Meilen, 6.11.2007
Organic chemistry practical course (OCPI)
HS 07
529-0229-00
Fabienne Vukotic
06-910-541
D-BIOL
Assistant: Guo Xiaoqiang
Synthesis of
4-(tert-butyl)-o-xylene
(1,2-Dimethyl-4-tert-butylbenzene)
1. Method
The method for the synthesis of 4-(tert-butyl)-o-xylene is an electrophilic
aromatic substitution reaction: A Friedl-Crafts alkylation of o-xylene with a tertbutyl group from tert-butyl chloride with Iron (III) chloride – a Lewis acid – as
catalyst.
2. Reaction Equation
Cl
FeCl3
+
H3 C
CH
CH3 3
- HCl
3. Mechanism
Friedel-Crafts-Alkylation with the Lewis acid FeCl3
Methyl substituents are -donors and therefore o/p-directing;
however the o-positions are sterically-hindered and thus only the para-product will be yielded.
not electrophilic
enough
Cl
H3 C

x
CH
CH3 3
but
Lewis acid

FeCl3
FeCl4
Cl

H3 C
C
H3 C
CH
CH3 3
CH
CH3 3
now much more
electrophilic
_
H
H
FeCl4
FeCl3
HCl
4. Physical and Chemical Properties of Substances
Calcium chloride
dihydrate
CAS: 10035-04-8
M = 147.02g/mol
ρ = 0.70 g/mL
mp = 175 C
Risk phrases
- R36: Irritating to the eyes
Safety phrases
- S22: Do not breathe dust
- S24: Avoid contact with skin
tert-Butyl chloride
CAS: 507-20-0
M = 92.57g/mol
ρ = 0.851 g/mL at 25 °C
bp =51-52 C
n20D =1.3848
mp = -25 C
CH toxicity class: 4
Risk phrases
- R11: Highly flammable
Safety phrases
- S7/9: Keep container tightly closed and in a wellventilated place
- S16: Keep away from sources of ignition - No
smoking
- S29: Do not empty into drains
- S33: Take precautionary measures against static
discharges
o-xylene
CAS: 95-47-6
M = 106.17g/mol
ρ = 0.878 g/mL at 25 °C
bp = 143-145 C
n20D =1.5054
mp = -26- -23 C
CH toxicity class: 4
MAK: 100ml/m3, 440mg/ml3
Risk phrases
- R10: Flammable
- R20/21: Harmful by inhalation and in contact with
skin
- R38: Irritating to the skin
Safety phrases
- S25: Avoid contact with eyes
Iron III chloride
(anhydrous)
CAS: 7705-08-0
M = 162.21g/mol
ρ = 0.75g/mL at 25 C
mp = 304 °C
CH toxicity class: 3?
Risk-phrases
- R22: Harmful if swallowed
- R38: Irritating to the skin
- R41: Risk of serious damage to eyes
Safety-phrases
- S26: In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice
- S39: Wear eye/face protection
Hydrochloride
CAS: 7647-01-0
M = 36.46g/mol
ρ = 1.19g/mL at 25 C
CH toxicity class: 2
MAK: 5ml/m3, 7mg/ml3
Risk-phrases
- R23:
- R35: causes severe burns
Safety-phrases
- S9: Keep container in a well-ventilated place
- S26: In case of contact with eyes, rinse
immediately with plenty of water and seek
medical advice
- S36/37/39: Wear suitable protective clothing,
gloves and eye/face protection
- S45: In case of accident or if you feel unwell, seek
medical advice immediately (show label where
possible)
HCl
Sodium bicarbonate
CAS: 144-55-8
O
+
Na
HO
O
-
bp = - 85 °C
mp = -114 °C
M = 84.01g/mol
ρ = 2.16 g/mL at 25 °C
CH toxicity class: 5
mp = 270 °C
Safety phrases
S24/25: Avoid contact with skin and eyes
Sodium chloride
CAS: 7647-14-5
M = 58.44g/mol
bp =1413 °C
ρ = 1.37g/mL
mp = 801 °C
CH toxicity class: non-toxic
NaCl
Safety phrases
S24/25: Avoid contact with skin and eyes
Magnesium sulfate
CAS: 7487-88-9
M = 120.36g/mol
mp = 1124 °C
CH toxicity class: non-toxic
O
2+
Mg
O
-
S
O
-
O
4-(tert-butyl)-o-xylene
CAS: 7397-06-0
Safety phrases
S22: Do not breathe dust
S24/25: Avoid contact with skin and eyes
M = 162.27g/mol
n20D =1.498
ρ = 0.871g/mL at 25 C
bp = 200 - 210 °C
CH toxicity class: Risk-phrases
- R36/37/38: Irritating to eyes, respiratory system
and skin
Safety-phrases
- S26: In case of contact with eyes, rinse
immediately with plenty of water and seek
medical advice
