`RGANIC CHEMISTRY
`
`
`
`
`
`V[5A11enM%.scho£rsta11
`Barbara
`
`
`1
`
`Second Edition
`
`Melvin L. Druelinger
`
` SteadyMed — Exhibit 1014 — Page 1
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`SteadyMed - Exhibit 1014 - Page 1
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`
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`
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`200
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`chapter Three Applications Using Laboratory Resources and Techniques
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`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 effectiveness 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.
`
`
`
`
`
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`Cleanup'& Disposal
`C
`Place the solvents used for recrystallization in a container labeled “nonhalogenated
`organic solvent waste.” Aqueous solutions can be washed down the drain with water.
`
`
`
`5
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`Critical Thinking Questions (The harder one is marhecl 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?
`.3. 4. Will the following pairs of solvents be suitable for doing a solvent—pair recrystal-
`lization? Explain.
`21.
`ethanol (bp 785°C) and water
`b. methylene chloride (bp 40°C) and water
`c.
`dimethylforrnarnide (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.
`
`5.
`
`6. Arrange the following solvents in order of increasing polarity: ethanol, ethyl
`acetate, petroleum ether, toluene, and acetone.
`
`7. Methylene chloride (CHZCIZ) is polar, whereas carbon tetrachloride (CCI4) is non-
`polar. Explain.
`_
`
`8. Carbon disulfide (CS2) is sometimes used as a recrystallization solvent. Will this
`solvent dissolve polar or nonpolar compounds? Explain.
`
`.
`.
`.
`.
`.
`Experiment 3.5: Separations Based upon Acidity
`
`and Basioity
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`Extraction is a technique in which a solute is" transferred from one solvent to another. ln
`this experiment, you will investigate acid—base extraction. You will:
`
`9
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`4-
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`o
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`o
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`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—arninobenzoate.
`
`Th
`drYi11g
`ratmlgnt
`(ethyl
`(ethy1 4
`one ch}
`FT!
`“aPhth~’
`
`.
`
`3
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`SteadyMed - Exhibit 1014;
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`
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`SteadyMed - Exhibit 1014 - Page 2
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`
`
`my 1:13
`
`erms of
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`recrys-
`
`Ltfld
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`3/ Of the
`,1, ethy1
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`) is non~
`
`will this
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`Experiment 3.5
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`Separations Based upon Acidity and Basicity
`
`201
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`Techniques
`Technique C
`Technique F
`Technique I
`
`Melting point
`Vacuum filtration
`Drying and extraction
`
`Background
`A water—insoIuble, 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.
`
`O
`O
`ll
`ll
`RCO-H + NaOH —) FlCO'Na"
`
`+ H20
`
`a water-insoluble
`
`carboxylic acid
`
`a watensoluble
`
`carboxylate salt
`
`Neutral and basic organic compounds remain in the organic layer. The two layers
`can then be separated. Addition of HC1 to the aqueous layer regenerates the water-
`insoluble carboxylic acid, which can then be filtered or extracted into an organic solvent:
`
`0
`0
`ll
`ll
`FlCO'Na+ + HCI j) FlCO-H + NaCl
`
`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:
`
`.
`
`FiNH2 + HCI —«—-~> HNH; or
`a water-insoluble
`a water-soluble
`
`ammonium salt
`amine
`Neutral compounds and acidic organic compounds remain in the organic solvent, where
`Nag
`W 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.
`
`Q
`
`FlNH3" CI‘ + NaOH :> FiNl-I2 + NaCI
`
`5
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`lather, In
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`
`a water-soluble
`ammonium salt
`
`a water-insoluble
`amine
`
`-
`
`. organic
`
`mtral
`
`‘Ht of a
`
`nzoic
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`_
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`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 (benzcic acid), an organic base
`(Ethyl 4-—an1inoben2oate), a neutral compound (naphthalene), and the organic salts
`(ethyl 4-arninobenzoate 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—ami11obenzoate. In Part B, you will use the flow
`
`SteadyMed — Exhibit 1014 — Page 3
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`SteadyMed - Exhibit 1014 - 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—ann'nobenzoate
`in microscale. In Part C, you will use the flow scheme to separate a mixture of benzoic
`acid and ethyl 4-arninobenzoate in miniscale.
