r n1c
`
`©
`
`Chemistry
`
`SECOND EDITION
`
`K. Peter C. Vollhardt
`University of California, Berkeley
`
`Neil E. Schore
`University of California, Davis
`
`!f~._ ~. :;~'.}-
`
`ti-:r~ ~-\ .-
`
`II
`W. H. Freeman and Company
`NEW YORK
`
`Illumina Ex. 1112
`IPR Petition - USP 10,435,742
`
`

`

`Cover Image by Torno Narashima
`
`About the Cover: Calicheamicin (at right), one of the most potent cancer fighters ever
`discovered, is shown approaching a strand of DNA, the genetic material of living cells.
`This anticancer agent has only recently been found in nature. The cover is adapted from a
`computer-generated image provided by K. C. Nicolaou (The Scripps Research Institute
`and the University of California, San Diego) and Michael Peak (The. Scripps Research
`Institute).
`Calicheamicin acts by undergoing an extraordinary transformation-into a short-lived
`chemical species called a radical, which then attacks the DNA of tumor cells. As you will
`see in Chapter 8, radicals underlie the course of many organic reactions, including damage
`to normal cells that promotes aging. Chapter 14 explains in detail the action of
`calicheamicin and other naturally occurring antibiotics, and Chapter 25 discusses chemical
`defenses against damage to human cells.
`
`Library of Congress Cataloging-in-Publication Data
`
`Vollhardt, K. Peter C.
`Organic chemistry / K. Peter C. Vollhardt, Neil E. Schore.-2nd ed.
`p.
`cm.
`
`Includes index.
`ISBN 0-7167-2010-8
`1. Chemistry, Organic.
`II. Title.
`QD251.2.V65
`547-dc20
`
`1994
`
`I. Schore, Neil Eric, 1948-
`
`93-15648
`CIP
`
`Copyright© 1987, 1994 by W. H. Freeman and Company
`
`No part of this book may be reproduced by any mechanical, photographic, or electronic
`process, or in the form of a phonographic recording, nor may it be stored in a retrieval
`system, transmitted, or otherwise copied for public or private use, without written
`permission from the publisher.
`
`Printed in the United States of America
`
`Second printing 1995, RRD
`
`

`

`42
`
`2
`Alkanes
`
`Hydrocarbons are molecules that contain only
`hydrogen and carbon
`
`We begin our study with hydrocarbons, which have the general empirical formula
`CxHy, Those containing only single bonds, such as methane, ethane, and pro 0
`pane, are called alkanes. Molecules such as cyclohexane, whose carbons form a
`ring, are called cycloalkanes. Alkanes lack functional groups; as a result, they
`are relatively nonpolar and unreactive. The properties and chemistry of the al(cid:173)
`kanes are described in the next section and in Chapters 3 and 4.
`
`Alkanes
`
`Methane
`
`Ethane
`
`Propane
`
`Double and triple bonds are the functional groups of alkenes and alkynes, re(cid:173)
`spectively. Their properties and chemistry are the topics of Chapters 11-13.
`
`Alkenes and Alkynes
`
`H "' C=CH2 HC=CH
`
`CH3/
`Propene
`
`Ethyne
`(Acetylene)
`
`Propyne
`
`Ethene
`(Ethylene)
`
`A special hydrocarbon is benzene, C6H6, in which three double bonds are
`incorporated into a six-membered ring. Benzene and its derivatives are tradition(cid:173)
`ally called aromatic, because some substituted benzenes do have a strnng fra(cid:173)
`grance. Aromatlc·compotinds are discussed in Chapters 15, T6, 22, and 25.
`
`Aromatic Compounds
`H
`CH3
`I
`I
`H
`H
`H
`H
`"-c~c.,,c/
`"-c~c-..........c/
`I
`II
`I
`II
`C
`C
`C
`C
`. / ~c,....--- "-
`/ ~c,....--- "-
`I
`I
`.
`H
`H
`H
`H
`H
`Benzene
`Methylbenzene
`(Toluene)
`
`H
`
`Many functional groups contain polar bonds
`
`Polar bonds determine the behavior of many classes of molecules. (Recall that
`polarity is due to a difference in the electronegativity of two atoms bound to each
`
`

