-
`
`Microscale and Miniscale
`
`RGANIC CHEMISTRY
`
`
`
`‘ A11enM1Schoffstall
`Barbara A. Gaddis
`
`Melvin L. Druelinger
`
`
`
`..._.__(:
`
`a
`
`-
`
`_
`Second Edition
`
`
`
`Liquidia - Exhibit 1011 - Page 1
`
`Liquidia - Exhibit 1011 - Page 1
`
`

`

`
`
`200
`
`Chapter Three
`
`Applications Using laboratory Resources and Techniques
`
`Results and Conclusionsfor Part B
`
`1. Calculate the percent recovery for the recrystallization process. Explain why it is
`not 100%.
`
`2. Explain and evaluate the effectivaness of the recrystallization solvent in terms of
`percent recovery and purity of the recrystallized solid.
`3. Suggest other solvents or solvent pairs that might have been used for this recrys~
`tallization.
`‘
`
`Cleanup” 8: Disposal
`
`Place the solvents used for recrystallization in a container labeled “nonhalogenated
`organic solvent waste.” Aqueous solutions can be washed down the drain with water.
`
`
`Critical Thinking Questions (The harder one is marked with a ‘2'.)
`1. List the main criteria for selecting a recrystallization solvent.
`
`2. When is it necessary to use a solvent-pair recrystallization?
`3. Why should the recrystallization solvent have a fairly low boiling point?
`4. Will the following pairs of solvents be suitable for doing a SOIVent-pair recrystal-
`lization? Explain.
`
`ethanol (bp 785°C) and water
`a.
`b. methylene chloride (bp 40°C) and water
`0.
`dimethylformarnide (bp 153°C) and diethyl ether (bp 37°C)
`If a solute is soluble 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.
`
`5.
`
`7. Methylene chloride (CHzclg) is polar, whereas carbon tetrachloride (CC14) is non—
`prar. Explain.
`
`8. Carbon disulfide (C82) is sometimes used as a recrystallization solvent. Will this
`solvent dissolve polar or nonpolar compounds? Explain.
`
`EXperiment 3.5: Separations Based upon Acidity
`, and BESlQltY.
`..
`_
`
`
`Extraction is a technique in which a solute is' transferred from one solvent to another. In
`this experiment, you will investigate acid—base extraction. You will:
`
`o
`
`o
`
`e
`
`o
`
`determine the solubilities of an organic acid, an organic base, and a neutral organic
`compound.
`
`design a flow scheme to 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 naphthalene, benzoic acid, and ethyl 4—arninobenzoate.
`
`use miniscale extraction techniques to separate and isolate a mixture of benzoic
`acid and ethyl 4—aminobenzoate.
`
`Tech
`Tel
`T61
`T6!
`
`Back
`A wate:
`
`easily a
`soluble
`
`NE
`can the
`insoiub
`
`'
`
`A
`insoiul:
`to a we
`
`
`
`Neutra
`they ca
`the arnj
`thl‘aCtl
`
`Th
`
`drying
`'- rating t
`In
`
`(ethyl
`(Ethyl 1
`3116 Chl
`Frr
`flaphth;
`
`Liquidia - Exhibit 1011 - Page 2
`
`Liquidia - Exhibit 1011 - Page 2
`
`

`

`Experiment 3.5
`
`Separations Based upon Acidity and Basiciiy
`
`201
`
`Ihy it is
`
`erms of
`
`recrys—
`
`Lted
`ter.
`
`1a 4..)
`
`:crystal-
`
`y of the
`
`)1, ethyl
`
`) is non—
`
`Will this
`
`tether. In
`
`, organic
`
`:utral
`
`:nt of a
`
`nzoic
`
`Te chniqu es
`Technique C
`Technique F
`Technique 1
`
`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.
`
`0
`0
`ll
`ll
`ECO—H + NaOH —> FlCO'Na+ + H20
`
`3 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 HCI to the aqueous layer regenerates the water-
`insoluble carboxylic acid, which can then be filtered or extracted into an organic solvent:
`0
`0
`il
`ll
`FiCO‘Na+ + HCI ——> RCO—H + NaCI
`
`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-soluble salt:
`
`FlNHg + HCI —————) RNH3+CI‘
`
`a water-insoluble
`amine
`
`a water-soluble
`ammonium salt
`
`Neutral compounds and acidic organic compounds remain in the organic solvent, where
`they can be removed. Addition of sodium hydroxide to the aqueous layer regenerates
`.the amine, which is now insoluble in the aqueous solution. The amine can be filtered or
`_ extracted into an organic solvent.
`
`RNH3+CI‘ + NaOH —> FiNH2 + NaCI
`
`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 solution to remove traces of water, filtering off the drying agent, and evapo—
`__ rating 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 organic salts
`__
`(Ethyl 4-aminobenzoate hydrochloride and sodium benzoate) will be tested in methyl-
`- ene chloride and water.
`.
`
`From the solubilities, you will construct a flow scheme outlining the separation of
`'- naphthalene, benzoic acid, and ethyl 4-arninobenzoate. In Part B, you will use the flow
`
`
`
`
`
`Liquidia — Exhibit 1011 - Page 3
`
`Liquidia - Exhibit 1011 - Page 3
`
`

