1. NUCLEOPHILIC SUBSTITUTION REACTIONS
HL Organic Chemistry:
NUCLEOPHILIC
SUBSTITUTION
REACTIONS

2. Types of Halogenoalkanes
methyl primary secondary tertiary
The carbon attached to the halogen determines
whether the haloalkane is considered:
methyl [only hydrogens]
primary (1°) [one methyl or alkyl]
secondary (2°) [two methyls or alkyls]
tertiary (3°) [three methyls or alkyls]

3. SUBSTITUTION REACTIONS
One group takes the place of another. Y + R X R Y + X
Y takes the place of X ( Substitution )
Y “displaces” X

4. NUCLEOPHILIC SUBSTITUTION
NUCLEOPHILIC DISPLACEMENT
leaving
group
substrate
nucleophile
product
The nucleophile “displaces” the leaving group.
This is a “substitution” reaction :
Nu substitutes for X (takes its place).

5. EXAMPLE 1 * (s) soluble insoluble iodide displaces bromide at carbon *
NaI is soluble in acetone, NaCl and NaBr are not

6. EXAMPLE 2 solvolysis of t-butyl chloride in water3 E1
competes
EXAMPLE 2
solvolysis of t-butyl chloride in water
water displaces chloride at carbon *
The extra proton is taken by a second water molecule.

7. DISPLACEMENT REACTIONS
NUCLEOPHILIC SUBSTITUTION REACTIONS
( substitution at carbon )
can be compared to …..
ACID-BASE REACTIONS
( substitution at hydrogen )

8. COMPARE THESE SUBSTITUTIONS
DISPLACEMENT AT CARBON
nucleophile
substrate
product
leaving
group
DISPLACEMENT AT HYDROGEN
base
acid
conjugate
acid
conjugate
base

9. THESE REACTIONS HAVE A
WIDE RANGE OF SUBSTRATES

10. COMMON SUBSTRATES ( Leaving group varies ) alkyl halides alcohols
require acid
and then
H2O leaves
tosylates
ABBREVIATION
alkyl p-toluenesulfonate

11. WIDE RANGE OF NUCLEOPHILES
THERE ARE ALSO A
WIDE RANGE OF NUCLEOPHILES
A WIDE VARIETY OF COMPOUNDS CAN BE MADE

12. NUCLEOPHILES Nucleophile Product Class alkyl halides alcohols ‘ ‘
A WIDE SELECTION OF NUCLEOPHILES MAKES POSSIBLE THE SYNTHESIS
OF MANY TYPES OF ORGANIC COMPOUNDS:
R-Y + Nu R-Nu Y
Nucleophile
Product
Class R X
alkyl halides
alcohols R O H ‘ ‘ R O R
ethers R C N
nitriles O
esters R ' C O R R ' C C R
alkynes R S H
thiols

13. THE NUCLEOPHILE DOES NOT HAVE TO BE CHARGED+ - H O + R B r H O R + B r H H O H
Under some circumstances
water will react. H + - H O R + H O + B r 3
Nucleophile
Product
Class R O H
alcohols ‘ ‘
ethers R O R
amines R N H 2
amines R ' N H R

14. REACTION 1
THE SN2 REACTION

15. SN2 - rate = k2 [RBr] [NaOH] bimolecular concerted substitution
55oC
rate = k2 [RBr] [NaOH]
k2 = liter/mole-sec -
bimolecular
concerted
SN2
substitution
nucleophilic
bimolecular

16. SN2 Concerted (one step) reaction Concerted (one step) reaction
transition
state TS
SN2 E N E Ea R G Y
starting D H
material
product

17. REACTION 2
THE SN1 REACTION

18. SN1 rate = k1 [RBr] unimolecular two steps slow fast substitution
55oC
rate = k1 [RBr]
k1 = liter/mole-sec
unimolecular
two steps
slow
SN1
fast
substitution
also
alkene (via E1)
nucleophilic
unimolecular

19. SN1 TWO STEP REACTION carbocation intermediate TS E TS N E Ea R G Ea Y2 N E Ea 2 R G Ea 1 Y
starting
step 1
step 2 D H
material
product

20. TWO SUBSTITUTION REACTIONS
A QUICK SUMMARY OF
TWO SUBSTITUTION REACTIONS
SN1 / SN2

21. SN2 RBr + NaOH ROH + NaBr 1) First Case rate = k2 [RBr] [NaOH]
Two similar reactions,
different kinetics.
RBr + NaOH ROH + NaBr 1)
First Case
55oC
methyl
SN2
rate = k2 [RBr] [NaOH]

22. 2)
Second Case
55oC
tertiary
SN1
rate = k1 [RBr]

23. MANY PARAMETERS INFLUENCE
NUCLEOPHILIC SUBSTITUTION

24. NUCLEOPHILIC SUBSTITUTION
MANY FACTORS INFLUENCE SN1 AND SN2 REACTIONS
SOME PARAMETERS :
a) solvent
b) temp.
c) pH
d) DH
a) structure
a) structure of R,
stereochemistry
a) bond strength
a) nature of X
b) atom used
b) atom used
b) concentration
c) concentration
c) base strength
c) bond strength
d) base strength
e) solubility
f) size

