Chemistry 1102

Charlie Bond
MCS Rm 4.16/4.27
Charles.Bond@uwa.edu.au
What is Organic Chemistry?
Organic Reactions I II
Alkanes (Ch 21)
Conformational Analysis (Ch 21)
Stereochemistry I II III (Ch 22)
Alkyl Halides I II (Ch 24)
Alcohols and Ether I II (Ch 24)

Problems from Brown&LeMay

Chapter 24
All questions cover lectures 9-12
Alkyl halides questions are towards the
end, alcohols towards the start

Structure
Haloalkane (alkyl halide): a compound
containing a halogen atom covalently
bonded to an sp3 hybridized carbon
given the symbol RX

Ahaloalkane
(analkylhalide)
3

Nomenclature - IUPAC
locate the parent alkane
number the parent chain to give the substituent
encountered first the lower number
show halogen substituents by the prefixes fluoro-,
chloro-, bromo-, and iodo- and list them in
alphabetical order with other substituents
locate each halogen on the parent chain
5

Br
3Bromo2methyl
pentane

4 Br
5

4Bromocyclohexene

5
4

OH
1

Cl
3 2

trans2Chloro
cyclohexanol
4

Nomenclature
several polyhaloalkanes are common
solvents and are generally referred to by
their common or trivial names
CH2 Cl2
Dichloromethane
(Methylenechloride)

CHCl3
Trichloromethane
(Chloroform)

CH3 CCl3
1,1,1Trichloroethane
(Methylchloroform)

CCl2 =CHCl
Trichloroethylene
(Trichlor)
5

Freons & Their Alternatives

The Freons are chlorofluorocarbons (CFCs)
among the most widely used are/were

CCl3 F
Trichlorofluoromethane
(Freon11)

CCl2 F2
Dichlorodifluoromethane
(Freon12)

At a 1930 ACS meeting, Thomas Midgeley announced the

synthesis of dichlorofluoromethane. He inhaled the vapors and
blew a candle out, thus demonstrating that it was neither toxic
nor flammable!
much lower ozone-depleting alternatives are the
hydrofluorocarbons (HFCs) and the hydrochlorofluorocarbons
(HCFCs), including

CH2 FCF3
HFC134a

CH3 CCl2 F
HCFC141b

Substitution & Elimination

Alkyl halides are used to demonstrate 2 types of reaction
nucleophilic substitution
-elimination
asanucleophile,
ethoxideionattacks
thiscarbon

nucleophilic
substitution

Br
-

+ EtO Na
H anucleophile
andabase
asabase,ethoxideion
attacksthishydrogen

ethanol
elimination
ethanol

OEt

+ Na Br

+ EtOH + Na+Br-

Nucleophilic Substitution
Nucleophile: a nucleus-loving reagent that
donates an unshared pair of electrons to
form a new covalent bond
in the following general reaction,
substitution takes place on a tetrahedral
(sp3 hybridized) carbon
leaving
group
Nu - +
Nucleophile

C X

nucleophilic
substitution

C Nu +

Nucleophilic Substitution
Some nucleophilic substitution reactions
Reaction: Nu
HO
RO
HS
RS
I

CH3Nu + X-

+ CH3X

CH3-OH

Analcohol

CH3-OR

Anether

CH3-SH

Athiol(amercaptan)

CH3-SR

Asulfide(athioether)

CH3-I

Analkyliodide
+

NH3

CH3-NH3

HOH

CH3-O-H

Analkylammoniumion
Analcohol(afterprotontransfer)

Mechanism
Chemists propose two limiting mechanisms for
nucleophilic displacement
a fundamental difference between them is the timing
of bond breaking and bond forming steps
At one extreme, the two processes take place
simultaneously; designated SN2
S = substitution
N = nucleophilic
2 = bimolecular (two species are involved in the ratedetermining step)
rate = k[haloalkane][nucleophile]
10

SN2
both reactants are involved in the transition
state of the rate-determining step
the nucleophile attacks the reactive center
from the side opposite the leaving group
Inversion of configuration
H
HO

C
H

Br

HO

Br

HH

Transitionstatewith
simultaneousbondbreaking
andbondforming

HO C

Br

H
H

11

http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/
12

SN2

An energy diagram for an SN 2 reaction

there is one transition state and no reactive
intermediate

13

SN1
In the other limiting mechanism, bond
breaking between carbon and the leaving
group is entirely completed before bond
forming with the nucleophile begins
This mechanism is designated SN1 where
S = substitution
N = nucleophilic
1 = unimolecular (only one species is involved
in the rate-determining step)
rate = k[haloalkane]
14

SN1
SN1 is illustrated by the solvolysis of tertbutyl bromide
Step 1: ionization of the C-X bond gives a
carbocation intermediate
H3C
C

Br

slow,rate
determining

CH3
C+

Br

H3 C
H3 C

H3 C CH3

Acarbocationintermediate;
carbonistrigonalplanar

15

SN1
Step 2: reaction of the carbocation (an electrophile)
with methanol (a nucleophile) gives an oxonium ion
CH3
CH3 O

or

+ C+ + OCH3

H H3 C CH3

fast

H3 C
O
H

CH3
C

H3 C
or+

CH3
CH3

CH3
C O

H3 C
H3 C

Step 3: proton transfer completes the reaction

H3 C
H3C
H3 C

+
O

CH3
H

+ O

H
CH3

fast

H3C
H3 C
H3C

CH3
C O

+
+H O

CH163

http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/
17

SN1
An energy diagram for an SN1 reaction

18

SN1
For an SN1 reaction at a stereocenter, the
product is a racemic mixture
C6 H5
C

Cl

Cl
(R)Enantiomer

-Cl

C6 H5
C+
H

CH3 OH
-H

Cl
Planarcarbocation
(achiral)

19

SN1
the nucleophile attacks with equal probability
from either face of the planar carbocation
intermediate
C6 H5
C+
H

C6 H5
CH3 OH
+

-H

Cl
Planarcarbocation
(achiral)

C6 H5
+

CH3 O C
H

Cl
(S)Enantiomer

C OCH3
H

Cl
(R)Enantiomer

Aracemicmixture

20

Evidence for SN Reactions

What effect does
the structure of the nucleophile have on rate?
the structure of the alkyl halide have on rate?
the structure of the leaving group have on
rate?
the solvent have on the reaction mechanism?

