METHODS OF DETERMINATION OF CONFIGURATION OF GEOMETRICAL ISOMERS, POC-III

1. METHODS OF DETERMINATION OF
CONFIGURATION OF GEOMETRICAL ISOMERS
BY- DIPESH GAMARE
SUBJECT-PHARMACEUTICAL ORGANIC CHEMISTRY-III

2. THE METHODS OF DETERMINATION OF CONFIGURATION ARE CLASSIFIED AS:
(I)Chemical methods and
(II) Physical methods
Chemical Methods These methods include:
(a) Absolute method: This method is based on the following observations.
(i) Functional groups in cyclic compound located cis to each other can be converted into cyclic lactones,
anhydrides or amides. e.g., maleic acid containing two –COOH groups cis to each other forms anhydride
easily. Hence, it can be identified as cis-(maleic acid). Similarly in fumaric acid the two –COOH groups are
on the opposite side, it can not form anhydride easily. Hence, it can be identified as trans-form.
(ii) Cis-isomers can be synthesized from the small rings but trans isomers can not be synthesized from
small rings.

3. (b) Through chemical reaction not affecting the configuration of the double bond: The synthesis of
trisubstituted alkene of known configuration is possible by syn addition of organo-copper reagent to
alkyne followed by alkylation.
(c) If we synthesize a product from a starting material of known configuration, then the configuration of
the product remains same as that of starting material.
(d) The stereoselective reaction helps to predict the configuration of the resulting product. One such
stereoselective reaction is Wittig reaction.

4.  Physical Methods The geometrical isomers differ from each other in their physical properties which
include:
 (a) Boiling point, melting point, density, refractive index and dipole moment
 (b) Acid strength
 (c) UV-visible spectra
 (d) Vibrational (IR-Raman) spectra
 (e) NMR (1H, 13C both)
 (f) X-ray, microwave spectra and electron diffraction methods.
 (a) The parameters like boiling point, melting point, density and refractive index are not very reliable for
prediction of configuration of the isomers. Dipole moment is variable for cis and trans isomer,
sometimes higher for trans and at times for cis isomer. Similarly, trans isomer has greater symmetry
than the cis. Therefore, trans has usually a higher melting point. e.g.,

5. (b) Acid Strength: The acid strength is strongly dependent on the configuration of the compound e.g. pKa
of cis and trans isomers of crotonic acid are.
The cis form (maleic acid) is more acidic in its first dissociation than trans form (fumaric acid) but the
acidity of second proton is reversed. This is because of intramolecular H-bonding formed within the
conjugate anion of maleic acid. It is stabilized to a greater extent than fumaric after first dissociation of
proton. In the second dissociation, in cis-two negative anion species close to each other is not favourable
as in fumaric, the trans form (the negative species further away). Hence, the trans form is more acidic than
cis in second dissociation.

6. (c) UV-visible Spectra: Cis isomer has two bulky groups on the same side. Hence, internally the molecule is
extremely crowded and thus has less resonance energy and less stable than trans isomer. The cis-isomer
suffers distortion and is forced to be non-coplanar and thus has absorption maxima at slightly shorter
wavelength than the trans isomer.
(d) Infrared and Raman Spectra: The difference in the IR spectra of two isomers may be pointed out in the
following regions. 1650 cm–1 (C = C), and 970 – 690 cm–1 (= C – H out of plane vibration). Similar for trans
1,2-dichloroethylene, dipole moment is zero, due to its symmetrical nature. Cis-isomer shows no IR
absorption but shows Raman absorption at 1577 cm–1. While trans-isomer shows strong IR absorption at
1590 cm–1 but shows no Raman absorption.

7. (e) NMR Spectra: Not only it gives you information regarding which functional groups are present, but
NMR spectra are also capable of giving information about the position and configuration of atoms
(environment) in the molecule.
NMR spectra can differentiate chemcally unlike protons. In a disubstituted ethylene, RHC = CHR’, where R
and R’ differ significantly in the way they influence the magnetic environment of the olefinic protons,
thereby these protons experience a resonance condition at differnt field strengths.
These olefinic protons are typically found in low field of the NMR spectrum and the hydrogens are said to
be deshielded. Trans isomer is strongly coupled and hence has a coupling constant of 17-18 c.p.s. (cycles
per second). While the coupling constant of cis-isomer ranges from 8-11 c.p.s. Similarly the difference in
chemical shifts of cis- and trans- isomers may be used to identify the configuration of the isomer.
(f) X-ray and Electron Diffraction: Single crystal X-ray diffraction is the most powerful tool for detailed
structural characterization of crystalline compounds. It reveals the spatial atomic arrangement providing an
image of the internal structure of the crystal.
Single crystal X-ray diffraction is the main source of information on the geometrical structure of the
molecules including bond distances, bond angles, conformations of flexible molecules as well as
intermolecular contacts.