MVCC Organic Chemistry Electrophilic Aromatic Substitution Lab Report

Nitration Virtual ExperimentPurpose: In this virtual experiment, you will be investigating the nitration of an aromatic
compounds, toluene. The nitration of an aromatic compound is an example of an Electrophilic
Aromatic Substitution (EAS) reaction. You will be using a mixture of nitric and sulfuric acids to
generate the required NO2+ electrophile. You will be collecting TLC and spectral data (1H and
13
C NMR) and measuring the melting point to confirm the product of the reaction. From the
identity of your product, you can draw some general conclusions about the directing effects of
the electron-donating substituents (such as alkyl groups) and make predictions about the
directing effects of electron-withdrawing substituents.
Figure 10.1 The nitration of toluene
Introduction: In an electrophilic aromatic substitution (EAS) reaction, the pi electrons of
benzene attack an electrophile (Y+), generating a high-energy carbocation intermediate. In the
second step, a base removes a proton, restoring the aromaticity of the ring. Notice where the
proton is removed from- it is removed from the carbon that has formed the bond with the
electrophile. The overall result of this reaction is that a proton on the aromatic ring has been
replaced by an electrophile.
Figure 10.2 General mechanism for electrophilic aromatic substitution reactions. (From Organic
Chemistry by Bruice, 8th Ed.)
Aromatic rings are stable and fairly unreactive, and so the electrophile in the reaction must be a
strong electrophile in order for the reaction to occur. Often these strong electrophiles are too
reactive to be stored and are instead generated in situ in the first step of the EAS reaction. For a
nitration reaction, the strong electrophile is the nitronium ion (NO2+). When the strong acid nitric
acid is mixed with the even stronger sulfuric acid, the nitric acid acts as a base, and accepts a
proton from the sulfuric acid. Loss of water then produces the strongly electrophilic nitronium
ion. The aromatic ring attacks the nitronium ion and subsequent removal of a proton forms the
Page 1 of 14
substitution product. In the strong acid mixture of nitric and sulfuric acids, the most likely
available base is water. Water is both produced in the generation of the nitronium ion, and
present in the original solutions of nitric and sulfuric acids.
Figure 10.3 Mechanism for the nitration of an aromatic ring.
For the EAS reaction of a substituted aromatic ring, such as the toluene starting material for this
reaction, the new electrophile could add to the ortho, meta, or para position.
Figure 10.4 Ortho, meta, and para isomers. (From Organic Chemistry by Bruice, 8th Ed.)
The first step of the EAS reaction to form the carbocation intermediate is the slow, ratedetermining step, of the mechanism (figure 10.5).
Figure 10.5 The reaction coordinate diagram for an EAS reaction. (From Organic Chemistry by
Bruice, 8th Ed.)
Page 2 of 14
If the aromatic ring is already substituted, it is the energy of the carbocation intermediate that
determines the position where the incoming electrophile is added. Alkyl groups are electrondonating by hyperconjugation, and the most stable (lowest energy) carbocation intermediates are
formed when the electrophile adds to the ortho and para positions as highlighted in figure 10.6.
All substituents that can donate electrons to the aromatic ring through hyperconjugation or
resonance are ortho/para directors.
Figure 10.6 How alkyl groups stabilize the carbocation intermediate of an EAS reaction. (From
Organic Chemistry by Bruice, 8th Ed.)
As you perform the virtual nitration of toluene, you will first notice the formation of a mixture of
ortho- and para-nitrotoluene. As the reaction progresses, you will start to observe the formation
of 2,4-dinitrotoluene. You will continue the reaction until all of the product has been converted
to 2,4-dinitrotoluene. Mass spectrometry will allow you to determine the molecular weight of the
product to confirm that two hydrogens have been substituted with nitro (NO2) groups. 1H and 13C
NMR will allow you to confirm where the nitro groups have been added to the ring. Comparison
of the product melting point to the literature melting point will also confirm the identity of the
product.
