Third Edition
`
`ORGANIC
`
`CHEMISTRY
`
`ROBERT THORNTON MORRISON
`
`ROBERT NEILSON BOYD
`
`New York University
`
`ALLYN AND BACON, INC.
`
`BOSTON
`
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`

`
`© COPYRIGHT 1973 BY ALLYN AND BACON, INC
`© COPYRIGHT 1966 BY ALLYN AND BACON, INC.
`© COPYRIGHT 1959 BY ALLYN AND BACON, INC.
`470 ATLANTIC AVENUE, BOSTON
`
`ALL RIGHTS RESERVED
`
`No part of the material protected by this copyright notice may I
`reproduced or utilized in any form or by any means, electronic u
`mechanical, including photocopying, recording, or by any inform
`tional storage and retrieval system, without written permissiu
`from the copyright owner.
`
`LIBRARY OF CONGRESS CATALOG CARD NUMBER:
`
`7
`
`Sixth printing .
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`. August, 1974
`
`PRINTED IN THE UNITED STATES OF AMERICA
`
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`

`
`Contents
`
`Preface
`Acknowledgments
`
`vii
`
`PART I The Fundamentals
`
`Structure and Properties
`
`Methane
`
`Energy of Activation. Transition State
`
`Alkanes
`
`Free-Radical Substitution
`
`Stereochemistry I. Stereoisomers
`
`Alkenes I. Structure and Preparation
`
`Elimination
`
`Alkenes II.
`
`Bond
`
`Reactions of the Carbon-Carbon Double
`Electrophilic and Free-Radical Addition
`
`.°‘S":"E*’N""
`
`Stereochemistry II.
`Stereoisomers
`
`. Alkynes and Dienes
`
`Preparation and Reactions of
`
`. Alicyclic Hydrocarbons
`
`10.
`
`Benzene
`
`Aromatic Character
`
`11.
`
`Electrophilic Aromatic Substitution
`
`12.
`
`Arenes
`
`13.
`
`Spectroscopy and Structure
`
`iii
`
`40
`
`73
`
`115
`
`143
`
`177
`
`225
`
`248
`
`283
`
`318
`
`337
`
`372
`
`405
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`
`iv
`
`14.
`
`15.
`
`CONTENTS
`
`Alkyl Halides
`Elimination
`
`Nucleop/7ilic Aliphatic Substitution.
`
`Alcohols 1. Preparation and Physical Properties
`
`16.
`
`Alcohols ll. Reactions
`
`17.
`
`18.
`
`19.
`
`20.
`
`Ethers and Epoxides
`
`Carboxylic Acids
`
`Aldehydes and Ketones
`
`Nucleophilic Addition
`
`Functional Derivatives of Carboxylic Acids
`Nucleopbilic Acyl Substitution
`
`21.
`
`Carbanions I
`
`A Idol and Claisen Condensations
`
`22.
`
`Amines I. Preparation and Physical Properties
`
`. 23.
`
`Amines II. Reactions
`
`24.
`
`Phenols
`
`452
`
`492
`
`518
`
`552
`
`579
`
`617
`
`658
`
`701
`
`727
`
`745
`
`787
`
`PART II Special Topics
`
`25.
`
`Aryl Halides
`
`Nucleop/1ilic Aromatic Substitution
`
`817
`
`26.
`
`27.
`
`28.
`
`29.
`
`30.
`
`31.
`
`32.
`
`Carbanions II
`Syntheses
`
`Malonic Ester and A cetoacetic Ester
`
`a.,[3-Unsaturated Carbonyl Compounds
`Addition
`
`Conjugate
`
`Rearrangements
`Nonclassical Ions
`
`and Neighboring Group Effects
`
`Molecular Orbitals. Orbital Symmetry
`
`Polynuclear Aromatic Compounds
`
`Heterocyclic Compounds
`
`Macromolecules. Polymers and Polymerization
`
`846
`
`865
`
`885
`
`925
`
`967
`
`1002
`
`1027
`
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`
`120
`
`STEREOCHEMISTRY I. STEREOISOMERS
`
`CHAP. 4
`
`specific rotation —
`
`observed rotation (degrees)
`length (dm) X g/CC
`
`where d represents density for a pure liquid or concentration for a solution.
