Transcript Experiment 16: - University of North Carolina Wilmington

Experiment 17:
NITRATION OF
p-methylacetanilide
H
N
O
C
H
CH3
+ HNO3
p-methylacetanilide
H2SO4
Acetic acid
N
O
C
CH3
NO2
Nitromethylacetanilide
Objectives:

To synthesize methylnitroacetanilide isomers
using an electrophilic aromatic substitution.

To purify product by recrystallization.

To identify and determine purity of product by
melting point, TLC and HPLC analysis.

To characterize product by analysis of 1H-NMR
and 13C-NMR spectra.
Before coming to lab…

Review these techniques:

TLC analysis

Recrystallization

Suction filtration

HPLC analysis

Melting Point Analysis
CHEMICAL EQUATION
H
N
O
C
H
CH3
+ HNO3
H2SO4
Acetic acid
N
O
C
CH3
NO2
H
N
O
C
CH3
or
NO2
4-methylacetanilide
4-methyl-2-nitroacetanilide
C9H11NO
MW: 149.19
C9H10N2O3
MW: 194.19
mp:148-151oC
mp: 92-95oC
INHALATION HAZARD,
INGESTION HAZARD
4-methyl-3-nitroacetanilide
C9H10N2O3
MW: 194.19
ELECTROPHILIC AROMATIC
SUBSTITUTION
E
+
E
H
+E
+
+ E
H
E
H
+
This reaction takes place in two steps:
1. Initial reaction of an electrophile, E+ with the
aromatic ring.
2. Loss of H+ from the resonance stabilized
carbocation intermediate to regenerate the
aromatic ring.
+ H+
MECHANISM
(Preliminary steps…)
• Reaction
of the aromatic compound with nitric acid
alone is slow and potentially hazardous.
• It is safer and faster to use a catalytic amount of
sulfuric acid.
•Sulfuric acid reacts with nitric acid to form the
nitronium ion, a powerful electrophile.
Sulfuric acid
Nitric acid
O
H O N O
+
O
H O S O H
O
• Sulfuric
nitronium ion
(STRONG electrophile)
H O
H O N O
+ HSO4-
O N O
+ H2O
acid protonates the hydroxyl group of
nitric acid, allowing it to leave as water and form
a nitronium ion.
MECHANISM
(Nitration of Aromatic Ring…)
• Electrophilic aromatic substitution by the nitronium
ion gives the nitro product.
O
O
H
H
N
CH3
+
+ O N O
O
N
CH3
O+ N O
H
• Attack on the electrophile
forms the sigma complex…
N
H
O
N + O
+ H3O
..
+
..
H3C
O H
H
• …loss of proton to water…
• …gives the aromatic
nitro product.
REACTIVITY OF AROMATIC
RINGS




The substituents ALREADY ON the aromatic
ring affect the reactivity of the aromatic ring,
or how FAST the substitution will occur.
The substituent ALREADY ON the aromatic
ring determines orientation of the substitution,
or the position of the second (INCOMING)
substituent.
Both the methyl group (-CH3) and the
acetamide group (-NHCOCH3) are o, p
activators.
The acetamide group is a STRONGER o, p
director than the methyl group.
Week 1:
Synthesis






Mix p-methylacetanilide and acetic
acid in 50 mL Erlenmeyer flask.
Prepare nitrating mixture in small
test tube (CAUTION!).
MODIFICATION: Cool this tube in
ice water!
Add nitrating mixture dropwise
while swirling.
Allow to react at room temp for 15
minutes.
Add cold deionized water.
Week 1:
Crude Product Isolation

Prepare suction filtration apparatus, seating
filter with cold deionized water.

Pour crude product slowly into center of
funnel. Rinse with cold deionized water.


MODIFICATION: Transfer solid and filter
paper to preweighed watch glass and place
in oven for 15 minutes to dry.
During this time, proceed to preparation of
filtrate for analysis, detailed on the next
slide!

Remove from oven. Reweigh (1A) and
calculate % yield (1B).

Prepare CRUDE PRODUCT TLC and HPLC
samples in small sample vials.
Week 1:
Preparation of Filtrate Samples



MODIFICATION: Transfer 2 mL filtrate to
a small test tube.
Add 10% NaHCO3 dropwise until neutral
(check every 5 drops with pH Hydrion paper).
Add 3 mL ethyl acetate. Cork tube and
shake to mix.

Allow layers to separate.

