Unit 3 Stereochemistry I1: Structure
Unit 3 Stereochemistry I1: Structure
Unit 3 Stereochemistry I1: Structure
Structure
Introduction
Objectives
Configuration and Fischer Projection Formulas
Configurational Notations
Racemic Mixtures and their Resolution
Asymmetric Synthesis
Walden inversion
Conformational Isomers and their Representation
Conformations of Ethane
Conformations of Butane
Conformations of Cyclic Systems
Conformationf of Cyclohexane
Conformations of Monosubstituted Cyclohexane Derivatives
Conformations of Disubstituted Cyclohexane Derivatives
Summary
Terminal Questions
Answers
3.1 INTRODUCTION
In Unit 2, you studied the geometrical and optical isomerism. The arrangement of
atoms or groups in space about a rigid frainework was referred to as
'configuratiba' in Unit 2. In geometrical isomerism you learnt that the geometrical
isomers can be assigned the configuration as cis- or trans- and E- or 2-,
depending upon the spatial arrangement of groups about the rigid framework. You
also studied about the existence of optical isomers such as enantiomers and
diastereomers. These optical isomers have different configurations,
In this unit, you will study how to designate the configuration of optical isomers.
We will also discuss how configuration is affected in chemical reactions. Under the
laboratory conditions, chemical reactions yield an equimolar mixture of the two
enatfttiomers. Here, you will also learn how to separate these mixtures in order to
obtain optically pure compounds.
Then we will shift the focus of our attention to conformational isomers and study
the conformational isomerism of simple straight chain and cyclic hydrocarbons.
Objectives ,
The term configuration was used earlier in case of geometrical isomers to indicate
the spatial arrangement of groups around a rigid framework. Similarly, the term
Fundamental Concepts configuration as applied to optical isomers indicates the spatial arrangemenr of
atoms or groups around the chiral centre.
You know that the actual molecules are three-dimensional in nature. SO, the spatial
arrangement of groups in a molecule, i.e. its configuration, can be specified either
by making its three-dimensional model or by writing the corresponding projection
formulas. Also, to specify the configuration of a molecule having several chiral
centres, the configuration at each chiral centre needs to be specified.
This specification of configuration for a molecule becomes more and more difficult
as the number of chiral centres goes on increasing. Thus, a need was felt for a
convention to represent the actual three-dimensional structure of molecules In two
dimensions, (i-e. in the plane of the paper) in a simple and convenient way. The
German chemist Fischer introduced such a convention. He called his
representations as projection formulas. These representations are now known after
his name as Fischer projection formulas.
Before proceeding to the study of Fischer projection formulas, it is necessary to
familiarise you with another representation known as perspective drawing. Such a
representation is used to represent three-dimensional structures of molecules in two
Emil Fischer
(Received Nobel Prize in 1902)
dimensions. Fig. 3.l(a) illustrates such a perspective drawing. In a perspective
drawing, a broken wedge represents the bond which is behind the plane of the
A Flscher projection formula 1s a -paper and the solid wedge represents the bond which points towards the observer
standard way of depicting in front of the plane of the paper. The other two bonds which are represented by
tetrahedral carbon atoms and ordinary lines show the substituents which are in the plane of the paper.
their substituents in two
d~menslons.
Let us !low learn how to write Fischer projection formula of the molecule whose
perspective drawing is shown in Fig. 3.l(a). It is better if you take the help of the
models supplied to you. Make a model of such a molecule by attaching four
different substituents to a tetrahedral carbon atom. Now look at the model in such
a way that the two substituents which point towards you are in the horizontal
plane and the other two substituents which point away from you are in the vertical
plane, as shown in Fig. 3.l(a). You can see in Fig. 3.l(b) that the angle between
the horizontal and vertical planes is a right angle. Hence, the substituents in the
horizontal plane are at right angles to the substituents in the vertical plane. We can
represent these two sets of substituents at right angles to each other in one plane
(obviously plane of paper), by drawing two lines at right angles to each other.
Then, the substituents are written in the position they appear to the observer, i.e.
the substituents which are at left and right of the observer are written at left and
plane of projection
Fischer
projection formula
c /"
OH
plane containing
plane"contarn1ng
methyl and ethyl
tyydrogcn atom and
groups
hydroxyl gioUp
Fig. 3.1 : Writing Fischer projection formula lor a moltcute :(a) perepecUve drawing of it molecnle
having one chirat arbon atom; (b) two substituents each in horlzoalal and vertical planes at
right angles to each other; (c) represcatation of moiecule in plane of paper; and (d) the
A2 Flacher projection fbrmuh.
right, respectively, and the other two substituents which appear above and below Stereochemistry - II
are written at above and below positions, as shown in Fig. 3.l(c). Further, we can
simplify Fig. 3.l(c) by removing the plane of paper shown in it and write the
structure of the molecule as shown in Fig. 3.1 (d), which is nothing but the Fiscber
projection formula for the compound shown in Fig. 3.l(a). Note that the chiral
centre is not shown in Fischer projections and it is assumed to be located at the
point of intersection of the horizontal and vertical lines.