`The specific rotation is as much a property of a compound as its melting point,
`boiling point, density, or
`refractive index. Thus the specific rotation of the
`2—methyl-l-butanol obtained from fuse] oil is
`
`MD20 = ——5.756°
`
`Here 20 is the temperature and D is the wavelength ofthe light used in the measure-
`ment (D line of sodium, 5893 A).
`
`
`
`4.6 Enantiomerism: the discovery
`
`The optical activity we have just described was discovered in l8l5 at the
`College de France by the physicist Jean-Baptiste Biot.
`In 1848 at the Ecole normale in Paris the chemist Louis Pasteur made a set of
`
`observations which led him a few years later to make a proposal that is the foun-
`dation of stereochemistry. Pasteur, then a young man, had come to the Ecole
`normale from the Royal College of Besancon (where he had received his baccalau-
`rent es sciences with the rating of ntzédiocre in chemistry), and had just won his
`docteur és sciences. To gain some experience in crystallography, he was repeating
`another chemist’s earlier work on salts of tartaric acid when he saw something
`that no one had noticed before: optically inactive sodium ammonium tartrate
`existed as a mixture of two different kinds of crystals, which were mirror images of
`each other. Using a hand lens and a pair of tweezers, he carefully and laboriously
`separated the mixture into two tiny piles——one of right-handed crystals and the
`other of left-handed crystals-much as one might separate right-handed and left-
`handed gloves lying jumbled together on a shop counter. Now, although the
`original mixture was optically inactive, each set of crystals dissolved in water was
`found to be optically active! Furthermore, the specific rotations of the two solu-
`tions were exactly equal, but of opposite sign; that is to say, one solution rotated
`plane-polarized light to the right, and the other solution an equal number of
`degrees to the left. In all other properties the two substances were identical.
`Since the difference in optical rotation was observed in solution, Pasteur
`
`concluded that it was characteristic, not of the crystals, but of the molecules. He
`
`proposed that, like the two sets of crystals themselves, the molecules making up
`the crystals were mirror images of each other. He was proposing the existence of
`isomers whose structures difi"er only in being mirror images of each other, and
`whose properties differ only in the direction of rotation of polarized light.
`
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`

`
`SEC. 4.7
`
`ENANTIOMERISM AND TETRAHEDRAL CARBON
`
`121
`
`There remained only for Van’t Hoff to point out that a tetrahedral carbon atom
`would account not only for the absence of isomers of formula CH3Y and CHZYZ,
`but also for the existence of mirror-image isomers~—erzanzz'omers—-like Pasteur’s
`tartaric acids.
`
`4.7 Enantiomerism and tetrahedral carbon
`
`Let us convince ourselves that such mirror—image isomers should indeed exist.
`
`Starting with the actual, tetrahedral arrangement for methane, let us make a model
`of a compound CWXYZ, using a ball of a different color for each different atom
`or group represented as W, X, Y, and Z. Let us then imagine that we are holding
`this model before a mirror, and construct a second model of what its mirror image
`would look like. We now have two models which look something like this:
`
`YCHOW
`
`Blue
`
`G[‘€€I‘l
`
`Red
`
`mirror
`I
`
`II II
`
`I
`
`IIIIII
`
`Red
`
`Yellow
`
`Blue
`
`Green
`
`which are understood to stand for this:
`
`mirror
`I
`
`g
`I
`
`‘
`E
`I
`
`I
`
`Y
`
`Y
`
`w
`
`x
`
`Y
`
`w
`
`x
`
`Y
`
`Not superimposables isomers
`
`Are these two models superimposable? No. We may twist and turn them as
`much as we please (so long as no bonds are broken), but although two groups
`of each may coincide, the other two do not. The models are not superimposable,
`and therefore must represent two isomers of formula CWXYZ.