25. STRUCTURE OF THE SUBSTRATE
SN1

26. SN1 - SUBSTRATE AND CARBOCATION
slow
R-X R+ X- + R+
Nu-
R-Nu +
fast
The energy of the carbocation
intermediate is an important
factor for an SN1 reaction.
The better ion
will have the
lower energy
pathway.
3o < 2o < 1o

27. SOLVOLYSIS OF tert-BUTYL BROMIDE
acetone
SN1

28. SOLVOLYSIS OF t-BUTYL BROMIDE
tertiary
+ H3O+
+ Br-

29. EFFECT OF INCREASING SUBSTITUTION - SN1
100%
RBr + H2O
ROH HBr
HCOOH
methyl primary secondary tertiary
108
1.0
1.7 45
Guess ?
relative
rate
increasing rate
rate
rel rate =
rate CH3Br
EFFECT OF SUBSTRATE ON RATE

30. STRUCTURE OF THE SUBSTRATE
SN2

31. SN2 - SUBSTRATE .. R H O : .. C : Br R R H O : .. H C : Br H H
large groups
introduce steric
hindrance .. C : Br R R H O : .. H
easy access
no steric
hindrance C : Br H H

32. EFFECT OF DEGREE OF SUBSTITUTION - SN2
methyl primary secondary tertiary
150 1
0.01
0.001
decreasing rate
rel rate =
rate EtBr
rate
EFFECT OF SUBSTRATE ON RATE

33. EFFECT OF BULKY SUBSTITUENTS - SN2
( substitution on the a carbon )
NEOPENTYL
slower than
t -butyl a a a a 17 1
0.03
3 x 10-6
decreasing rate
rel rate =
rate EtBr
rate
ALL ARE PRIMARY !

34. Summary for Substrates
Notice that benzyl
and allyl are good
for both SN1 and SN2
SN1
SN2
(fastest)
tertiary
methyl
(fastest)
BEST
BEST
benzyl
benzyl
allyl
allyl
secondary
primary
primary
secondary
WORST
bridgehead
tertiary
(slowest)
(bicyclic)
neopentyl
APPROXIMATE
RATE ORDERS
bridgehead
WORST
(bicyclic)
(slowest)

35. IS THE NUCLEOPHILE IMPORTANT
IN BOTH SN1 AND SN2 REACTIONS ?

36. SN1 rate = K1 [RX] SN2 rate = K2 [RX][Nu] NUCLEOPHILES
IMPORTANCE IN SN1 AND SN2 REACTIONS
Nucleophiles are unimportant in an SN1 reaction;
they are not involved in the rate-determining step.
SN1 rate = K1 [RX]
The nature of a nucleophile is only important to
an SN2 reaction.
SN2 rate = K2 [RX][Nu]

37. WHAT IS A
GOOD NUCLEOPHILE ?
SN2 REACTIONS

38. .. : Y WHAT IS THE IDEAL NUCLEOPHILE ? R : .. C : Br R R - X
SN2 REACTIONS Y : ..
LARGE
STERIC PROBLEMS
no way ! bad R
SMALL : .. X - C : Br
good R R
Smaller
is better !
For an SN2 reaction the nucleophile must find
the back lobe of the sp3 hybridized orbital to
which the leaving group is bonded.

39. EXPECTED “IDEAL” NUCLEOPHILES
cyanide -
ROD OR SPEAR
SHAPED
:C N: - + -
:N N N:
azide
SMALL
SPHERES
These types
should be
able to find
the target ! ..
:F:
:Cl: .. - -
etc.
Generally this idea is correct.

40. OUR EXPECTATION ……. - - - - F Cl Br I
We would expect the halides to be good nucleophiles:
ionic radii:
1.36 A A A A
smallest
ion - - - - F Cl Br I
and we would expect the smallest one (fluoride)
to be the best nucleophile,
….. however, that is not usually the case.

41. SN2 CH3-I + NaX CH3-X + NaI Rate = k [CH3I] [X-] k slowest fastest F-
RELATIVE RATES OF REACTION FOR THE HALIDES
MeOH
CH3-I + NaX
CH3-X + NaI
Rate = k [CH3I] [X-]
SN2 k F-
5 x 102
slowest
Cl-
2.3 x 104
Br-
6 x 105
fastest I-
2 x 107
* MeOH solvates like water but dissolves everything better.

42. COMPETITIVE NUCLEOPHILES

43. SN1 REACTIONS - - - IN SN1 REACTIONS ALL NUCLEOPHILES REACT
EQUALLY WELL
HOH, H+ .. -
solvolysis +
:Br: ..
slow .. -
:Cl: .. .. -
: I : ..
All react equally with the
carbocation. The amounts of
RCl, RBr and RI reflect their
starting concentrations in
the solution.