Nuclear Magnetic Resonance (NMR) Spectroscopy:
Any nuclei that contain an odd number of protons or an odd number of neutrons can be studied
by nuclear magnetic resonance (NMR) spectroscopy, but organic chemists tend to focus on
carbon and hydrogen. Organic chemists use NMR to identify the carbon-hydrogen and carboncarbon framework of an organic compound. For 1H NMR, there are 4 key pieces of information
that we can get from the spectrum:
1. The number of signals- number of chemically equivalent hydrogens
2. The chemical shift of the signals- type of proton(s)
3. The integration of the signals- number of protons that produce the signal
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4. The splitting of the signals- # of protons on adjacent carbon atoms
1. The number of signals. Chemically equivalent protons are protons that are in the same
environment, and each set of chemically equivalent protons produces its own signal in the 1H
NMR spectrum. For the relatively simple organic molecules we will be looking at, we can
assume that hydrogens that are attached to the same carbon atom are chemically equivalent,
unless there is restricted rotation- from a pi-bond or a ring. In the figure shown below, the
chemically equivalent hydrogens are designated by the same letter.
Figure 10.7 Determining chemically equivalent sets of hydrogens.
(From Organic Chemistry by Bruice, 8th Ed.)
2. The chemical shift of the signals. The chemical shift of a signal indicates the environment the
hydrogen is in. Hydrogens that are in electron-rich environments are shielded from the applied
magnetic field and appear at a lower ppm value. Hydrogens that are in electron-poor
environments are deshielded from the applied magnetic field and appear at a higher ppm value.
In general, proximity to an electronegative atom deshields hydrogen atoms. Hydrogens that are
attached to sp2-hybridized carbons are also deshielded.
The 1H NMR spectrum can be roughly divided into the 7 regions shown in figure 10.8 (one is
empty). This is a good, quick, guide to the types of hydrogens that are present in a molecule.
Figure 10.8 Seven regions of the 1H NMR spectrum. (From Organic Chemistry by Bruice, 8th
Ed.)
Page 4 of 14
A more detailed chart of approximate 1H NMR chemical shifts is shown below. A proton that is
affected by more than one functional group will show cumulative effects.
Figure 10.9 Approximate 1H NMR chemical shifts. (From Organic Chemistry by Bruice, 8th Ed.)
3. The integration of the signals. The area under each signal is proportional to the number of
chemically equivalent hydrogen atoms that produce the signal. The spectrometer will often show
the relative integration in arbitrary units, and you will then need to calculate the number of
hydrogens for each signal. From the units given, divide all by the smallest number, and then if
necessary, multiply all values by the same number to get a ratio of whole numbers. Add up the
values to ensure it matches the number of hydrogen atoms expected in the molecule.
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Figure 10.10 Solving for the integral ratio in a 1H NMR spectrum.
In Beyond Labz, the numbers above the peaks in the 1H NMR spectrum are the peak number
(they are counting the number of peaks from left to right). Below the spectrum is a table that has
those same peak numbers and the height of the integral trace. Calculate the integration as shown
above using these height values. The data in Beyond Labz is real data, and thus will show some
slight experimental error.
4. The splitting of the signals. Splitting of signals is caused by protons bound to adjacent carbon
atoms. The N + 1 rule describes the splitting of the signals, where N is equal to the number of
hydrogens bonded to adjacent carbons.
Figure 10.11 How to describe signals in 1H NMR spectrum.
For 13C NMR, only the number of signals and the chemical shift need to be considered. A table
of approximate chemical shift values for 13C NMR is shown in figure 10.12.
Figure 10.12 Approximate 13C NMR chemical shifts. (From Organic Chemistry by Bruice, 8th
Ed.)
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Figure 10.13 The virtual synthesis lab.
Virtual Lab Instructions
Help is available by clicking on the bell on the stockroom counter.
Part 1: Collecting the spectra of the starting material
1. To load the synthesis lab, under “Organic Worksheets”, select “Aromatic Substitution”
and then “VCL 8-1: Benzene Nitration”. Ignore the description as we will be doing a
slightly different experiment.
2. On the chalkboard (top right) mouse over “Benzene Nitration”, and you will see the
available chemicals. You will notice that there are 2 different aromatic compounds
available from the “stockroom”, so be sure to select the correct starting material to record
the spectra.
3. In your lab notebook, save the IR/FTIR, 1H-NMR 13C-NMR spectra for methylbenzene
(also known as toluene). On the chalkboard, click the “Spectra” box and scroll down to
find each of the starting chemicals. They are listed alphabetically. When you find
methylbenzene, click on the desired spectra type IR/FTIR and 1H-NMR then click on the
chemical’s name. The spectrum will open. To save the spectrum to your notebook, click
“Save” then copy the chemical name from the spectrum title. Then open your lab
notebook and paste the name of the chemical next to the spectrum file. Click “OK” to
close the spectrum window.
