1

A REVIEW OF ORGANIC REACTIONS

AND REAGENTS

FOR CHEMISTRY 551

January 2002

Dr. B.A. Keay

Department of Chemistry
University of Calgary
keay@ucalgary.ca
 2

The following schemes illustrate most of the reactions you were taught in Chemistry 351/353, 354
and/or 451/453. To do well in Chemistry 551 you need to know these reactions and the reagents
necessary to effect various chemical reactions. This list is only a guide. You should consult textbooks
and reference books for further information on each of these reactions. Links are provided for each entry.

Table of Contents
Chem 351/353 and 354 Reactions Page
Preparation of Alkanes 3
Reactions of Alkanes 3
Preparation of Alkyl Halides 4
Reactions of Alkyl Halides 5
Preparation of Alcohols 6
Reactions of Alcohols 8
Preparation of Ethers 9
Preparation of Alkenes 10
Reactions of Alkenes 10
Preparation of Alkynes 13
Reactions of Alkynes 13
Preparation of Epoxides 14
Reactions of Epoxides 14
Preparation of Aldehydes 15
Preparation of Ketones 16
Reactions of Aldehydes and Ketones 16
Preparation of Carboxylic Acids 20
Reactions of Carboxylic Acids 21
Preparation of Acid Halides and Anhydrides 22
Reactions of Acid Halides and Anhydrides 22
Preparation of Esters 23
Reactions of Esters 23
Preparation of Amides 24
Reactions of Amides 24
Preparation of Lactones 25
Reactions of Lactones 25
Reactions Involving Carbanions 25
Preparation of Amines 28
Reactions of Amines 29
Reactions of Benzene 30
Reactions of Diazonium Salts 31
Changing Directing Ability of Groups on Benzene Rings 32
Diels-Alder Reactions 33

Chem 451/453 Reactions

Pericyclic Reactions (Cope, Claisen, Oxy-Cope, etc.) 34
Other Sigmatropic Rearrangements 35
Dipolar Cycloadditons 36
Other Photochemical Reactions 37
Rearrangements 37
 3

PREPARATION OF ALKANES

1. Hydrogenation of alkenes
H2

Pd, Pt, or Ni

2. Reduction of alkyl halides

a. Hydrolysis of Grignard reagent
Mg H2O
R X R Mg X R H
ether
X=Cl, Br, I

(b) Reduction by metal and acid

Zn
R X R H
HCl

X=Cl, Br, I

3. Coupling of alkyl halides with organometallic compounds

Li CuI
R X R Li R CuLi
R
may be 1o, 2o or 3o R R'

X=Br or I R' X
should be 1o

REACTIONS OF ALKANES

1. Halogenation
hυ
R H + X2 R X

Reactivity: X2: Cl2 > Br2

H: 3o > 2o > 1o > CH3 H
 4

PREPARATION OF ALKYL HALIDES

1. From Alcohols
HX or PX3
R OH R X

X=Cl, Br or I

2. Halogenation of certain hydrocarbons

hυ
R H + X2 R X

Reactivity: X2: Cl2 > Br2

H: 3o > 2o > 1o > CH3 H

3. Addition of hydrogen halides to alkenes.

HX
C C C C
16 17 1112
H X
X=Cl or Br
H usually attaches to least subsituted
carbon atom in double bond (Markovnikov
addition)

4. Addition of halogens to alkenes or alkynes.

X2 2 X2 X X
C C C C C C C C
X X X X
X=Cl or Br
trans-addition across double bonds
in rings

5. Halide exchange

R X + NaI (or NaBr) R I (or Br) + NaCl

acetone
NaCl ppt's from
X=Cl or Br acetone and drive
1o >> 2o the reaction to
completion
 5

REACTIONS OF ALKYL HALIDES

1. Nucleophilic Substitution

R X + Z: R z

R X + HO- R OH alcohol

+ H2 O R OH alcohol

+ RO- R OR ether
(Williamson
ether synthesis)

+ -C R' R R' alkyne

+ R'-M R R' alkane coupling

M=Li or Mg

+ I- R I alkyl iodide

+ -CN R CN nitrile

+ R'COO- R COOR' ester

+ NH3 R NH2 primary amine

+ NH2R' R NHR' secondary amine

+ NHR'R" R NR'R" tetiary amine

+
+ PPh3 R PPh3 phosphonium salt
(for Wittig reaction)