`

`43
`
`- 2
`
`-1
`Functional Groups
`
`other.) Chapters 6 and 7 will introduce the haloalkanes, which contain polar
`carbon-halogen bonds as their functional groups. Another example is the
`hydroxy group, -0-H, characteristic of alcohols. The symbol R (for "radical"
`or "residue") is commonly used to describe a hydrocarbon-derived ·molecular
`fragment. Such fragments are called alkyl groups. Therefore a general formula
`for a haloalkane is R-X, where X stand.s for any halogen. Alcohols are similarly
`represented as R-0-H. The alkoxy group, -O-R, is the characteristic func(cid:173)
`tional unit of ethers, which have the general formula R-0-R'. The functional
`group in alcohols and those in some ethers can be converted into a large variety of
`other functionalities and are therefore important in synthetic transformations.
`chemistry is the subject of Chapters 8 and 9.
`·
`
`Haloalkanes
`
`Alcohols
`
`Ethers
`
`CH3CH2Cl
`Chloroethane
`(Ethyl chloride)
`
`CH30H
`Methanol
`
`.CH3CH20H
`Ethanol
`
`(Wood alcohol)
`
`(Grain alcohol)
`
`CH30CH3
`Methoxymethane
`(Dimethyl ether)
`(A refrigerant)
`
`CH3CH20CH2CH3
`Ethoxyethane ·
`(Diethyl ether)
`(An inhalation
`anesthetic)
`
`carb.onyl function, C==O, is found in aldehydes and ketones, and, in
`with an attached -OH, in the carboxylic acids. Aldehydes and ke(cid:173)
`are discussed in Chapters 17 and 18, the carboxylic acids and their deriva(cid:173)
`in Chapters 19 and 20.
`
`Aldehydes
`
`0
`II
`CH3CH or CH3CHO.
`Acetaldehyde
`
`.(A hypnotic)·-
`
`Ketones
`
`0
`0
`II
`II
`CH3CCH3
`CH3CH2CCH3
`Propanone
`Butanone
`(Acetone)
`(Methyl ethyl ketone)
`(Common solvents)
`
`elements give rise to further characteristic functional groups. For exam(cid:173)
`nitrogen compounds are amines. The replacement of oxygen in alco(cid:173)
`sulfu.r furnishes thiols.
`
`Carboxylic Acids
`
`0
`II
`HCOH or HCOOH
`Formic acid
`
`(Strong irritant)
`
`0
`II
`CH3COH or CH3COOH
`Acetic acid
`(In vinegar)
`
`Amines
`
`H
`I
`CH3NCH3 or (CH3)2NH
`N-Methylmethanamine
`(Dimethylamine)
`
`A Thiol
`
`CH3SH
`Methanethiol
`
`(Excreted after
`we eat asparagus)
`
`the next two pages) depicts a selection of common functional
`of compounds to which they give rise, a general structure, and
`
`~al fonnula
`:, and pro(cid:173)
`ans form a
`·esult, they
`· of the al-
`
`1e
`
`kynes, re(cid:173)
`:rs 11-13.
`
`H
`
`

`

`502
`
`14
`Delocalized Pi
`Systems
`
`14m I Overlap of Three Adjacent -p Orbitals:
`.
`Resonance in the 2 .. Propenyl (Allyl) sy·sHr
`
`What is the effect of a neighboring double bond on the reactivity of a ct
`center? Three key observations answer this question.
`···
`
`Dissociation Energies
`of Various C-H Bonds
`
`OBSERVATION I. The primary carbon-hydrogen bond in propene is
`-1
`tively weak, only 87 kcal mol
`.
`
`CH2=CHCH2+H
`DH 0 = 87 kcal mol- 1
`
`(CH3)3C+H
`DH0 = 93 kcal mol- I
`
`(CH3)2CH+H
`DH° = 94.5 kcal moC 1
`
`CH3CH2+H
`DH0 = 98 kcal mol-I
`
`/
`~ H2C=C
`
`H
`
`+ H ·
`
`"' CH2·
`
`2-Propenyl
`radical
`
`'\~-,
`A comparison with the values found for other hydrocarbons (see margin)J
`that it is even weaker than a tertiary C-H bond. Evidently, the 2-propenylf~
`· ·
`enjoys some type of special stability.
`OBSERVATION 2. 3-Chloropropene dissociates relatively fast under sJf
`(solvolysis) conditions and undergoes rapid unimolecular substitution thi
`a carbocation intermediate.
`· •.
`
`H
`
`/
`H2C=C
`"'-cH2 +
`2-Propenyl
`cation
`This-finding clearly contradicts our expectations (recall Section 7-5). lt app
`that the cation derived from 3-chloropropene is somehow more stable th9,_n';J
`primary carbocations. By how much? The ease of formation of the 2-prop
`cation in s61volysis · reactions has been found to be roughly equal to th~(
`secondary carbocation.
`
`OBSERVATION 3. The pKa of propene is about 40.
`
`H
`
`/
`-"
`40= H2C=C
`._------'-
`K- 10-
`"' CH2-
`2-Propenyl anion
`
`+
`+ H
`
`...
`Thus, propene is considerably more acidic than propane· (pK8 ~ 50),
`formation of the propenyl anion by deprotonation appears unusually]a_· ·
`How can we explain these three observations?
`
`Resonance stabilizes 2~propenyl (allyl) intermediates.
`Each of the preceding three processes generates a reactive carbon 'C:eg
`radical, a carbocation, or a carbanion, respectively-that is adjacent t9,,
`framework of a double bond. This anangement seems to impart speciaLst!i
`
`

