Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
Nucleophilic Aromatic Mechanism:
As we have already seen (chapter 12), the most common reaction of aromatic systems is
electrophilic aromatic substitution :
However, a fundamentally different type of reaction is possible for aryl halides under
certain conditions:
This reaction is similar to that of simple nucleophilic substitution at sp3 C
The fundamental requirements for this nucleophilic aromatic substitution reaction are:
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ortho- or para- nitro group or groups, and strong nucleophile, e.g. CH3Oor a very strong nucleophile, e.g. NH2-
There are two fundamental events to a nucleophilic substitution reaction:
1. formation of the new  bond from an Ar C to nucleophile
2. breaking of the  bond to the leaving group
Depending on the relative timing of these two events, two mechanistic pathways emerge:
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Addition-Elimination (add Nu, loose LG)
Elimination-Addition (loose LG add Nu)
Addition-Elimination Mechanism:
Summary
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The generally accepted mechanism for nucleophilic aromatic substitution in nitrosubstituted aryl halides is shown by example below:
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Farshid Zand
Organic Chemistry 233
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Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
Attack of the strong nucleophile on the halogen substituted aromatic carbon
forming an anionic intermediate.
Loss of the leaving group, the halide ion restores the aromaticity.
Kinetics of the reaction are observed to be second order.
The addition step is the rate determining step (loss of aromaticity).
Nucleophilic substitution, and therefore reaction rate, is facilitated by the presence
of a strong electron withdrawing group (esp. NO2) ortho or para to the site of
substitution, which stabilise the cyclohexadienyl anion through resonance.
Aryl halide reactivity : -F > -Cl > -Br > -I (note the contrast to simple
nucleophilic substitution)
The more electronegative the group the greater the ability to attract electrons
which increases the rate of formation of the cyclohexadienyl anion.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
Elimination-Addition Mechanism: Benzyne
Summary:
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This pathway is followed when the nucleophile is an exceptionally strong base
(e.g. amide ion, NH2-) and the absence of the strong electron withdrawing groups:
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Nucleophilic substitution can lead to substitution on either
o the same carbon that bore the leaving group (see addition mechanism
above)
o or on an adjacent carbon (see addition mechanism below)
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This is most readily apparent when the benzyne is substituted:
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
Aryl Grignards
Summary
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Aryl Grignards are formed by the reaction of aryl halides (X= Cl, Br or I) with
magnesium metal.
Typical solvents are normally anhydrous diethyl ether or tetrahydrofuran.
Halide reactivity : I > Br > Cl
Aryl Grignards undergo the sample types of reactions as alkyl Grignard reagents
(review)
Organolithium reagents can also be made.
Aryl Grignard reactions allow for the introduction of C substituents other than via
Friedel-Crafts alkylation or acylation reactions.
Benzyne
Structure
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Benzyne is an example of an aryne (-yne = triple bond)
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This is no ordinary triple bond as the second 
interaction results from a
weak interaction
2
of sp hybrid orbitals lying in the plane of the
ring.
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The triple bond is non-linear due to the constraints of
the 6-membered ring.
 Benzyne is strained and highly reactive.
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The image shows the electrostatic
potential for benzyne.
The more red an area is, the higher the
electron density and the more blue an
area
is, the lower the electron density.
Here we see the triple bond as a region
of high electron density (red).
As a result of the non-linear triple
bond, benzyne is highly reactive.
Benzyne is a reactive intermediate, an
tends to undergo addition reactions.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
Addition Reactions of Benzyne
Reaction type: elimination then addition
Summary
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The strained triple bond in benzyne makes it reactive towards addition reactions.
Additions of H2O and NH3 are commonly encountered are a result of the methods
of formation (see above).
Substituted benzynes can also be formed, where the subsequent addition reaction
typically gives mixtures of products:
Related Reactions
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Diels-Alder reactions of Benzyne
Addition reactions of Alkynes and Alkenes
MECHANISM OF THE ADDITION OF AMMONIA TO BENZYNE
Step 1:
The N in amide functions as the nucleophile and attacks the reactive triple bond C in
benzyne creating the new C-N bond and an intermediate carbanion.