`As predicted, mirror-image isomers do indeed exist, and thousands of instances
`besides the tartaric acids are known. There are, for example, two isomeric lactic
`
`COOH
`
`COOH
`
`CZH5
`
`C2115
`
`H\§>_OH HO_¢H HOCH2\¢IH H‘?/CH20H
`
`CH3
`
`CH3
`
`CH3
`
`CH3
`
`Lactic acid
`
`2-Methyl-l-butanol
`
`acids and two 2-met/1yl—I-butanols,
`sec-butyl chlorides.
`
`two chloroiodomet/1anesub‘bnic acids and two
`
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`
`122
`
`STEREOCHEMISTRY I. STEREOISOMERS
`
`CHAP. ,4
`
`H
`
`H
`
`CZH5
`
`C2H5
`
`I\¢—ci C1‘?
`
`H\§}’c1 C1~—§'H
`
`S03H
`
`S03H
`
`CH3
`
`CH3
`
`Chloroiodomethanesulfonic acid
`
`sec-Butyl chloride
`
`As we can see, the structures of each pair are mirror images; as we can easily
`verify by use of models, the structures of each pair are not superimposable and
`therefore represent
`isomers.
`(In fact, we have already verified this, since the
`models we made for CWXYZ can, of course, stand for any of these.)
`At this point we do not need to know the chemistry of these compounds, or
`even what structure a particular collection of letters (~COOH, say, or —~Cl-l;,,OH)
`stands for; we can tell when atoms or groups are the same or difierent from each
`other, and whether or not a model can be superimposed on its mirror image. Even
`two isotopes of the same element, like protium (ordinary hydrogen, H) and deu-
`terium (heavy hydrogen, D) are different enough to permit detectable isomerism:
`
`CH3
`
`CH3
`
`H\§—D D«-{é/H
`
`CGHS
`
`CGHS
`
`or —Deuterioethylbenzene
`
`We must remember that everything (except, of course, a vampire) has a mirror image,
`including all molecules. Most molecules, however, are superimposable on their mirror
`images, as, for example, bromochloromethane, and do not show this mirror-image
`isomerism.
`
`mirror
`I
`
`C1
`
`H
`
`»«- H
`
`Br
`
`:
`
`II
`
`:
`I
`i
`I
`
`H
`
`H
`
`Cl
`
`Br
`
`Bromochloromethane
`
`Superimposable: no isomerism
`
`3Mi'rro"r-image ’iso’rne’rs are called *en.ant’z'on'1ers. Since they differ from one
`another only in the way the atoms are oriented in space, enantiomers belong to the
`general class called stereoisomers. Later on we shall encounter stereoisomers that
`are not mirror images of each other; these are called diastereomers. Any two stereo-
`isomers are thus classified either as enantiomers or as diastereomers, depending
`upon whether or not they are mirror images of each other.
`
`The non-superimposability of mirror images that brings about the existence of enantio-
`mers also, as we shall see, gives them their optical activity, and hence enantiofners are "
`oftenireferred to as ‘(one kind of) optical z‘so’me'rs.fiWe shall make no use of the term
`optical isomer, since" it is hard to define—indeed, is often used undefined-—an,d of doubtful
`usefulness.
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`
`SEC. 4.9
`
`PREDICTION OF ENANTIOMERISM. CHIRALITY
`
`123
`
`4.8 Enantiomerism and optical activity
`
`Most compounds do not rotate the plane of polarized light. How is it that
`some do? It is not the particular chemical family that they belong to, since optic-
`ally active compounds are found in all families. To see what special structural
`feature gives rise to optical activity, let us look more closely at what happens when
`polarized light is passed through a sample of a single pure compound.
`When a beam of polarized light passes through an individual molecule, in
`nearly every instance its plane is rotated a tiny amount by interaction with the
`charged particles of the molecule; the direction and extent of rotation varies with
`the orientation of the particular molecule in the beam. For most compounds,
`
`because of the random distribution of the large number of molecules that make up
`even the smallest sample of a single pure compound, for every molecule that the
`light encounters, there is another (identical) molecule oriented as the mirror image
`of rhefirsr, which exactly cancels its effect. The net result is no rotation, that is,
`optical inactivity. Thus optical inactivity is not a property of individual molecules,
`but rather of the random dislribzition ofmolecules that can serve as mirror images of
`each other.