`

`202
`
`Chapter Three
`
`Applications Using Laboratory Resources and Techniques
`
`scheme to separate a mixture of naphthalene, benzoic acid, and ethyl 4—aminobenzoate
`in mieroscale. In Part C, you will use the flow scheme to separate a mixture of benzoic
`acid and ethyl 4-aminobenzoate in miniscale.
`
`com
`
`00,- Net
`
`NH
`
`Ni—la+ or
`
`naphthalene
`
`benzoic acid
`
`sodium
`benzoate
`
`COECHBCH3
`ethyl 4vamlno~
`benzoate
`
`COZCHEGHG
`ethyl 4-amino-
`benzoate hydrochloride
`
`The instructor may substitute other compounds for those shown here.
`
`Prelab Assignment
`
`1. Read Technique 1 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.
`E”
`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
`benzoic acid with NaOH.
`sodium benzoate with HCl.
`
`ethyl 4-aminobenzoate with HCl.
`ethyl 4-aminobenzoate hydrochloride with NaOH.
`naphthalene and NaOH.
`ethyl 4aminobenzoate with NaOH.
`5. Determine whether each of the five compounds1s predominantly ionically 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.
`
`bassinet»
`
`four other test tubes or wells. Repeat, using lO—ZOmmg samples of the other solutes. It is
`
`.
`M
`Experimental Procedure
`
`
`.
`Safety First!
`Always wear eye
`protection in the
`laboratory.
`
`1. Wear eye protection at all tunes 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 hood or in a well—ventilated area.
`4. NaOH and HCl are corrosive and toxic and can cause burns.
`
`
`,
`
`
`
`1
`.
`u
`>
`.
`.
`Part A: Determination 01 Solubtltttes
`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
`
`
`
`Liquidia - Exhibit 1011 - Page 4
`
`
`
`v
`i
`
`not or
`spatul
`chlori
`
`priate
`not 3.1
`see if
`the co
`
`is parl
`
`Resu
`Based
`
`napht
`extrac
`will bl
`
`amino
`
`may b
`from}
`O
`
`ami
`C313:
`Weigh
`
`Chm
`Melvin
`memfl
`benzoc
`
`Res“
`
`: I?
`' p‘c
`
`Liquidia - Exhibit 1011 - Page 4
`
`

`

`
`
`The McGraw-Hifl Companies
`
`% Higher Education
`
`MICROSCALE AND MNISCALE 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 database or retrieval system, without the prior
`written consent of The McGraw-Hill Companies, Inc. ,includiug. but not limited to, in any network or other electronic stop
`age or transmission, or broadcast for distance learning.
`
`Some ancillaries, including electronic and print components, may not be available to customers outside the United States.
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`This book is printed on acid—free paper.
`1234567890VNHNNH09876543
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`iSBN 0—07—2424564'
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`Publisher: KentA. Peterson
`Sponsoring editor: Thomas D. Timp
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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 Sadder Division. "
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`"Permission for the publication ofAldricthCD Library of PT NMR Spectra has been granted and all rights are reserved by
`Aldrich Chemical."
`
`All experiments contained in this laboratory manual have been performed safety by students in college laboratories under the
`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'mjurylor property damage clairmd to have resulted from
`the use of this laboratory manual.
`
`Library of Congress Cataloging-in-Publicafion Data
`Schoffstall, Allen M.
`Microscaie and miniscale organic chemistry laboratory experiments / Allen M.
`Schoffstall, Barbara A. Gaddis, Melvin L. Dmelinger.—-2nd ed.
`p.
`cm.
`,
`.
`Includes bibliographical references and index.
`ISBN 0—07—242456—7 (acid-free paper)
`1. Chemistry, Organic—Laboratory'manuals.
`Melvin L. HI. Title.
`
`I. Gaddis, Barbara A.
`
`ll. Druclinger,
`
`2004
`QD261 .834
`547.0078—dc21
`
`Www.mhhe.com
`
`2003008663
`CIP
`
`
`
`are?
`
`
`
`
`
`Liquidia — Exhibit 1011 - Page 5
`
`Liquidia - Exhibit 1011 - Page 5
`
`