Reactions of Benzenes Electrophilic Aromatic Substitution

1 Notation Structures and Nomenclature

Disubstituted benzene notation:

1,2 = 1,3 = 1,4 =

ortho- meta- para-
xylene xylene xylene

IUPAC: uses numbering system

•number round the ring to give substituents get the lowest numbers possible as usual
•all other things equal (and ONLY when all other things are equal), then do it alphabetically

NO2
3 2
4
Br 1 NO
4-Bromo-1,2-dinitrobenzene
2

Some aromatic compounds have their own IUPAC

names:

CO2H CH3
OCH3

anisole styrene benzoic acid toluene *

*
OH CHO NH2

phenol * benzaldehyd aniline naphthalene

e* *
* you need to be able to name substituted versions of those indicated with the * symbol for test
purposes

#1
O carbonon OH
carbon #1 by by
definition OH C definiti O2N
2
O2 N Br 5
6 2 CH2CH3

named as substituted benzoic

named as substituted
acid
phenol
2-bromo-6-nitrobenzoic acid
5-ethyl-2-nitrophenol

•drawing structures of benzenes

Benzenes : Page 1
 Accurate, Need to use this to
good keep track of
shorthand electrons in
mechanisms

Benzenes : Page 2
2 Miscellaneous Reactions of Benzenes
2.1 Reduction : Addition of Hydrogen
Catalytic addition of H2: forcing conditions required to add H2 to the benzene ring (breaks aromaticity)
H2
less reactive
aromatic Pd/C 50
Harder to
psi H2
reduce
Pt/1000 psi benzene ring
- aromatic

Side Chain Reduction

HO
NaBH4/ reduced to alcohol
EtOH adds hydrogen
O

- Zn(Hg)
withdrawing H reduced to alkane
HCl, H2O (Clemmenson
H reduction)
- removes
oxygen adds
hydrogen
•the first reaction we have already
seen
•the second reaction, a Clemmensen reduction, we have not seen. it reduces an aldehyde/ketone
all the way to an alkane. we will return to the mechanism later in the semester, for now this is
something you just "need to know", sorry! The rest of the molecule must be capable of
withstanding aqueous acid. If not, there is another reaction we can use, again, see later..........

Reduction of nitro to amine

NO2 - - R E D U C
NH2 donating re m o v e
withdrawing T I O N
s o x yg en
adds
H2/Pd/C hydrogen

•catalytic hydrogenation (seen already) reduces a nitro functionality into an amine, which converts
a withdrawing group into a donating group - need to know!!
•You may see OTHER reducing agents used to do this reduction elsewhere (examples are Fe/HCl
or Sn/HCl), but we only use H2/Pd/C in this course because we have seen it before and to minimize
the number of reducing agents we need to learn
•the Clemmensen reduction reduces nitro groups to amines very slowly, therefore we can usually
reduce an aromatic aldehyde/ketone using the Clemmensen reduction without also reducing a
nitro group that may also be on the benzene ring

2.2 Side-Chain Oxidation

•Permanganate oxidation (chromic acid reagents can also be used )
•Oxidizes any 1°, 2°, allyl chain to benzoate (-CO 2–), which is then converted into a carboxylic acid
using H3O+ in a second acid workup step
•interestingly, 3° carbons are NOT oxidized, a benzylic hydrogen is needed

Benzenes : Page 3
Example

- H 3C -withdrawing
HO
donating C
ANY alkyl group with a 2
ANY alkyl
1. KMnO4/-OH/boiling
benzylic hydrogen is t- group
t-Bu
Bu 2. H3O+ WITHOUT a
oxidized to a -CO H
2
benzylic hydrogen
HO2C is NOT oxidized
H3CH2C
OXIDATION
note LOSS of second carbon removes
atom hydrogen adds
oxygen
•NOTE: all carbon atoms that are part of the alkyl group being oxidized are LOST, except the
single carbon that is attached to the benzene ring, which becomes the carbon of the carboxylic
acid