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Part 2: EAS nitration of toluene
4. On the chalkboard (top right) mouse over “Benzene Nitration”, and you will see the
available chemicals. You will notice that there are 2 different aromatic compounds
available from the “stockroom”, so be sure to select the correct starting material.
5. Clicking and dragging adds reagents into the flask. Click on the toluene (AKA
methylbenzene) and drag it into the flask.
6. Click on the diethyl ether and add it to the flask. This is the solvent for the reaction.
7. Check to see that the reagent and the solvent have been added to the flask by hovering
your mouse over the flask. The contents of the flask will display on the chalkboard.
8. Drag the flask over to the clamp above the stirring hot plate.
9. You still need to add the nitric acid/sulfuric acid mixture. Find them on the bench top
(labeled HNO3 and H2SO4) and click and drag to the flask. Assume that you have enough
to completely react with the toluene starting material.
10. Check the chalkboard and verify that your flask contains the toluene, the diethyl ether,
and the nitric acid/sulfuric acid mixture.
11. This reaction requires heat. Click and drag the heating mantle below the flask.
12. To prevent the solvent from evaporating, add a reflux condenser to the flask.
13. Notice that the top of the condenser is sealed with a rubber septum. If we heat a closed
system, it will explode! Click and drag the nitrogen line to the top of the condenser.
14. Start the reaction by clicking the right knob on the stirring hotplate.
15. Monitor the reaction using TLC. Advance the clock in 1-hour intervals and take TLCs to
monitor the progress of the reaction. Save and label the TLCs in your notebook. Continue
the reaction until the TLC shows that the starting material has been consumed, and the
dinitro product has been completely formed. Note the amount of time (in hours and
minutes) required. Note the reaction time and any color changes in your e-notebook.
16. Stop the reaction by dragging the separatory funnel over to the flask. The chalkboard will
display what is in the flask, which should be the product, 2,4-dinitrotoluene and the
diethyl ether solvent.
17. Add water to the separatory funnel by clicking and dragging (or double-clicking). Recall
that the less dense ether layer (“organic layer”) will float on top of the aqueous layer. If
you hover your mouse over the layers, it will display if the layer is organic or aqueous
and the chalkboard will display the chemicals contained within the layer.
18. Remove the lower aqueous layer and discard it into the waste container by clicking and
dragging it first into the cork ring support, and then into the red waste container. Make
sure it only contains water before throwing it away!
19. Click and drag the ether layer to the cork ring support. You will notice when you do this
that the ether disappears from the flask. This step assumes that you evaporated the
solvent using a rotatory evaporator leaving you with just the product in the flask.
20. The product is a solid and can thus be purified by recrystallization. Perform the virtual
recrystallization by dragging the flask to the crystallization dish. Note the color of the
solid product.
21. Measure the melting point of the solid by clicking and dragging the capillary tube icon
from the melting point apparatus to the solid product. Mouse over the display on the
melting point apparatus to display the melting point and record it in your notebook. Note:
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A melting point should be a range, from when the solid first begins to melt, to when
melting is complete. Unfortunately, the virtual lab gives us only one temperature.
FTIR and NMR Spectra
After completing a reaction and working up the products, it is still necessary to confirm that the correct
product was formed. The most common tools used for this analysis are Fourier Transform Infrared (FTIR)
and Nuclear Magnetic Resonance (NMR) spectroscopy. In the virtual laboratory, 1H and 13C NMR
spectra are available. Details on interpreting FTIR and NMR spectra are found in your textbook.
To collect an FTIR spectrum of your product, click on the FTIR spectrometer located to the right of
the lab bench and drag the salt plate icon to the flask on the lab bench. A window containing the FTIR
spectrum for your product should now open. Identify the relevant peaks in the FTIR spectrum and
record the position and associated functional group for each in the FTIR table below. Save and label
the IR spectrum in the lab book.
22. Record the 1H NMR spectrum of the product by clicking on the NMR spectrometer and
dragging the sample tube to the solid product. This will display the 1H NMR spectrum on
the screen. You can type the name of the compound on the spectrum and click save to
save it to your lab notebook. Click ok to close the spectrum.