AlCl3
R X + ArH Ar R Friedel-Crafts reaction

3o halide is best otherwise carbocation rearrangements can occur

O O O O
R'-X
R - R R R alkylation of 1,3-
dicarbonyl systems
R=alkyl and/or OR R'
O O
R'-X R'
alkylation of ketone
enolates
 6

2. Dehydrohalogenation: Elimination
base
C C C C
H X

3. Preparation of Grignard reagent

ether
R-X + Mg R-Mg-X

4. Reduction
R-X + M + H+ R-H + M+ + X-

M=Mg, Na, Zn

e.g. Mg followed by water, Na/EtOH, Zn/HCl,

PREPARATION OF ALCOHOLS

1. Oxymercuration-demercuration
H2O NaBH4
C C
16 17
+ Hg(OAc)2 C C
11 12
C C
27 28
HO HgOAc HO H
Markovnikov addition

2. Hydroboration-Oxidation
H2O 2
3x C C
16 17
+ B 2 H6 C C
11 12
C C
2728
H BR2 H OH
diborane
anti-Markovnikov addition

3. Grignard synthesis
O ether H2O OH
+ R-Mg-X OMgX
R R
ketones or aldehydes

4. Hydrolysis of alkyl halides

-OH
R-X + R-OH + X-

usually requires a silver salt so can be

very expensive
 7

5. Aldol condensation
O base
2x R
H R
O O
R R
H H
R
OH

3-hydroxyaldehyde
may eliminate upon
workup
-usually restricted to a condensation between the same aldehyde
-crossed Aldol reactions provide complex mixtures of products

6. Reduction of ketones and aldehydes

R 1) H- R
O OH
2) acid workup H
H H
aldehydes 1o alcohols

R 1) H- R
O OH
2) acid workup R'
R' H

ketones 2o alcohols

-many sources of hydride

-most common are: NaBH4, LiAlH4, DIBAL-H

7. Reductions of acids and esters

R 1) LiAlH4 R
O OH
2) acid workup H
HO H

1o alcohols

R 1) LiAlH4 R
O OH
R'O 2) acid workup H
H
+ R'-OH

esters 1o alcohols

-NaBH4 will not reduce acids and esters

-reductions with LiAlH4 cannot be stopped at the aldehyde
 8

8. Hydroxylation of alkenes
KMnO4
C C + or C C
NaIO4 HO OH
cis-addition

MCPBA H2 O
C C C C
O H+
HO OH
epoxide
anti-addition
O

MCPBA = meta-chloroperoxybenzoic acid O

O
H
Cl

9. Hydrolysis of Esters
O H3O+ or O R'
+ HO
R OR' NaOH, H2O R OH

10. Misc.

C C + X2, H2O C C
X OH
X=Cl, Br or I
anti-addition

REACTIONS OF ALCOHOLS

1. Reaction with hydrogen halides

R OH + HX R X

reactivityof HX: HI > HBr > HCl

reactivity of ROH: allyl, benzyl > 3o > 2o > 1o

-poor yielding, rearrangements and eliminations
can occur

BETTER IS:
pyridine NaX
R OH + TsCl R OTs R X

1o alcohol is best X=Cl, Br or I

 9

2. Reaction with phosphorus trihalides

R OH + PX3 R X

X= Br or I

3. Dehydration
acid
C C C C
H OH
rearrangements may occur
3o > 2o > 1o

4. Reactions as acids: reaction with active metals.

R OH + M R OM

M = Na, K, Mg, Al, etc.

Reactivity: MeOH > 1o > 2o > 3o

5. Ester formation
O H+ O
R OH + R' OH R' OR

6. Oxidation
R PDC R R KMnO4
R
H OH H H OH
or Swern O or K2Cr2O7 R'
H R' O
oxidation
aldehyde ketone
R KMnO4
R R KMnO4
H OH
HO R" OH no reaction
H O
R'
carboxylic acid