Mechanism - isn't completely known, except first

step...
O
O–
benzylic hydrogens Mn + O3MnOH–
are reactive due to formation H H O O H
of stable intermediates C C
R R
•H-atom abstraction from the carbon attached to the ring (benzylic C-H), explains why 3° alkyl
groups are NOT oxidized, they have no such C-H bond

3 Electrophilic Aromatic Substitution : Many Reactions, One Mechanisms

Recall
electrophile (LA)

BrBr Br Br
exothermic reaction
nucleophile C C H = -30 kcal/mol
(LB) Br
Br
However

WEA electrophile (LA)

Br Br not aromatic
K
Br Br Br Br endothermic reaction
nucleophile H = +2 kcal/mol
(LB) X X product not aromatic!
•first step in the mechanism above is slow,it doesn't "go", benzene is a relatively poor nucleophile
and this step is particularly endothermic because it breaks aromaticity
•need a stronger electrophile to react with the poor benzene nucleophile

Solution

weaker electrophile stronger electrophile

Br Br + Br Br FeBr3

FeBr3
•Ferric bromide (FeBr3) is a Lewis acid catalyst, converts Br2 into a stronger electrophile

Br FeBr3
Benzenes : Page 4
 Br Br FeBr3 H Br exothermic
LA Br
+ H-Br + reaction
FeBr3 H= – 11
kcal/mol
LB Product still aromatic
"sigma-
complex"
•faster reaction, stronger electrophile

Benzenes : Page 5
•overall SUBSTITUTION instead of addition
•Lewis acid catalyst regenerated

General Mechanism for Electrophilic Aromatic Substitution:

LA/Electrophile
E E H E H E
H E
R.D.S.
+ H+

LB/
"sigma-complex"
Nucleophile
•The RATE DETERMINING STEP (R.D.S.) is the reaction between the benzene and the
electrophile, the benzene is the Lewis Base/Nucleophile in the R.D.S.
•Many reactions, depending upon the particular electrophile
•All same mechanism for all reactions, in each case we just need to identify the particular
electrophile, E+

energy R.D.S.
EH

E+
E+
H+

reaction coordinate

3.1 Halogenation of Benzene

•Substitution of a halogen for H on a benzene ring via electrophilic aromatic substitution
Cl
E+ electrophile = a Cl+ EQUIVALENT
Cl2/AlCl3 Cl Cl AlCl3 Cl Cl AlCl3

Br E+ electrophile = a Br+
Br2/FeBr3
EQUIVALENT
Br Br FeBr3 Br Br FeBr3

Lewis acid catalysts you can use almost interchangeably:

FeBr3 FeCl3 AlBr3 AlCl3
•generate the electrophile using a Lewis acid catalyst
3.2 Nitration of Benzene
NO2
NO2 this is the E+ electrophile
HNO3 needed to do the substitution
H2SO4

•where does the +NO2 electrophile come from?

Benzenes : Page 6
 OH O OH2
O N H-O S OH O O N O
N
O Nitronium
O O
ion
+ HSO4 Electrophile
•you may not need to know exactly how the +NO2 electrophile is formed, but you should know the
mechanism of the subsequent electrophilic aromatic substitution reaction

3.3 Sulfonation of Benzene

SO3
H2SO4 SO3H SO3H this is the E+ electrophile
needed to do the
substitution
p-toluene sulfonic acid (TsOH)

•where does the +SO3H electrophile come from?

