ORCAandMiniscal
`RGANIC CHEMISTRY
`
`nyExperiments
`
`‘Allen. Schoffstall
`BarbaraA. Gaddis
`MelvinL. Druelinger
`
`a .
`SecondEdition
`
`
`
`
`
`Liquidia - Exhibit 1011 - Page 1
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`Liquidia - Exhibit 1011 - Page 1
`
`

`

`
`
`200
`Chapter Three=Applications Using Laboratory Resources and Tkechniques
`
`Tech
`Te
`Tei
`Te
`
`Back
`A wate:
`easily ¢
`soluble
`
`Ne
`can the
`insolub
`
`*
`
`A
`insoluk
`to awa
`
`
`
`Neutra.
`they ca
`the amj
`extract:
`
`Th
`drying
`" Yating ¢
`In
`(ethy]
`(ethyl.
`ene ch
`Fr
`Haphth;
`
`Results and Conclusionsfor Part B
`1. Calculate the percent recovery for the recrystallization process. Explain whyit is
`not 100%.
`2, Explain and evaluate the effectiveness of the recrystallization solvent in terms of
`percent recovery andpurity of the recrystallized solid.
`3. Suggest other solvents or solvent pairs that might have been usedforthis recrys-
`tallization.
`.
`
`Cleanup & Disposal
`Place the solvents used for recrystallization in a container labeled “nonhalogenated
`organic solvent waste.” Aqueoussolutions can be washed downthe drain with water.
`
`
`Critical Thinking Questions (The harder one is marked with a +)
`J. List the main criteria for selecting a recrystallization solvent.
`Whenis it necessary to use a solvent-pair recrystallization?
`Whyshould the recrystallization solvent have a fairly low boiling point?
`
`ewKN Will the followingpairs of solvents be suitable for doing a solvent-pair recrystal-
`
`5.
`
`lization? Explain.
`a,
`ethanol (bp 78.5°C)} and water
`b. methylene chloride (bp 40°C) and water
`ce.
`dimethylformamide (bp 153°C) anddiethyl ether (bp 37°C)
`Ifa solute is solubie in cold solvent,is it necessary to test the solubility of the
`solute in the same solvent when hot? Explain.
`6, Arrange the following solvents in order of increasing polarity: ethanol, ethyl
`acetate, petroleum ether, toluene, and acetone.
`7. Methylene chloride (CH,CI,) is polar, whereas carbon tetrachloride (CC1,) is non-
`polar. Explain.
`8. Carbon disulfide (CS.) is sometimes used as a recrystailization solvent. Will this
`solvent dissolve polar or nonpolar compounds? Explain.
`
`4&
`
`+
`
`Experiment 3.5: Separations Based upon Acidity
`and Basicity _
`Extraction is a technique in whicha soluteistransferred from one solventto another, In
`this experiment, you will investigate acid-base extraction, You will:
`+
`determinethe solubilities of an organic acid, an organic base, and a neutral organic
`compound,
`design a flow schemeto separate an organic acid, an organic base, and a neutral
`compound,
`use microscale extraction techniques to separate and isolate each component of a
`mixture of naphthaiene, benzoic acid, and ethyl 4-aminobenzoate,
`use miniscale extraction techniquesto separate and isolate a mixture of benzoic
`acid and ethyl 4-aminobenzoate,
`
`*
`
`*
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`Liquidia - Exhibit 1011 - Page 2
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`Liquidia - Exhibit 1011 - Page 2
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`