23. By default, the NMR is set to record 1H- change to 13C by clicking the window on the
NMR spectrometer. Record the 13C NMR spectrum of the product by clicking on the
NMR spectrometer and dragging the sample tube to the solid product. This will display
the 13C NMR spectrum on the screen. You can type the name of the compound on the
spectrum and click save to save it to your lab notebook. To view the chemical shift values
(in ppm) mouse over each peak- the first number is the chemical shift. Click ok to close
the spectrum.
24. Your virtual experiment is now complete!
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Lab 10 Assignment (20 points)
Create a Reagent Table
1. Create a Table of reagents that includes all of the chemicals: toluene, nitric acid, sulfuric acid,
diethyl ether (solvent) and product(s). Your table will be the same as the one you made in the first
Dry lab. Include Chemical Name and structure, MW, density or concentration, mmol, molar
equivalents, amount in grams and/or mL. Assume that reaction uses 1 mL of toluene, 1 ml of 15.8
M nitric acid, 1 mL of 18.4 M sulfuric acid and 8 mL of diethyl ether. (2.5 points)
Toluene Spectra Complete the following tables and answer any questions regarding the spectra
of the starting material, toluene.
FTIR spectrum (0.5 pts):
FTIR
List position (cm-1) & functional group
4.
1.
5.
2.
6.
3.
7.
13
C NMR spectrum (0.5 pts):
Signal
1
~ Chemical shift in ppm
2
3
4
5
Page 10 of 14
1
H NMR spectrum (1 pt):
Signal
~ Chemical shift in
ppm
Height
Integration
Splitting
1
2
3
How long did the reaction take to complete? (0.5 pt)
Calculate the Rf values for each of the spots seen on TLC plates during the reaction. (0.5 pt)
2,4-Dinitrotoluene Product Spectra Complete the following tables and answer any questions
regarding the spectra, data, and observations of the product, 2,4-dinitrotoluene.
Data/Observations (0.5 pt)
color
melting point (˚C)
recrystallized 2,4-dinitrotoluene product
What is the literature value for the melting point range of 2,4-dinitrotoluene? Cite the reference
you consulted to find the melting point. (0.5 point)
FTIR (0.5 pt total):
FTIR
1.
List position (cm-1) & functional group
4.
5.
Page 11 of 14
2.
6.
3.
7.
Explain how the IR spectrum confirms or helps confirm that the product was created? (1 pts)
13
C NMR spectrum (0.5 pts total):
Signal
1
~ Chemical shift in ppm
2
3
4
5
6
7
(0.5 pt) Which signal corresponds to the methyl carbon? (Give the chemical shift in ppm).
1
H NMR spectrum (1.5 pts):
Signal
~ Chemical shift in
ppm
Height
1
2
3
4
Page 12 of 14
Integration
Splitting
Draw the structure of 2,4-dinitrotoluene assign the hydrogens to the 1H NMR signals (2 pts).
Questions
Draw the reaction mechanism for the following reaction. (3 pts)
1. If an additional nitro group where added to the 2,4-dinitrotoluene, what would the product be?
Give the structure and name of this product. What is the compound used for? (1.5 pts)
2. Predict what the major product(s) is/are for a nitration reaction with an electron-withdrawing
substituent, such as benzaldehyde. Explain why this will happen based on the reaction
intermediate. (You can test experiment out in the virtual lab!) (1.5 pts)
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3. Predict what the major product(s) for the reaction (1.5 pts)
Page 14 of 14
Reactions of Benzene
and its Derivatives
Chapter 22
Part 1
22-1
Electrophilic Aromatic Substitution
▪
Electrophilic aromatic substitution (EAS)
▪
How does benzene react with electrophiles?
▪
What is the reaction mechanism?
▪
What types of products can be made?
22-2
Electrophilic Aromatic Substitution
22-3
Electrophilic Aromatic Substitution
▪
Electrophilic aromatic substitution (EAS):
A reaction in which a hydrogen atom of an
aromatic ring is replaced by an electrophile.
22-4
EAS General Mechanism: Step 1
22-5
EAS General Mechanism: Step 2
22-6
Electrophilic Aromatic Substitution
1. Benzene acts as a nucleophile
and attacks an electrophile
A non-aromatic carbocation intermediate is formed
It is stabilized via resonance
2. A Hydrogen is deprotonated to re-aromatize the
benzene
What is the electrophile and how is it generated?
