5 Optical Rotation-1 - Organic Chemistry I Laboratory...

Organic Chemistry I Laboratory
Chirality and Optical Rotation:
Experiment 5
Determination of the Enantiomeric Purity of Naproxen
1
and Ibuprofen
2
Week 5
Background Reading
Zubrick, J. W. The Organic Chem Lab Survival Manual, 5
th
edition , Wiley & Sons, Inc., New York, 2000.
Recrystallization Pg 89-103.
Chromatography, TLC & GC Pg 185-198; 213-221.
Background Scenario:
Alleve

is the trade name for Proctor-Syntex Health Products' brand of naproxen (6-methoxy- α -methyl-2-
naphthaleneacetic acid). Naproxen is the active component of these tablets and as a chiral molecule, is one of a
growing class of enantiomerically pure drugs
3
. Only the ( S ) stereoisomer of naproxen has the desired
antiimflammatory activity and is safe to use. The ( R ) stereoisomer is reported to be a liver toxin.
4
Since it is much
more expensive to manufacture enantiomerically pure compounds, there is the potential for counterfeit supplies to
enter the market which are not enantiomerically pure. In other words, the compounds would contain some
mixture of the two enantiomers (R & S) instead of being 100% of the (S) stereoisomer. In this lab we will analyze
both naproxen and ibuprofen ( α -methyl-4-(2-methylpropyl)benzeneacetic acid) with regards to their
stereochemical purity.
Understanding the Techniques:
Polarimetry and Optical Rotation - The observed angle of rotation of the plane of polarization by an
optically active liquid, solution, or (more rarely) gas or solid is usually denoted by the symbol α . The angle may
be either positive (+) or negative (-) depending on whether the rotation is clockwise, to the right ( dextro ) or
counterclockwise, to the left ( levo ) as seen by an observer towards whom the beam of polarized light travels. It
may be noted that no immediate distinction can be made between rotations of α ± 180 n
o
( n = interger), for if the
plane of polarization is rotated in the field of the polarimeter by ± 180
o
, the new plane will coincide with the old
one. In fact α , as measured, is always recorded as being between -90
o
and +90
o
. Thus, for example, no
difference appears between rotations of +50
o
, +230
o
, +410
o
, or -130
o
. To make the distinction, one must measure
the rotation at least at one other concentration. Since optical rotation is proportional to concentration (see below),
if solutions of the above rotations were diluted to one-tenth of their original concentrations, their rotations would
become +5
o
, +23
o
, +41
o
, and -13
o
, values that are all clearly distinct. Readings taken at two different
concentrations almost always determine α unequivocally.