Professional Documents
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Esterification
Introduction
• Many esters have pleasant odors and some of them can even be found in nature.
Compound Flavor/Fragrance
Isoamyl acetate Banana Oil
Ethyl butyrate Pineapple
Octyl acetate Orange
Methyl anthranilate Grape
Methyl butyrate Apple
Benzyl acetate Peach
Methyl salicylate Oil of Wintergreen
Menthyl acetate Peppermint
• Esters are often used in fragrances or flavoring agents due to their organoleptics
properties.
• Some esters are used as sex pheromones i.e., isopropyl dodecenoates
(attracts female beetles, used in alternative pest control) or alarm
pheromones i.e., isoamyl acetate (honey bee)).
• Ester of p-aminobenzoic acid are used as local anesthetics with a short to moderate
half-life (benzocaine (ethyl), procaine (2-(diethylamino)ethyl), propoxycaine, etc.).
Theory I
• Esters can be obtained by a broad variety of reactions
• Fischer Esterification (used in Chem 30BL)
O
H+
RCO2H + R'OH R C OR' + H2O
• This approach
acid works well for primary
alcohol ester and most secondary alcohols,
but not for tertiary alcohols because of their high tendency to
eliminate water instead of forming an ester.
• Acyl chloride
• Works for tertiary alcohols as O O O
• Anhydride O O O
• Accessibility of anhydrides O
ROH/H +
OR
OH
ROH/H +
OR
-H2O OR
• Often also requires an acidic O O O
catalyst i.e., aspirin synthesis.
Theory II
• Example 1: Aspirin (Bayer AG,1899)
• It uses salicylic acid, acetic acid anhydride and a mineral acid
as catalyst (usually conc. phosphoric acid).
• The phenol group acts as the alcohol in the reaction.
Methyl salicylate
Topical analgesic
• Aspirin is considered a pro-drug for salicylic acid, which was long known
(Hippocrates, bitter willow bark extract, 5th century BC) to work against
inflammations and fever but it caused vomiting and nausea.
• The reaction of salicylic acid with methanol in the presence of a mineral
leads to the formation of methyl salicylate (Oil of wintergreen), which is
used as topical analgesic.
Theory III
• Intramolecular esterification afford lactones (i.e., coumarins).
• These reactions can usually be carried out under mild
conditions.
• Example 2: GHB (g-hydroxybutyric acid)
O
H+
HO COOH O Lacton
mild conditions
GHB GBL
O R2 R1 O
R1 O O OH
NaOH
O + 3 CH 3OH +
R2 O
O
O OH OH
R3
O
R3 O
• Trans-esterification: It converts oils into methyl esters that are much more volatile
than oils due to their lower molecular weight.
• It is important that water is absent during the reaction to avoid the formation of soap
(Na+ RCOO-, where R= C17H35, etc.).
• Food vs. Fuel debate (i.e., 80 gal/acre for soy and sunflower):
• 42 billion gallons of diesel in 2008 in the US: 525,000,000 acre (21.6 % of the US).
• If the gasoline is also included (135 billion gallons) about 70 % of the area is needed.
• In 2013, industry produced 1.8 billion gallons of biodiesel.
Theory V
• In the lab, an unknown carboxylic acid is reacted with an
unknown alcohol (both assigned by the TA).
+ O
H
RCO2H + R'OH R C OR' + H2O
acid alcohol ester
• Problems:
• The reaction is an equilibrium reaction with poor yields
if a 1:1-ratio of the reactants is used.
• The carboxylic acid is a poor electrophile (neutral).
• The alcohol is a poor nucleophile (neutral).
• The reaction is very slow at room temperature.
• Any water in the reaction mixture lowers the yield significantly.
Theory VI
• Mechanism of Fischer Esterification
•
O•
••
OH
R C OH OH
+
R C OH ••
+H R'–OH R C OH
••
H O R'
O– OH – H+
R C OH R C OH
+
OH
activated carbonyl R C OH
(charge separation) (no charge separation)
better electrophile O R'
+ H+
H2 O is a
+ •• good leaving
••
O – H+ OH –H2O
OH H group
R C OR' R C OR' R C O
H
OR'
• In the neutral state, the resonance structure with the charge separation is
a very minor contributor making the carbonyl function of the carboxylic
acid a poor electrophile.
• The situation changes in the protonated form of the carboxylic acid in
which the carbonyl carbon bears a larger positive charge (~0.2 units in
the case of acetic acid), which makes it a better electrophile.
Theory VII
• Le Châtelier Principle
• If equimolar amounts of the carboxylic acid and the alcohol were used, the
theoretical yield would be low i.e., 67 % (Keq=4).
O
H2O
R C OR'
Keq = 1–10
RCO2H R'OH
• One or all products have to be removed from equilibrium, which will not
work here because water and the esters have higher boiling points than the
alcohols.