`

`Experiment 3.5
`
`Separations Based upon Acidity and Basicity
`
`201
`
`7hy it is
`
`erms of
`
`recrys-
`
`scrystal-
`
`y of the
`
`a1, ethyl
`
`) is non-
`
`Will this
`
`\other. In
`
`_ organic
`
`‘utral
`
`mnt of a
`
`nzoic
`
`Techniques
`Technique C
`Technique F
`Technique I
`
`Melting point
`Vacuum filtration,
`Drying and extraction
`
`Background
`A water-insoluble, acidic organic compound such as a carboxylic acid or phenol can be
`easily separated from neutral and basic organic compounds by conversion to a water-
`soluble salt.
`
`Oo
`oO
`‘I
`II
`RCO-H + NaOH ——> RCONa* + HO
`
`a water-insoluble
`carboxylic acid
`
`a water-soluble
`carboxylate salt
`
`Neutral and basic organic compounds remain in the organic layer. The two layers
`can then be separated. Addition of HC] to the aqueous layer regenerates the water-
`insoluble carboxylic acid, which can then befiltered or extracted into an organic solvent:
`Oo
`Oo
`ll
`il
`RCO-Na* + HCl ——> RCO-H + Natl
`
`a water-soluble
`carboxylate salt
`
`a water-insoluble
`carboxylic acid
`
`A similar scheme can be used to separate a basic compound, such as a water-
`insoluble amine, from neutral or acidic organic compounds by conversion of the amine
`to a water-solublesalt:
`
`RNH, + HCl ——->» RNH,*Cr
`
`a water-insoluble
`amine
`
`a water-soluble
`ammonium salt
`
`Neutral compoundsandacidic organic compounds remain in the organic solvent, where
`they can be removed. Addition of sodium hydroxide to the aqueouslayer regenerates
`the amine, which is now insoluble in the aqueous solution. The amine can befiltered or
`extracted into an organic solvent.
`
`RNH;*Cr
`
`+ NaOH ——> ANH, + Nati
`
`a water-soluble
`ammonium salt
`
`a water-insoluble
`amine
`
`-
`
`The neutral compound remains in the organic solvent, where it can be recovered by
`drying the sohition to remove traces of water, filtering off the drying agent, and evapo-
`. Tating the solvent.
`In this exercise, the solubilities of an organic acid (benzoic acid), an organic base
`_ (ethyl 4-aminobenzoate), a neutral compound (naphthalene), and the organicsalts
`_- (ethyl 4-aminobenzoate hydrochloride and sodium benzoate} will be tested in methyl-
`--
`€ne chloride and water.
`From the solubilities, you will construct a flow scheme outlining the separation of
`- Tlaphthalene, benzoic acid, and ethyl 4-aminobenzoate. In Part B, you will use the flow
`
`
`
`
`
`Liquidia - Exhibit 1011 - Page 3
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`Liquidia - Exhibit 1011 - Page 3
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`

`

`
`
`202 Chapter Three=Applications Using Laboratory Resources and Techniques
`
`scheme to separate a mixture of naphthalene, benzoic acid, and ethyl 4-aminobenzoate
`in microscale. in Part C, you will use the flow scheme to separate a mixture of benzoic
`acid and ethyl 4-aminobenzoate in miniscale.
`
`CO.H
`
`CO; Nat
`
`NH
`
`NH," Clo
`
`naphthalene
`
`benzoic acid
`
`sodium
`benzoate
`
`GO,CH,CH,
`ethyl 4-amino-
`benzoate
`
`COsCH,CH,
`ethyl 4-amino-
`benzoate hydrochloride
`
`The instructor may substitute other compounds for those shown here.
`
`not ne
`
`Prelab Assignment
`
`spate]
`chlori
`|
`priate
`|
`notal
`|
`seeif
`|
`the co
`|
`is part
`
`
`
`|.
`
`Pe
`
`1. -Read Technique I on the theory and technique of extraction and do all assigned
`problems.
`2, Construct a solubility table similar to Table 3.5-1 in the experimental section.
`3.
`Identify the conjugate acid/conjugate base pairs for the structures above,
`4. Write the reaction (if any) and give the products for the reaction of each pair of
`reagents below. If no reaction occurs, write NR. Indicate whether the product will
`be water-soluble or water-insoluble.
`a.
`benzoic acid with NaOH.
`b.
`sodium benzoate with HCL.
`c.
`ethyl 4-aminobenzoate with HCL.
`d.
`ethyl 4-aminobenzoate hydrochloride with NaOH.
`e.
`naphthalene and NaOH.
`f.
`ethyl 4-aminobenzoate with NaOH.
`5. Determine whethereachof the five compoundsis predominantly jonically or cova-
`lently bonded. Based upon this answer, indicate whether the compound would be
`.
`.
`.
`expected to be more soluble in water or more soluble in methylene chloride.
`,
`
`Resu
`:
`Based
`napht
`extrac
`wall bx
`
`Part
`and -
`D
`evel:
`amino
`may b
`from I
`0
`
`walok
`Weigh
`
`Char
`Meltin
`meltin
`benzo:
`
`Resu
`, "
`
`‘
`
`Experimental Procedure
`
`
`
`Safety First!
`Always weareye
`protection in the
`laboratory.
`
`a
`1, Wear eve protection at all times in the laboratory.
`2. Wear gloves when handling reagents in this experiment.
`3. Methylene chloride is a toxic irritant and a suspected carcinogen. Do not breathe
`the vapors. Work under the hoodor in a well-ventilated area.
`4, NaOH and HC]are corrosive and toxic and can cause burns.
`
`
`
`
`;
`Part A: Determinationof Solubilities
`Obtain 20 small, dry test tubes or a spot plate. Place approximately 10-20 mg of ben-
`zoic acid into four of the test tubes or wells; place 10-20-mg of sodium benzoate into
`four othertest tubes or wells. Repeat, using 10-20-mg samples ofthe other solutes.It is
`
`Liquidia - Exhibit 1011 - Page 4
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`Liquidia - Exhibit 1011 - Page 4
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`