Similarly, the Fischer projection formula for one of the isomers of tartaric acid,
shown in Fig. 3.2(a), can be written as shown in Fig. 3.2(b).
COOH
The Fischer projections are very useful in case of molecules having many chiral
centres linked together to form a continuous chain. You will realise in Unit 20 of
Block 4 of this course the importance of these projection formulas in writing the
structures of carbohydrates.
Let us now learn the reverse of what we have done above, i.e. write the three-
dimensional structure of a molecule from its Fischer projections. For this, we have
to reverse the process we have just described. Always remember that in a Fischer
projection formula the vedcal lines represent the bonds that point away from you
and the horizontal lines represent the bonds that point towards you. Let us start
with a molecule having the Fischer projections as given below,
~r +
H
CH3
CI
The three-dimensional structure for this molecule can be written by using the
following steps:
i) Write a carbon atom at the intersection of the horizontal arld vertical lines in
Fischer projections, as shown below.
CH3
I
Br-C-C1
I
H
ii) Since the vertical lines represent the bonds away from the o b s e ~ e rand the
horizontal lines represent the bonds towards the observer, we can write the
structure of the molecule shown in step (i) as,
CH3
H
Fundamental Coneepts This can be translated into the perspective formula by viewing the molecule in such
a way that the two substituents (say, CH3 and Br) are parallel to the plane of the
While studying step (ii), use
paper. In such a situation, H will appear behind the plane of the paper and C1 will
models for wntlng the appear projecting in front of the plane of the paper leading to the perspective
- ~ r s p t i v efonnula. drawing of. the molecule as,
Different representations of How to interconvert Fischer Projections while maintaining the Configuration
--
(+) 2 bromobutane. Since there are many ways in which a given *moleculecan be oriented depending
upon which two substituents are chosen to point towards the observer; hence,
several different Fischer projections can be written for the same molecule. Let us
Br go back to Fig. 3.1 and instead of viewing the molecule as shown in Fig. 3.l(a),
/
'
H-C now let us view the molecule in such a way that the substituents CH3 and H point
~ C H ,
CHZCH~ towards the observer. Thus, the substituents will now appear as shown below.
Br \ For this orientation of the molecule, the Fischer projection formula can be written
C-H
as,
J I
.' ... . ~ , . , OH
I
I ~H~CH, which is another Fischer projection formula for the.same molecule as shown in
I Br Fig. 3.l(a). Because various Fischer projections are possible for a given molecule,
I
you should have a clear understanding of writing different correct Fischer
projections for a given molecule without going back and forth to the three-
I H dimensional model. Therefore, you should be able to write different Fisoher
projections for the same molecule from its given Fischer projection formula. For
this, there are some rules to be followed. These rules are as given below.
Actlvity 1. Rotation of the given Fischer projection tormula by 180" in the plane of the
paper yields another Fischer projection of the same molecule, i.e., ,
corresponding to the two
Fischer projection formulas
shown in rule 1. You can see
that they represent the two
Fischer projections of the
In other words, rotation of the Fischer projection in the plane of paper by 180'. !Stereocbeinistry- I1
does not alter the configuration.
Activity
2. Rotation of a Fischer projection formula of a compound in the plane of the
paper by 90" yields the Fischer projection formula of its enantiomer. It means
that such a rotation leads to a change in the configuration at the chiral centre. having a chiral carbon atam
Knked to four different
This is illustrated in the following example. substituents 1, 2, 3 and 4 as
shown below:
F* F, Br
C -
- c '*
rotation by 90°+ 1' ~ C I
Br I' '~r
3. A Fischer projection formula may not be lifted out of the plane of the paper
and turned over as showh below.
It has the following Fischer
projections, given by (a). I
Turn over
Br--+ CI ----j c l + Br
FORBIDDEN
This turn over leads to the Fischer projection formula of the enantiomer.
Thus, this operation on the Fischer projection changes the configuration at the
chiral centre. (b)
Make a model of the molecule
4. Interchange of two pairs of substituents leads to another Fischer projection of corresponding to the Fischer
the same isomer. Hence, no change in configuration is observed by this projection formula shown in (b)
operation. Let us understand this by the following example. If we have a as,
molecule represented by the following Fischer projection,
CHO
CH20H
On comparing these two models,
Interchange of one pair of substituents (i.e., - CHO and -CH20H) leads to YOU will find that they represent
the Fischer projection, the enantiomers.
CHzOH
I
CHO
Another interchange of second pair of substituents leads to the Fischer
projection as
H - 7 :
CHO
This when rotated by 180" yields
In the next section, you will learn about the specification of the configuration at a
given chiral centre. Before that check your knowledge of Fischer projections, by
answering the following SAQ.
Fundamental Concepb SAQ 1
Study each of the following pairs of Fischer projections carefully and decide
whether they represent the same isomer or an enantiomeric pair.
OH
(a)
....................................................................................................
i....,
3.3
-
CONFIGURATIONAL
-NOTATIONS
The existence of enantiomers poses special problem of their nomenclature. As the
enantiomers differ from each other in their sign of rotation, prefixes d and I were
used earlier to designate the dextrorotatory and levorotatory isomers, respectively.
