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 identify compounds and determine purity
of product sample using GC analysis.
To characterize reactants and product 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
diethyl ether or THF to yield an
organomagnesium halide: RMgX
DIETHYL 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+.
MECHANISM
H
CH 3 CH 2 CH 2 CH 2 Br + Mg
ether
CH 3 CH 2 CH 2 C




MgBr
n -B U T Y L B R O M ID E
H
G rig n a rd re a g e n t
(b u ty l m a g n e s iu m b ro m id e )
MgBr
H

CH 3 CH 2 CH 2 C
MgBr
O

MgBr


H
1. The Lewis acid Mg2+
forms an acid-base
complex with the basic
oxygen atom of the
ketone, making the
carbonyl group a better
acceptor.
CH 3
H 3C
C
H 3C
CH 3
C
CH 3
CH 2 CH 2 CH 2 CH 3
CH 3 CH 2 CH 2 CH 2
2. Nucleophilic addition of
butyl group to acetone
produces a tetrahedral
intermediate…
H
O
O
C
H 3C
H
O
H 3C
O
H
C
CH 3
3….which
reacts with
water when
aqueous HCl
is added,
undergoing
hydrolysis to
form the
product
alcohol.
CH 2 CH 2 CH 2 CH 3
2 -M E T H Y L -2 -H E X A N O L
+
HOMgBr
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
b u tyl m a g n e siu m b ro m id e
+
O
H
b u ta n e
HOMgBr
OVERVIEW


Heat alkyl halide, magnesium turnings, and
ketone in diethyl ether under reflux to
synthesize intermediate.
Hydrolyze intermediate with HCl to produce
neutral product.

Purify product by extraction.

Prepare GC sample.

Analyze product using GC to identify and
determine purity.
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.
CaSO4
drying
tube in
adapter
Keck clips
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.
iro n rin g
EXPERIMENTAL PROCEDURE
(Synthesis of alcohol product…)

Add acetone/ether to sep funnel.

Add to reaction mixture dropwise.

Cool reaction flask in water bath.
iro n rin g


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:
GC Results
Compound
GC Retention Times (min)
Standard
Sample
methanol
acetone
Area
Percent
Adjusted
Area
Percent
---
n-butyl bromide
2-methyl-2hexanol
octane
Record
retention times
for ALL peaks
in standard
chromatogram!
---
Record retention
times and area %
for ALL peaks
present in sample
chromatogram!
Calculate AA%
for
REACTANTS
AND PRODUCT
only!
Product Analysis
(IR Spectroscopy)
Table 18.2:
IR Analysis
Functional
Group
Base Values
n-butyl
bromide
2-methyl-2hexanol
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
OH
stretch
2500-3300
sp3 CH
stretch
2850-3000
C-O stretch
1000-1200
C-Br stretch
500-700
• IR spectra available on p. 157, 158 of the lab manual!
• In discussion, only refer to frequencies which indicate a
CONVERSION to product!
Product Analysis
(1H-NMR Spectroscopy)
Br
CH
1
2
CH
2
2
CH
3
2
CH
3
4
1
OH
H 3C
2
C
CH 2 CH 2 CH 2 CH 3
3
CH 3
1
4
5
6
Product Analysis
(13C-NMR Spectroscopy)
Br
CH
1
2
CH
CH
2
3
2
2
CH
3
4
NMR
solvent
1
OH
H 3C
2
C
3
CH 3
1
NMR
solvent
CH 2 CH 2 CH 2 CH 3
4
5
6
C1
29
Table 18.3:
NMR Analysis
1
OH
H 3C
Br
CH
1
2
CH
2
2
CH
2
3
n-butylbromide
(reactant)
CH
4
3
2
C
CH 2 CH 2 CH 2 CH 3
3
CH 3
1
4
5
6
2-methyl-2-hexanol
(product)
• Enter chemical shifts ONLY based on the spectra on page 157, 158.
• In discussion, only refer to signals 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

RECOVERED MAGNESIUM WASTE:
Unreacted magnesium & water rinse.
LIQUID WASTE:
Aqueous extracts and washes, crude
alcohol product.
 SOLID WASTE:
Magnesium sulfate.

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.
In-lab Question
(The following question should be answered in laboratory notebook.)

Draw the product, and a complete mechanism
for its formation, of the reaction between
propyl magnesium bromide with acetophenone.
O
MgBr
+
e th e r
?
In-lab Question
(The following question should be answered in laboratory notebook.)

During the experiment a student neglected to
completely dry the glassware prior to
assembling the apparatus. Write the chemical
equation that occurs between propyl magnesium
bromide and water, and explain how this would
affect the Grignard synthesis.