`I
`
`Optical inactivity requires, then, that one molecule of a compound act as the
`mirror image of another. But in the special case of CWXYZ, we have found (Sec.
`4.7) a molecule whose mirror image is not just another, identical molecule, but
`rather a molecule of a different, isomeric compound. In a pure sample of a single
`
`enantiomer, no molecule can serve as the mirror image of another; there is no
`exact canceling-out of rotations, and the net result is optical activity. Thus, the
`same non-superimposability of mirror images that gives rise to enantiomerism
`also is responsible for optical activity.
`
`4.9 Prediction of enantiomerism. Chirality
`
`oleéziles that are n‘ot_‘sijrpér2’mposable on their ‘nrirror images ‘are ‘chiral. 2‘
`Chirality is the necessary and sufficieiit condition for the existence of enan«
`tiomers. That is to say: a compound whose molecules are chiral can exist as enant1'o-
`mers; a compouml whose molecules are achiral (without chirality) cannot exist as
`enanfiomers.
`
`When we say that a molecule and its mirror image are superimposable, we
`mean that if——in our mind’s eye—we were to bring the image from behind the
`mirror where it seems to be, it could be made to coincide in all its parts with the
`molecule. To decide whether or not
`a molecule is chiral,
`therefore, we
`
`make a model of it and a model of its mirror image, and see if we can superimpose
`them. This is the safest way, since properly handled it must give us the right
`answer. It is the method that we should use until we have become quite familiar
`with the ideas involved; even then, it is the method we should use when we en—
`
`counter a new type of compound.
`After we have become familiar with the models themselves, ‘we can draw
`
`pictures of the models, and mentally try to superimpose them. Some, we find, are
`not superimposable, like these:
`
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`
`124
`
`STEREOCHEMISTRY I. STEREOISOMERS
`
`CHAP. 4
`
`mirror
`I
`
`I II
`
`1
`
`SO3H
`
`Cl
`
`1
`
`I l
`
`1
`
`C1
`
`SO3H
`
`Chloroiodomethanesulfonic acid
`
`Not superimposable: enantiomers
`
`These molecules are chiral, and we know that chloroiodomethanesulfonic acid can
`exist as enantiomers, which have the structures we have just made or drawn.
`Others, we find, are superimposable, like these:
`mirror
`
`CH3
`
`CH3
`
`CH3
`
`CH3
`
`Cl
`
`Cl
`
`Isopropyl chloride
`Superimposable : no enantiomers
`
`These molecules are achiral, and so we know that isopropyl chloride cannot exist
`as enantiomers.
`
`“I call any geometrical figure, or any group of points, chiral, and say it has
`clurality, if its image in a plane mirror, ideally realized, cannot be brought to coin-
`cide with itself.”—~Lord Kelvin, 1893.
`
`In 1964, Cahn, Ingold, and Prelog (see p. 130) proposed that chemists use the terms
`“chiral” and “chirality” as defined by Kelvin. Based on the Greek word for “hand”
`(clzeir), chirality means “handedness,” in reference to that pair of non-superimposable
`mirror images we constantly have before us: our two hands. There has been wide—spread
`acceptance of Kelvin’s terms, and they have largely displaced the earlier “dissymmetric”
`and “dissymmetry” (and the still earlier——and less accurate-“asymmetric” and “asym-
`metry”), although one must expect to encounter the older terms in the older chemical
`literature.
`
`Whatever one calls it, it is non—superimposability-on-mirror-image that is the neces-
`sary and sufiicient condition for enantiomerism; it is also a necessary-but not suflicient~
`condition for optical activity (see Sec. 4.13).
`
`4.10 The chiral center
`
`So far, all the chiral molecules we have talked about happen to be of the kind
`CWXYZ; that is, in each molecule there is a carbon (C"‘) that holds four different
`groups.