But it was realised that the sign of rotation does not tell about the absolute
configuration of the compound. Thus, to define the structure of a compound
completely, it was necessary to specify the configuration at each chiral centre.
One of the earliest attempts to specify the configuration is that of Fischer which
dates back to 1891. According to thls system, the configuration at a particular
carbon atom is designated by selecting a main chain in the molecule in the sense of
C!H~OH
glyceraldehyde the rules laid for nomenclature. The molecule is then oriented vertically in such a
way that the carbon atom numbered 1 in the chain is at the top. Then, the main
There is also a convention that substituent attached to the chiral centre is looked for. For example, in
the longest carbon chain forms glyceraldehyde, it is an -OH group. If in the Fischer projections of the compound
the vertical back bone of the the main substituent group is on the right, then the molecule is said to have D
Fischer projections with the most
highly oxidised carbon (if any) at configuration and when this main substituent is on the left, then the molecule is
the iop; and then the substituents said to have L configuration.
are projected horizontally.
Rosanoff (1906) suggested that a particular configuration be assigned to (+)-
Do not confuse d and I with D glyceraldehyde. The Fischer projection corresponding to this configuration is given
hnd L. The lower-case d and I below.
were used in many places in
older literature to specify the
direction o f rotation
(synonymously with ' + ' and
'- '). But D and L are used to
specify the configuration at the
chiral centre.
Thus, according to this system of designation of configuration as D or L. the
carbon chain in (+)-glyceraldehyde can be numbered and oriented as shown .
above. Here, the substituent on the chiral centre is hydroxyl (-OH) group. Since it
is on the right side, hence, (+)-glyceraldehyde has D configuration. Similarly, the' Stereochemlstry - 11
enantiomer of (+)-glyceraldehyde, i.e. (-)-glyceraldehyde will have L
configuration. Thus, we can designate the two enantiomers as D-(+)-
glyceraldehyde and L-(-)-glyceralkiehyde. Also a71 compounds having an The D, L system is useful in
arrangement of atoms similar to that at the chiral centre of (+)-glyceraldehyde at Specifying the for
the corresponding carbon atom are members of the D family. Similarly, we can carbohydrates and amin
state for the L family. Some examples of compounds belonging to D and L In the light of the fact tL-' "-
families are listed helow:
CHO Trx T n
evidences realised that the
COOH
D - ( + )-glycer- D - ( - )-lactic D - ( - )-tartaric
-aldehyle acid acid
COOH
L-( -)-glyceraldehyde L-(+ )-lactic arid
d L-(+ )-tartaric acid
The D, L system can be applied only-w-ien the main chain and the main
substituents can be unambiguously chosen; hence, in some cases, it is not possible
to assign the configuration by this system. For example, the molecules of the type
C1
I
F-C-H
cannot be assigned configuration according to. this system. Also there are cases
when it is difficult to assign.the configuration unambiguously to the molecules
contai;ing more than one chiral centre.
Thus, a more systematic way of denoting configurations was needed. The system
that emerged is called the R, S convention and is based on the actual three-
dimensional formula of the compound to be named. In this system, the
configuration at the chiral centre is assigned by assigning the order of yrr-edence
to the grdups attached to the chiral centre according to the specific set of rules.
These rules have been already listed as Cahn-Ingold-Prelog priority rules in Unit 2..
According to this.system, the configuration of a given chiral centre can be assigned
using the following steps:
1. Identify the four substituents attached to the carbon atom for which the
configuration is to be assigned.
2. Arrange these substittlents in the decreasing order of priority as
1 '> 2 s 3 > 4 which is determined by Cahn-Ingold-Prelog rules.
3. View the molecule in such a way that the substituent of lowest priority is away
from the observer.
I Fundamental Concepts
atom of lowest
priority away
from observer
4. When the.molecule is viewed in the way as suggested in step 3, the remaining
substituents 1, 2 and 3 appear as spokes of a wheel, with the carbon atom at
the centre of the wheel. as shown below.
clockwise;
therefore R
Now, trace a path starting from the substituent of highest priority to the substituent
next in order of priority, i.e., from 1 to 2 to 3. If this path is in clockwise
direction, as in the case of arrangement shown above, then the chiral centre is said
to have the R configuration (R from rectus, a Latin word meaning: right).
If this path from 1 to 2 to 3 has an anticlockwise direction, then the chiral centre
is said to have the S configuration (S from sinister, a Latin word meaning: left),
anticlockwise;
therefore S
Since the assignment of R or S configuration to the molecule requires a specific
orientation of the molecule in sp'ace, you should be able to write the three-
dimensional orientation of a molecule from its Fischer projections and vice versa.
Let us now take the example of D-(+)-glyceraldehyde and see how the
coofiguration at the chiral centre of a molecule can be assigned starting from its
Fischer projection. The Fischer projection formula of D-( + )-glyceraldehyde can
2
CHO
be written as H I OH The four substituents attached to the chiral
4 1
centre have the order of priorities as shown by the numbers 1 > 2 > 3 > 4.