O
O O O
S H-O S S H O S OH
+ O O
O OHO +
O O
LB/BB LA/BA electrophile

O O
O S O O S OH
H
H O SO3H
SO3H

benzene sulfonic acid

•Dissolve SO3 (sulfur trioxide, gas) in concentrated H2SO4, makes fuming sulfuric acid
•Lewis/Brønsted acid/base reaction protonates the sulfur trioxide, this is where the E+ electrophile
comes from in this case

3.4 Alkylation and Acylation of Benzene

•Carbon-carbon bond forming reactions, important!

alkylation R New C-C bond

R
NO2 SO3H E+ =R
E+ = NO2 E+ =SO3H

•so, all we need is an alkyl cation, i.e. a carbocation, and we have seen lots of ways to make those

Benzenes : Page 7
For example
H3C
H3C CH3
C CH2
C
H3C
CH3
H Br
LA/BA
H 3C LA/BA
HBr t-Bu
3 CCH3
t-Bu
+ C CH H C H
2
H 3C H 3C
LB/BB Br
LB/BB

•any carbocation should react with benzene to do substitution

•however, the standard conditions to make carbocations are not always convenient (strong
acid, silver salts, heating in polar protic solvents etc.), and a better Lewis catalytic method has
been developed

1. Friedel-Crafts Alkylation

Lewis Acid R
+ R-X New C-C bond
+HX

(FeCl3 or AlCl3 or FeBr3)

R AlCl3 R
+ Cl AlCl3
Cl+
LB LA Electrophile

Mechanism

AlCl3
H R

Cl
R
R

Example

AlCl3
+ Cl (+ HCl + AlCl3 )

But

AlCl3
+ +
Cl

H Cl
Benzenes : Page 8
 rearranged
isopropyl cation

•rearrangement of carbocation intermediate, usual carbocation problems

Benzenes : Page 9
Also

Cl AlCl3
AlCl3
+ Cl
faster!
slowe
r
•multiple additions occur because when 1 alkyl group adds, the new alkylated benzene becomes
more reactive than benzene itself

THREE PROBLEMS WITH FRIEDEL-CRAFTS ALKYLATION.......

1. Rearrangements
2. Multiple Additions
3. Doesn't work with benzenes that have electron withdrawing groups.....

withdrawing group SO3H

AlCl3
+ Cl X no reaction

•withdrawing groups "pull" electrons from the ring making it less reactive as a Lewis base/Nucleophile
•because the Friedel Crafts reaction is among the slowest of the electrophilic aromatic substitution
reactions, it is the most sensitive to strong withdrawing groups on the benzene ring, a Friedel
Crafts reaction won't go when other electrophilic aromatic substitution reactions will

2. Friedel-Crafts Acylation: solves problems 1 and 2 (above), but not 3

withdrawing group, deactivates towards further reaction
O
O O C
C Cl R
+ Cl C AlCl3
R
AlCl3
R
faster E+ slower
electrophil
e
O
O
C C + AlCl3
R + AlCl3
Cl Cl
R
acylium ion cannot rearrange

Examples

AlCl3
+ Cl + +

O O
O
Zn(Hg)
AlCl3
+ Cl
HCl/H2

Benzenes : Page
10
 no rearrangement

•acylation followed by reduction is the "approved" method for alkylating benzenes in this course!

Benzenes : Page
11
3. Friedel-Crafts for "1 carbon" (Gatterman-Koch Reaction)
O
O
C H
C H
CO / Cl AlCl3
HCl
AlCl3

•the Friedel Crafts reagent you would WANT to use in this case, formyl chloride, unfortunately
does not exist, since it is unstable and spontaneously dissociates into carbon monoxide (CO)
and hydrogen chloride (HCl)
•Therefore you have to make it "in situ", i.e. by mixing CO and HCl, a small of formyl chloride will
form, as shown below, which can then react with aluminum trichloride to produce a small amount of
the formyl cation that will then undergo electrophilic aromatic substitution with benzene

O AlCl3 O
C C
CO + Cl H + AlCl3
HCl
H Cl
formyl Formyl cation (E+)
chloride
unstable

•CuCl is also often included as a catalyst in addition to AlCl3, but we omit it here for
simplicity to minimize reagent memorization, but be aware that you may see CuCl
elsewhere

