Mosher Ester Analysis - Department of Chemistry and Physics

called kinetic resolution. Usually this is avoided by using an excess of the enantiopure
reactant and using reactions that are fast and irreversible.
In this lab, you will prepare a chiral ester of a chiral secondary alcohol, 1phenylethanol.
The ester is derived from the chiral carboxlic acid -methoxy-trifluoromethylphenylacetic
acid (MTPA, Mosher’s acid), shown below.
F3C
MTPA
Diastereomers, unlike enantiomers, have distinguishable physical and spectral
properties because they are not mirror images. Diastereomers have two (or more) chiral
centers. The added chiral center(s) can be the same or opposite configuration as that of
the original molecule. The matched and mismatched diastereomers will have different
spectra and can thus be distinguished as shown below for one of the enantiomers of
MTPA and scalemic 1-phenylethanol.
F3C
O
OCH 3
OH
+
OH
CH 3
single enantiomer mixture of enantiomers
mixture of diastereomers
MTPA is a useful chiral acid for analyzing enantiomeric excess for several
reasons. First, both enantiomers are available in high enantiomeric purity. Second, the
chiral center is adjacent to the carboxyl bringing it in close proximity to the chiral center
of the alcohol when the ester is prepared. Also, the chiral center is not able to be
racemized as it is quaternary and thus contains no acidic protons. Finally, the presence of
the trifluoromethyl group allows for clean analysis of enantiomeric excess by 19 F NMR,
which is uncomplicated by signals from the chiral alcohol, unlike the 1 H NMR spectrum.
However, 1 H NMR can also be used if the signals are sufficiently resolved. This also
allows for assignment of configuration based on a preferred conformation of the ester. In
this experiment, you will team up with a partner. You will be given a sample of 1phenylethanol
of unknown enantiomeric composition. One of you will prepare the (R)-
(+)-MTPA ester of your 1-phenylethanol sample and the other will prepare the (S)-(-)-
MTPA ester of the sample. You will then compare your 19 F NMR and 1 H NMR data and
determine both the enantiomeric excess and the major enantiomer present according to
the published methods by Mosher.
We will prepare our esters using N,N’-dicyclohexylcarbodiimide (DCC) to
activate the acid toward substitution and 4-dimethylaminopyridine (DMAP) as a catalyst.
*
O
OCH 3
OH
F3C
F3C
O
OCH 3
O
+
OCH 3
H
O
H
O
CH 3
CH 3