PREPARATION OF ETHERS

1. Williamson Synthesis

R X + RO- R OR
 10

PREPARATION OF ALKENES

1. Dehydrohalogenation of alkyl halides

Zn
C C C C
X X

X=Cl, Br or I

2. Reduction of Alkynes
H2 R R Na or Li R H
R C C R R C C R
H H NH3 H R
Lindlar
catalyst

REACTIONS OF ALKENES

1. Addition of hydrogen. Catalytic hydrogenation

H2
C C C C
Pt. Pd, or Ni H H

syn addition

2. Addition of halogens
X2
C C C C
X X
X=Cl or Br anti addition

3. Addition of hydrogen halides

HX

H X
X=Cl or Br

E.g.
Br
HBr HBr

no peroxides with peroxides Br

Markovnikov anti-Markovnikov
addition addition
 11

4. Addition of Water
H2O

H+ H OH

Markovnikov addition

5. Halohydrin formation

C C + X2, H2O C C
X OH
X=Cl, Br or I
anti-addition

6. Oxymercuration-demercuration
H2O NaBH4
C C
16 17
+ Hg(OAc)2 C C
11 12
C C
27
28
HO HgOAc HO H
Markovnikov addition

7. Hydroboration-Oxidation
H2O 2
3x C C + B 2 H6 C C C C
H BR2 H OH
diborane
anti-Markovnikov addition

8. Addition of carbenes

C C + ":CH2"
formed "in situ"
E.g.
HCCl3 + NaOH :CCl2

dichlorocarbene
(neutral electron defficient
species-very reactive)
 12

9. Epoxidation
MCPBA
C C C C
O
epoxide
O

MCPBA = meta-chloroperoxybenzoic acid O

O
H
Cl

10. Hydroxylation
KMnO4
C C + or C C
NaIO4 HO OH
cis-addition

11. Polymerization
-not useful in synthesis

12. Allylic Halogenation

NBS Br
H C C N
Br C C NBS=N-bromosuccinimide= O O
low conc.

13. Ozonolysis
reductive workup

O Me2S
C C + O3 O + O
O O or
Zn
aldehydes and
ozonide
ketones

H2 O 2
oxidative workup

O + O
OH
ketones and
carboxylic acids
 13

PREPARATION OF ALKYNES

1. Dehydrohalogenation of alkyl dihalides

X2 KOH H NaNH2

X X X

X=Cl or Br anti addition

2. Reaction of metal acetylides with primary alkyl halides

NaNH2 RX
H C Na+ R
R must be primary
X = Br or I

REACTIONS OF ALKYNES

1. Addition of hydrogen
H2 R R Na or Li R H
R C C R R C C R
H H NH3 H R
Lindlar
catalyst

H2 R R H2
2 x H2
H
HH H
Pd, Pt or Ni Pd, Pt or Ni Pd, Pt or Ni

2. Addition of halogens
X2 R X X2 R R
R C C R X
X R X X X

X2 = Cl2 or Br2

3. Addition of hydrogen halides

R X HX R R
HX
R C C R X
R HH X
H
HX = HCl, HBr, HI
 14

4. Addition of water
H2SO4 R OH R O
R C C R + H2O
HgSO4 H R H R

enol tautomerizes to ketone immediately

5. Formation of metal acetylides

NaNH2
H C Na+

PREPARATION OF EPOXIDES

1. From alkenes
MCPBA
C C C C epoxide
16 17 28 27
O
-the more electron rich the double bond
the better the yield O

MCPBA = meta-chloroperoxybenzoic acid O

O
H
Cl
O O
H 2O 2
O
NaOH

-only with conjugated enones, i.e. electron poor double bonds

2. From halohydrins
NaOH
C C + X2, H2O C C C C
X OH O
X=Cl, Br or I anti-addition X and OH must be
anti-periplanar for
epoxide to form

REACTIONS OF EPOXIDES

1. Acid-catalyzed opening
H+ Z: Z
C C C C C C
11 12 39 38 11 12
O O+ OH
H

anti-opening
 15

2. Base opening
Z
Z:- + C C C C
O OH
anti-opening

Z:- can be: RO-, RS-, R2NH, etc.

3. Reaction with Grignard reagents

H+ workup R
R-Mg-X + C C C C
O OH
anti-opening

PREPARATION OF ALDEHYDES

1. Oxidation of primary alcohols

R PDC R
H OH H
or Swern O
H
oxidation
aldehyde

2. Oxidation of methylbenzenes
H Cl2, heat H water
H X
H or X H
Br2, benzoyl O
peroxide
benzaldehyde

3. Reduction of acid chlorides

R LiAlH(OBu-t)3 R
H
Cl O O
acid chloride aldehyde

4. Reimer-Tiemann reaction
OH
CHCl3, NaOH OH O

H
70 oC

-must have a phenol and aldehyde is always

introduced into the ortho position to the hydroxy
group
 16

PREPARATION OF KETONES

1. Oxidation of secondary alcohols

R KMnO4
R
H OH
or K2Cr2O7 R'
R' O
ketone

2. Friedel-Crafts acylation
R R
AlCl3
Cl + Ar-H Ar
O O

3. Reaction of acid chlorides with organocopper compounds

R'
CuX Cl R'
O
R-Li R2CuLi R
O

4. Ethyl acetoacetate synthesis

O O
CH3 CH3 1. NaOMe, MeOH
EtO
O
+ EtO
O
OEt
2. 10% HCl workup
ethyl acetoacetate

