Laboratory Report
Organic chemistry practical course (OCP1)
HS 07/08
04.11.2007
Lorenz Schwarzer
D-Biol
Assistant: Zhu Liang
Synthesis of Benzocaine
(ethyl-4-aminobenzoate)
CH3
O
H2N
O
Method
1. Reduction of aromatic para-nitrobenzoic acid by tin to para-aminobenzoic acid
2. Esterification of para-aminobenzoic acid by sulphuric acid and ethanol to
benzocaine
1. Reduction
Reaction equation
O
OH
OH
Sn
H2N
N
O
O
O
3Sn
C7NO4H + 6H+ + 6e-
→
→
3Sn2+ + 2eC7NO2H3 + 2H2O
3Sn + C7NO4H + 6H+
→
3Sn2+ + C7NO2H3 + 2H2O
2NH3 + 2H2O + 2Sn2+
→
Sn(OH)2 + 2NH4+
Physical properties of the substances
Para-nitrobenzoic acid
O
OH
Molar weight
Density
Melting point
Boiling point
R-Phrases
R22
R41
N
O
O
S-Phrases
S26
S39
167.12 g/mol
1.58 g/ml
237
°C
Sublimes
°C
Harmful if swallowed.
Risk of serious damage to the
eyes.
In case of contact with eyes, rinse
immediately with plenty of water
and seek medical advice.
Wear eye / face protection.
Tin
Sn
Molar weight
Density
Melting point
Boiling point
R-Phrases
S-Phrases
118.71
7.265
231.93
2602
2
g/mol
g/ml
°C
°C
Hydrochloric acid (conc.)
Molar weight
Density
Melting point
Boiling point
H-Cl
R-Phrases
36.46
1.19
-40
84
R 34
R 36
R 37
R 38
S 26
S-Phrases
g/mol
g/ml
°C
°C
Causes burns
Irritating to eyes
Irritating to respiratory system
Irritating to skin
In case of contact with eyes, rinse
immediately with plenty of water
and seek medical advice.
Ammonia
Molar weight
Density
Melting point
Boiling point
R-Phrases
17.03
0.69
-77.73
-33.34
R10
R23
R34
R50
S1/2
Flammable
Toxic by inhalation
Causes burns
Very toxic to aquatic organism
Keep locked up and out of the
reach of children
S16 Keep away from sources of
ignition – no smoking
S36/37/39 Wear suitable protective
clothing, gloves and eye/face
protection
H
H
N
H
g/mol
g/ml
°C
°C
S-Phrases
Para-aminobenzoic acid (PABA)
Molar weight
Density
OH
Melting point
H2N
Boiling point
R-Phrases
O
S-Phrases
137.14
1.37
187-189
-
g/mol
g/ml
°C
°C
Educts
Substance
p-nitrobenzoic acid
Tin
Hydrochloric acid
Amount
Molar amount
g
2.89
7.04
~13
mol
0.018
0.059
0.41
3
Volume
ml
~15
Experimental accomplishment
1. 2.89g p-nitrobenzoic acid, 7.04g Tin (little balls) and 15ml conc. HCl were put
in a round bottom flask (fitted with a reflux condenser). The mixture was
heated up to 115°C for about 20min (caution gases). The solution becomes
clear.
2. The solution is decanted and the remaining tin washed with water and
decanted again.
3. With conc. Ammonia the solution is adjusted to pH 9, and then it was heated
up again for 20min. Filtered with vacuum.
4. The solvent was evaporated with vacuum.
5. The crystals were recristallized from ethanol/water (2:8)
Experimental setup
Reflux condenser
Thermometer
Filter
Oilbath
67
4 5
8
3
11
9
21
4 5
3
2
1
67
8
9
1
0
Vacuum
Heating apparatus
Filtration apparatus
4
Results
IR-Spectrum-bands [cm-1]
3250-3400
1690-1760
1540
N-H stretch (amines)
C=O stretch (carboxylic acid)
NO2 stretch (nitro compounds)
If you compare the IR-spectrum of the product with the Reference spectrums of paminobenzoic acid and p-nitrobenzoic acid, you can see that most of the product is
still p-nitrobenzoic acid. The reduction of p-nitrobenzoic acid didn’t go well.