Now, the molecule is to be viewed in such a way that the substituent of lowest
priority, numbered 4, which is a hydrogen in this case, is away from the viewer. In
ather words, in the Fischer projection formula, this substituent should find a-place
at the bottom end. Thus, we have to transform the above Fischer projection into
another Fischer ~roiectionas shown below:
T h l ~new Fischer projection corresponds to the following perspective drawing. Slereochemiclr) - I t
1
H0H.C C 4 CHO
3 2
H
4
The molecule is then projected in such a way that H is at the back.
I
OH
Use models to understand the
I transformations from perspective
H (C '-c*O drawing to the assignment of
HOHlC 2 configuratron.
3
Then, by overlooking this H, path from 1 - 2 -- 3 is traced as illustrNed below.
There is another way which allows the assignment of configuration without having
to visualise the three-dimensional structure of the molecule. Let us study it.
I
4 -----, neglect it and tmce the palh
from 1 to 2 to 3. Since this
path is in clockwise direction,
hence the configuration is R.
Similarly, in case of ( + )-2-butanol, H
the order of priority of substituents is OH > CH3CH, > CH3 > H. If the
I 2 3 4
molecule is viewed in such a way that the H is at the back, then the other
substituents appear as shown below:
Now trace the path from 1 to 2 to 3 which is anticisckwise in this case. Hence, the
configuration of the Carbon atom marked by asterisk (*) is S.
In the compounds containing more than one chiral centre, the configuration is
specified at each of these centres. For example, in case of 2,3-dichlorobutane. the
priorities of substituents at the C-2 and 61-3 chiral centres are C1 > -&H >
I 2\
CH3
CH3 > H. Focusing our attention on C-2 carbon, the path from substituents 1 to
3 4
2 to 3 has anticlockwise direction; hence, it has S configuration. Similarly, at C-3
carbon also, tbe path from 1 to 2 to 3 is in anticlockwise direction. Hence, it also
has S configuration. Thus, this isomer of 2,3-dichlorobutane is named as,
With the determination of (2S, 35')-2,3-dichlorobutane.
absolute configuration of (+)-
tartaric acid, the absolute -
configuration of its enantiomer It is not difficult to decide whether a molecule 'has R or S configuration if the
(-)-tartaric acid was also actual arrangement of the groups about the chiral centre is known. But, how to
established. The (-)- tartaric acid determine the actual arrangement of the groups? Until 1951, the absolute
and ( + )- glyceraldehyde were configuration of any optically active compound was not known. In 1951, Bijvoet
known to have the same relative
configuration. ,Thus, the absolute
determined the absolute configuration of (+)-tartaric acid using a soehisticated
configuration of modification of X-ray diffraction called anomalous dispersion. Then, the absolute
( + )-glyceraldehyde was also configurations of all other compounds whose configurations had been related to
established; and the configuration (+)-tartaric acid were also revealed.
assigned earlier to
(+)-glyceraldehyde arbitrarily To determine the configuration, one must have a pure sample of the compound.
was found to be correct. But this is not usually the case and most ofLen in chemical reactions one gets a
mixture of enantiomers. In the next section, we will study in detail about these
mixtures and their separation into enantiomers. Before that answer the following
SAQ.
SAQ 2
Assign the configuration as R or S to each of the following compounds:
Stereochemistry - I1
3.4 RACEMIC MIXTURES AND THEIR RESOLUTION
The pfiysical properties of a racemic mixture are different from those of the pure
enantiomers. For example, the melting point of the either enantiomer of
t-hydroxypropanoic acid (lactic acid) is 326 K but the racemic 2-hydroxypropanoic
acid (lactic acid) has a melting point of 291 K. Also, since a racemic mixture
contains equal amounts of enantiomers, optical rotation of one enmtiomer is
cancelled by an equal and opposite rotation of the other enantiomer. Hence, a
racemic mixture is optically inactive although its constituents are optically active.
the iodide group is substituted by the hydroxide group. When the incoming
group (OH- group in this case) is a nucleophile, (means seeking a nucleus;
obviously an electron rich species), then the reaction is called nucleophilic
substitution reaction.
The nucieophilic substitution reactions can be unimolecular or bimolecular,
depending upon the number of molecules involved in the rate-determining step
of the reaction. When the rate-determining step involves a single molecule, the
reaction is called a u~imolecularsubstitution reaction and is denoted as S1,.
The S,1 reactions involve a positively charged carbon atom as an intermediate
which is called a carbocation. Such a carbocation is shown below.
% '
substituuon / t 'unimolecular
nucleophil~c
equal amounts 7
(racems rn~xlure)
L. undamenlsl
I
Concepts
I
are formed in equal amounts and the product obtained is a racemic mixture.
Once a racemic mixture is obtained, the next step is to separate this mixture into
its pure components. The separation of a racemic mixture into the enantiomers is
called resolution. The first resolution was that of tartaric acid by Pasteur in, 1848.
Tartaric acid was obtained as a by-product of wine making and was found almost
always as its dextrorotatory 2R,3R stereoisomer. Occasionally, an optically inactive
sample of tartaric acid was obtained.