Example - to add a methyl group to benzene, first add the corresponding formyl group to form an
aldehyde, then reduce
CO / HCl CHO Zn/Hg CH3

AlCl3 HCl/H2O

4 Reactions of Disubstituted Benzenes

•DIRECTING and ACTIVATING effects of substituents
Recall electron donating and withdrawing groups on pi-systems

increasing electron withdrawing

increasing electron donating ability
ability

F3C – O

N C
R C
+ F O–
 NH2
R C R+
O NH 

NR2
HO3S RO C Cl H Ar
O O
= O N 
+ OH
N 2 O CH O C R
O + Br CH2 OR
R3N R2N C
+
the halogens are electron withdrawing when attached to a -system
even though they have non-bonding electrons due to electronegativity

Summary of electron donating and withdrawing effects on electrophilic aromatic substitution

Benzenes : Page
12
D D
increasingly faster rates with increasingly
+ stronger E (activating) electron donating groups
+ E
D-groups are ortho- and para-
directing
E

Benzenes : Page
13
 W W
increasingly slower rates with increasingly stronger
+ (deactivating) electron withdrawing
+
E
groups E W-groups are meta-directing

X
X the "exceptions"
E somewhat slower rates with halogens (X), weakly
+ deactivating

+ X- are ortho- and para-directing

E E

4.1 Donating Groups : Activating and Ortho- and Para-Directing

O2 N

donatin Me HNO3
g + + NO2
H2SO4
40% 3% NO2 57% Why is this??

•the methyl group is a weak donating (D-)

group

NO2 H H NO NO2 H NO2

2
NO2

"3°" "2°" "2°"

H H H
NO2 NO NO "2°" NO2
2 2
"2°" "2°" NO
2

H NO2 H NO2 H NO2

NO2 "2° "2°" NO2
"3°"
"

•the methyl donor group stabilizes the charge for ortho and para attack, but not meta attack
Here is a partial reaction energy diagram for the first step in the mechanism comparing benzene and
toluene

H
relative NO2on benzene
energy
meta
R + NO2 H +
versu NO2 position
NO s
2 on
O 2N H toluene
H
Benzenes : Page
14
 NO2 ortho position on toluene
reaction coordinate

Benzenes : Page
15
•The donating group makes attack at both the meta and ortho/para positions faster than for simple
benzene (the Ea smaller for both reactions with the methyl substituent), but attack at ortho/para is
faster than for meta
•Reaction does not occur at the meta position because reaction there is slow, it is NOT, it is just
not as fast as reaction at the ortho- and para-positions

•Electron Donating groups are o- and p- directing

•Electron Donating groups are activating (make reaction go faster)
•The stronger the electron donating group, the faster the reaction

4.2 Withdrawing Groups : Deactivating and Meta-Directing

NO2 NO2 NO2 NO2

HNO NO2
3

H2SO4 + +
NO2
6% 1
%
NO2
93%
•the sigma complex is LEAST destabilized for meta-
addition

NO2 O N+ O
NO2 electron withdrawing
NO2
ortho H group destabilizes
additio the sigma-
n complex

NO2 O O
N+
electron withdrawing group
meta does not DIRECTLY destabilize
additio H the
n sigma-complex
NO2 NO2

NO2 O O
N+
electron withdrawing
para group destabilizes
additio the sigma-
n complex

NO2 H NO2

NO2 ortho position

HNO on
2
nitrobenzene

NO2
O2N NO2 meta position
on
H
nitrobenzene
versus +
NO2
H
on benzene
NO2

Benzenes : Page
16
•Reaction does not occur at the meta position because reaction there is fast, it is NOT, it is just
not as slow as reaction at the ortho- and para-positions

•electron Withdrawing groups are m- directing

•electron Withdrawing groups are deactivating (make reaction go slower)
•the stronger the electron withdrawing group, the slower the reaction

