`CLAYTON H. HEATHCOCK
`
`INTRODUCTION TO
`
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`Page 1 of 6
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`SENJU EXHIBIT 2042
`LUPIN v. SENJU
`IPR2015-01097
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`
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`THIRD EDITION
`
`Introduction to
`Organic Chemistry
`
`A ndrew Streitwieser, Jr.
`Clayton H. Heathcock
`UNIVERSITY OF CALIFORNIA, BERKELEY
`
`Macmillan Publishing Company
`
`New York
`
`Collier Macmillan Publishers London
`
`Page 2 of 6
`
`
`
`CoRyright (!:> 1985 Macmillan Publishing Company, a division of Macmillan, Inc .
`
`Printed in the United States of America
`
`All rights reserved. No part of this book may be reproduced or transmitted in any form or by any
`means, electronic or mechanical, including photocopying, recording, or any information storage and
`retrieval system, without pennission in writing from the Publisher.
`
`Earlier editions. copyright@ 1976 and 1981 by Macmillan Publishing Co., Inc. Selected illustrations
`have been reprinted from Orbital and Eltctron Dtnsiry Diagrams: An Application of Computer Graph(cid:173)
`ics. by Andrew Streitwieser, Jr. , and Peter H. Owens, copyright© 1973 by Macmillan Publishing
`Co., Inc.
`
`Macmillan Publishing Company
`866 Third Avenue, New York, New York 10022
`
`Collier Macmillan Canada, Inc.
`
`Library of Congress Cataloging in Publication Data
`
`Slreitwieser, Andrew.
`Introduction to organic chemistry.
`
`I. Heathcock, Clayton H.
`
`Includes index.
`I. Chemistry, Organic.
`JI. Title.
`547
`QD251.2.S76 1985
`ISBN 0-0'2-418140-4 (Hardcover Edition)
`ISBN 0-02-946720-9 (International Edition)
`
`84-15399
`
`Printing.
`
`I 2 3 4 5 6 7 8
`
`Year: 5 6 7 8 9 0 I 2 3
`
`I SBN 0-02-418140- 4
`
`L
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`Page 3 of 6
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`456 "
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`7 Chap. 17
`Carboxyiic
`Acids
`
`Page 4 of 6
`
`becomes less important than the nonpolar hydrocarbon tail (R). Consider the reaction
`of a carboxylic acid such as dodecanoic acid with hydroxide ion..
`
`K H20 + CH3(CH2)mCO2‘
`
`CH3(CH2),oC0OH + 0H‘
`
`(17-3)
`
`The equilibrium constant for reaction (17-3) may be derived as follows.
`
`lCH3(CH2)1oC02”'llH*]
`K“ : _———._..____ = 1.3
`[CH3(CH3)wC0OH]
`
`X
`
`_
`10 5M
`
`Kw = lH*l{0H‘1 = 10'” M2
`
`Rearranging (17-S), we have
`
`H+ : 10-” M
`
`Substituting (17-6) into (17-4) and expanding, we have
`
`(
`
`17.4
`
`)
`
`(17-5)
`
`17-6
`
`lCH3(CH2)l0C02h]
`= [CH3(CH2)wC0OH][OH‘]
`
`=
`
`X 109 M-1
`
`Equation (17-7) is merely the equilibrium expression for reaction (17-3). The large
`value of K shows that the reaction proceeds to completion; dodecanoic acid is con-
`verted by aqueous sodium hydroxide completely into the salt, sodium dodecanoate.
`Note that the anions of carboxylic acids are named by dropping —ic from the name of
`the parent acid and adding the suffix —ate. Although dodecanoic acid is a neutral
`molecule, sodium dodecanoate is a salt. Dissolution of this salt gives an anion and a
`cation, which can be solvated by water. It is not surprising that the solubility of sodium
`dodecanoate (1.2 g per 100 mL) is much greater than that of dodecanoic acid itself
`(00055 g per 100 mL).
`
`EXERCISE 17.5 Equation (17-7) can he used to calculate the ratio of ionized and
`nonionized dodecanoic acid at a given pH, by inserting the proper value for [OH‘]. Calculate
`
`this ratio for pH = 2, 4, 6, and 8.
`
`D. Soaps
`
`The sodium and potassium salts of long-chain carboxylic acids (“fatty acids") are
`obtained by the reaction of natural fats with sodium or potassium hydroxide. These
`salts, referred to as soaps, have the interesting and useful ability to solubilize nonpolar
`organic substances. This phenomenon can easily be understood if one considers the
`structure of such a salt.
