Experiment 9:
Properties of Stereoisomers of
Menthols
Objectives




To study physical properties of stereoisomers
using TLC and melting point analyses.
To study the optical rotation of enantiomers
using polarimetry.
To practice assigning the absolute
configuration of stereoisomers using the R-S
convention.
To learn to identify the relationship between
stereoisomers.
Menthol Stereoisomers
Each stereoisomer has 3 stereogenic centers
4
3
CH3
CH3
CH3
5
5
R
S
6
R
4
1
OH
2
CH3
3
CH3
CH3
5
6
4
1
OH
2
CH3
(l)-menthol
(d)-menthol
o
o
mp = 43-45 C
CH3
mp = 43-45 C
3
CH3
5
6
4
1
OH
2
CH3
(d)-isomenthol
o
mp = 77-83 C
3
6
1
OH
2
CH3
CH3
(d)-neomenthol
mp = -22 oC
Since each menthol isomer has 3 stereocenters,
menthol has a total of 8 stereoisomers.
(2n, where “n”= # of stereogenic centers)
Fischer Projections
Press flat
W
X
Y Z
Z
Z
C
W C
Y
X
W C
Y
X
Stereochemical Relationships
Diastereomers
Diastereomers
CH3
CH3
Cl
H
H
OH
H
Cl
Cl
H
H
Cl
HO
H
HO
H
H
OH
CH3
CH3
"A"
CH3
CH3
"B"
Enantiomers
CH3
"C"
CH3
"D"
Enantiomers
Diastereomers
Diastereomers
Diastereomers and Meso Forms
COOH
COOH
H
HO
OH
H
COOH
2R, 3R
HO
H
COOH
COOH
H
H
OH
HO
H
OH
H
OH
HO
H
COOH
2S, 3S
COOH
2R, 3S
COOH
2S, 3R
Look closely at these two… There is a plane of symmetry.
The top half of the molecules is identical to the bottom half!
The plane of symmetry makes them achiral,
although they do have chiral centers.
Identifying Stereochemical
Relationship



Identify stereocenters.
Assign absolute configuration to each
stereocenter.
Determine stereochemical relationship
based on absolute configurations.


ENANTIOMERS
 Different absolute configuration at ALL
stereocenters
DIASTEREOMERS
 Same absolute configuration at SOME
stereocenters, different at some.
Physical Properties of Stereoisomers

Enantiomers:



SAME: mp, d, solubility.
DIFFERENT: direction of rotation of plane-polarized light.
Diastereomers :

DIFFERENT: mp, d, solubility, AND direction of rotation of
plane-polarized light.
Table 9.1
Compound
(l)-menthol
(d)-menthol
(d)-isomenthol
(d)-neomenthol
TLC Rf values
unitless!
 2 decimal places
ONLY!

Table 9.2
Compound
Literature Melting Point
(oC)
Experimental Melting
Point (oC)
(l)-menthol
(d)-menthol
(d)-isomenthol
(d)-neomenthol
XXX
Optical Activity & Polarimetry
Clockwise rotation = dextrorotatory (d )
Counterclockwise rotation = levorotatory (l )
Calculating Specific Rotation
    cl
t
  
t

lc
(solvent)
Table 9.3
This solution is prepared for you by
dissolving 3.0 g of menthol in 10 mL of
ethanol!

Concentration (c) (g/mL)
measure the height of the liquid in
the polarimeter tube in cm, then
convert to dm!

Cell pathlength (l) (dm)

Temperature (t) (oC)
Observed optical rotation
(o)
Enter the value for the reading from
the polarimeter with the blank
correction applied!

Literature value specific rotation (o)
Calculated specific rotation
(o)
Room temperature = 25 oC
-50o
This is NOT the same thing as the
OBSERVED ANGLE OF ROTATION!
You must calculate this value!

Safety Concerns
• Ethyl acetate, hexane, and ethanol
are extremely flammable!
• Sulfuric acid is very corrosive! Use
extreme caution at all times!
WASTE MANAGEMENT

Place used TLC solvent from sample
preparation and TLC developing chambers
into container labeled, “Organic Waste
(Stereochemistry)”.

Place all used TLC capillary tubes in the
broken glass container.

Place used TLC plates and filter papers in
yellow solid waste can.