Step 2:
An acid/base reaction. Rapid protonation of the reactive carbanion from the ammonia
forms the aniline and anotheer molecule of the amide ion.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
Diels-Alder Reactions of Benzyne
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Benzyne can undergo Diels-Alder reactions leading to the formation of fused ring
systems with an aromatic component:
DIENE
DIENOPHILE
PRODUCT
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A milder, more convienient method for the generation of benzyne involves
treating 1,2-bromofluorobenzyne with magnesium metal:
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The strained triple bond makes benzyne a good dienophile
Aryl Halides Questions:
1. How could you prepare the following aryl halides from benzene ?
(a) chlorobenzene
(b) fluorobenzene
(c) iodobenzene
(d) 1-bromo-3-chlorobenzene
(e) 1,4-dibromobenzene
(f) 1,3,5 tribromobenzene
2. Identify the major products formed by the reaction of bromobenzene with each of the
following :
(a) HNO3 / H2SO4 / heat
(b) Br2 / FeBr3
(c) CH3CH2Cl / AlCl3 / heat
(d) H2SO4 / heat
(e) CH3CH2COCl / AlCl3 / heat
(f) Mg / THF then CO2 followed by aq. acid work-up
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
3. What are the major products of the reactions of each of the following with phenyl
magnesium bromide followed by a regular acidic work-up ?
(a) CH3CH2CHO
(b) C6H5CHO (benzaldehyde)
(c) CH3COCH3 (propanone)
(d) D2O
(e) C6H5CO2CH3
(f) C6H5CO2H
(g) CH3CH2OH
(h) C6H5CN
4. Based on the definitions discussed in Chapter 11, is benzyne an aromatic compound ?
5. What is the product of the reaction of benzyne with each of the following:
(a) 1,3-butadiene
(b) furan
(c) H2O
(d) NH3
Aryl Halides Answers
Question 1.
A.
Chlorine atoms can be introduced fairly
simply by treating benzene with chlorine in the
presence of a Lewis acid catalyst like iron (III)
chloride.
B.
The most common method for introducing fluorine is via the Schiemann reaction of the
diazonium salt using HBF4. Diazonium salts are obtained from anilines.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
C.
The most common method for introducing iodine is again via the diazonium salt , by
treating it with potassium iodide.
D.
Since both -Cl and -Br are ortho- / para- directing, we cannot just introduce them using
the halogen and iron (III) trihalide method. The alternative is via the diazonium reactions
and a Sandmeyer reaction. This also means we can use the nitro- group to set up the
required meta arrangement.
E.
Since bromine is an ortho / para director but the large size of the bromine to some degree
sterically inhibits ortho substitution, 1,4-dibromobenzene can be obtained by treating
benzene with excess Br2 and the Lewis acid catalyst iron (III) bromide.
F.
In order to complete this synthesis, we need to use aniline.... this powerful activating
group allows for the introduction of 3 bromines in the correct arrangement (in fact it is so
reactive, a catalyst is not even needed, and the reaction is almost instantaneous at room
temperature), then the amino group, -NH2, can be removed by diazotisation and the
introduction of a H.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
QUESTION 2.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
QUESTION 3.
A collection of reactions of an aryl Grignard reactions.... you should compare them with
those of ethyl magnesium bromide (see chapter 14 questions). In each case remember
that there is a aqueous acid work-up.
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Farshid Zand
Organic Chemistry 233
Chapter - 16
Lecture notes
Department of Chemistry
San Diego Mesa College
QUESTION 4.
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Yes benzyne is aromatic..... it has a cyclic, planar, conjugated, 6
electron system.
Note that the second  bond (shown as the blue orbitals in the
diagram to the right) of the triple bond is perpendicular and
therefore cannot overlap with the aromatic 
system (shown as cyan orbitals). This means that
the two electrons associated with this bond are not
part of the conjugated system.
 Benzyne is very reactive due to the strain of the
triple bond due to its incorporation into the six
membered ring.
QUESTION 5.
Benzyne has a reactive triple bond undergoing addition reactions, including the DielsAlder reaction:
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