44. SN2 REACTIONS - - - FOR SN2 REACTIONS, THE SIZE AND NATURE OF
THE NUCLEOPHILE IS IMPORTANT - Cl - - Br I
Different amounts of
RCl, RBr, and RI are found
even when they are equi-
molar in the original solution.

45. THE BOTTOM LINE
SN1
CARBOCATIONS REACT WITH ALL NUCLEOPHILES EQUALLY
The nucleophile is not involved in the rate-determining step.
SN2
BETTER NUCLEOPHILES REACT FASTER GIVING MORE PRODUCT
The nucleophile is involved in the rate-determining step.

46. HOW CAN YOU TELL IF IT IS SN1 OR SN2 ?
1) LOOK FIRST AT THE NUCLEOPHILE
You cannot do a reasonable SN2 reaction without a good Nu.
If you have a poor nucleophile, SN1 is probable.
2) NEXT CHECK THE SUBSTRATE
Primary is bad for SN1 …..
Tertiary is bad for SN2
3) FINALLY LOOK AT THE SOLVENT
SN2 is best in nonpolar and polar aprotic solvents, but can also
happen in water or EtOH.
SN1 needs a polar solvent.

47. * SOME HELPFUL HINTS ! DECISION CHART
LOOK FIRST AT THE NUCLEOPHILE, THEN THE SUBSTRATE
GOOD NUCLEOPHILE *
Good Nucleophile in high concentration = SN2
unless it is a strong base
however, 1o substrates
can give SN2 at low T
RO-
HO-
H2N-
…. however, SN2 needs a 1o or 2o
substrate (or 1o benzylic) not 3o
SUBSTRATE
…. prefers a nonpolar solvent
but will proceed even in a
polar solvent (aprotics best)
SOLVENT
strong bases like
all substrates with
a beta hydrogen
(anti-coplanar)
3o >> 2o > 1o
STRONG
BASE

48. * SOME HELPFUL HINTS ! DECISION CHART
LOOK FIRST AT THE NUCLEOPHILE, THEN THE SUBSTRATE
POOR NUCLEOPHILE *
Poor nucleophile (solvolysis) = SN1
or low concentration
…. however, the
substrate needs
to be 3o or benzylic
or allylic (or 2o)
SUBSTRATE
…. also, in SN1 the
carbocation needs a
reasonably polar solvent
SOLVENT
watch for rearrangements
REARRANGEMENT

49. Summary of material you
MUST know for the
HL Chemistry exam

50. IB Style Rxn Pathways
Haloalkanes are the starting reactants for all substitution reactions
SN1 uses slow heterolytic cleavage of the carbon – halogen bond to form a carbocation intermediate as the rate limiting step
The intermediate then reacts rapidly with a nucleophile (Nu-) to form the final product
The energy profile for an SN1 reaction shows two humps in the reaction pathway (see slide)
You MUST USE CURLY ARROWS to show this process for IB exam credit!

51. SN1 General Example
L = “Leaving Group” (in this case a halogen)

52. SN1 General Example (IB Version)

53. SN1 NaOH Example (IB)

54. SN1 TWO STEP REACTION carbocation intermediate TS E TS N E Ea R G Ea Y2 N E Ea 2 R G Ea 1 Y
starting
step 1
step 2 D H
material
product

55. IB Style Rxn Pathways
The SN2 reaction involves the simultaneous breaking of the carbon-halogen bond and the formation of the carbon-nucleophile bond
The transition state has a 5 bonded metastable carbon complex which releases the halogen while the covalent bond to the nucleophile remains
Again, you must be able to use CURLY ARROWS to write out this mechanism

56. SN2 General Example
The halogen is a specialized case of a “leaving group” (L)
Note the 5 bonded carbon in the single step mechanism transition state
The double cross on the center diagram is the symbol for transition state
The energy profile only has a single curve

57. SN2 General Example (IB)

58. SN2 NaOH Example (IB)

59. SN2 Amine Example (IB)

60. SN2 Nitrile Example (IB)

61. SN2 Concerted (one step) reaction Concerted (one step) reaction
transition
state
SN2 E N E Ea R G Y
starting D H
material
product

62. Summary of IB SN Information (1)
Slightly positive charged carbons are attacked by negative nuclophiles
Primary halogenoalkanes react via SN2
Rate = k[R-X][OH]
Tertiary halogenoalkanes react via SN1
Rate = k[R-X]
Secondary halogenoalkanes can react via either route, and will probably not be asked on the DP exam

63. Summary of IB SN Information (2)
As the halogen changes from Cl→ Br→ I, carbon-halogen bond polarity decreases, whereas reaction rate increases
SN1 reactions occur faster than SN2
The rate of reaction for halogenoalkanes is:
Tertiary > Secondary > Primary
Nitriles can be converted into: (1) amines using hydrogen gas (with a nickel catalyst) or (2) carboxylic acids using an acid (typically HCl)

64. 20.2.6: Reactions of Nitriles (IB)

65. Words to the Wise
You have just seen the minimum you need to know about Nucleophilic Substitution Reactions in this mini-review
Read your IB Text Book and review material.