`
`
`
`COZH
`
`CO2‘ Nat
`
`NH2
`
`NH; Cl“
`
`naphthalene
`
`benzoic acid
`
`sodium
`benzoate
`
`COECHZCH3
`ethyl 4—amino~
`benzoate
`
`COZCHECH3
`ethyl 4-amino-
`benzoate hydrochloride
`
`The instructor may substitute other compounds for those shown here.
`
`Prelab Assignment
`
`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.
`5*’
`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 Na0H.
`b.
`sodium benzoate with HCI.
`c.
`ethyl 4—aminobenzoate with HCI.
`
`ethyl 4-arninobenzoate hydrochloride with NaOH.
`d.
`naphthalene and NaOH.
`e.
`ethyl 4-arninobenzoate with NaOH.
`f.
`5. Determine whether each of the five compounds is 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.
`
`Experimental Procedure
`
`Sadfety First!
`Always wear eye
`protection in the
`laboratory.
`
`1. Wear eye protection at all times in the laboratory.
`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.
`
` Part A: Dstei'm.inatio1-1 ofSolul91'iiiies
`
`Obtain 20 small, dry test tubes or a spot plate. Piace approximately 10-20 mg of ben-
`zoic acid into four of the test tubes or Wells; place l0—20~mg of sodium benzoate into
`four other test tubes or wells. Repeat, using lO—20wmg samples of the other solutes. It is
`
`SteadyMed - Exhibit 101
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`
`
`
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`not he
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`spatul
`chlori
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`not al
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`the co
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`Part
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`Devel«
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`Weigh
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`SteadyMed - Exhibit 1014 - Page 4
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`
` The Mcfirawflill Companies
`
`Higher Education
`
`MICROSCALE AND MENISCALE ORGANIC CHEMISTRY LAB EXPERIMENTS
`SECOND EDITION
`
`Published by McGraw-I-Ijll, a business unit of The McGraw»Hil1 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., including, but not limited to, in any network or other electronic stor-
`age or transmission, or broadcast for distance learning.
`‘
`
`Some ancillaries, including electronic and print components, may not be avaiiable to customers outside the United States.
`
`
`
`This book is printed on acid—frce paper.
`
`I234567890VNl-IIVNI-109876543
`ISBN 0-07-24-2456m7
`
`Publisher: Kenna. Peterson
`
`Sponsoring editor: Thomas D. Timp
`Senior developmental editor: Shirley R. Oberbroeckling
`Senior marketing manager: Tamara L Good»Hodge
`Project manager: Joyce Walters
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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."
`‘
`'
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`"Permission for the publication ofAldrich./ACD Library ofET NMR Spectra has been granted and all rights are reserved by
`Aldrich Chemical."
`
`this laboratory manual have been performed safely by students in college laboratories under the
`All experirnents contained
`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 injury or 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 rniniscale organic chemistry laboratory experiments 1’ Allen M.
`Schofifstall, Barbara A. Gaddis, Melvin L. Druelinge’r.——-2nd ed.
`p.
`cm.
`_
`Includes bibliographical references and index.
`ISBN 0—07—242456—7 (acid-free paper)
`1. Chemistry, Organic—Laboratory'rnanuals.
`Melvin L.
`III. Title.
`
`1. Gaddis,BarbaraA.
`
`II. Druelinger,
`
`2004
`QD261 .S34
`547'.0078—dc2l
`
`\vww.mhhe.com
`
`2003008663
`Cl?
`
`SteadyMed - Exhibit'lO14 - Page 5
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`SteadyMed - Exhibit 1014 - Page 5