Organic Reaction

Addition
Substitution
Elimination
Rearrangement

by Yuris, S.Si., M.Si

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 Organic Reaction
Reactivity (Thermodynamic
parameters, DG, DS)
Intermediet Study
Acid-base principle

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 p-bond lobes represent areas of high electron density
Therefore, the p-bond is susceptible to attack by
electron deficient molecules, called electrophiles, E+

Electrophilic Addition
E+ C C + A B A C C B

H X
H C C X
Alkyl Halides

H OSO3H
H C C OSO3H
Alkyl hydrogen Sulfate
C C
H OH
H+ H C C OH
Alcohols

X X X C C X
Dihaloalkanes
Mechanism
Slow
C C C C + X
H
H X

fast
C C X C C
H H X

X- is the nucleophile, and the carbocation is the electrophile

The electrophile is a Lewis acid, its accepted a pair of electrons,

the simplest Lewis acid is H+
The nucleophile is a Lewis base, its donated a pair of electrons
 Slow
C C C C O
H O S O H
H OSO2OH
O

Fast C C
H OSO3H

Markovnikov’s Rule H atom adds to the carbon atom

which already has the most H
atoms
H H Br H
H2C C CH3 H2C C CH3
H Br Markovnikov addition
Unsymmetrical Alkene Product
 H CH3 CH3 CH3

+C H +C H +C CH3 +C CH3

H H H CH3

INCREASING STABILITY OF CARBOCATIONS

This determines the selectivity

of addition of HX onto an
unsymmetrical alkene
 H CH3 H CH3
Slow
C C H C C
H H H H
Br
H Br 2o Carbocation prefered

H CH3 H CH3
Slow
C C C C H
CH3 CHBr CH3
H H H
2-Bromopropane
H
is the main product H Br 1o Carbocation
H2
BrH2C C CH3
3o > 2o > 1o
1-Bromopropane – little formed Carbocation stability
The Slow Step is the Rate Determining Step
Bromination of DB – This is an Ionic Mechanism

C C Test for DB or TB
C C + Br
Decloroization of Br2/CCl4
Br  Br
Br -

1. Bromine molecule becomes polarised

2. Bromine bond breaks heterolytically

3. Formation of Bromonium cation and Bromide anion

Br Br Contrast with reaction

between Bromine and
C C C C Alkanes
Br Br
colourless

4. Back-side nucleophilic attack – opening of three membered ring

5. Stereospecific Product
Hydrogenation – “Reduction”
Pt or Pd - catalyst
C H solvent, pressure
C H
C H C H

Pt - catalyst
solvent, pressure
C H H C H
2X
C H H C H

Example
Pt
ethanol, 1 atm

cyclohexene cyclohexane
 H H H H
n
C C C C
Polymers are large H H H H n

molecules containing ethylene Polyethylene

many identical repeating H

C C
CH3
n
H CH3

units (100-1000000)
C C
H H H H n
propylene
Polypropylene

Polymerisation reaction is a repetition H Cl

H Cl
reaction which combines many small C C
n
C C
molecules of monomer (alkene) to H H H H n
form a polymer vinyl chloride Poly(vinylchloride), PVC

F F
F F n
C C C C

Addition polymer is a F F F F n

polymer in which the Tetrafluoroethene Teflon

monomer simply add H H

together with no other C C n
H H
products formed besides H C C
polymer H n

Styrene
Polystyrene
Ethanol content; Beer, 3-9% ; Wine, 11-13% ; Whisky, 40-45% ; Vanilla Extracts,
35% ; Night Nurse, 25% ; Listerine, 25%

Preparation of Ethanol
- Fermentation of Sugar – Break down of sugar to CO2
and Ethanol by Yeast Enzymes
- Industrial Process – Hydration of Ethene
H H H2O
CH3CH2OH
H3PO4 , 300C
H H
Naming Alcohols hydroxy or alcohol group
CH3 OH CH3 CH2 CH2 OH
CH3 CH2 OH
Methyl alcohol
(methanol) Ethyl alcohol (ethanol) Propyl alcohol (propanol)

CH3 CH OH CH3 CH2 CH CH2 CH3

CH3 CH2 OH
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Isopropyl alcohol 2-Ethyl-1-butanol
 Electrophilic Substitution

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Naming Aromatic Hydrocarbons
F CH2CH3 CH3 NH 2