REACTIONS OF ALDEHYDES AND KETONES

1. Oxidation
Aldehydes

KMnO4 or
R-CHO or Ar-CHO R-CO2H or Ar-CO2H
K2Cr2O7
acidic workup

Methyl Ketones-haloform reaction

O O KOCl
or R-CO2H or Ar-CO2H + CHCl3
R Ar
acidic workup
 17

2. Reduction to alcohols
Aldehydes
NaBH4, MeOH
R-CHO or Ar-CHO R-CH2OH or Ar-CH2OH
or LiAlH4
acidic workup

Ketones

O O NaBH4, MeOH OH OH
or or
R R' Ar R' R R' Ar R'
or LiAlH4

3. Reduction to hydrocarbons
O O Zn(Hg)
or or
Ar H Ar R' Ar H Ar R'
conc. HCl

Clemmensen reduction-must be an aromatic aldehyde or ketone

O H2NNH2

R NaOH, heat R R'

R'

Wolff-Kishner reduction

4. Reductive amination
O H2NR NHR

R NaCNBH3 R R'
R'
pH 5

5. Addition of cyanide
O HO
H+ CN
+ -CN
R R' R R'
cyanohydrin
 18

6. Addition of derivatives of ammonia

G
O HO N
NHG
+ H2N-G
R R R'
R R' R'

H2N-G Product

H2N-R N imine
R
H2N-OH N oxime
OH

H2N-NH2 N hydrazone
NH2

H2N-NHAr N phenyl
NHAr hydrazone

H2N-NHCONH2 N semicarbazone
NHCONH2

7. Addition of alcohols
O H+ R"O
OR"
+ 2 R"OH
R R' R R'
aldehyde or ketone acetal or ketal

8. Addition of Grignard reagents

O HO
H+ workup R"
+ R"-Mg-X
R
R R' R'

9. Halogenation of ketones
O O
H+ workup
R + X2 R

H X
X2 = Cl2, Br2, or I2

10. Addition of carbanions

a) Aldol condensation
CH3 CH3 1% HCl O
H + H
O O H
or -OH
 19

b) Reactions related to aldol condensation

O O
NaOH
Ar
+ Ar-CHO

c) Alkylation of Ketones
O O
1) LDA, -78oC, THF

2) MeI

O
1) KOtBu, HOtBu

2) MeI

Enamine Formation Followed by Alkylation

O N
N N
H MeI

enamine

H3O+

O
 20

d) Wittig reaction
X-
X-CH2R + Ph3P Ph3P+-CH2R
phosphonium salt

n-BuLi
R H
O
+ Ph3P=CHR
R' H R' H
nonstabilized ylid
mainly Z-isomer

O H R
O
+ EtO2P=CHR
R' H R' H
stabilized ylid
mainly E-isomer

Wittig reactions can be done with unhindered ketones

O H H

+ Ph3P=CH2

PREPARATION OF CARBOXYLIC ACIDS

1. Oxidation of primary alcohols

R KMnO4
R
H OH
NaOH HO
H O
0 oC
carboxylic acid

2. Hydrolysis of Esters
O H3O+ or O R'
+ HO
R OR' NaOH, H2O R OH

3. Oxidation of alkylbenzenes
R KMnO4 CO2H -length and nature of R group does not matter
-sidechain is cleaved to leave one carbon atom at
NaOH the oxidation level of an acid
heat
 21

