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

CH3

OH

CH3 CH3

CH3

OH

CH3 CH3

CH3

OH

CH3 CH3

CH3

OH

CH3 CH3

(l)-menthol

mp = 43-45 oC

(d)-menthol

mp = 43-45 oC(d)-isomenthol

mp = 77-83oC

(d)-neomenthol

mp = -22 oC

R

R

S

Each stereoisomer has 3 stereogenic centers

Since each menthol isomer has 3 stereocenters, menthol has a total of 8 stereoisomers.

(2n, where “n”= # of stereogenic centers)

1

23

4

5

6

1

23

4

5

6

1

23

4

5

6

1

23

4

5

6

Fischer Projections

C XW

Z

Y

C

W X

Y Z

Press flat

C

Z

Y

XW

Stereochemical Relationships

CH3

Cl H

CH3

H OH

CH3

H Cl

CH3

HO H

CH3

Cl H

CH3

HO H

CH3

H Cl

CH3

H OH

"A" "B" "C" "D"

Enantiomers Enantiomers

Diastereomers

Diastereomers

Diastereomers

Diastereomers

Diastereomers and Meso FormsCOOH

H OH

COOH

HO H

COOH

HO H

COOH

H OH

COOH

H OH

COOH

H OH

COOH

HO H

COOH

HO H

2R, 3R 2S, 3S 2R, 3S 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 TLC Rf values

(l)-menthol unitless! 2 decimal places ONLY!

(d)-menthol

(d)-isomentho

l

(d)-neomenth

ol

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

clt

(solvent) cl

t

Table 9.3

Concentration (c) (g/mL) This solution is prepared for you by dissolving 3.0 g of menthol in 10 mL of ethanol!

Cell pathlength (l) (dm) measure the height of the liquid in the polarimeter tube in cm, then convert to dm!

Temperature (t) (oC) Room temperature = 25 oC

Observed optical rotation (o) Enter the value for the reading from the polarimeter with the blank correction applied!

Literature value specific rotation (o) -50o

Calculated specific rotation (o) 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.