3. This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
Topicity of Ligands and Faces: Introduction
• In certain molecules, such as propionic acid (A; Figure 1), a
nonstereogenic center (here Cα) can be transformed into a
stereogenic center by replacement of one or other of two
apparently identical ligands by a different one. Such ligands are
called “homomorphic” from Greek homos meaning same and
morphe meaning form. They are identical only when separated
from the rest of the molecule.
analogous replacement of HB gives rise to the enantiomeric
(R)-lactic acid. The Cα centre in propionic acid has, therefore, been
called a “prochiral” as well as “prostereogenic centre.”
• Thus the replacement of HA at Cα in propionic acid by OH
generates the chiral centre of (S)-lactic acid, whereas the
4. Topicity of Ligands and Faces: Introduction
• HA and HB at such a centre are called “heterotopic ligands” from
Greek heteros meaning different and topos meaning place.
Prochiral axes and planes may similarly be defined in relation to
chiral axes and planes.
• Substitution is one of the common ways of interconverting organic
molecules, another is addition. The chiral centre in lactic acid (B
and C; Figure 2) can also be generated by the addition of hydride
(e.g., from sodium borohydride or lithium aluminium hydride ) to
the carbonyl group of pyruvic acid (A; Figure 2).
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
5. Topicity of Ligands and Faces: Introduction
• Depending on the face of the keto acid (pyruvic acid) the hydride
adds to, either (S)- or (R)-lactic acid is obtained. The addition of
hydride ion (H-) to the front/top face of the keto acid as depicted in
Figure 2 will give rise to (R)-lactic acid (B), whereas (S)-lactic
acid is obtained by addition of the nucleophile to the rear face of
the C=O group. Thus the carbonyl group in pyruvic acid is also
said to be prochiral and to present two heterotopic faces.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
6. Topicity of Ligands and Faces: Introduction
• A prochiral axis (in chloroallene A; Figure 3) can be converted
into the chiral allenes, B and C by replacement of HA and HB by
C1 separately.
• Ligands (atoms or groups in a molecule) and faces may be
homotopic or heterotopic. Heterotopic ligands and faces may be
either enantiotopic or diastereotopic. It may be pointed out that
topicity describes the relationships of two or more homomorphic
ligands (or faces) which together constitutes a set.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
7. Topicity of Ligands and Faces: Introduction
• In view of the interrelationship between topicity of ligands and
isomerism in general, it may be instructive to draw a classification
diagram (Figure 4) for topicity and to compare it with that drawn
for isomerism.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
8. This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
Homotopic Ligands and Faces
• Two criteria, namely, a substitution (or addition) criterion and (or)
a symmetry criterion are employed to determine the topic
relationships of homomorphic ligands and faces (only one test
suffices).
Substitution and Addition Criteria
• Two homomorphic ligands are homotopic if substitution (or
replacement) of first one and then the other by a different ligand
leads to the same structure. (The replacement ligand must be
different not only from the original one but also from all other
ligands attached to the same atom.). Examples of homotopic
ligands are shown in Figure 5.
9. This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
Homotopic Ligands: Substitution Criterion
• The two hydrogen atoms in methylene bromide (A; CH2Br2) are
homotopic because replacement of either by, say, chlorine gives the
same CHClBr2, molecule (B).
• The three methyl hydrogen atoms in acetic acid (C; CH3CO2H)
are homotopic because replacement of any one of them by, say,
chlorine gives one and the same chloroacetic acid (D).
• The two methine hydrogen atoms in (R)-(+)-tartaric acid (E) are
homotopic because replacement of either of them, for example by
deuterium, gives the same (2R,3R)-tartaric-2-d acid (F).
• The three methyl hydrogen atoms in methyl chloride (CH3Cl) are
homotopic because replacement of any one of them by, say,
bromine gives one and the same dibromochloromethane
(CHClBr2).
10. Homotopic Ligands: Substitution Criterion
Br Br Br Br
I
C I - C - H
HA-----..Cl I HB----. Cl I I
H A - C - H e .,. H - C - C I - C I - C -
H
I I I I
Br
B
Br
A
Br
B'
Br
B
The molecules Band B' are superposable. They are interconverted by a
180° in-plane rotation about a vertical axis.