Transfer TOP LAYER to a clean test tube.

Filtrate
Prepare HPLC and TLC samples of FILTRATE
using 5 drops of this solution for each.
Remember to add appropriate sample solvent
for each!
Week 1:
Purification

Transfer crude product to 50 mL flask.

Dissolve in 90:10 ethanol/water.

Cool to room temp, then to 0oC.

Suction filter.


Prepare RECRYSTALLIZED PRODUCT
TLC and HPLC samples.
Transfer small filter paper and product
to a preweighed large filter paper and
submit to instructor to dry until next lab
period! Also, submit all TLC samples to
instructor.
Table 17.1
Theoretical yield (g)
1A
Major product
mass from
synthesis (g)
1B
% yield
from synthesis
2A
Major product
mass after
recrystallization
(g)
2B
Overall
% yield
Experimental melting
range (oC)
Product Appearance
should have this calculated based on the limiting reagent prior
to coming to lab.


Obtain 1st lab, after drying in oven.
If this calculated value is >100%, you must return the crude
product to the oven to dry for a longer period of time.
 1A/theoretical yield.


Obtain 2nd lab, at the beginning of the lab period.

2A/theoretical yield.

Obtain 2nd lab period.

Record the physical state and color of your product.
Table 17.2
Can calculate 1st lab.
 Review calculation in Experiment 13.

Atom Economy
Can calculate 1st lab.
 Review calculation in Experiment 13.

Experimental Atom Economy
Can calculate 2nd lab, after product has
been purified and dried.
 Review calculation in Experiment 13.

E product
Can calculate 2nd lab, after final
product mass has been obtained.

Cost per Gram
Week 2:
Product Analysis

TLC Analysis






HPLC Analysis


Prepare TLC plate with 6 lanes.
Apply 3 provided standards along with samples of crude
product, filtrate, and recrystallized product.
Develop in 2:1 ethyl acetate/hexane.
Visualize with UV lamp.
Identify compounds and calculate Rf value.
Compare sample chromatograms to provided standard to
identify compounds in each sample submitted.
Melting Point Analysis


Obtain the experimental melting point of your purified
product.
Compare to the literature value to determine degree of
purity.
Table 17.3
TLC Rf values
Compound
Standards
All Rf values
are unitless!
 All Rf values
are 2 decimal
places ONLY!

p-methylacetanilide
Crude
sample
Filtrate
sample
If reactant
present in this lane,
it explains product
loss!

If major product
present in this lane,
it explains product
loss!

4-methyl-2nitroacetanilide
4-methyl-3nitroacetanilide
Recrystallized
sample
Table 17.4
Standards
Compound
Retention
times
(min)
Crude
Filtrate
Sample
Sample
Retention
times
(min)
Area
%
Retention
times
(min)
Recrystallized
Sample
Area
%
Retention
times
(min)
p-methylacetanilide
4-methyl2-nitroacetanilide
4-methyl3-nitroacetanilide
• All samples are submitted for analysis during 1st lab period. Samples
will be run, and chromatograms returned during 2nd lab period!
Area
%
Product Analysis
(NMR Spectroscopy)
O
H
C
N
8
CH3
9
1
H
6
H
NO2
2
3
5
4
CH3
7
H
Table 17.5
O
H
N
C
8
N
CH3
8
1
6
2
5
3
CH3
7
C
9
1
4
O
H
6
CH3
9
NO2
2
3
5
4
CH3
7
• Enter chemical shifts ONLY based on the spectra on pages 139 and 146.
• Notice that the reactant is the product from Experiment 16. You should
have already analyzed the NMR spectra!
SAFETY CONCERNS


Nitric acid and sulfuric acid are very
corrosive! Use EXTREME caution when in
use!
Ethanol is flammable! Be careful when
heating!
WASTE MANAGEMENT



Place all liquid waste from SYNTHESIS portion of
experiment into the bottle labeled “Aqueous Waste
(Nitration)”.
Place all liquid waste from RECRYSTALLIZATION/TLC
portion of experiment into the bottle labeled “Organic
Waste (Nitration)”.
Place all used TLC spotters and melting point
capillaries in broken glass container, NOT trashcan!
CLEANING




Clean all glassware with soap, water, and brush
if necessary.
Rinse all glassware with wash acetone before
returning to lab drawer.
DO NOT return any glassware dirty or wet to
lab drawer!
All hotplates and MelTemps must be unplugged
from outlets, with cords wrapped neatly.