Experiment 18:
THE GRIGNARD REACTION
Mg
CH3CH2CH2CH2Br
CH3CH2CH2CH2MgBr
ether
O
CH3
CH3
CH3CH2CH2CH2
C
OMgBr
CH3
H3O
C
CH3
CH3
+
CH3CH2CH2CH2
C
CH3
OH
Objectives:




To synthesize a 3o alcohol from an alkyl
halide and a ketone using a Grignard
reaction.
To purify product using a liquid extraction
method.
To determine purity using GC analysis.
To characterize starting materials and
products using IR, 1H-NMR, and 13C-NMR
spectra.
Before coming to lab…

Review the following techniques:




Extraction
Drying organic solvents with MgSO4
Preparing GC samples
You will be expected to perform these
will little review, as you learned these
techniques in the first semester lab.
CHEMICAL EQUATION
Mg
CH3CH2CH2CH2Br
CH3CH2CH2CH2MgBr
ether
O
CH3
CH3
CH3CH2CH2CH2
C
OMgBr
CH3
H3O
C
CH3
CH3
+
CH3CH2CH2CH2
C
CH3
OH
MAKING THE
GRIGNARD REAGENT

Organic halides react with magnesium metal in
ether or THF to yield an organomagnesium
halide: RMgX
ETHER
R-X + Mg -------------> R-Mg-X
or THF
Where R= 1o, 2o, or 3o alkyl, aryl or alkenyl
X= Cl, Br, I

+
MgX
- C
The C-Mg bond is a highly polar covalent bond.
The carbon atom is both nucleophilic and basic
making it very reactive with a wide variety of
E+.
WHEN THE GRIGNARD
REAGENT MEETS WATER…


Since the carbon atom of a Grignard reagent is
so nucleophilic and basic, it reacts with proton
donors (Brönsted acids) such as H2O, ROH,
RCOOH, RNH2 to yield hydrocarbons.
This makes it extremely important to keep the
reaction flask and solvent completely dry of
water.
H
+
MgBr
butyl magnesium bromide
+
O
H
butane
HOMgBr
MECHANISM
CH3CH2CH2CH2Br + Mg
n-BUTYL BROMIDE
ether
 
CH3CH2CH2CH2 MgBr
Grignard reagent
(butyl magnesium bromide)
O
O
C
CH3CH2CH2CH2 MgBr
C
H 3C
CH3
MgBr
H 3C
H 3C
CH3
CH3CH2CH2CH2
O
MgBr
C
CH3
CH2CH2CH2CH3
ACETONE
1. Lewis acid Mg2+ forms
an acid-base complex with
basic oxygen atom of
acetone making the
carbonyl group a better
acceptor.
2. Nucleophilic addition of
butyl group to acetone
produces a tetrahedral
intermediate…
O
H
3….which
reacts with
water when
HCl is added,
undergoing
hydrolysis to
form the
product
alcohol.
H
H 3C
O
H
C
CH3
CH2CH2CH2CH3
2-METHYL-2-HEXANOL
+
HOMgBr
EXPERIMENTAL PROCEDURE
(Synthesis of Grignard reagent…)





Place Mg turnings in 50mL flask and
place a CaSO4 tube in the top
IMMEDIATELY!
Clamp flask to ring stand and set up
remainder of reflux with addition
apparatus.
Start reaction with a small amount of nbutylbromide and ether by scratching
Mg surface and stirring with glass rod.
Add remaining n-butylbromide and
ether to sep funnel.
Add to reaction mixture dropwise.
iron ring
EXPERIMENTAL PROCEDURE
(Synthesis of alcohol product…)

Add acetone/ether to sep funnel.

Add to reaction mixture dropwise.

Cool reaction flask in water bath.
iron ring


Transfer cooled liquid to 125 mL
Erlenmeyer flask.
Add an ice cube and NH4Cl.
EXPERIMENTAL PROCEDURE
(Purification…)






Set up an extraction apparatus.
Transfer the liquid from the flask to the
funnel.
Extract with 5%HCl, 10% NaHCO3, and
Sat. NaCl.
Transfer organic layer to a 50 mL flask
and dry over MgSO4.
Transfer dried organic liquid to a
beaker.
Submit a GC sample.
Table 18.1
Compound
GC Retention Times
(min)
Standard
Adjusted
Area %
Sample
methanol
---
acetone
n-butyl bromide
2-methyl-2-hexanol
octane
Record
retention times
for ALL peaks
in standard
chromatogram!
The product is only
pure if the sample
chromatogram
indicates presence
of GC solvent and
expected product
ONLY.
---
Record retention
times for any
peaks present in
sample
chromatogram!
Calculate AA%
for
REACTANTS
AND PRODUCT
only!
Product Analysis
(IR Spectroscopy)
Table 18.2
Functional
Group
Base Values
acetone
n-butyl
bromide
2-methyl-2hexanol
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
OH
stretch
2500-3300
sp3 CH
stretch
2800-3000
C=O stretch
1680-1740
C-O stretch
1000-1200
C-Br stretch
500-700
• IR spectra available on p. 155 of the lab manual!
• In discussion, only refer to frequencies which indicate a
CONVERSION to product!
Product Analysis
(1H-NMR Spectroscopy)
Br
CH2
1
CH2
2
CH2
CH3
3
4
1
OH
H3C
2
C
CH2 CH2 CH2 CH3
3
CH3
1
4
5
6
Product Analysis
(13C-NMR Spectroscopy)
NMR
solvent
NMR
solvent
Table 18.3
1
OH
H3C
Br
CH2
1
CH2
2
CH2
CH3
3
4
n-butylbromide
(reactant)
2
C
CH2 CH2 CH2 CH3
3
CH3
1
4
5
6
2-methyl-2-hexanol
(product)
• Enter chemical shifts ONLY based on the spectra on page 154.
• In discussion, only refer to frequencies which indicate a CONVERSION
to product!
SAFETY CONCERNS
• Diethyl Ether is EXTREMELY flammable.
Use extreme caution at all times!
• Be sure to wear goggles at ALL times
during this experiment!
• GLOVES are available upon request!
WASTE MANAGEMENT



Unreacted magnesium should be rinsed
with water and placed in “Recovered
Magnesium (Grignard)” container.
Aqueous extracts and washes:
“Aqueous Waste (Grignard)” container.
Crude Alcohol product: Transfer to
bottle labeled “Grignard product (2methyl-2-hexanol, Student Prep”.
CLEANING




Rinse condenser and Claisen adapter
with wash acetone only.
Clean all other glassware with soap,
water, brush, and rinse with wash
acetone.
Leave all ground glass jointware in lab
hood for inspection. DO NOT place any
in lab drawer.
DO NOT return any glassware to lab
drawer dirty or wet.