4. Carbonation of Grignard reagents

HCl
R-Mg-X + CO2 R-CO2- R-CO2H

5. Hydrolysis of nitriles
H+ or
R-CN + 2 H2O R-CO2H + NH3
base

REACTIONS OF CARBOXYLIC ACIDS

1. Acidity. Salt formation

R-COOH + NaOH R-COO- Na+ + H2 O

2. Conversion into functional derivatives

a) Conversion into acid chlorides
O SOCl2 O

R OH R Cl
PCl5
or PCl3

b) Conversion into esters

O O
H+
+ HOR' + H2O
R OH R OR'

c) Conversion into amides

O O
SOCl2 NH3 O
R OH R Cl R NH2

3. Reduction
O
LiAlH4
R OH R OH

1o alcohol

4. Reaction with X2
Hell-Volhard-Zelinsky reaction

O Br2 or Cl2 O
R R
OH OH
red phosphorus X
 22

PREPARATION OF ACID HALIDES AND ANHYDRIDES

From Carboxylic Acids
Acid Chlorides

O O O
SOCl2
Cl
R OH R Cl Cl
or
oxalyl chloride O
oxalyl chloride

Acid Anhydrides

O P2O 5 O O
O
+
R OH R OH R O R

O O O O
+
R Cl R OH R O R

REACTIONS OF ACID CHLORIDES AND ANHYDRIDES

Acid Chlorides
O O O O
+
R Cl R OH R O R
anhydride

O R2Cd O
water
R R R OH
acid
ketone
O
O HOR' O
LiAlH(OiPr)3 R Cl
R H R OR'
aldehyde ester
OH H2NR2 O
LiAlH4
R H R NR2
alcohol amide
Acid Anhydrides
O
O O O
H2NR2 water
+ acid 2 R OH
R NR2 R O R acid
amide

HOR' O

R OR'
+ acid

ester
 23

PREPARATION OF ESTERS
1. From acids
O O
H+
+ HOR' + H2O
R OH R OR'

2. From acid chlorides or anhydrides

O O
+ HOR' + HCl
R Cl R OR'

O O O O
+ HOR' +
R O R R OR' R OH

anhydride

3. From esters: Transesterification

O O
H+
+ HOR" + HOR'
R OR' R OR"

REACTIONS OF ESTERS
1. Conversion into acids and acid derivatives
a) Conversion into acids. Hydrolysis
O H+ or HO- O
+ H2 O + HOR'
R OR' R OH

b) Conversion into amides

O O
H+ + HOR'
+ NR2 R NR2
R OR'
heat

c) Conversion into esters. Transesterification

O O
H+
+ HOR" + HOR'
R OR' R OR"

2. Reaction with Grignard reagents

O R"

R OR'
+ 2 R"MgX
R R"
OH

3o alcohol
 24

3. Reduction to alcohols
O
LiAlH4
R OR' R OH + HOR'

1o alcohol

4. Reaction with carbanions. Claisen condensation

O NaOR' O O
R R
2 OR' OR'
heat R

3-keto esters

PREPARATION OF AMIDES
1. From acid chlorides
O O
SOCl2 HNR2 O
R OH R Cl R NR2

2. From nitriles
N HCl O
R R NH2
H2 O
heat

REACTIONS OF AMIDES
1. Preparation of acids
O H2SO4 O
R NH2 R
H2 O OH

heat

2. Reduction to amines
O
LiAlH4
R NR2 R NR2

an amine
 25

PREPARATION OF LACTONES
Baeyer-Villiger Reaction
O
MCPBA O O

-ring expansion and formation of lactone

-oxygen atom introduced to side of ketone that
is most substituted

H O HO O P2O 5 O O

remove water
-5 and 6 membered lactones are easest to form

REACTIONS OF LACTONES
O O OH OH
LiAlH4

diol

O O DIBAL-H O OH

-78 oC, DCM

lactol

REACTIONS INVOLVING CARBANIONS

1. Halogenation of ketones
O Br2 or Cl2 O
R R
R' R'
H+ or HO- X

2. Nucleophilic addition to carbonyl compounds

a) Aldol condensation
H+ or
O NaOR' OH O O
H+
2 R R H
H R H
heat R R
 26

b) Reactions related to aldol condensation

H+ or
O NaOR' OH O R' O
H+
2 R R R'
R' R R'
heat R'
R R
ketone

c) Addition of Grignard and organolithium reagents

O R'MgX OH O R'MgX OH
R H + or R H +
R OR'' or R R'
R'Li R' R'
R'Li

aldehyde +
esters OR''
H
O R'MgX OH
+ or
R R" R R"
R'Li R'

ketone
d) Wittig reaction
R" R" R'
O
+ R3P R'
R H R H
ylid
aldehyde mixture of E and Z

