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5001 Nitration of phenol to 2-nitrophenol and 4-nitrophenol
OH
OH
OH
NO2
KNO3, H2SO4
+
NO2
C6H6O
(94.1)
KNO3 (101.1)
H2SO4 (98.1)
C6H5NO3
(139.1)
Classification
Reaction types and substance classes
electrophilic substitution of aromatics, nitration
aromatics, phenol, nitroaromatics
Work methods
microwave-assisted reaction, stirring with magnetic stir bar, adding dropwise with an addition
funnel, heating under reflux, steam distillation, extracting, shaking out, filtering,
recrystallizing, draining of gases, use of an ice cooling bath
Instruction (batch scale 270 mmol)
Equipment
Microwave system ETHOS 1600, glass tube (40 cm, NS 29), 500 mL Erlenmeyer flask, 500
mL three-neck flask, internal thermometer, 2 wash bottles, adapter with ground-glass joint
and hose coupling, magnetic stirrer, magnetic stir bar, (cross stirrer), addition funnel with
pressure balance, reflux condenser, large distillation apparatus, 250 mL round bottom flask,
suction flask, Buechner funnel, desiccator, ice bath
Substances
phenol (mp 41 °C)
potassium nitrate
conc. sulphuric acid
hydrochloric acid (0.5 M)
aqueous sodium hydroxide solution (2 M)
active charcoal
ice
25.4 g (270 mmol)
50.0 g (495 mmol)
50.6 g (27.5 mL, 495 mmol)
100 mL
250 mL
2g
1
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Reaction
The reaction apparatus consists of a 300 mL three-neck flask with magnetic stir bar,
(preferably cross stirrer), internal thermometer and addition funnel with pressure balance. To
the free opening of the flask an adapter with ground-glass joint and hose coupling is attached
which is connected with a draining pipe for the potentially developping nitrous fumes. The
pipe is connected with an empty safety wash bottle and this with another wash bottle,
containing 250 mL 2 M sodium hydroxide solution.
Initially in a 500 mL Erlenmeyer flask 25.4 g (270 mmol) phenol are dissolved as completely
as possible in 100 mL water.
In the three-neck reaction flask 50.0 g (495 mmol) potassium nitrate are dissolved in 100 mL
water. Under cooling in an ice bath, 50.6 g (27.5 mL, 495 mmol) conc. sulphuric acid are
added. Then, at an internal temperature of 10-15 °C, the phenol-water mixture is added in
small portions as follows: Each time after strong shaking of the Erlenmeyer flask, a small
portion of the mixture is filled into the addition funnel and then rapidly added dropwise to the
intensively stirred solution in the three-neck flask. The above indicated internal temperature
(10 to 15 °C) must not be exceeded, since already at 20 °C nitrous fumes start developing.
Immediately after completion of the addition the reaction flask is taken from the ice bath, the
thermometer is replaced through a temperature sensor and the apparatus is installed with a
reflux condenser in the microwave system (see "Technical Instructions: Standard refluxing
apparatus in the microwave system "). The gas drainage is installed on the reflux condenser.
The reaction mixture is irradiated under stirring for 90 seconds with 900 W at a temperature
not exceeding 60 °C and then the heated reaction mixture is stirred for further 60 seconds
without microwave irradiation. Then the reaction flask is immediately cooled down to room
temperature in an ice bath (about 15 minutes).
Work up
In order to remove the excessive nitrating acid, the reaction mixture is diluted with 200 mL
ice water and the aqueous phase is carefully decanted from the oil. The oil in the flask is
washed three times with 50 mL water each, whereby the water is carefully decanted each
time.
The isomers are separated by means of steam distillation: To the remaining oil in the reaction
flask 300 mL water are added, the flask is equipped with a large distillation bridge and the
receiving flask is cooled in an ice bath. The apparatus is again installed in the microwave
system (see above). The distillation mixture is heated under stirring in 5 minutes with 800 W
to boiling (target temperature 105 °C) and distilled at 500 W in 30 minutes.