Superposable molecules (C3 rotation passing through
C-C02H unit)
C02H C02H
D
HO
OH
.H
.A----.D HA
HO
OH HB----.D
H He
C02H
F
C02H
E
Cl
I
H - C - C 0 2 H
I
H
D
H
I
H - C - C 0 2 H
I
Cl
D
C02H
H OH
HO D
/ C l
H
I
HA
I
H /
HB----.Cl y
C I - C - C 0 2 H H8 - C - C 0 2 H
I I He
" '
D
H C
He
Cl
C02H
F
The molecules are superposable, one is converted to the other
by a 180° turn
Figure 5: Homotopic ligands
11. Homotopic Faces: Addition Criterion
• Two corresponding faces of a molecule (usually, but not invariably,
faces of a double bond) are homotopic when addition of the same
reagent to either face gives the same product.
• Addition of HCN to acetone will give the same cyanohydrin (A;
Figure 6), no matter to which face addition occurs and addition of
bromine to ethylene similarly gives BrCH2CH2Br irrespective of the
face of approach. The two faces of the C=O bond of acetone and of
the C=C bond of ethylene are, thus homotopic.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
12. Homotopic Faces: Addition Criterion
• Ethanol is formed by the addition of MeMgI to either face of the
C=O bond of formaldehyde. Thus, the two faces of the C=O bond
of formaldehyde are homotopic.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
• Consequently, two faces of the C=O of any symmetrically
substituted carbonyl compounds, such as ketones of the type R2CO,
e.g, acetone, 3-pentanone, benzophenone, etc., are homotopic.
13. Homotopic Ligands: Symmetry Criterion
• Ligands are homotopic (by internal comparison) if they can
interchange places through operation of a Cn symmetry axis. Thus
the bromine atoms in methylene bromide (A; symmetry point
group C2v) are homotopic since they exchange places through a
180° turn around the C2 axis (C1
2).
• Similarly, the methine hydrogen atoms of (+)-tartaric acid (B) are
interchanged by operation of the C2 axis (the molecule belongs to
point group C2). Homotopic atoms in methylene bromide, and
active-tartaric acid are shown in Figure 8.
• The three methyl hydrogen atoms of CH3CO2H are homotopic
when rotation is fast. Rotation around the H3C-CO2H axis is rapid
on the time scale of most experiments. Under this condition the
three methyl H’s will exchange their places under the operation of
C3 symmetry axis.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
14. Homotopic Ligands: Symmetry Criterion
U v
Br ,,
,H
A
/
f
i
.
.
g
C
T
v
)Cr< Br
cl
C2v= C2 + 2uv planes passing
through Br-C-Br and HA and H8 ,
each containing the C2 axis
Two H's and two Br's in dibromomethane (CH2Br2) are homotopic.
B
A Br
I
H A - C - H 8
I
Br
HA and H8 are exchangeable
by operation of C2 axis
1 co H
2
180°in-plane rotation
about a vertical axis
H A 2
- 0 H
HO----'+--He
H8
3 -
0 H
I and II are superposable
(HA = H8 and ignoring the
numbering)
t C02 H
II
C2 axis at the mid point of C2-C3 bond
perperdicular to the projection formula;
Point group: C2
Two H's (HA and H8 ) , two OH's and two C 02H's are homotopic.
Figure 8: Symmetry criteria: Homotopic atoms
3
4C02H
I
(+)-Tartaric acid
(2R, 3R)
HO
2
15. Homotopic Ligands: Symmetry Criterion
• The presence of a symmetry axis in a molecule does not guarantee
that homomorphic ligands will be homotopic. It is necessary that
operation of the symmetry axis make the nuclei in question
interchange places. Thus in 1,3-dioxolane (Figure 9), in its average
planar conformation, the hydrogen atoms (HE and HF) at C-2 are
homotopic, since they are interchanged by operation of the C2 axis
(the symmetry point group of the molecule is C2v).