Fluorobenzene Ethylbenzene
Toluene Aniline
O
OH C Cl -ortho Cl
OH
Cl -meta
Phenol
Cl
Benzoic Acid 1,2-Dichlorobenzene 1,3-Dichlorobenzene
CH3 CH3
-para Cl
O 2N NO 2 CH3

Br
NO 2 o-Xylene m-Bromostyrene
Cl
1,4-Dichlorobenzene 2,4,6-Trinitrotoluene (TNT)
Electrophilic Aromatic Substitution
H E
H H H H
E X
+ H X
H H H H
H H

Electrophilic attack – Slow Rate Determining Step

E E E
E H H H
sp3 Transition State or Wheland Intermediate
E
Delocalised Cyclohexadienyl cation
H
Fast Step is the loss of a proton ---rapid re-aromatization

+ E - H+ E
H

E.g. Nitration of benzene

HNO3(c), H2SO4(c) NO2

Sir Christopher Ingold's ideas (1930s), terminology and

nomenclature for reaction mechanisms (e.g. electrophilic,
nucleophilic, inductive, mesomeric, SN1, SN2 etc) were
generally accepted and employed everywhere.
The Nitration of Benzene

_ _
O O O O
O +N +N
+ electrophilic attack
N
+
slow =
O +
electrophile

H O + O
O2 N N NO2
- H+
+
fast =
Generating NO2+
Sulfuric acid is a stronger acid than nitric acid

O O
_ _
H O S O H O S O + 2 H+
O O
H
HO NO2 O+ NO2 NO2+ + H2O
H
H+

NO2
NO2
H
NO2
- [H+]
Nitrobenzene
Friedel-Crafts Alkylation

AlCl3 or FeCl3 R
+ RX + HX

Lewis Acid Catalyst is used to activate the alkyl halide

H
 slow CH2CH3
CH3CH2Cl AlCl3
- + AlCl4

Cl
Cl Al Cl
H
CH2CH3 Cl CH2CH3
+ HCl
fast
+ AlCl3
 HALOGENATION

Cl2, AlCl3 Cl

Professor Charles Friedel

and Professor James Crafts
Br2, FeBr3 Br

The Halogen is polarised

Br
Br Br FeBr3 H + FeBr4
 Conclusions
Aromatic Compounds are resonance stabilized
This gives them added stability
They undergo Electrophilic Substitution Reactions
Upon substitution, the fast step is the loss of a proton to regenerate
aromaticity

H Br H Br H Br
+ +

Br double-headed arrows
FeBr4
+ HBr

FeBr3
Regenerate the catalyst – so only a small amount is required
 Nucleophilic Substitution

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 SN2 – Substitution, Nucleophilic, Bimolecular

H3C CH3 CH3

H C OTs Nu C OTs Nu H
H H H H
Nu
Transition State

Rate = k [CH3CH2OTs] [ Nu- ] ---------Bimolecular

Backside Nucleophilic Attack – Inversion in Configuration

H3C CH3 CH3
H C Br HO C Br HO H
C6H13 H C6H13 C6H13
HO
S-(+)-2-Octanol
R-(-)-2-Bromooctane Transition State
Optically Active
Enantiomericaly Pure
Concerted Mechanism
Inversion of Stereochemistry
 SN1 – Substitution, Nucleophilic, Unimolecular
(CH3)3CCl + 2 H2O (CH3)3COH + 2 H3O+ + Cl -

Slow Step (RDS)

CH3 CH2
H3C C Cl + Cl
CH3 H3C CH3
Aided by polar Solvent Stable 3o Carbocation
ions are stabilized via solvation

CH2 Fast Step CH3

Professor George Olah H3C C O H
Nobel Prize 1994 H3C CH3 CH3 H
O H
Carbocation is sp2-planar H
- H+
more stable Front or Backside Attack
R H H CH3
R C > R C > R C
R R H H3C C O H
R groups are electron releasing CH3
- delocalise the positive charge tert-Butyl alcohol
 CH2CH3
H3CH2CH2C - HBr HO C CH3
H3C C Br CH2CH2CH3
H3CH2C H3CH2CH2C +
S-3-Bromo-3-methylhexane H3C C OH
H3CH2C
1:1 Mixture of R- and S-3-Methyl-3-hexanol

The Carbocation intermediate is

attacked by water from either
side by the same rate
 Nucleophilic Addition

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Useful in Synthesis
H  - H H
118o C O 118o C C
H3C 121o H 121o H

Resonance Structures
H
H Most Reactive Group –
C O C O
H3C p-electrons + polarisation
H3C