The 2-nitrophenol, which accumulates as yellow solid in the distillate, is sucked off over a
Buechner funnel and dried in the desiccator.
Yield: 9.80 g (70.5 mmol, 26%); mp 45 C
The distillation residue is cooled in the refrigerator over night to 4° C, then the precipitation is
sucked off over a Buechner funnel. For recrystallization 100 mL 0.5 M hydrochloric acid are
added to the solid in a 250 mL round bottom flask, 2 g active charcoal are added, then the
2
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flask is installed with a reflux condenser in the microwave system and the mixture is shortly
heated until reflux: Therefore the contents of the flask is heated in 3 minutes with 800 W from
room temperature to 104 °C and the temperature is kept for 2 minutes with 500 W. The hot
mixture is filtered by decanting the orange solution from the oily phase over a folded filter
into an Erlenmeyer flask. For completion of the crystallization the filtrate is kept for some
time in the refrigerator. The colourless needles of 4-nitrophenol are sucked off and dried in
the desiccator.
Yield: 1.88 g (13.5 mmol, 5%); mp 114 °C
Comments
The microwave treatment follows immediately after the addition of the phenol, without postreaction time. Before the radiation procedure the mixture still contains 25% educt (see
analytics). Through immediate ice cooling after the microwave treatment and a rapid
removing of the excessive nitrating acid, a second nitration of the phenol can be avoided to a
large extent.
As side products p-benzoquinone and 2,4-dinitrophenol could be detected (see analytics).
Waste management
Waste disposal
Waste
aqueous phase of the reaction mixture
aqueous phase of the steam distillation
mother liquor from recrystallization
aqueous solution from the wash bottle
filtered active charcoal
Disposal
solvent water mixtures, halogen free
solvent water mixtures, halogen free
solvent water mixtures, containing halogen
aqueous waste, alkaline
solid waste, free from mercury
Time
Nitration 30 minutes
Steam distillation about 1 hour
Recrystallization 30 minutes
Break
After washing out of nitric acid, before the distillation (keeping the oil in the refrigerator)
Degree of difficulty
Medium
3
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Analytics
Temperature-time-dependence of the working steps in the microwave field
phenol nitration in the microwave field
70
1000
900
60
700
600
40
500
30
T1 [°C]
400
Energie [W]
Temperatur [°C]
800
mit Eisbad
Kühlen
50
Energie [Watt]
300
20
200
10
100
0
0
50
100
150
200
250
300
350
0
450
400
Zeit [sec]
steam distillation of o-nitrophenol in the microwave field
120
900
800
100
700
Temperatur [°C]
500
60
400
Energie [W]
600
80
300
40
200
T1 [°C]
20
Energie [Watt]
100
0
0
500
1000
1500
2000
2500
3000
3500
4000
0
4500
Zeiz [sec]
Reaction monitoring with GC
Sample preparation:
Before and after the microwave treatment, a sample is taken from the oil phase and
50 mg of the sample are dissolved in 1 mL dichloromethane. 3 µL from this solution
are injected.
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GC-conditions:
column:
inlet:
carriergas:
oven:
detector:
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HP-5; length 30 m, internal diameter 0.32 mm, film 0.25 µm
split injection 194:1
H2, pre-column pressure 31 kPa
3 min isotherme at 50 °C, then with 8 °C/min to 320 °C
300 °C
Percent concentration was calculated from peak areas.