• On the other hand, the geminal hydrogen
atoms at C-4, or C-5, are not interconverted
by the C2 symmetry operation and are
therefore heterotopic (HA with respect to HB
and HC with respect to HD). However, HAand
HD are homotopic (as are HB and HC), being
interchanged once again by the C2 axis.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
16. Homotopic Ligands: Symmetry Criterion
• The two hydrogen atoms in each of the three dichloroethylenes
(1,l-, cis-1,2-, trans-1,2-) and the four hydrogen atoms in methane
(CH4), (H2C=CH2), (H2C=C=CH2),
ethylene and allene are
homotopic. It might be noted that, in a rigid molecule, the number
of homotopic ligands in a set cannot be greater than the symmetry
number of the molecule in question.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
17. This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
Homotopic Ligands: Symmetry Criterion
• In allene, the geminal hydrogens are interchangeable in pairs by
rotation around the molecular axis (C2 axis) while the non-geminal
hydrogens are interchangeable through rotation around the two C2
axes perpendicular to the former. All the four hydrogen atoms are
thus homotopic.
• This proves that if ligands A and B are found homotopic through
rotation around one Cn axis and ligands B and C through rotation
around another Cn axis, all three (A, B, and C) form a set of
homotopic ligands.
• The two methine hydrogens (as also two OH and the two CO2H
groups) of (+)-tartaric acid are interchangeable through rotation
around a C2 axis either in the eclipsed conformation or in an anti
conformation. These pairs of ligands are, therefore, homotopic.
18. This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
Homotopic Faces: Symmetry Criterion
• Faces of double bonds are homotopic when they can be
interchanged by operation of a symmetry axis. Since there are only
two such faces, the pertinent axis must, of necessity, be of even
multiplicity so as to contain C2.
• Thus, the two faces of acetone are interchanged by the operation of
the C2 axis (the molecule is of symmetry C2v); the two faces of
ethylene (D2h) are interchanged by operation of two of the three C2
axes (either the one containing the C=C segment or the axis at right
angles to the first one and in the plane of the double bond).
• The faces in acetone, ethylene, 1,1-dichloroethylene, cis-1,2-
dichloroethylene, and allene (H2C=C=CH2) are homotopic.
19. Homotopic Faces: Symmetry Criteria
• The addition criterion tends to be confusing when applied to a
molecule like ethylene where addition occurs at both ends of the
double bond. In such cases, it is advised either to use the symmetry
criterion or to choose epoxidation as the test reaction for the
addition criterion.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
• The faces in acetone, ethylene, 1,1-dichloroethylene, cis-1,2-
dichloroethylene, and allene are exchangeable by C2 axis.
20. Homotopic Faces: Symmetry Criteria
• cis-2-Butene contain two homotopic faces. It gives the same
epoxide on reaction at either face as shown in Figure 12.
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
21. Homotopic Ligands
• The hydrogens in cyclopropane are exchangeable
either by C3 or C2. Therefore, all the six hydrogens are
homotopic. C3 axis exchanges all the hydrogens which
This Lecture is prepared by Dr. K. K. Mandal, SPCMC, Kolkata
are above the plane or below the plane. The C2 axis
substitution of either hydrogen of the two by another ligand, say Br,
gives the same molecule. Hydrogens on C3 are also homotopic.
Here, B and C are identical chiral molecules. The hydrogen atoms
at C1 and C2 are exchangeable when the molecule is rotated about
the C2 axis.
(perpendicular to C3 axis) exchanges one pair of
geminal hydrogens, and two pairs of vicinal
hydrogens which are anti to each other.
• The hydrogen atoms on C-1 and C-2 of trans-1,2-
dichlorocyclopropane (Figure 13) are homotopic since the
22. Homotopic Ligands
This Lecture isprepared by Dr. K. K. Mandai, SPCMC, Kolkata
Cl Cl H
Br
and
replacement of
•
HAandH 8
by Br in turn
3
H
I
I
I
I
I
I
A
H
B c
Structures B and C are superposable. A C2 rotation passing
through methylene carbon and midway of the opposite C-C
bond converts C into B. HA and H8 are, thus, homotopic.
Figure 13: Homotopic ligands
Cl