Benzenes : Page
17
4.3 Halogens are DIFFERENT! They are Deactivating BUT Ortho- and Para-Directing!
•Electron donation versus withdrawing isn't black versus white, it isn't really binary like that
•There is a continuum, from very strong withdrawing, to weaker withdrawing to not withdrawing or
donating at all (H), to weakly donating to strongly donating.
•So we shouldn't be surprised that there are substituents that are very close to the middle, like H,
for reasons that cancel
•THIS is the HALOGENS, they are VERY CLOSE TO THE MIDDLE
increasing electron withdrawing ability increasing electron donating ability

F3C O
R C O NH2
F Cl R NH C
N C neither R NR2
O Br Ar
HO3S H O
RO C OH
O N O CH CH2 O C R
2
OR
+ R2N C
R3
N
halogens are CLOSE THE MIDDLE of the CONTINUUM
•The halogens are ELECTRONEGATIVE, therefore withdrawing via the INDUCTIVE EFFECT,
BUT, the HALOGENS also have non-bonding electrons that could, in principle, be donated
•THE HALOGENS THUS HAVE MIXED BEHAVIOR AS SUBSTITUTENTS
•The HALOGENS are electron-withdrawing, and therefore DEACTIVATING
However, HALOGENS are also ORTHO- and PARA-directing since they can stabilize the
intermediate cation (sigma complex) by RESONANCE DONATION of a pair of NON-BONDING
ELECTRONS for reaction in the ortho- and para-positions, but not in the meta- position

Example
Cl H
Cl Cl
SO3H
H
SO3H
SO3H

• We should not be surprised that there is a substituent type that is in the middle, this is the halogens!

4.4 Predicting Products for Multiply-Substituted Benzenes

•When there is more than one substituent, consider the following....
1) The most electron donating group determines the directing effects (electronic)
NO2
D-group OCH3 W-group
in reactions with
an electrophile

reacts faster by a factor of 104!!!

2) But we also need to consider steric effects!

D
OCH3 OCH3
D D HO3S
SO3 +
NO2 NO2
H2SO4 SO3H
NO two products
2
W
D formed
Benzenes : Page
18
 OCH3 OCH3
not formed SO3H
for not
electronic formed
reasons for steric
NO2 reasons NO2
HO3S

•The -OCH3 group DIRECTS the reactivity because it is ACTIVATING

•reaction occurs at the ortho- and para-positions with respect to the -OCH3 group, except that
ONE of the ortho- positions is "blocked" due to steric hindrance
Examples
D
OCH3 OCH3 OCH
D D 3
Br not
Br2
+
FeBr3 formed Br

NO2 NO2 NO2

W

•The -OCH3 group DIRECTS the reactivity because it is ACTIVATING

•reaction occurs at the ortho- position with respect to the -OCH3 group, the para-position
in this case is BLOCKED, we can't substitute the -NO2 substituent
•The two ortho-positions in this case are equivalent (by symmetry), reaction at either gives the same
product

#1
CH3 Cl CH3
Cl2 Not
#2 CH3
AlCl3 + Cl forme
d
#1 CH3 CH3 CH3 (steric)

•Reaction at positions #1 is equivalent, gives the same products, reaction at position #2 does not
occur for steric reasons
#1
HO3S CH3 CH3
SO CH CH
CH3 3 +
#2
CH 3 3
H2SO4
3

both HO3S
#2
formed
#1

•Positions #1 and positions #2 are equivalent, reaction at each #1 gives the same product same for
#2
•Electrophilic aromatic substitution reactions CAN give more than one product, we need to be aware
of this
SD OMe OMe
WD HO3S
HO3S O
STILL W
get Friedel
Cl O
Crafts acylation SD