GC of the reaction mixture before the microwave treatment
Retention time (min)
5.0
6.5
9.6
17.2
Substance
p-benzoquinone
phenol
2-nitrophenol
4-nitrophenol
Peak area %
1
25
34
40
GC of the reaction mixture after the microwave treatment
Retention time (min)
6.0
10.4
17.0
Substance
p-benzoquinone
2-nitrophenol
4-nitrophenol
Peak area %
4
40
56
5
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GC of the product 2-nitrophenol after the steam distillation
Retention time(min)
10.4
Substance
2-nitrophenol
Peak area %
> 99.5
GC of the product 4-nitrophenol
Retention time (min)
5.1
16.4
17.6
Substance
p-benzoquinone
2,4-dinitrophenol
4-nitrophenol
Peak area %
0.3
1.1
98.6
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H NMR spectrum of the product 2-nitrophenol (300 MHz, CDCl3)
OH
8.4
8.2
8.0
7.8
7.6
7.4
7.2
7.0
1
(ppm)
6
NO2
2
5
3
4
11
10
9
8
7
6
5
4
3
2
1
(ppm)
δ (ppm)
10.58
8.10
Multiplicity
S
dd,
Number of H
1
3
J3, 4 = 8.4 Hz
J3, 5 = 1.7 Hz
3
dt,
J5, 6 = 8.5 Hz
3
J5, 4 = 8.5 Hz
4
J5, 3 = 1.7 Hz
3
ddd, J6, 5 = 8.5 Hz
4
J6, 4 = 1.5 Hz
5
J6, 3 = 0.4 Hz
3
dt,
J4, 3 = 8.4 Hz
3
J4, 5 = 8.5 Hz
4
J4, 6 = 1.5 Hz
Assignment
O-H
1
3-H
1
5-H
1
6-H
1
4-H
4
7.58
7.15
6.99
7.26
solvent
7
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C NMR spectrum of the product 2-nitrophenol (300 MHz, CDCl3)
150
140
130
120
110
100
90
80
70
(ppm)
Assignment
δ (ppm)
155.1
137.5
133.7
125.1
120.2
119.9
76.5-77.5
13
OH
C-1
C-5
C-2
C-3
C-4
C-6
solvent
1
6
NO2
2
5
3
4
C NMR spectrum of the product 4-nitrophenol (300 MHz, acetone-D6)
200
180
160
140
120
100
80
60
40
(ppm)
δ (ppm)
164.3
141.7
126.9
116.5
206, 30
Assignment
C-1
C-4
C-3, C-5
C-2, C-6
solvent
OH
1
2
6
3
5
4
NO2
8
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H NMR spectrum of the product 4-nitrophenol (300 MHz, acetone-D6)
OH
1
2
6
8.0
7.6
3
5
7.2
4
(ppm)
NO2
10
9
8
7
6
5
4
3
2
1
(ppm)
δ (ppm)
9.80
8.15
7.02
2.04
3.1
Multiplicity
s
d (AA´)
d (XX´)
Number of H
1
2
2
9
Assignment
O-H
3-H, 5-H
2-H, 6-H
acetone
water
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IR spectrum of the product 2-nitrophenol (KBr)
0,560
0,50
0,45
2922,50
952,99
1944,70
543,77
0,40
3107,01
418,43
1738,24
0,35
783,41
864,51
Egy
0,30
1078,34
1023,04
0,25
521,65
816,58
1369,58
3239,85
1129,95
0,20
1587,09
1476,49
3446,49
1612,90
o-Nitrophenol
0,15
1447,00
753,91
1236,86
1262,67
1310,59
665,43
1174,19
1531,79
0,129
4000,0
3000
2000
1500
1000
400,0
cm-1
(cm-1)
3445, 3240
Assignment
O-H-valence, superimposed by
C-H-valence, arene
C=C-valence, arene
N=O-valence, asymm. and. symm.
1610, 1590
1530, 1310
IR spectrum of the product 4-nitrophenol (KBr)
1,26
1,2
1,1
2922,50
1,0
1918,89
3077,49
0,9
1697,69
488,47
1052,53
3608,85
0,8
Egy
536,40
746,54
0,7
0,6
691,24
599,07
624,88
0,5
0,4
1107,83
1200,00
0,3
842,39
p-Nitrophenol
1609,211494,93 1340,09
1292,16
1590,78
0,2
3365,31
0,15
4000,0
3000
2000
1500
1000
400,0
cm-1
(cm-1)
3365
1610, 1590
1495, 1340
Assignment
O-H-valence, superimposed by
C-H-valence, arene
C=C-valence, arene
N=O-valence, asymm. and. symm.
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