`

`'|||i
`
`.
`
`LeI''i1
`
` The McGraw-Hill Companies
`
`Baa Higher Education
`
`MICROSCALE AND MINISCALE ORGANIC CHEMISTRY LAB EXPERIMENTS
`SECOND EDITION
`
`Published by McGraw-Hill, a business unit of The McGraw-Hill Companies, Inc,, 1221 Avenue of the Americas, New York,
`NY 10020, Copyright © 2004, 2000 by The McGraw-Hill Companies,Inc. All rights reserved, No part of this publication
`may be reproduced or distributed in any form or by any means, or stored in a databaseor retrieval system, without the prior
`written consent ofThe McGraw-Hill Companies,Inc., including, but not limited to, in any networkor other electronic stor-
`age or transmission,or broadcastfor distance learning,
`Some ancillaries, including electronic and print components, may not be available to customers outside the United States.
`
`This book is printed on acid-free paper.
`1234567890 VNH/VNHO9876543
`
`ISBN 0-07-242456-7
`
`Publisher: KentA. Peterson
`Sponsoringeditor: Thomas D, Timp
`Senior developmental editor! Shirley R. Oberbroeckting
`Senior marketing manager! Tamara L. Good-Hodge
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`“Permission for the publication herein of Sadtler Standard Spectrar has been granted, and all rights are reserved, by BIO-
`RAD Laboratories, Sadtler Division.”
`
`"Permission for the publication ofAldrich/ACD Library of FT NMR Spectra has been grantedandall rights are reserved by
`Aldrich Chemical.”
`
`All experiments contained in this laboratory manual have been performed safely by students in college laboratories underthe
`supervision of the authors. However, unanticipated and potentially dangerous reactions are possible due to failure to follow
`proper procedures, incorrect measurement of chemicals, inappropriate use of laboratory equipment, and other reasons. The
`authors and the publisher hereby disclaim any liability for personal iinjuryor property damage claimed to have resulted from
`the use of this laboratory manual.
`
`Library of Congress Cataloging-in-Publication Data
`Schoffstall, Allen M.
`Microscale and miniscale organic chemistry laboratory experiments / Allen M.
`Schoffstall, Barbara A. Gaddis, Melvin L. Druelinger.—-2nd ed.
`p cm -
`|
`Includes bibliographical references and index,
`ISBN 0-07-242456-7 (acid-free paper)
`i, Chemistry, Organic—Laboratory manuals.
`Melvin L.
`If. Title.
`
`1. Gaddis, BarbaraA.
`
`II. Druelinger,
`
`2004
`QD261.834
`547.0078—de21
`
`www.inhhe.com
`
`2003008663
`cyp
`
`
`
`
`
`Liquidia - Exhibit 1011 - Page 5
`
`Liquidia - Exhibit 1011 - Page 5
`
`