`
`‘F
`C2H5~*C|*—-CHZOH
`
`5‘
`CH3—(!:’*—*COOH
`
`5‘
`C2H5——(JI*-CH3
`
`‘F
` (%*—CH3
`
`CH3
`
`OH
`
`Cl
`
`D
`
`2-Methyl-l—butanol
`
`Lactic acid
`
`sec-Butyl chloride
`
`oz-Deuterioethylbenzene
`
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`
`SEC. 4.10
`
`THE CHIRAL CENTER
`
`125
`
`A carbonatom‘ to which four difl'ehen‘t groups:a?r.e attachedzzis a chiral center. (Some-
`times it is called chiral carbon. when it is necessary to distinguish it from chiral
`
`nitrogen, chiral phosphorus, etc.)
`Many—but not all——molecules that contain a chiral center are chiral. Many——
`but not all~—chiral molecules contain a chiral center. There are molecules that
`
`contain chiral centers and yet are achiral (Sec. 4.18). There are chiral molecules
`that contain no chiral centers (see, for example, Problem 6, p. 315).
`The presence or absence of a chiral center isithus no criterion of chigr-ality.
`However, most of the chiral molecules that we shall take up do contain chiral
`centers, and it will be useful for us to look for such centers; if we find a chiral
`
`center, then we should consider the possibility that the molecule is chiral, and
`hence can exist in enantiomeric forms. We shall later (Sec. 4.18) learn to recognize
`the kind of molecule that may be achiral in spite of the presence of chiral centers;
`such molecules contain more than one chiral center.
`
`After becoming familiar with the use of models and of pictures of models,
`the student can make use of even simpler representations of molecules containing
`chiral centers, which can be drawn much faster. This is a more dangerous method,
`
`however, and must be used properly to give the right answers. We simply draw a
`cross and attach to the four ends the four groups that are attached to the chiral
`center. The chiral center is understood to be located where the lines cross. Chemists
`
`have agreed that such a diagram stands for a particular structure: the horizontal
`lines represent bonds coming toward us out of the plane of the paper, whereas the
`vertical lines represent bona's going away from us behind the plane of the paper.
`That is to say:
`
`CZH5
`
`C2!-I5
`
`H\.éD{c1 of
`
`CH,
`
`CH,
`
`can be represented by
`
`C2H5
`
`H—-1——~Cl
`
`CH3
`
`C2H5
`
`c1+H
`
`CH3
`
`In testing the superimposability of two of these flat, two—dimensional repre-
`sentations of three—dimensional objects, we must follow a certain procedure and
`obey certain rules. First, we use these representations only for molecules that
`contain a chiral center. Second, we draw one of them, and then draw the other as
`
`its mirror image. (Drawing these formulas at random can lead to some interesting
`but quite wrong conclusions about isomer numbers.) Third, in our mind’s eye we
`may slide these formulas or rotate them end for end, but we may not remove them
`from the plane of the paper. Used with caution, this method of representation is
`convenient; it is not foolproof, however, and in doubtful cases models or pictures
`of models should be used.
`‘
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`
`126
`
`STEREOCHEMISTRY I. STEREOISOMERS
`
`CHAP. 4
`
`
`
`4.11 Enantiomers
`
`Isomers that are mirror images of each other are called enantiomers. The two
`different lactic acids whose models we made in Sec. 4.7 are enantiomers (Gr.:
`enantio-, opposite). So are the two 2—methyl-l-butanols, the two sec—butyl chlorides,
`etc. How do the ‘properties of enantiomers compare?
`Enantiomers have identical physical properties, except for the direction of
`rotation of the plane of polarized light. The two 2—methy1-l-butanols, for example,
`
`(+ )-2-Methyl-1-butanol
`
`(— )-2—Methyl-1-butanol
`(Fermentation Product)
`
`Specific rotation
`Boiling point
`Density
`Refractive index
`
`+ 5.756’
`l28.9°
`0.8193
`1.4107
`
`’
`
`-5.756’
`128.9“
`0.8193
`1.4107
`
`have identical melting points, boiling points, densities, refractive indices, and any
`other physical constant one might measure, except for this: one rotates plane-
`polarized light to the right, the other to the left. This fact is not surprising, since
`the interactions of both kinds of molecule with their fellows should be the same.