R" R'
O R"
+ R3P R'
R R" R R"

ketone ylid
mixture of E and Z

3. Nucleophilic acyl substitution

a) Claisen condensation
O NaOR' O O
R R
2 OR' OR'
heat R
3-keto esters
 27

4. Nucleophilic aliphatic substitution

a) Coupling of alkyl halides with organometallic compounds
Li CuI
R X R Li R CuLi
R
may be 1o, 2o or 3o R R'

X=Br or I R' X
should be 1o

b) Synthesis of acetylides
NaNH2 RX
H C Na+ R
R must be primary
X = Br or I

c) Alkylation of malonic ester and acetoacetic ester

O O NaOR' O O
+ R"X
R'O OR' R'O OR'
heat
malonic ester R"

O O
NaOR' O O
R OR' + R"X
R OR'
heat
acetoacetic esters R"

d) Alkylation of ketones
O O
R 1) LDA, -78 oC, THF R R'

2) R'X

kinetic control

O R' O
R 1) KOtBu, HOtBu, heat R

2) R'X

thermodynamic control
 28

5. Addition to conjugated carbonyl compounds. Michael addition

R
O OCuLi O
R2CuLi water

R R
Micheal addition or enolate
conjugate addition

R
O OCuLi O
R2CuLi R'X R'

R R
enolate trans-stereochemistry

Robinson Annelation

O O

NaOMe
+
O O MeOH O

6. Reformansky Reaction
O O O
Zn
+ R'' R''
R R' OMe OMe
Br R OH
R'

PREPARATION OF AMINES
1. Reduction of nitro compounds
Ar-NO2 Zn, HCl Ar-NH2
or or
R-NO2 H2, Pd/C R-NH2

2. Reaction of halides with ammonia or amines

RX RX RX
RX
R2NH R3N R4N+ X-
NH3 RNH2

1o amine 2o amine 3o amine quaternary

ammonium
salt
 29

3. Reductive amination
O H2NR NHR

R NaCNBH3 R R'
R'
pH 5

4. Reduction of Nitriles
LiAlH4
N
R or R NH2
2H2, Pd/C

5. Hofmann degradation of amides

O KOBr
NH2 + CO3-
R NH2 R

chain loses one carbon

atom in length

O
KOBr NH2
NH2

rearrangement with
retention of stereochemistry

REACTIONS OF AMINES
1. Basicity. Salt Formation
HCl Cl-
R2NH R2N+H2

2o amine ammonium salt

2. Alkylation
RX RX RX
RX
R2NH R3N R4N+ X-
NH3 RNH2

1o amine 2o amine 3o amine quaternary

ammonium
salt

3. Conversion into Amides

O O

R2NH + R' Cl R' NR2

amide
 30

4. Hofmann Elimination from Quaternary Ammonium Salts

+
NR2 RI NR3
NaOH, heat

REACTIONS OF BENZENE
Electrophilic Aromatic Substitution of Benzene

Br
Cl

Br2, FeBr3 Birch Reduction

Cl2, FeCl3
Na, NH3(l)

SO3H SO3, H2SO4 NO2

HNO3, H2SO4

X
O
R AlCl3
R Cl
AlCl3
O
R
R

Friedel-Crafts Alkylation
rearrangements can occur with Friedel-Crafts Acylation
primary halides

Reactions to Remove Groups to give Benzene

Br
Cl NH2

Mg, ether
Mg, ether then H2O
then H2O
1) NaNO2, HCl
2) H3PO2
SO3H KOH, heat
 31

Eelectrophilic Aromatic Substitution on Substituted Aromatic Systems

Ortho/para Directors Meta Directors

strong -NR2
+ strong
-NR3
-NH2 -NO2
-OH -CN
-OR -SO3H
-NHCOMe -CHO
-OCOMe -COMe
-R -CO2H
weak -H
-CO2Me
-CONH2
-NH3 weak
+
Activators Deactivators
-make benzene ring electron richer -make benzene ring electron poor

Halides are deactivating but ortho/para directors!!

