Synthesis of Benzocaine

Davide Giordano: davideg@student.ethz.ch

23. November 2009

Assistant: Rui Wang
















2
1 Theory

1.1 Reaction



1.2 Mechanism




2 Toxicological data

p-aminobenzoic acid R22 Harmful if swallowed
R36/37/38 Irritating to eyes, respiratory system and skin
R43 May cause sensitisation by skin contact
S26 In case of contact with eyes, rinse immediately with plenty of
water and seek medical advice
S36 Wear suitable protective clothing

EtOH R11 Highly flammable
S7 Keep container tightly closed
S16 Keep away from sources of ignition - No smoking

H
2
S0
4
R35 Causes severe burns
R35 Causes severe burns
S26 In case of contact with eyes, rinse immediately with plenty of
water and seek medical advice
S30 Never add water to this product


3
S45 In case of accident or if you feel unwell seek medical advice
immediately (show the label where possible)

Benzocaine R43 May cause sensitisation by skin contact
R36 Irritating to eyes
S24/25 Avoid contact with skin and eyes
S37 Wear suitable gloves

NaHCO
3
S24/25 Avoid contact with skin and eyes
3 Experimental Tasks
3.1 Equipment



3.2 Procedure

Reaction: 5.4350 g of p-aminobenzoic acid were placed in a 500ml round flask and then
80ml of ethanol (99% puriss.) were added. It has been swered gently to help dissolve the solid. 5ml of
concentrated sulfuric acid were carefully added. A reflux condenser was attached and the mixture
stirred for 75 at 130 C in oil bath.

Isolation: The mixture was cooled down to room temperature in ice bath, then the
contents was transferred to a 250ml beaker and neutralized cautiously with dropwise addition of sat.
Na
2
CO
3
solution until the pH was approximately above 7. (A huge was needed; it was difficult to
reach basic pH). Some water was added and the mixture cooled in an ice bath for 15min to complete
the crystallization process. The crude product was collected by vacuum filtration.

Recrystallization: The crude product were put in a round flask and heated up till 120C. Hot
ethanol was added dropwise and until all the oil was dissolved. A small amount of hot water was
added droop wise solution until cloudiness was appeared and then again a few drops of ethanol
were added. The mixture was stirred while cooling in an ice bath. Finally the Benzocaine was
collected by vacuum filtration and kept in the fume hood overnight to dry.


4
reactant
molar
weight
[g/mol]
density
(20C)
[g/cm
3
]
volume
[ml]
weight
[g]
quantity
[mol]
equivalent
melting
point [C]
p-aminobenzoic
acid
137.14 1.380 -- 5.435 0.040 1 188-189
H
2
S0
4
98.08 1.84 5 9.200 0.094 >2 337
EtOH 46.07 0.79 80 63.200 1.372 >34 -114

4 Characterization

4.1 Literal physical data

product
molar weight
[g/mol]
melting point
[C]
Benzocaine 165.19 88-90

4.2 Results

mass of the received Benzocaine: 4.062g = 0.025mol

measured melting point: 85.9 86.8C

yield: 62.0%


IR-Spectroscopy:

IR bands [cm
-1
] interpretation
3420 3222 N-H valence
2985 2957 arom. C-H(sp
2
) valence
2900 aliph. C-H(sp
3
) valence
1679 1594 C=O (?)
1514 - 1441 arom. C=C valence

5 Discussion

I do not have much to say: the yield is ok, purity shouldnt be bad, because by comparing the
measured IR-Spec. to a literal one, you will see that all bands are here, this time also the intensity is
ok (except 1170 882 and the last part of the fingerprint region). Also I have to say, that the
interpretation of the bands wasnt easy, I had difficulties to find e.g. the values for C=O which in true
should be above 1700.


5
Just the measured melting point wasnt very well, I dont know, may be there where some remaining
solvent. Or maybe the last step of the recrystallization wasnt done in the right way (oli water
EtOH).





6 References

[1] SIGMA-ALDRICH
Date accessed: 16.11.2009 on http://www.sigmaaldrich.com
[2] Nachhaltigkeit im organisch-chemischen Praktikum
Date accessed: 16.11.2009 on www.oc-praktikum.de
[3] Merck Chemicals (2009) Product catalog Online Database.
Date accessed: 16.11.2009 on http://www.merck-chemicals.de/
[4] Spectral Database for Organic Compounds, SDBS
Date accessed: 16.11.2009 on http://riodb01.ibase.aist.go.jp/sdbs/cgi-
bin/direct_frame_top.cgi


7 Appendix

Lab journal (copy)
Literal IR spectroscopy [4]
IR spectroscopy
Procedure [2]
Physical data & safety [1],[3]













6