Nucleophilic Acyl Addition
Grignard Synthesis of 2-methyl-2-hexanol
Introduction
The Grignard reaction is one of the most versatile reactions in Organic chemistry. A Grignard “reagent” is and
extremely strong base/nucleophile. It is the conjugate base of an Alkane, which are very weak acids.
Aldehydes and Ketones undergo Nucleophilic Acyl Addition. The Grignard Reagent is a strong enough base to
cause the carbon of the carbonyl group in the Aldehyde or Ketone to behave as an acid. The Grignard can be used to
produce alcohols, esters and carboxylic acids.
Reaction
Step 1 Preparation of the Grignard Reagent
Mg
Br
Ether/Dry
MgBr
Step 2 Reaction of the Grignard with Acetone
O
MgBr
+
OMgBr
Step 3 Acidification of the Alcohol Salt
H3O+
OMgBr
+ MgOHBr
OH
Procedures
1. Equipment Required
a. 100 ml round bottom flask
b. Claisen adapter
c. Separatory funnel
d. 25 or 50ml graduated cylinder
e. Reflux condenser
f. Heating mantle
g. Ice bath
2. Chemicals
a. Magnesium metal
b. Diethyl ether, anhydrous
c. 1-butyl bromide
d. 10% sodium bicarbonate solution
e. Ice
3. Preparation of the Grignard Reagent.
a. Weigh 2.43 grams of Mg, 0.1 mole. Add it to the 100 ml round bottom
flask.
b. Use the graduated cylinder and add 20 ml of ether to the magnesium in
the 100 ml round bottom flask.
c. Clamp the flask at the neck and allow enough room below to add heat
using a heating mantle or cooling, an ice bath.
d. Attach the Claisen adapter.
e. Add 11.0 ml of 1-bromobutane to the separatory funnel and 20 ml of
ether. Attach this to the “arm” that is not directly above the round
bottom.
f. Attach the condenser directly above the round bottom. The condenser
should be cooled. Water in at the bottom and out at the top.
g. Add approximately 1/3 of the 1-bromobutane-ether mixture to the
round bottom.
4.
5.
6.
7.
i. Heat the mixture with the mantle until boiling. Remove the heat
source. Continue this cycle until the mixture boils on its own.
Have an ice bath ready to moderate the reaction if it becomes too
vigorous.
h. After the mixture stops reacting spontaneously heat it with a mantle for
an additional 15 minutes.
Reaction of the Grignard with Acetone
a. Add 7.4 ml of acetone, 0.1 mole to the separatory funnel and 10 ml of
ether.
b. Insert the round bottom flask in an ice bath.
c. Add the acetone/ether mixture to the Grignard reagent slowly with
cooling. Stir frequently during the addition.
Acidification of the salt of the alcohol.
a. Add 25 ml of ice water from the previous step to the separatory funnel
followed by 10 ml of concentrated sulfuric acid.
b. Deliver the acid solution slowly with external cooling to the salt of the
alcohol via the attached funnel. After addition, no solids except a small
amount of unreacted magnesium metal should remain.
Purification and separation of the Alcohol.
a. Transfer the mixture to a clean separatory funnel.
b. Drain the lower layer aqueous layer into a beaker.
c. Drain the ether layer into another small beaker.
d. Add the original aqueous layer back to the funnel and extract with two
10 ml portions of ether.
e. Add the ether extracts to the original ether layer.
f. Return the ether extracts to the sep funnel.
i. Wash with two 10 ml portions of 10% sodium bicarbonate.
ii. Drain the wash layers and discard.
g. Dry the remaining ether layer over CaCl2 until it is clear.
Recovery of the 2-methyl-2-hexanol
a. Set up a simple distillation to remove the ether, to be saved and collect
the alcohol
b. Distill the alcohol into a preweighed sample vial.
8. Product Analysis
a. Determine the actual yield of the product.
b. Measure its refractive index.
c. Run the IR. Label the following
i. Identify the O-H stretch
ii. Identify the C-H stretch
iii. Identify Methylene and Methyl stretch
iv. Identify the C-O stretch.