`
`CH3CHQCHBCHECHQCHQCHZCH2CH2CH2CH2CH2CH2CH2C H2CO._. - K -*
`
`The molecule has a polar ionic region and a large nonpolar hydrocarbon region. In
`aqueous solution a number of carboxylatc ions tend to cluster together so that the
`hydrocarbon tails are close to each other, thus reducing their energy by the attractive
`van der Waals forces enjoyed by normal hydrocarbons. The surface of the sphere-like
`cluster is then occupied by the highly polar CO2“ groups. These polar groups face the
`medium, where they may be solvated by H10 or paired with a cation. The resulting
`spherical structure, called a ruicelle, is depicted in cross section in Figure 17.3. The
`wavy lines in the figure represent the long hydrocarbon chains of the salt molecules.
`Organic material such as butter or motor oil that is not normally soluble in water may
`“dissolve” in the hydrocarbon interior of a niicelle. The overall process of soap
`solubilization is diagramrned schematically in Figure 17.4.
`
`Page 4 of 6
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`
`
`H20
`
`co2-
`
`H20
`
`457
`
`Sec. 17.4
`Acidity
`
`,,.,.
`, .
`
`H20
`
`-o2c
`
`H20
`
`H20
`
`H20
`
`co2-
`
`H20
`
`C02-
`
`H20
`
`H20
`
`C02-
`
`H20
`
`FIGURE 17.3 Cross section of a micelle.
`
`+
`
`grease,
`insoluble in H20
`
`soap,
`soluble in H 20
`
`FIGURE 17.4 Schematic diagram of soap solubilization.
`
`solubilized grease
`
`Certain bacteria can metabolize soaps . This degradation is most rapid when there are no
`branches in the hydrocarbon chain of the soap molecule. Since the naturally occurring
`fatty acids are all unbranched compounds, soaps derived from natural fats are said to be
`biodegradable. Before 1933 all cleaning materials were soaps. In that year the first syn(cid:173)
`thetic detergents were marketed. Detergents have the useful property of not forming the
`hard "scum" that often results from the use of a soap with hard water. This scum is
`actually the insoluble magnesium and calcium salts of the fatty acid. The first detergents
`were alkylbenzenesulfonates. Like soaps , they had a large nonpolar hydrocarbon tail and
`a polar end .
`
`R-Q -so3-K+
`
`R = branched alkyl chain
`
`However. being branched compounds , these early detergents were not rapidly biodegrad(cid:173)
`able. Since the materials could not be completely metabolized by the bacteria that operate
`in sewage treatment plants, they were passed into natural waterways with the treated
`sewage and often reappeared as foam or suds on the surface of lakes and rivers. After an
`
`Page 5 of 6
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`
`
`458
`
`Chap. 17
`CarboxyUc
`Acids
`
`intensive research project, the detergent industry in 1965 introduced linear alkanesul·
`fonate detergents (Section 25.5.8).
`
`Since the new detergents are straight-chain compounds, they can be metabolized by
`bacteria.
`
`- -1
`
`L
`
`17.5 Spectroscopy
`A. Nuclear Magnetic Resonance
`
`The resonance positions for various types of hydrogens in carboxylic acids are summa(cid:173)
`rized in Table 17.5. Hydrogens attached to C-2 of a carboxylic acid resonate at roughly
`the same place as do the analogous hydrogens in aldehydes and ketones. The very
`low-field resonance of the carboxy proton is associated with the dimeric hydrogen(cid:173)
`bonded structure discussed in Section 17. l. The spectrum of 2-methylpropanoic acid is
`shown_ in Figure 17.5.
`The CMR chemical shifts of carboxylic acids are similar to those seen with alde(cid:173)
`hydes (Table 14.4), except that the carbonyl carbon itself resonates at much lower
`field. Representative data are summarized in Table 17 .6.
`
`TABLE 17.5 Chemical Shifts of
`Carboxylic Acid Hydrogens
`Chemical Shift, o, ppm
`
`Type of Hydrogen
`
`CH3COOH
`RCH2COOH
`R 2CHCOOH
`RCOOH
`
`2.0
`
`2.36
`
`2.52
`about 10-13
`
`1300
`
`1200
`
`1100
`
`1000
`
`900
`
`800
`
`700
`
`600
`
`500
`
`400
`
`300
`
`200
`
`0 H1
`100
`-tt-
`
`--t-------
`
`12.2 ppm
`
`)
`
`_ .
`
`. -
`
`7 .0
`
`5.0
`
`4.0
`ppm (8}
`
`3.0
`
`2.0
`
`1.0
`
`FlGURE 17.5 NMR spectrum of 2-methylpropanoic acid , (CHJhCHCOOH .
`
`L
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`Page 6 of 6