Benzenes : Page
19
 AlCl3

•The -OMe is the STRONGEST DONATING group, IT DIRECTS the reactivity because it is MORE
ACTIVATING than the weakly donating -Me substituent
•Reaction occurs at one para- position with respect to the -OMe group, the two ortho-positions
are BLOCKED, we can't substitute the -SO3H or the -CH3 substituents
•BUT WAIT! How can we have a Friedel Crafts reaction on a ring that has a strong -W substituent,
the -SO3H, doesn't that break our "rule? This is a problem with rules! Note that we also have 2
donating (activating)

Benzenes : Page
20
substituents that offset the deactivating effect of the withdrawing -SO3H. And so, we have to use
some common sense and adapt the "rule" that there is no Friedel Crafts reactions with strongly
withdrawing substituents accordingly when there are also strong donating substituents

5 Synthesis of Substituted Benzenes

Examples
o,p-directing
Cl Cl
Cl
Cl2 HNO3 NO2
FeBr H2SO +
4
3

NO2
m-
directing NO2
HNO3 Cl2
NO2
H2SO4
FeBr3
Cl

•note the different products from the two last reaction sequences, the ORDER MATTERS

CO2
1. KMNO4 CO2H
H Cl2 makes
–
OH, META-
Heat AlCl
disubstitued
2. H3O + 3 benzene
Cl

Cl CO2H
KMNO4 Cl
Cl2 makes
AlCl3 + –OH, Heat
ORTHO-
H3O+ disubstitued
benzene
Cl separate the orth-
isomer from the para-
isomer

•again, isomeric products from different reaction sequences

•where necessary, "separate the isomers" to complete a benzene synthesis sequence

O NO2
NO2

HNO3 Cl
O
H2SO4 AlCl3
No Reaction
W-group deactivates
towards F-C Acylation

RECALL: Friedel Crafts acylation (above) cannot be performed on the benzene that has a strong
electron withdrawing substituent

Benzenes : Page
21
Compare:
O O O

Cl HNO3
H2SO4
AlCl3
NO2
Zn/Hg Zn/
HCl/H2 Hg
O HCl/H2O

NO2 HNO3
+
H2SO4
NO2
NO2

Example Synthesis Problem #1

Synthesize the trisubstituted benzene derivative on the right from benzene
•work backwards using retrosynthetic approach, ask which substituent you are able to "add"
backwards

CH2CH3 CH2CH3
SO3 H2SO4
separate
the
isomers SO3H
Br Br
O
C Br2/FeBr3
l AlCl3

O CH2CH3 SO3H
O SO Zn/ Br
Hg
3
2 W- groups, not
H2SO4 SO3H HCl/H2O SO3H obvious which
"wins"

•At each step (backwards), ask "which of the substituents can be generated, decide
which reaction to do on that basis
•Eventually you don't have to actually write out all of the possible reactions, you
can analyze the possibilities in your head
•It would be difficult to predict that Friedel-Crafts acylation should be the first step in
the synthesis problem above, these problems are definitely best solved backwards

Benzenes : Page
22
Example Synthesis Problem #2
NH2

O O Zn(Hg
NH2 ) Cl
NH2
HNO3 Cl SO3H
separate
isomersthe HCl/H2O
H SO
2 4
Cl AlCl3 Cl SO3
SO3H SO3H H SO
2 4
NO2

Cl2 NH2 O O NH2 NH2

NO2
AlCl3 Zn(Hg)
Cl
H2/Pd/C
Cl HCl/H O
Cl AlCl3 2 Cl
Cl
separate
the
isomers

•Of course, there may be more than one possible solution to these problems, as above
•In reality even these reactions have complications that we don't really have the time to get into
here, specifically, once the amine is formed the Freidel crafts reaction becomes very slow again
even though the amine is very activating, because the amine will also undergo a Lewis acid base
reaction with the AlCl3, making it less donating, organic can be complicated sometimes!

