Experiment 21:
ESTERS:
SYNTHESIS AND FRAGRANCE
O
O
+
H2SO4
OH
OH
acetic
acid
+
isoamyl
alcohol
O
isoamyl
acetate
H2O
Objectives:




To synthesize an ester from acetic acid
with isoamyl alcohol under reflux by
Fischer esterification.
To purify the product through acid-base
extraction and simple distillation.
To identify and analyze the purity of the
product using GC analysis.
To characterize the reactant and product
using NMR and IR spectra.
Before coming to lab…

Review these techniques:

Reflux

Acid-Base Extraction

Simple distillation

Drying over MgSO4

GC Analysis
FISCHER ESTERIFICATION


Fischer esterification is an acid catalyzed nucleophilic
acyl substitution.
Net effect is the replacement of an –OH of a
carboxylic acid with the –OR of an alcohol to produce
an ester.
O
R

O
H
+
H
O
C
O
R'
H
+
R
O
C
R'
+
H
O
It is an equilibrium reaction with an unfavorable Keq,
thus we can improve product yield in several ways:
 Use an excess of the alcohol reactant.
 Use an excess of the carboxylic acid reactant.
 Remove water as it forms.
H
FISCHER ESTERIFICATION
H
O
C
H3C
CH3
O
+
OH
H
OSO3H
C
H3C
+
OH
H
OH
C
CH3
•
Carboxylic acids are not reactive enough to undergo
nucleophilic addition directly.
•
By using sulfuric acid as a catalyst, the carbonyl
group oxygen is protonated to give the carboxylic
acid a positive charge. This makes it more
reactive.
MECHANISM
1. Protonation
of the
carbonyl
oxygen
activates the
carboxylic
acid…
O
C
H3C
1
H
CH3
O
+
H
OSO3H
+
C
OH
H3C
C
OH
2
3. … yielding
a tetrahedral
intermediate.
H
3
OH
CH3
H3C
OH
2. …toward
nucleophilic
attack by the
alcohol…
H
C
C
H 3C
O
HO 4
5
H
4. Transfer
of a proton
from one
oxygen to
another yields
a second
tetrahedral
intermediate…
CH3
6
H
H3C
O
H
C
O
H3C
H
6. Loss of a
proton and
expulsion of H2O
regenerates the
acid catalyst and
gives the ester
product.
O
H
C
O
H
5…and
converts the
OH group into
a good leaving
group.
CH3
H
O
H3C
C
H 3C
H
C
O
CH3
H2O
H2SO4
OVERVIEW

Synthesize product ester under reflux.

Neutralize acetic acid with 10% NaHCO3.




Extract in ether, then wash with 10%
NaHCO3.
Dry organic layer.
Perform simple distillation to remove ether
from product.
Obtain final product mass, calculate %
yield, prepare GC sample.
EXPERIMENTAL PROCEDURE
(SYNTHESIS)
• Combine
acetic acid, isoamyl alcohol
and sulfuric acid in a 25 mL round
bottom flask.
CaSO4 tube
• Clamp flask to ring stand and add 3
boiling chips.
water out
• Place water cooled condenser on top
of flask, with a CaSO4 drying tube in
the top.
water in
• Heat to reflux. Reflux 30 minutes.
• Cool to room temp.
• Add 10% NaHCO3 slowly to flask.
25mL
heating mantle
to voltage regulator
iron ring
EXPERIMENTAL PROCEDURE
(PURIFICATION)
• Transfer
liquid to separatory funnel.
• Rinse reaction flask with ether and
transfer to separatory funnel.
• Wash the organic layer with 10% NaHCO3.
• Transfer the organic layer to a clean
flask.
125
mL
• Dry over MgSO4.
• Transfer liquid to a preweighed 50 mL
round bottom flask.
50mL
• Clamp flask to ring stand.
50mL
EXPERIMENTAL PROCEDURE
(PRODUCT ISOLATION)
• Set
up a simple distillation
apparatus, using a 25 mL round
bottom as the receiving flask.
•Collect all distillate that boils under
40oC.
water out
water in
• Record distillation range, Ti-Tf.
Heating Mantle
• Allow reaction flask to cool to room
temperature.
• Reweigh 50 mL flask to determine
final product mass (actual yield) and
calculate % yield.
• Prepare GC sample.
iron ring
to
voltage
regulator
50mL
PRODUCT!!!
25mL
WASTE
SOLVENT
Table 21.1:
Experimental Results
Theoretical yield (g)
Actual yield (g)
% yield
Calculated value based on
limiting reagent!
(50mL RB flask + product) –
(Empty 50mL RB flask)
ACTUAL YIELD
THEORETICAL YIELD
X 100
PHYSICAL STATE, COLOR
Product Appearance
Table 21.2:
GC Analysis
Compound
GC Retention Times (min)
Standard
Sample
Area Percent
Adjusted
Area Percent
methanol
SOLVENT
isoamyl alcohol
REACTANT
isoamyl acetate
PRODUCT
EXPERIMENTAL PROCEDURE
(IR ANALYSIS)
CH3
5
CH3CHCH2CH2OH
4
3
CH3
2
1
O
5
CH3CHCH2CH2OCCH3
4
3
2
1
6
7
Table 21.3:
IR Analysis
Functional
Group
sp3 CH
stretch
Base Values
Acetic acid
Isoamyl
alcohol
Isoamyl
acetate
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
2850-3000
C-O stretch
1000-1300
OH stretch
2400-3600
C=O stretch
1640-1750
EXPERIMENTAL PROCEDURE
(NMR ANALYSIS)
CH3
5
CH3CHCH2CH2OH
4
3
2
CH3
1
O
5
CH3CHCH2CH2OCCH3
4
3
2
1
6
O
C
H3C
1
2
OH
3
7
SAFETY CONCERNS
CAUTION:
H2SO4
is a
STRONG ACID!
WASTE MANAGEMENT
• All aqueous washes from the extraction
can be flushed down the drain with plenty
of water!
• Ester product and distilled ether should be
placed in the bottle labeled, “ORGANIC
WASTE (Esters)”.
CLEANING



Clean round bottom flasks and distillation
glassware with wash acetone only!
Separatory funnel and all other glassware
should be cleaned with soap, water, and a
brush if necessary, followed by a wash
acetone.
DO NOT return any glassware to lab
drawer dirty or wet!
In-lab Question
(The following question should be answered in laboratory notebook.)
a.
Draw the product, and a complete mechanism for its formation, of the reaction
shown below.
O
C
OH
+
CH3OH
0.25 g used
OCH3
1.0 g used
H2SO4
0.01 g used
?
In-lab Question
(The following question should be answered in laboratory notebook.)
Based on the chemical equation shown in the previous question,
calculate the theoretical yield of the product. Show calculations
based on all reactants.