-F
-Cl
-Br
-I
REACTIONS OF DIAZONIUM SALTS
Formation of and Reaction of Diazonium Salts

NO2 NH2
Zn, HCl

Cl

NaNO2,
HCl
Br
N
N CuCl

Cl-
+
Diazo dyes N2 I
KI
H3PO2 or NaBH4

HBF4
H2O, heat
H2SO4 CuCN F
Cu, NaNO2 (aq)
NO2

OH
CN

Cl-
+
N2 warm

CO2H
Benzyne
 32

CHANGING DIRECTING ABILITY OF GROUPS ON BENZENE RINGS

Changing Activators into Deactivators

CO2H
KMnO4

NH2 R
NaNO2, HCl

see diazonium wagonwheel

Changing Deactivators into Activators

NO2 NH2

CHO
H2NNH2, KOH

heat

Zn, HCl
 33

DIELS-ALDER REACTION

diene dienophile

Normal electron demand Diels-Alder reaction requires the dienophile have at least one
electron withdrawing group attached and the diene should be electron rich.

Reverse electron demand Diels-Alder reaction requires the diene have at least one
electron withdrawing group attached and the dienophile should be electron rich.

Endo vs Exo Products

O
H
+ O +
H
O
exo product endo product
-thermodynamic product -kinetic product

Endo product forms the fastest due to secondary orbital overlap and is the kinetic product.
Exo product forms if the reaction proceeds for a longer period of time (i.e. and is reversible).
The exo product is thermodynamically more stable due to less steric crowding.

Regiochemistry
Diels-Alder reactions with unsymmetrical electron rich dienes and electron poor dienophiles
give mainly cyclohexenes with the substituents in either a 1,2- or 1,4- orientation.

R R
EWG EWG
+

1,2-product

R R
+
EWG EWG

1,4-product
 34

PERICYCLIC REACTIONS
These are examples of [3,3] Sigmatropic Rearrangements
Cope Reaction

R' R'

R R

Oxy-Cope Reaction

HO R' HO R' O R'

H
R R R

Aza-Cope Reaction

R2N R' R2N R' O R'

H3O+
H
R R R
enamine
Claisen Reaction
H H
R' R'
O O

R R

4-enal

Ortho-ester Claisen Reaction

OR OR
R' R'
O O

R R
4-enoate
Ortho-amide Claisen Reaction
NR2 NR2
R' R'
O O

R R

4-enamide
 35

OTHER SIGMATROPIC REARRANGEMENTS

You have been shown[1,3] and [1,5]-H and alkyl shifts with heat or light.
These will not be shown here.

[1,2] Wittig Rearrangement

n-BuLi
O OH

[2,3] Wittig Rearrangement

n-BuLi
O OH

[1,2] StevensRearrangement

base
+ S
S

Sommelet-Hauser Rearrangements ([2,3] Rearrangement)

+
S base S
 36

DIPOLAR CYCLOADDITIONS
+ + B 18
B - B 8 A B A C
A C3 A C -
C 13
D E D E
D E D E

e.g.

O
+
N N MeO2C N
MeO N
-
a)
CO2Me
CO2Me

+
O
-O O O
O
b) O

ozonide

Electrocyclic Reactions
Follow the Woodward-Hoffman Rules (Chem 453)
heat

[2 + 2] Cycloadditions
light
+

O light O
+
R R' R
R'
Paterno-Buchi reaction

not all permutations are shown

 37

OTHER PHOTOCHEMICAL REACTIONS

Barton Reaction

R NO R ON R
HO NOCl O
light HO

O O
O
nitrite ester

-conversion of a delta methyl group to an OH into an aldehyde

H OH
O R N R
HO
HO

O
O
aldehyde oxime

REARRANGEMENTS
Arndt-Eistert Synthesis
-chain lengthened by one carbon atom N2

O +
O H2O O H2 O O
+ CH2N2 R R
R Cl R CHN2 Ag2O OH
ketene
Wolff Rearrangement

Wagner-Meerwin Migrations
-formation of carbocations followed by migration of alkyl, H, or aryl groups
R1 H R2 R1
R2 OH + H+
R3 R5
R3 R5

Benzil-Benzilic Acid Rearrangement

O OH
Ar NaOH Ar
OH
Ar Ar
O O

Pinacol Rearrangement

OH O
H+ R3
R3
R2 R4 R2 R4
R1 R1
OH

Beckmann Rearrangement
O OH H
N
HONH2 N O
H+

oxime lactam
 38

Hofmann Rearrangement

O
NH2
NaOBr N C O hydrolysis
NH2 17

isocyanate retention of
stereochemistry

Curtius Rearrangement
hydrolysis
O O
NaN3 heat N C O
Cl N3 53

acyl azide isocyanate

Schmidt Reaction

OH + HN3