6 Nucleophilic Aromatic Substitution

•Substitute using a nucleophile (not electrophile)
•Substitutes for a halogen (not hydrogen)
•Two Mechanisms: 1) Addition-elimination 2) Elimination-addition, we consider Addition/Elimination
only

ELECTROPHILIC Aromatic Substitution: basic principle

H
H E E
E
+
electrophile H +
proton leaves
electrons "left
behind"
•the substituted H atoms "leaves" in the form of a proton, formally the electrons in the C-H bond
are "left behind" and are needed to complete the bonding with the electron deficient electrophile

NUCLEOPHILIC Aromatic Substitution: basic principle

•when a nucleophile substitutes, can't substitute for a hydrogen, since the electrons must also
"leave" (the nucleophile brings its own electrons, hydride anion (H-) is a very poor leaving group,
need a better leaving group that can "take" the electrons, need a conventional leaving group such
as halide

X XNu Nu
Nu :X +
nucleophile elimina
addition
Benzenes : Page
23
 halide anion leaves takes electrons

•the X- can be a good leaving group, BUT, there are no SN1 or SN2 reactions at an sp2 hybridized
carbon atom
•one way round this is the addition/elimination mechanism

Benzenes : Page
24
 Nu Nu
X X Nu
X Nu XNu W
W W W W X
+
elimination
addition leaving group
W W W W
W
•When a NUCLEOPHILE is the reactant, then substitution occurs for a halogen, not hydrogen, as
occurs when an electrophile is the reactant
•Only works with W = strong withdrawing group in ortho- or para- position
•Only works with strong nucleophile

Examples
strong nucleophile

strong W O2N Na OCH3

Cl O2N OCH + Cl–
CH3OH, 3
Heat

moderate nucleophile
Cl H Cl
N H NH
strong NH3 2
W H + H–Cl
NO NO Hea
NO2 NO2 NO2
2
strong
2
t NO2
W

Benzenes : Page
25
7 Summary of Aromatic Reactions
Do NOT start studying by trying to memorize the reactions here!
Work as many problems as you can, with this list of reactions in front of you if necessary, so that
you can get through as many problems as you can without getting stuck on the reagents/conditions,
and so that you can learn and practice solving reaction problems. Use this list AFTER you have
worked all of the problems, and just before an exam. By then you will have learned a lot of the
reagents/conditions just by using them and you will only have to memorize what you haven't
learned yet. Then do the following:
•Cover the entire page of reagents/conditions with a long vertical strip of paper, see if you can write
down the reagents/conditions for each reaction, check to see which you get correct, if COMPLETELY
correct, circle Y, if incorrect or even slightly incorrect, circle N. In this way you keep track of what
you know and what you don't know.
•Keep coming back to this list and so the same thing only for those reactions you circled N, until all
are circled Y.

Knowing the reagents/conditions on this page is INSUFFICIENT to do well on an exam since you will
ALSO need to recognize how to use and solve reaction problems in different contexts, this page
ONLY helps you to learn the reagents/conditions that you have not YET learned by working
problems.

O
Zn (Hg)
Y/N
HCl /H2O
(Clemmenson reduction)

Et Me HO2C CO2H
1. KMnO4 / –OH/boil
Y/N
t- 2. H3O+ t-
Bu NH2
NO2
Bu H2/Pd/C
Y/N

Br
Br2
Y/N
FeBr
3 Cl
Cl2 Y/N
AlCl
SO3H
3
Y/N
SO3
H2SO4 NO2
Y/N
HNO3
H2SO
4

Cl /AlCl3 +
Y/N
(Friedel-Crafts alkylation)
do not use in synthesis
O
O /AlCl C
3
Cl Y/N
(Friedel-Crafts acylation) H

CO/HCl/AlCl3 (CuCl) CO
Y/N
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 (Gatterman Koch reaction)
CuCl should be included, we omit it for simplicity
Cl NaOCH3/CH3OH OCH3
Y/N
O2N NO2 (nucleophilic aromatic substitution) O2N NO2

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Benzenes : Page
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