One day Pasteur was viewing the crystals of sodium ammonium double salts of
(+)-tartaric acid .and inactive tartaric acid. H e found that the crystals of the
double salt of (+)-tartaric acid were hemihedral, (see Fig. 3.3a). But the crystals
of the double salt of inactive acid were not the crystals of just one type, but a
mixture of two types and these two types of crystals were mirror images of each
other [see Fig. 3.3(a) and (b)]. He separated the two types of crystals with a pair
Pasteur had thus performed the.first resolution by human hands! Before this the
levorotatory form of tartaric acid was not known. It is now known that the double
salt of race~nictartaric acid forms two types of crystals, as shown in Fig. 3.3(a)
and (b), only at temperatures below 299 K. Had the temperature of Pasteur's
laboratory been above this temperature, he would have obtained the crystals of the
type shown in Fig. 3.3(c) and he would not have made this discovery.
\
enantiomeric mixture is treated with a chiral substance t o convert it i t o a mixture
of diastereomers. Since the diastereomers have different physical prop rties, they
can be separated using physical methods. The enantiomers are then regenerated
from each diastereomer. The gcneral scheme for resolution involving the formation
of diastereomers is depicted in Fig. 3.4. The advantage of acid-base properties is
also taken in obtaining the d;astereomers. For example, if we want to resolve a n
acid A which is present as a mixture of the enantiomers (+)-A and (-)-A as
shown in Fig. 3.4 (a); then we choose either of the enantiomers of base B, which
is, say, ( + )-B in this case. When the base ( + )-B is added t o the racemic mixture
of acid A, diastereomers of the type (+)-A(+)-B and (-)-A(+)-B, as shown in
Fig. 3.4(b), are obtained. These diastereomers can then be separated using physical
methods, [see Fig. 3.4(c)].
The individual enantiomers of acid A are then regenerated fr.om each of the above
diastereomers by treatment with a mineral acid, Fig. 3.4 (d). Similarl:, we can
resolve a racemic mixture of a base using a chiral acid. The chiral reagents which
2 are used for resolving a racemic mixture are called resolving agents. A number of
a racemic rnixlure a resolving agent mixture of
added as a single diastereomeric
of a chiral adduc~
compound enantiomer
Fig. 3
C) Diprtoreomers separated. d) Enmtiomcn regenerated from dlmtereomsn.
resolving agents are available, many of them are naturally occurring acids and OH
bases. For example, chiral bases such as biucine, strychnine and quinine are used I
for resolution. On the other hand, chiral acids such as (+)-tartaric acid, (-)-malic HOOCCH2CHCOOH
acid and (-)-mandelic acid are used for resolution of racemic bases. Analogous malic acid
methods for resolution of compounds containing other functional groups have also
been developed. @:cwH
mudelic r i d
P
I
I H H
brucine strychnine
quinine
(antimalarial
drug)
Chromatographic methods for resolution using chiral adsorbents have alsb been
developed. In such methods, one of the enantiomers gets adsorbed on the chiral
Fundamental Concept, ad5orbent more strongly than the other leading to their partial separation. The
drawback with chromatographic resolution is that it is not quantitative.
As pointed out earlier, the resolution is effective only under a chiral influence.
Such an influence can also be exerted using enzymes. The enzymes are highly
selective with regard to stereochemistry of the co4pounds with which they interact.
Hence, they can perform the resolution by metabolising only one enantiomer and
rejecting the other. For example, the racemic ammonium tartarate when fermented
using yeast or a mold (Penicillium glaucum), showed that the dextrorotatory
isomer is consumed faster by the mold leaving behind the pure levorotatory
isomer. A disadvantage of the resolutions of this type is that the more reactive
enantiomer is usally not available and we get only one enantiomer at the end of
the resolution.
Pufe enantiomers can also be obtained using synthetic methods, without the
necessity of resolution. In the next section, you will study about these methods in
detail.
-
The first asymmetric synthesis was carried out by varc/wald in 1904 who obtained
optically active (-)-2-methylbutanoic acid starting from ethylmethylmalonic acid.
The scheme of reactions is shown below.
COOH COOH[(-) - brucine] COOH
I (-)-brucine - 1 I
CH3 - C - C2H5 > CH3 -C -C2H5 + CH3-C -C2H5
I I I
COOH COOH COOHE(-) - brucine]
1 /
ethylmethylmalonic diastereomeric half
acid brucine salts
I
heat 443 K
- co,
COOH [(-) - brucine] ' H
heat 443 K
- co, I
I I
CH3 - C - C2H5 CH3 - C - C2H5
I I
H COOH [(-) - brucine]
I" 1 Ha
COOH H
I I
H COOH
\ /
enantiomers of
2-methylbutanoic acid
Since the two half brucine salts are diastereomeric, they yield the enantio,ners of
2-methylbutanoic acid in different amounts, wifh the4 levo isomer predominating.
An example of partial asymmetric synthesis using optically active substrate is given Stereochemistry - 11
below. Here, the attacking CN-ion can approach the carbonyl carbon from two
directions as shown, leading to the formation of enantiomeric products.
