Laboratory Report 04.11.2007

Organic chemistry practical course (OCP1)

HS 07/08

Lorenz Schwarzer

D-Biol

Assistant: Zhu Liang

Synthesis ofBenzocaine

(ethyl-4-aminobenzoate)

Method

  1. Reduction of aromatic para-nitrobenzoic acid by tin to para-aminobenzoic acid
  1. Esterification of para-aminobenzoic acid by sulphuric acid and ethanol to benzocaine

1. Reduction

Reaction equation

3Sn →3Sn2+ +2e-

C7NO4H + 6H+ + 6e-→ C7NO2H3 + 2H2O

3Sn + C7NO4H + 6H+→3Sn2+ + C7NO2H3 + 2H2O

2NH3 + 2H2O + 2Sn2+→Sn(OH)2 + 2NH4+

Physical properties of the substances

Para-nitrobenzoic acid
/ Molar weight / 167.12 / g/mol
Density / 1.58 / g/ml
Melting point / 237 / °C
Boiling point / Sublimes / °C
R-Phrases / R22Harmful if swallowed.
R41Risk of serious damage to the eyes.
S-Phrases / S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
S39Wear eye / face protection.
Tin
Sn / Molar weight / 118.71 / g/mol
Density / 7.265 / g/ml
Melting point / 231.93 / °C
Boiling point / 2602 / °C
R-Phrases
S-Phrases
Hydrochloric acid (conc.)
H-Cl / Molar weight / 36.46 / g/mol
Density / 1.19 / g/ml
Melting point / -40 / °C
Boiling point / 84 / °C
R-Phrases / R 34Causes burns
R 36 Irritating to eyes
R 37Irritating to respiratory system
R 38Irritating to skin
S-Phrases / S 26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
Ammonia
/ Molar weight / 17.03 / g/mol
Density / 0.69 / g/ml
Melting point / -77.73 / °C
Boiling point / -33.34 / °C
R-Phrases / R10Flammable
R23Toxic by inhalation
R34Causes burns
R50Very toxic to aquatic organism
S-Phrases / S1/2Keep locked up and out of the reach of children
S16Keep away from sources of ignition – no smoking
S36/37/39 Wear suitable protective clothing, gloves and eye/face protection
Para-aminobenzoic acid (PABA)
/ Molar weight / 137.14 / g/mol
Density / 1.37 / g/ml
Melting point / 187-189 / °C
Boiling point / - / °C
R-Phrases
S-Phrases

Educts

Substance / Amount / Molar amount / Volume
g / mol / ml
p-nitrobenzoic acid / 2.89 / 0.018 / -
Tin / 7.04 / 0.059 / -
Hydrochloric acid / ~13 / 0.41 / ~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

Heating apparatus Filtration apparatus

Results

IR-Spectrum-bands [cm-1]3250-3400N-H stretch (amines)

1690-1760C=O stretch (carboxylic acid)

1540NO2 stretch (nitro compounds)

If you compare the IR-spectrum of the product with the Reference spectrums of p-aminobenzoic 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
Reference IR-spectrum of p-aminobenzoic acid
Reference IR-spectrum of p-nitrobenzoic acid

2. Esterification

Reaction equation

Mechanism

Physical properties of the substances

Ethanol
/ Molar weight / 46,07 / g/mol
Density / 0.79 / g/ml
Melting point / -114.4 / °C
Boiling point / 78.37 / °C
R-Phrases / R11Highly flammable
S-Phrases / S7Keep container tightly closed
S16Keep away from sources of ignition
Sulfuric acid (H2SO4)
/ Molar weight / 98,07 / g/mol
Density / 1.84 / g/ml
Melting point / 10 / °C
Boiling point / 338 / °C
R-Phrases / R35Causes severe burns
S-Phrases / S1/2Keep locked up and out of the reach of children
S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
S30Never add water to this product
S45In case of accident or if you feel unwell, seek medical advice immediately
Sodium Carbonate (Na2CO3)
/ Molar weight / 105.99 / g/mol
Density / 2.5 / g/ml
Melting point / 851 / °C
Boiling point / decomposes / °C
R-Phrases / R36Irritating to eyes
S-Phrases / S22Do not breathe dust
S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice
Benzocaine
/ Molar weight / 165.19 / g/mol
Density / 1.17 / g/ml
Melting point / 89-92 / °C
Boiling point / 172 / °C
R-Phrases / R36/37/38 Irritating to eyes, respiratorysystem and skin
R43May cause sensitization by skin contact
S-Phrases / S24Avoid contact with skin
S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice
S37/39 Wear suitable gloves and eye / face protection

Educts

Substance / Amount / Molar amount / Volume
g / mol / ml
p-aminobenzoic acid / 3.12 / 0.023 / -
Ethanol / ~19 / ~0.41 / ~15
Sulfuric acid / ~0.5 / ~0.0055 / ~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

Heating apparatus Separation funnel

Results

Melting pointToken: 89.7°C

Benzocaine (literature): 89-92°C

PABA (literature): 187-189°C

IR-Spectrum-bands [cm-1]3250-3400N-H stretch (amines)

1735-1750C=O stretch (esters)

1690-1760C=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
Reference IR-spectrum of benzocaine

Literature

  • CrossFire Beilstein

1