SECTION 6: SATURATED
HETEROATOM COMPOUNDS
(STUDENT MANUAL, PAGES 34–44)
BONDS ARE POLARISED. TWO CLASSES:
1. —C—–M
e.g.
2. —C—–X
Most important functional groups:
a. R—Hal (F, Cl, Br, I)
b. (H—O—H)
R—O—H
R—O—R'
c. (H—S—H)
R—S—H
R—S—R'
H
d. H N H
H
R N H
R'
R N H
R'
R N R"
1
Also note:
H
H C OH
H
CH3
H C OH
H
CH3
H C OH
CH3
CH3
H3C C OH
CH3
REMINDERS FROM FIRST YEAR:
Reactivity of the C—X bond is due to:
1. BOND POLARISATION
—C—–X
—C—–M
Reacts with:
2. LONE PAIRS ON X (or empty orbitals on M)
Leads to acid–base behaviour
3. BOND STRENGTHS
C—X is weaker than C—H
C—Cl
C—O
C—N
2
ACID–BASE PROPERTIES
1. BEHAVIOUR AS ACIDS:
H
CH3
CH3
O
O
O
H
+
B:
H
+
B:
HO–
+
BH+
NH2–
+
BH+
CH3 + B:
+
B:
RNH2 +
B:
NH3
HO–H + Na
H2 + Na+OH–
CH3O–H + Na
3
2. BEHAVIOUR AS BASES:
:
:
O
CH3
H
H3C
O
+
H+ X–
+ –
+
H
X
CH3
:
:
H
:
CH3
O
H+ X–
N
H
H
+
H+ X–
CH3
N
+
CH3
H+ X–
NH4+ X–
:
:
H
:
H
+
H
O+
H H
4
TYPICAL REACTIONS OF
COMPOUNDS WITH C—X BONDS
H
H
H
C
C
H
H
Br
SUBSTITUTION:
H
H
H
C
C
H
H
Br
ELIMINATION:
H
N.B.: substitution and
compete with each other!
H
H
C
C
H
H
Br
elimination
always
5
COMPETITION BETWEEN SN AND E
1) EFFECT OF Nu:
THE MORE BASIC THE Nu, THE MORE
CHANCE OF ELIMINATION
(i.e., ATTACK AT H+ RATHER THAN AT C+)
OH–
versus
H2O
H2O
versus
NH3
2) SIZE EFFECTS:
SN:
E:
ATTACK IS AT C
ATTACK IS AT H
 ANY STERIC HINDRANCE FAVOURS E
 BULKY Nu
 CROWDED C+ SITE
3) HIGHER TEMPERATURE FAVOURS E
FROM G = H – TS
6
FURTHER ASPECTS OF
NUCLEOPHILIC SUBSTITUTION
R3C—L + :Nu
R3C—Nu + :L
In principle, this process is reversible.
To favour the forward SN reaction:
 A good nucleophile should be a poor leaving
group; and
 A good leaving group should be a poor
nucleophile.
What makes a nucleophile “good”?
 A good nucleophile tends to be a good base.
e.g. OH–
e.g. (CH3)2NH
H2O
CH3O–
CH3NH2
CH3OH
NH3
Less clear cases, e.g. CH3O– vs CH3CO2–:
Look at their conjugate acids: stronger acid
implies weaker conjugate base.
7
 Going down a group in the periodic table gives
better nucleophiles (lower electronegativity;
atoms can “donate” electrons more readily).
HS–
R3P:
HO–
R3N:
H2S
I–
H2O
Br–
Cl–
For the reaction CH3–Br + Nu– → CH3–Nu + Br–
Nu
H2O NH3
ClOH– CH3O–
I–
SH–
Relative
1
700
1000 16000 25000 100000 125000
reactivity
Taken from McMurry, 6th edition, page 353
What makes a leaving group “good”?
 As above: poor Nu usually means good L; but
 The weaker the C—L bond, the better the
leaving group.
CH3—OH
CH3—Cl
CH3—Br
CH3—I
Note the oddity: I– is one of the best nucleophiles, but also one
of the best leaving groups!
 For anions, the weakest bases (i.e., derived
from the strongest acids) are the best leaving
groups.
R—OSO2R' + OH–
R—OH + –OSO2R'
8
 Stabilised anions are better leaving groups
than unstabilised anions.
O
–
O S R'
O
For the reaction CH3–L + Nu– → CH3–Nu + L–
L–
OH–
Cl–
Br–
I–
R'SO2O–
Relative <<1
200 10000 30000 60000
reactivity
Taken from McMurry, 6th edition, page 354
 One can change some poor leaving groups into
better leaving groups by modifying them.
e.g. CH3–OH + NaBr → CH3–Br + NaOH
Activate the leaving group with H+: use HBr
instead of NaBr:
: :
CH3 OH
H+ Br–
9
NUCLEOPHILIC SUBSTITUTION
(SN) REACTIONS: MECHANISMS
REACTION MECHANISMS ARE DETAILED
DESCRIPTIONS OF:

THE EVENTS THAT OCCUR DURING
CHEMICAL REACTIONS;

THE ORDER IN WHICH BONDS ARE
BROKEN AND FORMED;

THE RELATIVE RATES OF DIFFERENT
STEPS IN THE REACTION;

STEREOCHEMICAL FEATURES.
TWO MAIN MECHANISMS FOR SN
REACTIONS:
SN 1
SN 2
10
R3C—Br + OH–
→
R3C—OH + Br–
SN1
SN2
TIMING
L LEAVES BEFORE
Nu ATTACKS
Nu ATTACKS, L LEAVES
SIMULTANEOUSLY
KINETICS AND RATE LAW
UNIMOLECULAR
BIMOLECULAR
11
ENERGY PROFILE
Energy
Energy
reaction
reaction
STEREOCHEMISTRY
12
EFFECT OF STRUCTURE
IMPORTANCE OF C+: DIRECTION OF Nu
APPROACH IS N.B.
EFFECT OF Nu STRENGTH
EFFECT OF LEAVING GROUP
EFFECT OF SOLVENT
13
FURTHER ASPECTS OF BASEINDUCED ELIMINATION
IN SN REACTIONS, Nu ATTACKS CARBON
IN ELIMINATIONS, Nu ATTACKS HYDROGEN
Nu–
H
CH2 CH2
Br
DEPENDING ON REACTANT’S STRUCTURE,
DIFFERENT PRODUCTS ARE POSSIBLE
CH3
CH3CH CHCH3
CH3CH2 CHBr
CH2
CH3CH2 CH
Preferences?
14
CAN MODIFY POOR LEAVING GROUPS TO
FACILITATE REACTION (same as with SN).
e.g.
OH
base
–H2O
OH
MECHANISMS OF E REACTIONS
TWO MAIN MECHANISMS:
E1
E2
15
THE E1 MECHANISM:
LEAVING GROUP LEAVES BEFORE THE
BASE ATTACKS (similar to SN1)
H
C
C
L
SIMILAR ARGUMENTS TO SN1 FOR:

KINETICS

SOLVENT EFFECTS

STRUCTURAL EFFECTS: more chance of
E1 mechanism with
16
THE E2 MECHANISM:
BASE ATTACKS H, L LEAVES SIMULTANEOUSLY, i.e. CONCERTED (similar to SN2)
BUT NOTE STEREOCHEMICAL CONDITION:
H AND L MUST BE ALIGNED
H
C
C
L
because orbitals must overlap to make the  bond:
H
C
C
L
KINETICS:
17
AN EXAMPLE OF E1 versus E2
Br
OH–
H3C
IF E1 operates:
Br
H3C
IF E2 operates:
Br
H3C
18
ALTERNATIVE ELIMINATIONS
H
H3C
O
H
C
H
H
H
O
H
C
C
H
H
H
H3C
O
H
C
H
CH3
H3C
O
H
C
CH3
CH3
19
ORGANOMETALLICS
—C—–M
PREPARATION: by exchange with halides
REACTIVITY:
20