*
Use models to understand this
example of partial asymmetric
synthesis.
Q
H...
~ 2 ~ 5 '
=,, , CN
H/ O
'H
Many reactions of this type are known and in some of these reactions, the extent
of stereoselectivity approaches 100%.
right circularly
+ left circularly -
- plane-polarised The origin of chiral biological
polarsed Itght polarised lighl light molecules is attributed to the
enantlorners 2 effect of circularly polarised light
in the early phases of evolution
Fig. 3.5 :The electric fields of right- and left- circularly polarised light which add vectorially to give of
plane-polarised light.
the two helices are enantiomeric. The vector addition of these two forms leads
I to plane-polarised light. Such right-circularly polarised light was used in the
addition of bromine to 2,4,6-trinitrostilbene t o yield the dextrorotatory product.
r
NO2
- - righf-circularly
polarised light
NOz
2.4.6-trinimtilbeae dextrorot~toryi~omer 75
Fundamental Concepts In this section, you have studied about how to obtain opticaIly attive compounds
starting from optically inactive compounds. In the next section, you will study
about the transformation of one enantiomer into another enantiomer which in fact
involves the inversion of configuration. This phenomenon was first discovered by
Walden and is known as Wald~nInversion. Let us now study this phenomenon.
---
KOH
COOH COOH
L-(-)-malic acid D-( + )-chlorosuccinic acid
( *goH 1 &OH
COOH COOH
-
- PCl,
H+, OH
KOH
COOH COOH
L-(-)-chlorosuccinic acid D-( + )-malic acid
You can see that L-(-)-malic acid was converted to its enantiomer, D-(+)-malic
acid in a two stage process. Similarly, L-(-)-chlorosuccinic acid was converted into
its enantiomeric D-( +)-chlorosuccinic acid. Since an enantiomer is obtained,
configuration at the chiral centre must have changed in one out of the two
reaction stages. The step in which the inversion of configuration takes place is said
to have undergone the Walden inversion. Iri some cases, the Walden inversion has
been reported to be 100%. Note that the reactions in which the inversion is not
complete, lead to racemisation.
The Walden inversion is a ruIe for bimolecular nucleophilic substitution reactions.
The term bimolecular refers to the fact that two species undergo bonding changes
in the transition state of the reaction. These reactions are represented in short as
S,2 reactions. The stereochemistry af one such reaction is shown in the box.
If in the S,2 reaction, the attack of the nucleophile is from one side and the
leaving group leaves from the opposite side simultaneously, as is shown in the
tbansition state in the following example, then, such reactions proceed with the
inversion of configuration. And, if the species that undergoes inversion has the
same substituents on it before and after the inversion, the product obtained is t k
enantiomer of the starting compound, as was the case studied by Walden.
s@-hybridisedcarbon
76 I lransltion slate
1
Thus, we can conclude that SN1 type of reactions involve racemisation whereas SN2
type of reactions are accompanied by inversion of configuration.
Till now you were studying about the configurational isomers in which the
configuration at the chiral centre cannot be changed without breaking the bonds.
Let us next study about those stereoisomers which are interconvertible without
breaking the bonds between the atoms.
The various spatial arrangements obtained by rotation about the single bonds are
called conformations. Among the different conformations of a molecule, the stable
ones are known as conformers or conformational isomers. The simplest molecule
which shows these conformations is ethane. Before starting the study of
conformations of various molecules, let us learn how to represent these
conformations which are again three-dimensional spatial arrangements o f a
molecule, in two-dimensions. You have already learnt about the Fischer projections
for representing the configuration of a compound. Two types of representations,
namely, Newman projections and Sawhorse projections are used to show the
conformations. We will first study the Newman projections.
U H Nrwmnn rmie~inn 1
I
atom nearer to the observer is represented by a point and the three groups
attached to it are shown by three lines emerging from this point [Fig. 3.6(b)].
The rear carbon is shown by a circle and the three substituents attached to this YOU are advised to use the
in unde' .
carbon are shown by three lines emerging from the edge of the circle. The .angle, 8, representations.
between the H - C - C plane and the C - C - H plane of an H - C - C - H unit is
called the dihedral angle.
Let us now understand how to write the sawhorse projections.
I
Sawhorse Projections
In this representation, the carbon-carbon single bond is represented by a line and is
I
oriented diagonally backward, i.e., the left hand carbon projects towards the
viewer and the right-hand carbon projects away from the viewer. This is illustrated
in sawhorse projections for ethane in Fig. 3.7. Analogous to the Newman
projections, here also the substituents ?n each carbon are shown by lines.
H
I Remember that
H
Fig. 3.7 : Sawhorse representation of ethane.
Make a model of ethane
molecule in which one C - H
bond on each carbon atom has a
different colour. Rotate along the
C - C single bond and try to
'
make eclipsed and staggered
conformations. Convince yourself
that they have the dihedral angles
as 0' and 60e, respectively. -
3.9 CONFORMATIONS OF BUTANE
(343 CH3
Similar to the case of ethane, various conformations of butane are possible due to
rotation of the C-C bond forrncd by the carbon atoms numbered as 2 and 3.