• Thus, an excess of one the reactants has to be used.
• The carboxylic acids cannot be used in excess because all of them are
solids.
• The reaction in the lab uses an excess of the alcohol:
• The alcohol doubles up as the solvent and as a reactant in the reaction.
• Usually about 4-10 fold molar excess in the literature (a five-fold molar
excess is used in the Chem 30BL lab i.e., 10 mmol of the carboxylic acid
are reacted with 50 mmol of the alcohol).
Theory VIII
• A strong mineral acid is usually used as catalyst:
• The carboxylic acid is neutral and a weak electrophile.
• The mineral acid protonates the carbonyl carbon atom and increases
its electrophilic character.
• All of the alcohols (log Kow= -0.77 (MeOH), -0.24 (EtOH), 0.05 (iso-PrOH),
t=0
t >> 0
(water just added)
0.25 (PrOH)) and the sulfuric acid (log Kow= -2.20) are soluble in water.
• The carboxylic acid and the sulfuric acid can be NaHCO Extraction:
3
RCO2R'
the ester and traces of the alcohol remain in the H2SO4 1. mix R'OH
Na+RCO2–
1 39, 1
20 70 120 170
does not contain cotton or CaCl2! • What is the setup for the vacuum
distillation?
• Collect product from Hickman head • What should the student do if he had a
• Acquire an infrared spectrum and the liquid in the Hickman head and also in the
refractive index of the ester. Submit the flask/vial?
rest of the sample, even if it is solid or Acquire an infrared spectrum for
semi-solid) for NMR analysis (label vial both liquids and only submit the
and sign in the sample as well) “ester” for NMR analysis
Characterization I
• Infrared Spectrum n(OH)
• Benzoic acid
• n(C=O)=1689 cm-1
• n(OH)=2300-3300 cm-1 n(C=O)
n(C-OH)
• n(C-OH)=1030 cm-1
• Methanol
• n(OH)=3347 cm-1 n(OH)
• n(C-OH)=1030 cm-1
n(C-OH)
• Methyl benzoate
• n(C=O)=1724 cm-1
• n(COC)=1112, 1279 cm-1
• No OH peaks in the ester n(C=O) n(COC)
Characterization II
• Refractometry light
angle
8.0
O 5.0
ortho
7.5
s, 3 H 4.5
7.0
6.5
OCH3 t, 2 H
4.0
6.0
t, 1 H meta
3.5
5.5
5.0
para
3.0
4.5
4.0 2.5
3.5
2.0
3.0
2.5
1.5
2.0
1.0
1.5
1.0
0.5
0.5
0.0 0.0
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 8.40 8.30 8.20 8.10 8.00 7.90 7.80 7.70 7.60 7.50 7.40 7.30 7.20 7.10 7.00
Characterization IV
• 13C{1H}-NMR Spectrum for Methyl benzoate
120 120
115
O
115 O
110
10
110 9
6 7
128.40(5;3) 128.45(5;3)
105 105
6 7 CH3
129.70(2;6)
130.19(2;6)
5 1 OH
100 100
5 1 O 9
8
95 95
90 8 90
85 4 2 85
4 2
80
3 80 3
75 75
70 70
65 65
60 60
55 132.80(4) 51.00(9) 55
133.76(4)
50 50
45 45
40 40
35 35
30 30
25 25
20
166.80(7)
CDCl3 20
170.39(7) 130.02(1)
CDCl3
15 76.28(Sol.) 15
77.08(Sol.) 76.28(Sol.)
77.88(Sol.) 77.08(Sol.)
10 10 77.88(Sol.)
5 5
0 0
170 160 150 140 130 120 110 100 90 80 70 60 50 40 180 170 160 150 140 130 120 110 100 90 80 70
Characterization V
• What is that?
120
17 115
110
16 128.00
128.45
105 129.50
130.19 65.90 15.20
15
100
14 95
90
13
85
12
80
75
11
70
10
65
9 60
50
7
45 76.28
77.08
77.88
6 40
35
5
30
4
25
3 20
170.39 166.30
15
2
10
1
5
0 0
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 150 100 50 0
General Hints
• The reaction should be started as soon as possible in order to have
a long enough reaction time.
• Dry glassware is very important here.
• The reaction mixture has to be properly refluxed.
• The air condenser has to be properly cooled with a wet paper towel,
which has to have an intimate contact with the air condenser (no
Hickman head here!!).
• The purer the final product is, the easier the analysis of the NMR
spectra will be.
• The student should submit something even if it is a “solid” that just
had a pleasant odor to it.
• It is advisable to acquire a refractive index of the alcohol.
• Do not obtain the melting point for the carboxylic acid.