22-7
EAS Reactions of Benzene
22-8
EAS Reactions of Benzene
22-9
Chlorination of Benzene
22-10
Bromination of Benzene
22-11
Chlorination
22-12
Bromination
▪
Energy diagram for the reaction of benzene with
bromine.
22-13
Nitration: Generate Electrophile
22-14
Nitration: Mechanism
22-15
Nitration
▪
A particular value of nitration is that the nitro group
can be reduced to a 1° amino group, -NH2.
22-16
Sulfonation
▪
Carried out using concentrated H2SO4 containing
dissolved SO3 (oleam).“fuming sulfuric acid”
▪
The electrophile is either SO3 or HSO3+ depending
on experimental conditions.
22-17
Sulfonation
22-18
Reactions of Substituted Benzenes
▪
Which product or products are formed?
22-19
Di- and Polysubstitution
▪ -OCH3 is ortho-para directing.
▪ -COOH is meta directing.
22-20
Di- and Polysubstitution
Orientation of nitration of monosubstituted benzenes.
Y=
Su bstitu ent ortho
meta
–
para
ortho +
p ara
meta
55
38
99
96
trace
4
30
100
trace
OCH3
CH3
44
58
Cl
70
4
–
Br
37
1
62
99
1
COOH
18
80
2
20
80
CN
NO2
19
6.4
80
93.2
1
0.3
20
6.7
80
93.2
22-21
Di- and Polysubstitution
▪ Electron Donating Groups and halogens form ortho
and para products “Ortho/Para-directing”
▪ Electron Withdrawing Groups form meta products
“Meta-directing”
22-22
Practice
22-23
Di- and Polysubstitution
▪
Substituent effects on the rate of nitration
22-24
Di- and Polysubstitution
▪
Orientation:
▪ Certain substituents direct preferentially to ortho & para
positions; others to meta positions.
▪ Substituents are classified as either ortho-para.
directing or meta directing toward further substitution.
▪
Rate
▪ Certain substituents cause the rate of a substitution to be
greater than that for benzene itself; others cause the rate
to be lower.
▪ Substituents are classified as activating (faster) or
deactivating (slower) toward further substitution.
22-25
Di- and Polysubstitution
:
OH
OR
Moderately
activating
O
NHCR
O
NHCAr
O
OCR
:
:
:
O
OCAr
R
NO2
NH3
+
I:
:
Moderately
deactivating
O
O
O
CH
CR
COH
O
CNH 2
SO3 H
:
:
Br :
:
:
Cl :
:
:
F:
:
Weakly
deactivating
Strongly
deactivating
:
Weakly
activating
:
:
NR2
:
:
NHR
:
:
NH2
:
Strongly
activating
:
Ortho-para Directing
Directing Effects of Substituents
Meta Directing
▪
O
COR
C N
CF3
CCl3
22-26
Di- and Polysubstitution
▪
From the information in table, we can make these
generalizations:
▪ Alkyl, phenyl, and all other substituents in which the atom
bonded to the ring has an unshared pair of electrons
are ortho-para directing. All other substituents are meta
directing.
▪ All ortho-para directing groups except the halogens are
activating toward further substitution. The halogens are
weakly deactivating.
22-27
Theory of Directing Effects
▪ -OCH3; assume meta attack.
22-28
Theory of Directing Effects
▪ -OCH3: assume ortho-para attack. Only ortho attack is
shown.
▪ For more extra practice draw the
▪ resonance structures for the para product
22-29
Theory of Directing Effects
▪ -NO2; assume meta attack.
22-30
Theory of Directing Effects
▪ -NO2: assume ortho-para attack. (only ortho is shown)
22-31
Theory of Directing Effects
▪
▪
▪
The rate of EAS is limited by the slowest step in the
reaction.
In EAS the rate-determining step is attack of E+ by
the aromatic ring to give a resonance-stabilized
carbocation intermediate.
The more stable this cation intermediate, the faster
the rate-determining step and the faster the overall
reaction.
▪ Electron donating groups stabilize the carbocation
▪ Electron withdrawing groups destabilized the carbocation
22-32
Theory of Directing Effects
▪
For ortho-para directors, ortho-para attack forms a
more stable cation than meta attack.