One reason could be that we used tin as balls instead of powdered tin.
For the esterification of the p-aminobenzoic (PABA) acid to benzocaine I had to take
some PABA from the Assistant
IR-Spectrum of the Product
5
Reference IR-spectrum of p-aminobenzoic acid
Reference IR-spectrum of p-nitrobenzoic acid
6
2. Esterification
Reaction equation
CH3
O
OH
H2SO4 / EtOH
H2N
H2N
O
O
Mechanism
CH3
CH3
O
OH
O
+
HO
OH
HO
+
OH
C
HO
HO
O
OH
CH3
H+
NH2
+
H
OH
NH2
NH2
NH2
NH2
Physical properties of the substances
Ethanol
OH
H3C
Molar weight
Density
Melting point
Boiling point
R-Phrases
S-Phrases
46,07
0.79
-114.4
78.37
R11
S7
S16
7
g/mol
g/ml
°C
°C
Highly flammable
Keep container tightly closed
Keep away from sources of
ignition
Sulfuric acid (H2SO4)
Molar weight
Density
Melting point
Boiling point
R-Phrases
S-Phrases
HO
O
98,07 g/mol
1.84 g/ml
10
°C
338
°C
R35 Causes severe burns
S1/2 Keep locked up and out of the
reach of children
S26 In case of contact with eyes, rinse
immediately with plenty of water
and seek medical advice.
S30 Never add water to this product
S45 In case of accident or if you feel
unwell, seek medical advice
immediately
S
O
OH
Sodium Carbonate (Na2CO3)
Molar weight
Density
Melting point
+ O
Boiling point
+
Na
Na
R-Phrases
S-Phrases
O
O
R36
S22
S26
105.99 g/mol
2.5 g/ml
851
°C
decomposes
°C
Irritating to eyes
Do not breathe dust
In case of contact with eyes, rinse
immediately with plenty of water
and seek medical advice
Benzocaine
CH3
Molar weight
Density
Melting point
Boiling point
R-Phrases
165.19 g/mol
1.17 g/ml
89-92
°C
172
°C
R36/37/38 Irritating to eyes, respiratory
system and skin
R43 May cause sensitization by skin
contact
S24 Avoid contact with skin
S26 In case of contact with eyes, rinse
immediately with plenty of water
and seek medical advice
S37/39 Wear suitable gloves and eye /
face protection
O
H2N
O
S-Phrases
8
Educts
Substance
Amount
Molar amount
g
3.12
~19
~0.5
p-aminobenzoic acid
Ethanol
Sulfuric acid
mol
0.023
~0.41
~0.0055
Volume
ml
~15
~1
Experimental accomplishment
1. 3.12g PABA from the Assistant (reduction didn’t work), 15ml of ethanol and
1ml of H2SO4 were added to a bottom flask. The Solution was heated under
reflux for 2h (with stirrer).
2. Then cooled down and neutralized with 10% Na2CO3 until the pH was over 9.
3. Extracted with ether in the separation funnel. Dried with sodium sulphate.
4. The ether and ethanol were evaporated. A white powder appeared.
Experimental setup
Reflux condenser
Thermometer
Oilbath
67
4 5
8
3
11
9
21
4 5
3
2
1
67
8
9
1
0
Heating apparatus
Separation funnel
9
Results
Melting point
Token:
Benzocaine (literature):
PABA (literature):
IR-Spectrum-bands [cm-1]
3250-3400
1735-1750
1690-1760
89.7°C
89-92°C
187-189°C
N-H stretch (amines)
C=O stretch (esters)
C=O stretch (carboxylic acids)
With the aid of the comparisons of the token IR-spectrum with the reference
spectrum, it is not clear if the product is PABA or Benzocaine, but if you compare the
token melting point with the literature values of BABA and Benzocaine, the product
can be identified as benzocaine.
IR-Spectrum of the Product
10
Reference IR-spectrum of benzocaine
Literature





CrossFire Beilstein
http://riodb01.ibase.aist.go.jp/sdbs/cgi-bin/cre_index.cgi?lang=eng
http://en.wikipedia.org
http://www.chemexper.com
http://www.chemblink.com
11