`

`The reason is resonance and the resulting electron delocalization: Each
`may be described by a pair of equivalent contributing resonance struc(cid:173)
`These three-carbon intermediates have been given the name allyl (followed
`appropriate term: radical, cation, or anion). The activated carbon is la(cid:173)
`allylic.
`
`503
`
`14-1
`Overlap of Three
`Adjacent p
`orbitals
`
`Resonance in the 2-Propenyl (Allyl) System
`
`[CH2=CH-CH2 ~ CH2-CH=CH2]
`Radical
`.
`
`or
`
`+ I \
`' ~+
`[CH2=CH-CH2 ~ CH2-CH=CH2J
`Cation
`
`•.··n
`
`f.-; ~ 0i
`
`[CH2=CH-CH2 ~ CH2-CH=CH2]
`Anion
`
`or
`
`or
`
`Remember that resonance
`forms are not isomers
`but partial molecular rep(cid:173)
`resentations. The true
`structure (the resonance
`hybrid) is derived by
`their superposition, better
`represented by the
`dotted-line drawings at
`the right of the classical
`picture.
`
`_/{~>-
`ti·2epropenyl (allyl) pi system is represented by three
`9lecular orbitals
`Wlstabilization of the 2-propenyl (allyl) system by resonance can also be de(cid:173)
`stribedin terms of molecular orbitals. Each of the three carbons is sp 2 hybridized
`;'hcfbears ap orbital perpendicular to the molecular plane (Figure 14-1). Make a
`d~l: The structure is symmetric, with equal C-C bond lengths.
`1;dgnoring the er framework, we can combine the three p orbitals mathematically
`t 0g1\ie three 'TT molecular orbitals. This process is analogous to mixing two
`,9111ic-orbitals to give two molecularotbitals·describing a 7rbond (Figures 11-1
`JI J 1.:3), except that there is now a third atomic orbital. Of the three resulting
`qlecular orbitals, one ( 'TTI) is bonding and has no nodes, one ( 'TT2 ) is nonbond(cid:173)
`lif (in other words, it has the same energy as a noninteractingp orbital) and has.
`"nfnode, and one ( 'TT3) is antibonding, with two nodes, as shown in Figure 14-2.
`,1{D~0
`
`er bond
`
`FIGURE 14!~ I The three
`p orbitals in, the 2-prop(cid:173)
`enyl (allyl) group overlap,
`giving a symmetric struc(cid:173)
`ture with delocalized elec(cid:173)
`trons. The er framework is
`shown as black lines.
`
`

`

`71'3, antibonding
`
`E
`
`71'2, nonbonding
`
`m .
`
`.
`
`.
`
`n1, bonding
`
`IFiGURE 14°'.2 The three
`n molecular orbitals of
`2-propenyl (allyl), obtained
`by combining the three
`adjacent atomic p orbitals.
`
`7T3--
`
`7T2--
`
`E
`
`~l-
`1-
`1l-
`7Tl -1l-
`-1l-
`
`•• ~ . .. - ...
`~ .. · +·•. ~ ••
`!FIGURE i 4°3 The Aufbau principle is used to fill up the 7T molecular orbit~lsJ
`2-propenyl (allyl) cation, radical, and anion. In each case the total energy of the?"
`electrons is lower than that of three noninteracting p orbitals. Partial cation, ri;dic1f
`or anion character is present at the end carbons in these systems, a result of thit"·
`tion of the lobes in the n2 molecular orbital.
`
`8
`
`We can use the Aufbau principle to fill in the appropriate number of w e\
`(Figure 14-3). The cation, with a total of two, contains only one filled o·,
`7Tl. For the radical and the anion, we place one or two electrons, respe:tf
`into the second molecular orbital, 71'2 • In all cases, the total 71'-electron eii~t·
`the system is lower (more favorable) than that expected from three nonintef'
`p orbitals-essentially because 1r1 is greatly stabilized and filled in allJ
`"c;;I
`whereas the antibonding level, 71'3, stays empty throughout.
`The resonance formulations for the three 2-propenyl species indicate tha[
`mainly the two terminal carbons that accommodate the charges in the i()11S bf
`odd electron in the radical. The molecular-orbital picture is consistent with'
`view: The three strnctures differ only in the nu_mber of electrons present infyd
`, which possesses a node passing through the central carbcm;th
`ular orbital 71'2
`fore, very little of the electron excess or deficiency will show up at this poi·
`
`Partial Electron Density Distribution in the
`2-Propenyl (Ally!) System
`
`H
`I
`C
`H2C/··~CH2
`½·
`½ •
`
`In summary, allylic radicals, cations, and anions are unusually . ..
`, .
`Lewis terms, this stabilization is readily explained by resonance. In~olesif
`orbital description, the three interacting p orbitals form three new moles
`orbitals: One is considerably lower in energy than the p level, another oge)
`the same, and a third moves up. Because only the first two are populated
`electrons, the total 7T energy of the system is lowered.
`· ···
`
`A consequence of delocalization is that resonance-stabilized allylic intenif
`can readily participate in reactions of unsaturated molecules. For exmrtp
`
`,,-,:·:t;
`
`