Names al – aldehydes, one - ketones

H H H H
C O C O C O C O
H H3C CH3CH2 CH3CH2CH2CH2
Methanal Ethanal Propanal Pentanal
(formaldehyde) (acetaldehyde)
 H O

H O
Benzaldehyde H

trans-Cinnamaldehyde

S
O
H H
Acrolein (2-propenal) Thiopropionaldehyde
(propanethiol)
- lachrymator and pleasant "odour"
from barbacuing meat - lachrymator from chopped onion

Formalin, 35-40% formadehyde in water

Preservative that reacts with
proteins causing them to resist decay
Coelacanth, “prehistoric fish”
 O H CH3
O O O

H3C CH3
OCH3 Butadione
(butter flavour)
OH
Carvone
Vanillin (spearmint flavour)
O

O O CH2 CH3
H3C CH
CH3
H3C CH3 H3C C CH3
H2
Propanone Butanone 3-Methyl-2-pentanone
(ACETONE)
O O

CH3 Benzophenone

Acetophenone
 Carbonyls readily undergo Nucleophilic Attack
-
O O O H
C  C C
H N R H N R
RNH2 H ANHYDROUS
Conditions are required for
imine formation
O H
C
C Imine
N
H N R R

- H2O

Reaction between an amine and a carbonyl compound

Organometallics add to carbonyls to give alcohols
H
Ether
MgBr C O MgBr
H H
C O H3O+
H
H
C O H
C O + MgBr H
C OH Benzylalcohol
Ether
2. H3O+

Triphenylmethanol

Benzyl Group
Phenyl, Ph Group
Ph
 Nucleophilic Addition Reactions

H H H
O O O
H C H R C H R C R
Ph Ph Ph
Primary alcohols Secondary alcohols tertiary alcohols

_
your adding Ph

O O
O
C C
H H R H C
R R
Formaldehyde Aldehydes Ketone
+ + +
Ph MgI Ph MgI Ph MgI
 CH3CH2 CH2CH3 Ethers (Lewis base) stabilize the
..O.. Grignard Reagent making it
more reactive
Mg Br

.. ..
O
CH3CH2 CH2CH3

Organometallic Reactions must always be done under anhydrous conditions

- 
Mg Br

H H
O Grignards are powerful bases and
will deprotonate water

_
H + OH
Esterification – condensation reaction, where H O is lost 2

O O
+ CH3CH2 OH
CH3 OH CH3 O CH2 CH3
Acetic acid Ethyl acetate
HCl or H2SO4
(ethanoic acid)
H+(catalyst)
O O
+ H3C OH
Ph OH Ph O CH3
Benzoic acid Methyl benzoate
H+(catalyst)

O O O

O H O O
Ethyl propanoate Methyl formate vinyl acetate

Alcohol part appears first in the name

 Redox Reactions

Addition of Oxygen or Removal of Hydrogen is OXIDATION

Removal of Oxygen or Addition of Hydrogen is REDUCTION

H H O
+O - 2H +O - 2H
CH4 CH3OH C O C O C
H HO O
R Reduction
H
C O R C O
Oxidation
H H H
Aldehydes Primary Alcohols

R Reduction
H
C O R C O
Oxidation
R R H
Ketones Secondary Alcohols
Examples of Reduction Reactions
H
CH3 O CH3 O
H2 , Pd-C
H
H3C H H3C
H
3-Methylbutanal
3-Methylbutanol
H
O H
O
H2 , Pt

Cyclohexanone Cyclohexanol

Examples of Oxidation Reactions

H OH
OH
Overoxidation
K2Cr2O7, H2SO4, H2O O O
Amines are bases because of the lone pair on the
nitrogen atom - red litmus paper to blue

H Cl H
NH2 N H Cl
H
Base + Acid = Ammonium Salt

O
O
H O
O H O
+ 2 N(CH2CH3)3 O +
O 2 HN(CH2CH3)3
triethylamine O
oxalic acid triethylaminium oxalate
Aniline is useful in the synthesis of many other aromatic compounds

NO2
HNO3, H2SO4

NO2 NH2
Sn, HCl

phenylamine
= aniline
Aniline can be converted into useful diazonium salt

NH2 N N + Cl-
NaNO2, HCl

0C
benzenediazonium chloride

N N + Cl- Nuc
Nuc-

- N N
N N + Cl- CN
CuCN
+ KCN
- N N
Benzene nitrile

N N + Cl- I
NaI

- N N
iodobenzene

N N + Cl- Br
HBr, CuBr

- N N
bromobenzene