`
`Only the direction’ of rotation is different; the amount of rotation is the same, the
`specific rotation of one being +5.756°, the other -5.756’. It is reasonable that
`these molecules, being so similar, can rotate light by the same amount. The
`molecules are mirror images, and so are their properties: the mirror image of a
`clockwise rotation is a counterclockwise rotation-—and of exactly the same
`magnitttde.
`
`Enantiomers have identical chemical properties except toward optically active
`reagents. The two lactic acids are not only acids, but acids of exactly the same
`strength; that is, dissolved in water at the same concentration, both ionize to
`exactly the same degree. The two 2-methyl—1-butanols not only form the same
`productsmalkenes on treatment with hot sulfuric acid, alkyl bromides on treatment
`with HBr, esters on treatment with acetic acid—but also form them at exactly the
`same rate. This is quite reasonable, since the atoms undergoing attack in each
`case are influenced in their reactivity by exactly the same combination of substi-
`tuents. The reagent approaching either kind of molecule encounters the same
`environment, except, of course, that one environment is the mirror image of the
`other.
`
`In the special case of a reagent that is itself optically active, on the other hand,
`the influences exerted on the reagent are not identical in the attack on the two
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`SEC. 4.12
`
`THE RACEMIC MODIFICATION
`
`127
`
`enantiomers, and reaction rates will be difi"erent—so different, in some cases, that
`reaction with one isomer does not take place at all. In biological systems, for
`example, such stereochemical specificity is the rule rather than the exception, since
`the all-important catalysts, enzymes, and most of the compounds they work on,
`are optically active. The sugar (+)-glucose plays a unique role in animal metab-
`olism (Sec. 34.3) and is the basis of a multimillion-dollar fermentation industry
`(See. 15.5); yet (—)-glucose is neither metabolized by animals nor fermented by
`yeasts. When the mold Penicilliunt glaucum feeds on a mixture of enantiomeric
`tartaric acids, it consumes only the (+)-enantiomer and leaves (—)-tartaric acid
`behind. The hormonal activity of (—)—adrenaline is many times that of its enantio-
`mer; only one stereoisomer of chloromycetin is an antibiotic. (+)-Ephedrine not
`only has no activity as a drug, but actually interferes with the action of its enan-
`tiomer. Among amino acids, only one asparagine and one leucine are sweet, and
`only one glutamic acid enhances the flavor of food. It is (—)-carvone that gives
`oil of spearmint its characteristic odor; yet the enantiomeric (+)—carvone is the
`essence of caraway.
`Consider, as a crude analogy, a right and left hand of equal strength (the
`enantiomers) hammering a nail (an optically inactive reagent) and inserting a
`right—handed screw (an optically active reagent). Hammering requires exactly
`corresponding sets of muscles in the two hands, and can be done at identical rates.
`Inserting the screw uses different sets of muscles:
`the right thumb pushes, for
`example, whereas the left thumb pulls.
`Or, let us consider reactivity in the most precise way we know: by the tran-
`sition-state approach (Sec. 2.22).
`Take first the reactions of two enantiomers with an optically inactive reagent.
`The reactants in both cases are of exactly the same energy: one enantiomer plus
`the reagent, and the other enantiomer plus the same reagent. The two transition
`states for the reactions are mirror images (they are enantiomeric), and hence are
`of exactly the same energy, too. Therefore, tlieienergy diilferences.between.re‘ac«
`tants and transition states+—-the E,,m,’s——:are ide1it:ica1,—and so-are the —ratesVof
`reaction.
`
`Now take the reactions of two enantiomers with an optically active reagent.
`Again the reactants are of the same energy. The two transition states, however,
`are not mirror images of each other (they are diastereorneric), and hence are of
`diflerent energies; the Eacjs are different, and so are the rates of reaction.
