`LUPIN v SENJU
`IPR2015-01105
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`THIRD EDITION
`
`~ Introduction to
`Organic Chemistry
`
`Andrew Streitwieser, Jr.
`
`Clayton H. Heathcock
`UNIVERSITY OF CALIF(‘JRNI/1 , BERKELEY
`
`}
`l
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`Macmillan Publishing Company
`Collier Macmillan Publishers
`London
`
`New York
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`PAi%E2OF5
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`PAGE 2 OF 5
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`Copyright © 1985 Macmillan Publishing Company. a division of Macmillan. Inc.
`Printed in the United States of Arrietica
`
`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 (9 1976 and 198i by Macmillan Publishing Co., Inc. Selected illustrations
`have been reprinted from Orbital and Electron Density Diagrams.‘ An Application of Computer Graph-
`ics, by Andrew Streitwieser, Jr., and Peter H. Owens. copyright © I973 by Macmillan Publishing
`Co., Inc.
`
`Macmillan Publishing Company
`866 Third Avenue. New York, New York l0022
`
`Collier Macmillan Canada, Inc.
`
`Library of Congress Cataloging in Publication Data
`
`Streitwieser, Andrew,
`Introduction to organic chemistry.
`
`Includes index.
`
`1. Chemistry. Organic.
`II. Title.
`
`[_
`
`I-Ieathcock, Clayton H.
`
`54?
`1985
`QD25l.2.S'.l6
`ISBN 0-U2-M8140-4 [Hardcover Edition)
`ISBN 0-02~946'i20-9 {International Edition)
`
`fat-I5399
`
`Printing:
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`l2345678
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`Year: 56';'890l23
`
`ISBN E|-EIE-llluflilillll-I-I
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` 23,5 Quaternary Ammonium Compounds
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`Amines
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`A. Tertiary Amines as Nucleophiles
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`
`
`Recall that there is a correlation between Lewis basicity and the nucleophilicity of a
`species (Section 9.4). Amines are more basic than alcohols or ethers, and they are also
`more nucleophilic. For example, a mixture of diethyl ether and methyl iodide does not
`react under ordinary conditions, but triethylamine and methyl iodide react violently at
`room temperature. If the reaction is carried out in a solvent to moderate its vigor, the
`product, which is a tetraalkylamrnonium iodide, may be obtained in good yie1d_
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`(c,H,),o + CH3I £> no reaction
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`(C,H,),N + CH3I Hi»
`ether
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`(c,H5),tT1cH3 1-
`methyltriethylammonium iodide
`
`Such compounds, which have four alkyl groups replacing the four hydrogens of the
`ammonium ion, are called quaternary ammonium compounds. Since they are ionic,
`they are generally water soluble and have fairly high melting points. They often de-
`compose at the melting point.
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`(CH3),,N" Cl‘
`tetramethylammoniurn chloride
`m.p. 420°C
`
`(CH3CH2CH2)4N" Br‘
`tetrapropylammoniurn bromide
`rn.p. 252°C
`
`Quaternary ammonium compounds are important as intermediates in some reactions
`that we shall encounter and also occur in nature. Acetylcholine, which is important in
`
`the neural transport system of mammals, is an example.
`
`
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`(‘H3
`("3
`CH3COCH2CH2ll\‘CH3 Br‘
`
`ca,
`acetylcholine bromide
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`Quaternary ammonium hydroxides are as basic as alkali hydroxides. They decompose
`on heating (Hofmann degradation; Section 23.7.E) and find use as base catalysts in
`organic systems.
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`
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`B. Phase-Transfer Catalysis
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`
`
`In Section 1 1.6.?‘ we learned that chloroform reacts with strong bases to form
`dichlorocarbene, which can then add to double bonds to give dichlorocyciopropanes. If
`a solution of cyclohexene in chloroform is stirred with 50% aqueous sodium hydrox-
`ide, only small yields of the cyclopropane are formed. The hydroxide ion stays in the
`aqueous phase, and the only reaction that occurs is at the interface between the organic
`and aqueous phases. However, if a small amount of bcnzyltriethylammonium chloride
`is added to the heterogeneous mixture,
`rapid reaction occurs and 7,7—dichloro-
`bicyclo[4. I Olheptane is isolated in 72% yield.
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`697
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`Sec. 23.5
`
`Quaternary
`Antrnonium
`
`Compounds '
`
`Q +
`
`c,,H,cH,1i.'Et, GI‘
`_.._._._..__..____)
`50% aq,NaOH
`
`1
`
`C1
`
`(72%)
`
`To understand what has happened, we need to recognize that although the quaternary
`ammonium compound is a salt soluble in water, it also has a large organic group and
`has solubility in organic solvents as an ion pair. Although the quaternary ammonium
`chloride was used because of its availability and greater convenience in handling,
`chloride ion is swamped by the large excess of hydroxide ion in the aqueous solution.
`In the heterogeneous mixture some benzyltriethylarnmonium hydroxide ion pairs are
`distributed into the chloroform layer. Hydroxide ion is especially reactive in this
`medium because of the reduced hydrogen bonding. Dichlorocarbene is produced in the
`chloroform solution,
`in which there also is a high concentration of cyclohexene.
`
`C6H5CI-I2NEt3+(aq.) + OH‘(aq.) ;» C5H_.,CH2NEt3+ OH*(CHCl3)
`
`C3H5CHz.T~iEt3+ on~ + CHCI3 ———9 H20 + C6H5CH2NEt3+ cc13-
`
`C6H5CH2NEt3* 0:313" .__> :cc12 + C6H5CH2NEt3+ cr
`
`The benzyltriethylammoniurn chloride ion pairs diffuse into the aqueous phase, where
`the ammonium ion can again pick up a hydroxide ion and begin the cycle anew. The
`key to the procedure is the solubility of the quaternary ammonium salt in both water
`and organic solvents.
`‘
`
`C6H5CH2N(CH2CH3)3+ on-I
`soluble in both water and organic solvents
`
`The technique is called phase-transfer catalysis and can be applied to a number of
`different types of reaction. The general procedure is to use concentrated solutions with
`an aqueous and an organic phase. The quaternary ammonium salt used need only have
`organic groups that are sufficiently large to provide solubility in organic solvents.
`Among the ones commonly used are tetrabutylamrnoniurn, rnethyltrioctylammonium,
`and hexadecyltrimethylammonium salts. Some additional examples of applications of
`phase—transfer catalysis are given below.
`
`CI-l3(CH3).,CH=CH2 (benzene soln.) [CH'(Cfl: CH3(CH2}7C0OH
`
`4G—50°C
`
`(9l%}
`
`C6H5CH2COCH3 + CH3(CH2)3Br £*.'.*=.°i“‘-:”Fi=_°1‘s CH3COCHCH._,CH3CH2C.H3
`50%:-iq.Na0H
`
`J C
`
`GH5
`(90%)
`
`Cl-l3(CH2)9Br
`
`man:
`
`CH3(CH2)9SCN
`
`300%)
`
`Note that the examples include allcylation, oxidation, and displacement reactions, that
`the anions are not restricted to hydroxide ion and that various temperatures may be
`used.
`
`For each of the three foregoing examples of'phase—transfer catalysis,
`EXERCISE 23.7
`what species are in the aqueous phase? In the organic phase? Which species are passing from
`
`one phase to another?
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