ANDREW STREETWEESER, JR.
`
`CLAYTON H. HEATHCOCK
`
`”§"i=~§§RD EDITEQN
`
` CHEMISTRY
`
`
` ORGANIC
`
`-ifi—-.-—--I-__'3_-u
`
`.
`
`_
`
`._.,,._..._..-
`
`._.__._..__.__.,.__1_...~r_;..,_g—.g-.n..y; {g-‘aw-i_~. H‘,-‘=. 4:1,.-=-.
`
`.'....,.—-.-'.e.'.r-_-.--:..,-_-.:':-'s'.L-..‘:.--'.:::-.:.==..a:' .-era‘
`
`Page 1 of 6
`
`SENJU EXHIBIT 2042
`
`INNOPHARMA V. SENJU
`IPR2015-00903
`
`SENJU EXHIBIT 2042
`INNOPHARMA v. SENJU
`IPR2015-00903
`
`Page 1 of 6
`
`

`
`
`
`THIRD EDITION
`
`«Introduction to
`Organic Chemistry
`
`Andrew Streitwieser, Jr.
`Clayton H. Heathcock
`
`UNIVERSITY OF CALIFORNIA, BERKELEY
`
`Macmillan Publishing Company
`
`New Y0:-k
`
`Collier Macmillan Publishers
`
`London
`
`Page 2 of 6
`
`Page 2 of 6
`
`

`
`Copyright © 1985 Macmillan Publishing Company, a division of Macmillan, Inc.
`Printed in the United States of America
`
`All rights reserved. No pan 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 permission in writing from the Publisher.
`
`Earlier editions, copyright © 1976 and 1981 by Macmillan Publishing Co, Inc. Selected illustrations
`have been reprinted from Orbital and Electron Denrirp Liiagrams: An Applicatrorr of Computer Graph-
`ics, by Andrew Streitwieser, IL, 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.
`
`Includes index.
`
`1. Chemistry. Organic.
`II. Title.
`
`I. Heathcock. Clayton H.
`
`54?
`I935
`QD25l.2.S7‘6
`[SBN 0-0‘_3-4l8lr10-4 (Hardcover Edition}
`ISBN 0-02—946720-9 (lntemational Edition)
`
`84-15399
`
`Printing;
`
`|2345678
`
`Year‘. 567890|?3
`
`ISBN Cl-DE-lllE:LllEl-Ll
`
`Page 3 of 6
`
`Page 3 of 6
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`

`
`456 "
`
`Chap. 17
`
`Carboxyfic
`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-.
`
`
`CH3(CH2)1oCOOH + OH‘ —‘- H20 + CH_,(cH,),,,co,-
`
`(17-3)
`
`The equilibrium constant for reaction (1?-3) may be derived as follows.
`
`[CH3(CH ) CO ”‘.[H+]
`K,, = ~—-——2—"3—-i—— -_— 1.3
`[CH3(cH,),,,co0H]
`
`X
`
`10‘-‘M
`
`Kw = lH*ll0H‘l = 10"“ M“
`
`Rearranging (17-S), we have
`
`H+ = 10'” M
`
`Substituting (1736) into (17-4) and expanding, we have
`
`K = E9iL, = 1.3 x109 M-1
`[CH3(CH2)wCOOH][OH‘]
`
`1?-4
`
`)
`
`(
`
`(17-5)
`
`1?-6
`
`(17.7)
`
`Equation (17-7") is merely the equilibrium expression for reaction (17-3). The large
`value of It’ 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
`(0.00S5 g per 100 mL).
`
`EXERCISE 17.5 Equation (17-7) can be used to calculate the ratio of ionized and
`nonionized dodecanoic acid at a given pH, by inserting the proper value for [0H' ]. 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.
`
`cH3cH,.cH,cH,cH,cH,CH,.CH,CH,cH,cH,cH,cH,.cH,cH,co,- K*
`
`The molecule has a polar ionic region and a large nonpolar hydrocarbon region. In
`aqueous solution a number of carboxylate 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 ofthe sphere-like
`cluster is then occupied by the highly polar CO2‘ groups. These polar groups face the
`medium, where they may be solvated by H30 or paired with a cation. The resulting
`spherical structure, called a rnicelle, 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 ruicelle. The overall process of soap
`solubilization is diagran-irned schematically in Figure l7.4.
`
`Page 4 of 6
`
`

`
`457
`
`Sec. I 7.4
`
`Acidity
`
`grease.
`insoluble in H20
`
`44'
`.-;3:"
`
`‘=5.5}.
`
`_“'
`1‘.
`
`
`
`.;'-'-a:.._-r:-
`
`
`
`;
`*3
`
`
`
`.:_...._.~-
`
`FIGURE 17.3 Cross section of a micelle. 5.
`
`
`.
`.
`.
`.
`.
`.
`.
`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-
`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 alkylbenzenesulfonares. Like soaps, they had a large nonpolar hydrocarbon tail and
`a polar end.
`
`soluble in H30
`
`solubilized grease
`
`FIGURE 17,4 Schematic diagram of soap solubilization.
`
`1
`
`J
`
`R : branched alkyl chain
`
`However. being branched compounds, these early detergents were not rapidly biodegrad-
`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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`Page 5 of 6
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`

`
`,.
`
`-Ir
`I.‘..
`458
`~"a
`
`Chap. 17
`
`Corboxylic
`Acids
`
`intensive research project, the detergent industry in 1965 introduced linear a1kar1esul-
`fonate detergents (Section 25.5.8).
`
`2
`
`CH CH CHLSO — PU
`3‘
`2)"
`“
`3
`Since the new detergents are straight—cha.in compounds,
`L bacteria.
`
`they can be metabolized by
`
`J
`
`17.5 Spectroscopy
`
`A. Nuclear Magnetic Resonance
`
`The resonance positions for various types of hydrogens in carboxylic acids are summa-
`rized in Table 17.5. Hydrogens attached to C-2 of a carboxylic acid resonate at roughly
`the same place as do the analogous hyclrogens in aldehydes and ketones. The very
`low—field resonance of the carboxy proton is associated with the dimeric hydrogen-
`bondcd 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-
`hydes (Table 14.4), except that the carbonyl carbon itself resonates at much lower
`field. Representative data are summarized in Table 17.6.
`E
`
`TABLE 17.5 Chemical Shifts of
`
`Carboxylic Acid Hydrogens
`
`Type of Hydrogen
`
`Chemical Shift, 5, ppm
`
`CI-l3C0OH
`
`RC!-l2C00H
`
`RECHCOOH
`RCOOH
`
`2.0
`
`2.36
`
`2.52
`about
`l0« l3
`
`IIDO
`
`I000
`
`900
`
`800
`
`TOO
`
`
`
`FIGURE 17.5 NMR spectrum of Zmethylpropanoic acid. (CH3)2CHC00H.
`
`Page 6 of 6
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`Page 6 of 6