- S36: Wear suitable protective clothing
5. Experimental Setup
Calcium chloride dihydrate
cotton
drying tube
20o
reflux cooler
20o
in
out
HCl
NS 14
15o
500 mL
reaction
LaboBib
300
50
©
AN
AN
AUS
AUS
1500
100
0 U/min
250
500
o
C
200
150
1000
750
funnel rests on water surface
200
250 m L
150
100
50
separatory funnel
organic phase
aqueous phase
100
100 mL
75
50
beaker with water
setup for vacuum distillation
NS 29
75o
-45 o
microdistillation
NS 29
-75 o
NS 29
100 m L
LaboBib
300
50
75o
safety bottle
Manometre
oil bath
©
AN
AN
AUS
AUS
1500
100
vacuum
0 U/min
250
500
o
C
200
150
1000
750
100
mL
50 mL
100
mL
6. Amounts of Substance used
Substance
tert-butyl
chloride
o-xylene
measured
amount [ml]
7.76
[g]
[mmol]
eq
6.60
71.3
1.2
7.2
6.3
60
1.0
7. Experimental Section (Procedure)
The tBuCl from the previous synthesis has to be filtrated first. 7.0 mL tBuCl and
7.2 mL o-xylene are mixed in a two-neck round bottom flask. 0.2 g of the
catalyst FeCl3 is added carefully as this will lead to a vigorous reaction. After
10 min, when all HCl is gone, another 0.76 mL tBuCl is added. It is stirred for 1h,
then heated up slowly to 200 °C. At this temperature, it is heated for 20min. It
is allowed to cool down to RT and then filtered. The filtrate is washed twice
with saturated NaHCO3 (2 x 10 mL) and once with 10 mL NaCl.
It is dried over MgSO4 over night and then filtered.
The crude product is further purified by vacuum distillation under 24 mbar. The
fraction of 90-95 °C is collected and characterized.
8. Yield
The theoretical yield is 0.06mol. The experimental yield is 3.5 mL = 3.0 g =
0.019mol.
The yield percentage therefore is 32%
9. Characterization
Refractive index
A refractive index of nD=1.4959 was measured. The literature value for 4-tBu-oxylene is n20D =1.498.
IR-Spectrum (see attachement)
bands [cm-1]
~ 3030
2975
2867
1507
1450
1392
interpretation
unsat. C-H
sat. C-H
aromatic ring
CH3
Literature spectrum
10. Remarks and Discussion
The yield is not very good for the following reasons: There was loss due to the
vigorous reaction which caused some spilling out. Further, the substances
have to filtrated twice which is connected with some loss as well. The washing
was very difficult because the phases would not clearly separate and the
organic phase would stick to the surface of the separatory funnel. Last, the
distillation had to be done twice because all the components boiled over.
This could be taken care of the second time by using a bigger flask.
11. Literature
Coblentz Society, Inc., "Evaluated Infrared Reference Spectra" in NIST
Chemistry WebBook, NIST Standard Reference Database Number 69,
Eds. P.J. Linstrom and W.G. Mallard, June 2005, National Institute of
Standards and Technology, Gaithersburg MD, 20899. NIST Chemistry
Webbook. 27. Oct. 2007 <http://webbook.nist.gov>.
EMolecules - Searching the World's Chemistry. 2007. EMolecules, Inc. 28 Oct.
2007 <http://www.emolecules.com>.
IGS Giftliste. 31 July 2007. BAG. 28 Oct. 2007
<http://igs.naz.ch/igs/igsServer/de.kisters.igs.igs40.servlets.igs40Servlet>.
Kirste, Burkhard. "Chemikalien: Sicherheitsdaten." Institut für Chemie und
Biochemie an der FU Berlin. 28 July 1994. FU Berlin. 27 Oct. 2007
<http://www.chemie.fu-berlin.de/chemistry/safety/chemsafety.html>.
"Risk & Safety." Sigma-Aldrich. 2007. Sigma-Aldrich Co. 27 Oct. 2007
<http://www.sigmaaldrich.com/Help_Pages/Help_Welcome/Product_
Search/Risk___Safety_Statements.html#Safety%20Phrases>.
Sigma-Aldrich. 2007. Sigma-Aldrich Co. 27 Oct. 2007
<http://www.sigmaaldrich.com/Area_of_Interest/Europe_Home/
Switzerland__Schweiz_.html>.