`
`4.12 The racemic modification
`
`_‘A: mz‘xture._of equal parts of enantiomers ‘iscalled a racemic "modification. A
`racemic moclzfication .z's.optically inactive.‘ when f€I13IltlO1’T16I'S' are mixed together,
`the rotation. caused by a molecule of one isomer. is exactly canceled by anequal and
`opposite rotation caused by amolecule of it—s,e11an_tiomer.
`The prefix j-_ is used to specify the racemic nature of the particular sample, as,
`for example, (i)—lactic acid or (i )-2—1nethyl~l-butanol.
`It is useful
`to compare a racemic modification with a compound whose
`molecules are superimposable on their mirror images, that is, with an achiral
`compound. They are both optically inactive, and for exactly the same reason.
`Because of the random distribution of the large number of molecules, for every
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`128
`
`STEREOCHEMISTRY l. STEREOISOMERS
`
`CHAP. 4
`
`molecule that the light encounters there is a second molecule, a mirror image of
`the first, aligned just right to cancel the effect of the first one. ln a racemic modifica-
`tion this second molecule happens to be an isomer of the first; for an achiral com~
`pound it is not an isomer, but another, identical molecule (Sec. 4.8).
`(For an optically active substance uncontaminated by its enantiomer, we have
`seen, such cancellation of rotation cannot occur since no other molecule can serve
`
`as the mirror image of another, no matter how random the distribution.)
`
`
`
`The identity of most physical properties of enantiomers has one consequence
`of great practical significance. They cannot be separated by ordinary methods:
`not by fractional distillation, because their boiling points are identical; not by
`fractional crystallization, because their solubilities in a given solvent are identical
`(unless the solvent is optically active); not by chromatography, because they are
`held equally strongly on a given adsorbent (unless it
`is optically active). The
`separation of a racemic modification into enantiomers~—the resolution of a racemic
`modification-«is therefore a special kind of job, and requires a special kind of
`approach (Sec. 7.9).
`
`The first resolution was, of course, the one Pasteur carried out with his hand lens and
`tweezers (Sec. 4.6). But this method can almost never be used, since racemic modifica-
`tions seldom form mixtures of crystals recognizable as mirror images. Indeed, even
`sodium ammonium tartrate does not, unless it crystallizes at a temperature below 28°.
`Thus partial credit for Pasteur’s discovery has been given to the cool Parisian climate»-
`and, of course, to the availability of tartaric acid from the winemakers of France.
`The method of resolution nearly always used—~one also discovered by Pasteur———
`involves the use of optically active reagents, and is described in Sec. 7.9.
`Although popularly known chiefly for his great work in bacteriology and medicine,
`Pasteur was by training a chemist, and his work in chemistry alone would have earned him
`a position as an outstanding scientist.
`
`4.13 Optical activity: a closer look
`
`We have seen (Sec. 4.8) that, like enantiomerism, opticalaetivity results fromw
`and only from—4—chirality: "the non-suiperimposability of certain molecules on their -
`mirror images. Whenever we observe (molecular) optical activity, we know we are
`dealing with chiral molecules.
`Is the reverse true ? Whenever we deal with chiral molecules——with compounds
`that exist as enantiomers——must we always observe optical activity? No. We have
`just seen that a 50:50 mixture of enantiomers is optically inactive. Clearly, if we
`are to observe optical activity, the material we are dealing with must contain an
`excess of one enantiomer: enough of an excess that the net optical rotation can
`be detected by the particular polarimeter at hand.
`Furthermore, this excess of one enantiomer must persist long enough for the
`optical activity to be measured. If the enantiomers are rapidly interconverted,
`then before we could measure the optical activity due to one enantiomer, it would
`be converted into an equilibrium mixture, which——since enantiomers are of exactly
`the same stability——~must be a 50:50 mixture and optically inactive.
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`SEC. 4.14
`
`CONFIGURATION
`
`129
`
`Even if all these conditions are met, the magnitude——and hence the detectability-
`of the optical rotation depends on the structure of the particular molecule concerned.
`In compound I, for example, the four groups attached to the chiral center differ only in
`chain length.