▪ In this case ortho-para products are formed faster than
meta products.
▪
For meta directors, meta attack forms a more stable
cation than ortho-para attack.
▪ In this case meta products are formed faster than orthopara products.
22-33
Activating-Deactivating
▪
▪
Any resonance effect, such as that of -NH2, -OH,
and -OR, that delocalizes the positive charge on the
cation intermediate lowers the activation energy for
its formation, and has an activating effect toward
further EAS.
Any resonance or inductive effect, such as that of
-NO2, -CN, -C=O, and -SO3H, that decreases
electron density on the ring deactivates the ring
toward further EAS.
22-34
Activating-Deactivating
▪
Any inductive effect, such as that of -CH3 or other
alkyl group that releases electron density toward the
ring activates the ring toward further EAS.
▪
EDG’s make benzene a better nucleophile
▪
Any inductive effect, such as that of halogen, -NR3+,
-CCl3, or -CF3 that decreases electron density on
the ring deactivates the ring toward further EAS.
▪
EWG’s make benzene a worse nucleophile
22-35
Activating-Deactivating
▪ For the halogens, the inductive and resonance effects run
counter to each other, but the former is somewhat
stronger.
▪ The net effect is that halogens are deactivating but orthopara directing.
22-36
Di- and Polysubstitution
▪ The order of steps is important.
CH3
COOH
HNO3
K2 Cr2 O7
H2 SO4
H2 SO4
CH3
NO2
NO2
p-N itroben zoic
acid
COOH
COOH
K2 Cr2 O7
HNO3
H2 SO4
H2 SO4
NO2
m-N itroben zoic
acid
22-37
Reactions of
Benzene and
its Derivatives
Chapter 22
Part 2
22-38
Friedel-Crafts Alkylation
▪
Friedel-Crafts alkylation forms a new C-C bond
between an aromatic ring and an alkyl group.
+
Benzene
Cl
AlCl3
+ HCl
2-Chloropropane
Cumene
(Isoprop yl chlorid e) (Isopropylbenzen e)
22-39
Friedel-Crafts Alkylation
Step 1: Lewis acid-Lewis base reaction to form an alkyl
cation as an ion pair.
Step 2: Electrophilic aromatic addition.
+
+
+
R
H
R
+
H
H
R
+ R
A resonance-stabilized cation
Step 3: Take a proton away to regenerate the aromatic
ring.
22-40
Friedel-Crafts Alkylation
▪
There are three major limitations on Friedel-Crafts
alkylations:
1. Carbocation rearrangements are common.
22-41
Other Aromatic Alkylations
▪
Carbocations are generated by
▪ Treatment of an alkene with a proton acid, most
commonly HX, H2SO4, H3PO4, or HF/BF3.
+
Benzen e
CH3 CH=CH2
Prop ene
H3 PO4
Cumene
22-42
Other Aromatic Alkylations
▪ Treatment of an alcohol with H2SO4 or H3PO4 or HF/BF3
generates a carbocation electrophile.
+
Benzene
HO
H3 PO 4
2-Methyl-2-propanol
(tert- Butyl alcohol)
+ H2 O
2-Methyl-2phenylpropane
(tert- Butylbenzene)
22-43
Friedel-Crafts Alkylation
Draw the product and complete mechanism.
22-44
Friedel-Crafts Alkylation
2. Alkylation fails on benzene rings bearing one or more
strongly electron-withdrawing groups.
Y
+ RX
AlCl3
N o reacti on
Wh en Y Equ als A n y of Th es e G rou p s, th e Ben ze n e
Ri ng D oe s N o t U n d ergo Fri ed el -Crafts A lk ylation
O
CH
O
CR
SO3 H
C N
CF3
CCl3
O
COH
NO2
O
COR
NR3
O
CNH2
+
3. Overalkylation can occur.
22-45
Friedel-Crafts Acylation
▪
Friedel-Crafts acylation forms a new C-C bond
between a benzene ring and an acyl group.
O
O
+ CH3 CCl
Benzen e
AlCl3
Acetyl
ch loride
Cl
+ HCl
Acetop henone
O
O
AlCl3
4-Phenylbutan oyl
chlorid e
+ HCl
-Tetralon e
22-46
Friedel-Crafts Acylation
Step 1: Lewis acid-Lewis base reaction.