21

Nucleophilicity
Nucleophilicity:
Nucleophilicity a kinetic property
measured by the rate at which a Nu
attacks a reference compound under a
standard set of experimental conditions
for example, the rate at which a set of
nucleophiles displaces bromide ion from
bromoethane in ethanol at 25C
CH3CH2Br + NH3

CH3CH2NH3

+ Br-

22

Nucleophilicity
Effectiveness Nucleophile
-

good

moderate

Br , I
CH3 S- , RSHO-, CH3 O-, ROO
O
CH3 CO-, RCOCH3 SH, RSH, R2 S
NH3 , RNH2 , R2 NH, R3 N

poor

H2 O
CH3 OH, ROH
O
O
CH3 COH, RCOH

An efficient nucleophile should be the conjugate base of a weak acid.

An efficient leaving group is the conjugate base of a strong acid

23

Structure of the alkyl halide

SN1 reactions
governed by electronic factors,
factors namely the
relative stabilities of carbocation intermediates
relative rates: 3 > 2 > 1 > methyl

SN2 reactions
governed by steric factors,
factors namely the relative
ease of approach of the nucleophile to the site
of reaction
relative rates: methyl > 1 > 2 > 3
24

Structure of the Haloalkane

Steric factors
compare access to the reaction center in
bromoethane and 2-bromo-2-methylpropane
(tert-butyl chloride)

25

Structure of the Haloalkane

Effect of electronic and steric factors in
competition between SN1 and SN2
reactions

26

The Leaving Group

the best leaving groups in this series are the
halogens I-, Br-, and Cl OH-, RO-, and NH2- are such poor leaving
groups that they are rarely if ever displaced in
nucleophilic substitution reactions
Rarelyactasleavinggroups
innucleophilicsubstitution
Greaterabilityasleavinggroup andeliminationreactions
O
I- > Br- > Cl- >> F- > CH3 CO- > HO- > CH3 O- > NH2 -

Greaterstabilityofanion;greaterstrengthofconjugateacid
27

Hang on! Why are Br- and I- both

good nucleophiles and good
leaving groups?
They are at the bottom of their group in the periodic table
and thus highly polarisable (soft).
This means their lone-pair electrons are very high in
energy.
This means that although they are poor bases, they can
lower the energy of the transition state for an SN2
reaction.
Bottom line: using the analogy of basicity and
nucleophilicity works well when comparing variants of the
same atom (CH3O- vs HCOO-), but not so well when
comparing compact atoms such as O,N,F with large
polarisable atoms such as I, Br.
28

The Solvent
Protic solvent:
solvent a solvent that can donate a
hydrogen bond (e.g. contains OH)
these solvents favor SN1 reactions; the
greater the polarity of the solvent, the easier it
is to form carbocations in it
Protic
Solvent
Water
Formicacid
Methanol
Ethanol
Aceticacid

Structure
H2 O
HCOOH
CH3OH
CH3CH2OH
CH3COOH

Polarity
ofSolvent

29

The Solvent
Aprotic solvent:
solvent cannot donate a hydrogen
bond
it is more difficult to form carbocations in
aprotic solvents
aprotic solvents favor SN2 reactions
Aprotic
Solvent

Structure

Polarityof
Solvent

O
Dimethylsulfoxide CH3 SCH3
(DMSO)
O
CH3 CCH3
Acetone
Dichloromethane
Diethylether

CH2 Cl2
(CH3 CH2 )2 O

30

Summary of SN1 and SN2

Typeof
Haloalkane

SN 2

SN 1
SN 1doesnotoccur.Themethyl
cationissounstablethatitis
neverobservedinsolution.

Methyl
CH3 X

SN 2isfavored.

Primary
RCH2 X

SN 2isfavored.

SN 1doesnotoccur.Primary
carbocationsaresounstablethat
theyareneverobservedinsolution.

Secondary
R2 CHX

SN 2isfavoredinaprotic
solventswithgood
nucleophiles.

SN 1isfavoredinproticsolvents
withpoornucleophiles.

Tertiary
R3 CX

SN 2doesnotoccurbecause
ofsterichindrancearound
thesubstitutioncenter.
Substitution Inversionofconfiguration.
ata
Thenucleophileattacks
stereocenter thestereocenterfromthe
sideoppositetheleaving
group.

SN 1isfavoredbecauseoftheeaseof
formationoftertiarycarbocations.
Racemization.Thecarbocation
intermediateisplanar,andattackby
thenucleophileoccurswithequal
probabilityfromeitherside.
31

Nucleophilic Substitution
Examples: predict the product of each reaction, the mechanism, and the
stereochemistry of the product

Cl
+ CH3OH

1.

CH3OH

+-

Br + Na I

2.

DMSO

Br
3.

+ CH3S- Na+

acetone

Br
4.

Na+SH-

acetone

32