Fig. 3.9 shows the potential energy variation for irarious conformations of butane.
0 60 I20
I
I BO
dihedral mgle (degrees)
I
240 300
I
360
!=o). i
Fig. 3.9 : Potential energy diagram for the conformatluns of butane.
Actlvity
AS the f~gureshows, when the dihedral angle 1s zero, the conformation 1s called
eclipsed conformation. As the dihedral angle increases to 60°, we get another along the C2- C, single bond.
conformation which ~scalled gauche or skew conformation. Further rotation of the Try to make various
C,-C, bond yields another eclipsed conformation when the dihedral arigle is 120". conformations shown in Fig. 3.9
e in this conformation CH3 and H are eclipsed whereas in the earlier
~ b t that
eclipsed conformation two methyl groups were eclipsed. Hence, this eclipsed Butane has two conformers,
conformation is at a little lower enerav level than the earlier eclipsed conf~rmation. namelv anti and pauche
When the two methyl groups are maximum apart, i.e.. when the dihedral angle is
18O0, then the c~nformationis known as anti conformation. Note that this is the
most stable conformation of butane because it has the lowest energy value. On
conformations. The anti
conformer is more stable as
compared to the
I
shown in Fig. 3.9.
further rotation. another set of eclipsed and gauche conformations result. The
difference in energy between the anti and gauche conformations is about
7 64 kT mol-'. At room tem~erature.butane is a mixture of 72% anti and 28% 79
I
Fundamental Concepts gauche conformations. Similar to ethane, in this case also, the interconverdon of
these conformations is rapid and if one-wants to separate them, one has to make
the interconversion slow by working at very low temperatures of about 43 K.
Hassel and Barton received The study of conformations or conformational analysis is helpful in explaining the
Nobel Prize in Chemistry in 1969 specificity of reactions; particularly, the reactions observed in living systems where
for their contributions in the such a specificity is exhibited by virtue of the particular conformations of the
field of conformational analysis. compounds,
At this stage, you can check your understanding about conform?tinns of simple
straight chain alkanes by answering the'following SAQ.
SAQ 4
a) Write sawhorse projections for the two gauche conformations of butane.
c) What relationship d o these two gauche conformations have with each other?
...........................................................................................................
..............+......................................................................,. i..................
I suggested that the stability of such compounds could be related to the tetrahedral
bond angle of 109.5'. The deviation from this angle could cause a strain in the
molecule leading to its decreased stability. This type of instability is called angle
strain. ~ c c o r d i n gto this explanation, as the deviation from the tetrahedral value
I decreases, the stability should increase. Thus, the stability should increase from
cyclopropane - cyclobutane - cyclopentane. As the deviation in angle from. the
tetrahedral angle of 109.5" is minimum in case of cyclopentane, Baeyer predicted it
to be most stable. Cyclohexane and higher cycloalkanes according to him would be
less stable than cyclopentane because the angles of larger polygons deviate more
and more from the ideal tetrahedral angle.
The experimental values of heat of combustion per methylene group showed that
the energies for the first three cvcloalkanes are in the fnllowine order.
cycloprcrpane > cyclobutane > cyclopentane. This order is consistent with the Steworhemistry - n
predictions of the Baeyer's strain theory. But in case of cyolohexane, the heal of
combustion is less indicating its greater stability. Further increase in the ring size
does not affect the heat of combustion much, indicating a constant value of about General equation for combustion
652.7 kJ mol-1 per methylene group in contradiction to the prediction of Baeyer of alkanes is
Sttain Theory that with the increase in the ring size, angle strain must increase.
c n ~ 2 n 2+ + (-T)
02
3n+l -
\ - 1
Baeyer's theory failed because of the assumption that the cycloalkanes are planar. alkane oxygen
Of course, cycloyropane has to be planar because three carbons must lie in a single
plane. But other larger cycl~alkanesare not planar and are puckered. Puckering of n c 0 2+ (n + I) H 2 0 + heat
rings relieves the angle strain. You will study about this in detail in case of carbon water
cyclohexane in the following discussion. dioxide
u
Fig. 3.N : Strained planar conformation of cyclohexnne showing eclipsed hydrogens.
Sachse in 1890 pointed out that two nonplanar models for cyclohexane are possible
which are frke from a n ~ l e.!rain. These are called chair and boat conformations
and are shown in Fig. 3.11.
a'
C-H. W r C-Hbonds
eq~arid
cqautorial
rxi*
baadr
mdtogether
There are two types of hydrogens in the chair form of cyclohexane. The six hydrogens
which are above and below the plane of the carbon ring are called axial hydrogens.
Note that the axial bonds are alternately directed up and down on the adjacent
carbon atoms. The second set of hydrogens is called equatorial hydrogens and are
located approximately along the equator of the molecule. Given below are the steps
to enable you to represent the axial and equatorial bonds correctly on the chair
cnnfnrqation of cvclohexane.
Fundamental Conceflts Steps
1) Draw the chair conformation of cyclohexane.aa,
and then draw axial bonds alternately up and down as represented below.
