`vvork quite well in that they utilize a chemical reaction to aid in sep-
`aration frorn nonacidic or nonbasic impurities.
`Another method of precipitation involves precipitating\-. the com-
`pound as a derivative and then converting the derivative back to the
`original compound. An example of this is to dissolve an amine in ether,
`precipitate it as the hydrochloride by passing in hydrogen chloride,
`and convert the hydrochloride back to the amine with sodium hydrox~
`ide solution. Again,
`this method is useful because it involves separa-
`tion through the use of a reaction.
`_
`V
`One method of precipitation which is usually relatively unsuccessful
`involves dissolving the compound in one solvent and precipitating by
`the addition of -another solvent in which it is insoluble. This procedure
`usually leads to coprecipitation and relatively little purification. If two
`solvents are to be used, the compound should be recrystallized from
`a"rnixture of-the two solvents as described in the preceding section.
`
`Distillation
`
`If the compound is relatively impure, crystallization usually entails
`considerable loss of material, and several recrystallizations are re~
`quired to effect complete purification. The procedure often may be
`
`SteadyMed - Exhibit 1012 - Page 6
`
`SteadyMed - Exhibit 1012 - Page 6