Synthesis and Analysis of Organic and Inorganic Compounds (CM3102)

2017 Spring

Week 4, 5: Grignard Reaction and Column Chromatography

Objectives:
1. To learn the anhydrous reaction techniques.
2. To be able to predict the relative Rf values of organic compounds based on their polarity.
3. To exercise the routine column chromatographic separation in organic chemistry laboratories.

Reference:
L. T. Alty et al. J. Chem. Educ. 2016, 93, 206209.
A sequence of a Grignard reaction and an acid-catalyzed dehydration will be conducted for the
synthesis of 1,1-diphenylethylene (DPE), which will be purified by column chromatography to remove
more polar impurities such as acetophenone and 1,1-diphenylethanol. Whereas the dehydration step
is described as a separate reaction in this paper, it will be simplified as an acidic aqueous workup in
our experiment.

Synthetic Scheme:
O HO Me
MgBr +
H 3O
Me +
Et2O

Experimental Procedure:
Week 4: Synthesis of DPE via Grignard reaction and dehydration.
Week 5: Purification of DPE by column chromatography on silica gel.

Grignard Reaction and Acid-Catalyzed Dehydration:

1. A 100 mL two-neck round-bottom flask is equipped with a septum, a magnetic stir bar, a reflux
condenser, and a drying tube. The drying tube is blocked with a small piece of cotton and filled with
granular anhydrous CaCl2 (6.5 g). The apparatus is dried with a heat gun and cooled to room
temperature.
If your glassware is wet, your experiment will fail.

2. Acetophenone (0.65 mL) and anhydrous Et2O (12 mL) are added to the dry round bottom flask. The
solution is stirred and cooled in an ice bath for several minutes. Then, a 1.0 M solution of PhMgBr in
THF (10 mL) is added slowly over 5 minutes. A precipitate will form as the addition proceeds.

3. The ice bath is removed and the reaction mixture is stirred for 25 minutes. After the reaction mixture
is cooled in an ice bath again, H2O (10 mL) is added slowly dropwise.
More precipitate will be observed.
 Synthesis and Analysis of Organic and Inorganic Compounds (CM3102)
2017 Spring

4. Concentrated hydrochloric acid (4 mL) is added slowly dropwise at the same temperature.
The precipitate should dissolve completely. Otherwise, more acid needs to be added. Dehydration will
take place at this stage.

5. The biphasic mixture is diluted with H2O (12 mL) and transferred to a 125 mL separatory funnel.
The organic layer and the aqueous layer are collected separately. The aqueous layer is added back to
the separatory funnel and extracted with Et2O (20 mL). The two organic layers are combined in an
Erlenmeyer flask and dried over anhydrous MgSO4 (or Na2SO4). The mixture is filtered through a filter
paper (or a glass frit) into a 100 mL round-bottom flask.
The combined organic layers may be washed with saturated aqueous NaHCO3 solution prior to drying.

6. The filtrate is spotted on a TLC plate (silica adsorbent, aluminum backed, UV active) along with
three reference standards of acetophenone, 1,1-diphenylethanol, and DPE by using a glass capillary.
The TLC plate is eluted with a 2:1 mixture of hexanes:CH2Cl2 in a closed TLC chamber.

7. The TLC plate is removed from the chamber and the solvent front is marked with a pencil
immediately. After the plate is dried, it is examined under UV light and visible spots are marked.
The TLC plate should be drawn accurately in the notebook and the Rf values of all of the spots on the
plate should be calculated to two decimal places in order to identify them by comparison to reference
standards.

8. The filtrate is concentrated under reduced pressure by a rotary evaporator and the residue is stored.

Column Chromatography:
1. A chromatography column with a glass frit and a stopcock is firmly clamped in a fume hood.
The column should be positioned vertically. Solvents should flow freely through the frit.

2. While the stopcock is closed, a slurry of silica gel (7.5 g) in a 2:1 mixture of hexanes:CH2Cl2 (20 mL)
is swirled and poured quickly into the column.
The amount of silica gel can be adjusted based on the size of a column. A funnel may be used in
order to prevent spills.

3. After the adsorbent settles down, the column is tapped gently to improve the packing uniformity and
to level the surface of the stationary phase. The stopcock is opened and the solvent is eluted rapidly
by applying air pressure.
By recycling the collected solvent, the slurry can be added as much as possible. The solvent level
must not drop below the top of the adsorbent which should be kept wet at all time during separation. A
small layer of sea sand may be added on top of the adsorbent to protect the surface.
 Synthesis and Analysis of Organic and Inorganic Compounds (CM3102)
2017 Spring

4. The crude mixture is gently loaded to the column with a long Pasteur pipet. A minimal amount of the
eluent (a 2:1 mixture of hexanes:CH2Cl2) is used to rinse the flask and the inside wall of the column
for complete loading.
The surface of the column should not be disturbed during the loading process.

5. After the crude mixture is completely adsorbed, it is eluted with a 2:1 mixture of hexanes:CH2Cl2.
Fractions are collected in test tubes and analyzed by TLC.
The Rf values of acetophenone, 1,1-diphenylethanol, and DPE are approximately 0.10, 0.07, and 0.72,
respectively.

6. The fractions containing pure DPE are combined into a round-bottom flask that is at least twice the
total volume of the solution and concentrated under reduced pressure by a rotary evaporator. The
identity and purity of the product is analyzed by NMR and IR spectroscopy.

Safety Considerations:
All the chemical reagents and organic solvents must be handled in a well-ventilated fume hood. Finely
powdered silica gel is very harmful if inhaled. Capillary TLC spotters may cause lacerations to the skin
and eyes. Protective gloves and safety goggles should be worn at all times.

Before you come to the lab

1. Be aware of the chemical and physical properties of compounds in this experiment.

2. Read the MSDS (material safety data sheet) of all the chemicals used in this experiment.

Pre-Lab Question