You can notice the sawhorse representation of the staggered bonds in the above
chair conformation. This staggered nature of bonds can also be visualised in the
Newrnan projections of the chair conformation of cyclohexane as shown below:
staggered 'arrangement of
I--DD---
bonds in ch
chair conformation
of cyclohexane
However, a similar representation of the boat form of cyclohexane shows the
boat
I
twist (skew) boat
I1
The twist boat form is more stable than the boat conformation but is less stable
than the chair conformation by about 2.51 kJ mol-1. As the chgr conformation is
the most stable form, most of the molecules of cyclohexane exist in the chair
form. The available experimental d a b indicate that no more than one or two
molecules per thousand exist in the skewboat conformation.
A chair conformation is also convertible into another chair conformation by the
process known as ring flipping. This interconversion, as shown in Fig. 3.12, occurs
via the intermediate half-chair and skew-boat conformations. The energy profile
for such an interconversion is shown in Fig. 3.12. The ring flipping requires an
energy of 45.18 kJ mol-1 and even at room temperature, this interconversion is
very fast.
Halfchair
Halfchair
Chair Chair
e' axial
CH?
QCH3
equatorial
H
You are advised to use models Remember that the ring flipping interconverts these t,wo forms with the methyl
while studying this section and group changing from axial to equatorial and vice "ersa. Also, since these two
the next section. stereoisomers are not enantiomers, they are diastereomers. They have different
energies or different stabilities. Let us now examine what happens when the methyl
group occupies the axial position. In this position the methyl group is relatively
close to the axial hydrogens at C-3 and C-5 carbon atoms. As the distance
between the hydrogen of the methyl group and the C-3 or C-5 hydrogen atom is
less than the sum of the van der Waal's radii for the two hydrogens; van der
Waal's repulsio& destabilise the axial conformation of methylcyclohexane.
Such a situation IS avoided in the equatorial conformation in which the methyl'
group occupies equatorial position and hydrogen is axial. The axial hydrogen,
being smaller in size as compared to methyl group, experiences smaller van der
Waals; repulsions. Thus, equatorial conformation of a monosubstituted
5%
95 %
(less stable)
(more stable)
40% H
60%
3%
97%
1,2-Dimethylcyclohexane
Let one of the methyl groups occupy an axial position at C-1 carbon as shown
here, interactions between the
CH3
CH3
42, = H a y H ,
H~
cis-1.2-dimethylcyclohexane
Another possibility in which both the methyl groups occupy axial position lead to
the trans arrangement of the groups. Note that this trans conformation is
1,3-Dimethylcyclohexane
Let the C-1 nlethyl group in this molecule occupy the axial position. Then, the
C-3 methyl group can have either axial or equatorial position.
Let us now study each of these two possibilities one by one.
i) When the C-3 methyl group is axial,
Then, both the methyl groups are on the same side and you can see that this
arrangement is cis. Ring flipping of this cis conformation leads to another cis form
in which both methyl groups occupy equatorial positions. (Do it yourself with the
models.)
ii) When the C-3 methyl group is equatorial,
The trans form has one methyl group in equatorial position and the other methyl
group in the axial position whereas the cis form in its more stable conformation
has both the methyl group oriented equatorially; therefore, in this case the cis'
form with diequatorial substituents is more stable {han the trans form. Let us now
apply the same considerations to 1.4-dimethylcyclohexane.
1,4-Dimethylcyclohexane
Let the C-l methyl group occupy an axial position. The C-4 methyl group can be
either axial or equatorial. Let us consider both these possibilities.
i) When the C-4 methyl group is axial, it leads t o the trans arrangement of Stereuchemislr~- 11
methyl groups. This chair conformation having the diaxial arrangement of methyl
groups by ring flipping can change into chair form having diequatorial
arrangement of methyl groups.
ii) When the C-4 methyl group is in equatorial position, we have cis arrangement
of methyl groups. The two equivalent chair conformations shown below represent
such an arrangement.
Note that these two equivalent chair conformations have one axial and one
equatorial methyl substituents.
A comparison of these cis and trans conformations shows that since the trans
conformation permits both the methyl groups to occupy equatorial sites; hence, it
is more stable as compared to the cis form which has one substituent each in the
axial and equatorial positions.
In other disubstituted cyclohexanes, when the two substituents are different, the
stable isomer is the one in which the larger substituent occupies the equatorial
position.
Using your knowledge of conformations of cyclohexane systems, answer the
following SAQ.
SAQ 5
Which of the two isomers in each of the following pairs would be more stable?
Fundamental Concepts
iii) H
* cl&cl
H
C1
(a) (b)
------- - - --------- - - - - - - -
iv) H e c H 3 c~3
CH3
CH3
, CHI (b)
CH3
CH3 (a)
----- ------------ ,--- - ---
7
*
3.11 SUMMARY
3.13 ANSWERS
3. H HI
(b) 60"
(c) They are .enantimeric in nature.
5. (i) a (ii) ti (iii) b (iv) b
Ht
Terminal Questions
1. (a)
CH3
C2H5
H
~r
(b)
H
z2 COOH (c)
OH
CH3 COOH