Benzocaine (2 steps) - Laboratory Report PDF

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The Synthesis of benzocaine ...

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Laboratory Report 04.11.2007 Organic chemistry practical course (OCP1) HS 07/08 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 Molar weight

118.71 2

g/mol

Density Melting point Boiling point R-Phrases S-Phrases Hydrochloric acid (conc.) Molar weight Density Melting point Boiling point H-Cl R-Phrases Sn

R 34 R 36 R 37 R 38 S 26

S-Phrases

7.265 231.93 2602

g/ml °C °C

36.46 1.19 -40 84

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

H H

Molar weight Density Melting point Boiling point R-Phrases

17.03 0.69 -77.73 -33.34

g/mol g/ml °C °C

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

N H

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

Amount

Molar amount g 2.89

mol 0.018 3

Volume ml -

Tin Hydrochloric acid

7.04 ~13

0.059 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

Reflux condenser

Thermometer

Filter Oilbath 4 3 21

5 6 7 8 1 19

4 3 2

1

5 6 7 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 OH

O H 2S O

H2N

4

/ E tO H H2N

O

O

Mechanism

7

CH3 CH3

O

O

+

HO

OH

OH

HO +

OH

C

H

+

H

OH

HO HO

O

OH

CH3

+

NH2

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

g/mol g/ml °C °C

Highly flammable Keep container tightly closed Keep away from sources of ignition

Sulfuric acid (H2SO4)

HO O

Molar weight Density Melting point Boiling point R-Phrases S-Phrases

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

8

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

Educts Substance p-aminobenzoic acid Ethanol Sulfuric acid

Amount

Molar amount g 3.12 ~19 ~0.5

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). 9

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 4 3 21

5 6 7 8 1 19

3 2

4 1

5 6 7 8 9 1 0

Heating apparatus

Separation funnel

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. 10

IR-Spectrum of the Product

Reference IR-spectrum of benzocaine

11

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

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