`
`(|3H2CH3
`CH3CHZCH2CH2CH2CH2—~$——CH2CH2CH2CH3
`CH ZCH 2CH 3
`I
`
`Ethyl-n-propyl-n-butyl—n—hexylmethane
`
`It has been calculated that this compound should have the tiny specific rotation of 0.0000l°
`——far below the limits of detection by any existing polarimeter. In 1965, enantiomerically
`pure samples of both enantiomers of I were prepared (see Problem 19, p. 1026), and each
`was found to be optically inactive.
`
`At our present level of study, the matter of speed of interconversion will give
`us no particular trouble. Nearly all the chiral molecules we encounter in this book
`lie at either of two extremes, which we shall easily recognize: (a) molecules—like
`those described in this chapter—which owe their chirality to chiral centers; here
`interconversion of enantiomers (configurational enantiomers) is so sl0w—~—because
`bonds have to be broken——that we need not concern ourselves at all about inter-
`conversion; (b) molecules whose enantiomeric forms (conformational enantiomers)
`are interconvertible simply by rotations about single bonds; here—for the com-
`pounds we shall encounter—interconversion is so fast that ordinarily we need not
`concern ourselves at all about the existence of the enantiomers.
`
`4.14 Configuration
`
`The arrangement of atoms that characterizes a particular stereoisomer is called
`its configuration.
`Using the test of superimposability, we conclude, for example, that there are
`two stereoisomeric sec-butyl chlorides; their configurations are I and II. Let us
`
`C2“:
`
`C2H5
`
`H
`
`C1
`
`C1
`
`H
`
`CH3
`
`1
`
`CH3
`
`II
`
`sec-Butyl chloride
`
`say that, by methods we shall take up later (Sec. 7.9), we have obtained in the
`laboratory samples of two compounds of formula CZHSCHCICH3. We find that
`one rotates the plane of polarized light to the right, and the other to the left; we
`put them into two bottles, one labeled “(+)—sec-butyl chloride” and the other
`“ ( — )—sec-butyl chloride.”
`We have made two models to represent the two configurations of this chloride.
`We have isolated two isomeric compounds of the proper formula. Now the
`question arises, which configuration does each isomer have? Does the (+)-isomer,
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`139
`
`STEREOCHEMISTRY I. STEREOISOMERS
`
`CHAP. 4
`
`say, have configuration I or configuration 11? How do we know which structural
`formula, I or II, to draw on the label of each bottle? That is to say, how do we
`assign configuration?
`Until 1949 the question of configuration could not be answered in an absolute
`sense for any optically active compound. But in that year I. M. Bijvoet—most
`fittingly Director of the van’t Hoff Laboratory at the University of Utrecht (Sec.
`4.2)—reported that, using a special kind of x—ray analysis (the method of anomalous
`scattering), he had determined the actual arrangement in space of the atoms of an
`optically active compound. The compound was a salt of (+)-tartaric acid, the
`same acid that—~almost exactly 100 years before——had led Pasteur to his discovery
`of optical isomerism. Over the years prior to 1949, the relationships between the
`configuration of (+)-tartaric acid and the configurations of hundreds of optically
`active compounds had been worked out (by methods that we shall take up later,
`Sec. 7.5); when the configuration of (+)—tartaric acid became known, these other
`configurations,
`too,
`immediately became known. (In the case of the sec-butyl
`chlorides, for example, the (—)-isomer is known to have configuration I, and the
`(+)-isomer configuration II.)
`
`4.15 Specification of configuration: R and S
`
`Now, a further problem arises. How can we specify a particular configuration
`in some simpler, more convenient way than by always having to draw its picture?
`The most generally useful way yet suggested is the use of the prefixes R and S.
`According to a procedure proposed by R. S. Cahn (The Chemical Society, London),
`Sir Christopher Ingold (University College, London), and V. Prelog (Eidgenossiche
`Technische Hochschule, Zurich), two steps are involved.
`Step 1. Following a set of sequence rules (Sec. 4.16), we assign a sequence of
`priority to the four atoms or groups of atoms attached to the chiral center.
`in the case of CHClBrl, for example, the four atoms attached to the chiral
`center are all difierent and priority’ depends simply on atomic number, the atom
`of higher number having higher priority.