Step 2: Break a bond to give stable molecules or
ions, in this case an acylium ion.
••
An acyl
chloride
••
O
••
R-C Cl
Cl
+ Al-Cl
Cl
Aluminum
chloride
(1)
O + Cl
(2)
••
R-C Cl Al Cl
••
Cl
A molecular complex
with a positive charge
charge on chlorine
O
R-C + AlCl4An ion pair
containing an
acylium ion
22-47
Friedel-Crafts Acylation
▪ An acylium ion is represented as a resonance hybrid of
two major contributing structures.
▪
Friedel-Crafts acylations are free of a major
limitation of Friedel-Crafts alkylations; acylium ions
do not rearrange.
22-48
Acylation
22-49
Friedel-Crafts Acylation
▪
A special value of Friedel-Crafts acylations is
preparation of unrearranged alkylbenzenes.
Reductions can be used to remove the carbonyl
group.
22-50
Friedel-Crafts Acylation
▪
A special value of Friedel-Crafts acylations is
preparation of unrearranged alkylbenzenes.
Reductions can be used to remove the carbonyl
group.
22-51
Nucleophilic Aromatic Substitution
▪
Aryl halides do not undergo nucleophilic substitution
by either SN1 or SN2 pathways.
▪
They do undergo nucleophilic substitutions, but by
mechanisms quite different from those of
nucleophilic aliphatic substitution.
Nucleophilic aromatic substitutions are far less
common than electrophilic aromatic substitutions.
▪
22-52
Nucleophilic Aromatic Substitution
▪
When heated under pressure with aqueous NaOH,
chlorobenzene is converted to sodium phenoxide.
▪ Neutralization with HCl gives phenol.
–
Cl
+
O Na
+ 2 NaOH
H2 O
o
press ure, 300 C
Ch lorobenzen e
+ NaCl + H2 O
Sodium
ph enoxide
22-53
Nucleophilic Aromatic Substitution
▪ The same reaction with 2-chlorotoluene gives a mixture of
ortho- and meta-cresol.
CH3
Cl
CH3
OH
1 . NaOH, heat, p res sure
2 . HCl, H2 O
CH3
+
OH
2-Meth ylp henol 3-Methylphen ol
(o-Cresol)
(m-Cresol)
▪ The same type of reaction can be brought about using
sodium amide in liquid ammonia.
CH3
CH3
+ NaNH2
Cl
NH3 (l)
o
(-33 C)
CH3
+ NaCl
+
NH2
NH2
4-Methylaniline 3-Methylanilin e
(p-Toluid ine)
(m-Toluidin e)
22-54
Nucleophilic Aromatic Substitution
▪
Step 1: Take a proton away and simultaneously
break a bond to make stable molecules or ions.
22-55
Nucleophilic Aromatic Substitution
▪
Step 2: Make a new bond between a nucleophile
and an electrophile.
22-56
Nucleophilic Aromatic Substitution
▪
Step 3: Add a proton. Proton transfer from NH3 to
the carbanion intermediate gives one of the
observed substitution products and generates a
new amide ion.
22-57
Benzyne Intermediates
▪ -Elimination of HX from a haloarene gives a benzyne
intermediate.
CH3
CH3
NaNH 2
H
Cl
-elimin ation
A b enzyne
intermediate
22-58
Nuc. Substitution by Addition-Elimination
▪ When an aryl halide contains electron-withdrawing NO2
groups ortho and/or para to X, nucleophilic aromatic
substitution takes place readily.
–
Cl
NO2
Na2 CO3 , H2 O
+
O Na
NO2
1 0 0 oC
NO2
1-Ch loro-2,4dinitrobenzen e
NO2
Sodiu m 2,4-din itroph enoxide
▪ Neutralization with HCl gives the phenol.
22-59
Nucleophilic Aromatic Substitution
▪ Step 1: Make a new bond between a nucleophile and
an electrophile.
▪ Step 2: Break a bond to give stable molecules and
ions.
O
+N
O
Cl + Nu-
slow, rate
determining
(1)
NO2
O
+N
O
Cl
Nu
NO2
O
fast
(2)
+N
O
Nu + :Cl
NO2
A Meisenheimer complex
22-60
22-61