Extraccion De Ibuprofeno Y Naproxeno De Tabletas

Organic Chemistry I Laboratory
Chirality and Optical Rotation: Experiment 5
Determination of the Enantiomeric Purity of Naproxen1 and Ibuprofen2 Week 5
Background Reading
Zubrick, J. W. The Organic Chem Lab Survival Manual, 5th edition, Wiley & Sons, Inc., New York, 2000.
Recrystallization Pg 89-103.
Chromatography, TLC & GC Pg 185-198; 213-221.
Background Scenario:
Alleve is the tradename 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 drugs3. 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.4Since 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 isclockwise, 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 ± 180no (n = interger), for if the
plane of polarization is rotated in the field of the polarimeter by ± 180o, the new plane will coincide with the old
one. In fact α, asmeasured, is always recorded as being between -90o and +90o. Thus, for example, no
difference appears between rotations of +50o, +230o, +410o, or -130o. 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 originalconcentrations, their rotations would
become +5o, +23o, +41o, and -13o, values that are all clearly distinct. Readings taken at two different
concentrations almost always determine α unequivocally.
Biot discovered that the observed rotation is proportional to the length of the cell or tube containing the
optically active liquid or solution and the concentration c (or density in the case of a pureliquid): α = [α]cl (Biot's
law). The value of the proportionality constant [α] depends on the units chosen; in polarimetry it is customary to
express l in decimeters, because the cells are usually 0.25, 0.5, 1, or 2 dm in length, and c in grams per milliliter
(g mL-1) or (and this is preferred for solutions) in g 100 mL-1. Thus:
[α] = α/l (dm) c(g mL-1) = 100 α/l (dm) c(g 100 mL-1)
The valueof [α], the so-called specific rotation, depends on wavelength and temperature which are
usually indicated as subscripts and superscripts, respectively. Thus, [α] 25
D denotes the specific rotation for light of
the wavelength of the sodium D-line (589 nm) at 25oC. In addition, [α] also depends on solvent and
concentration. This is usually done by adding such information in parentheses, thus[α] 20
546 = -10.8 ± 0.1 (c = 5.77,
95% ethanol) denotes the specific rotation at 20oC for light of wavelength 546 nm in 95% ethanol solution at a
concentration of 5.77 g 100 mL-1. Technically the units for [α] will be deg cm2 g-1. However, the formal units are
almost never explictly given in the literature. Instead, [α] will be reported in degrees.
1 Walsh, T. D.; Koontz, C. S. J. Chem....