NUCLEOPHILIC SUBSTITUTION AND ELIMINATION
A STUDENT WHO HAS MASTERED THE MATERIAL IN THIS SECTION SHOULD BE
ABLE TO:
1.
Define, recognize, and give examples of each of the following terms:
Nucleophilic substitution, elimination, substrate, nucleophile, leaving group
SN1, SN2, E1, and E2 reactions; rate-determining step
Retention, inversion, racemization (reaction stereochemistry)
Polar and nonpolar, protic and aprotic solvents
2.
Predict the product or products of nucleophilic substitution and elimination reactions,
including the stereochemistry where appropriate. Note that the statement of the problem
will usually not say which of the reaction types is occurring in any individual case.
In the presence of a strong base/nucleophile, SN2 and E2 reactions are favored over SN1 and
E1. When the base/nucleophile is strong, SN2 is favored over E2 when the substrate is
methyl or 1˚. The opposite is true when the substrate is 2˚ or 3˚; in those cases E2 is
favored (no SN2 reactions occur in 3˚ substrates). Exception: If the base/nucleophile is the
very bulky tert-butoxide anion, E2 reactions occur even in 1˚ substrates.
If the base/nucleophile is weak, substitution is favored. The substitution is SN2 in methyl
and most 1˚ and 2˚ substrates, and is SN1 in most 3˚ substrates. E1 reactions are usually
very minor pathways in real substitution and elimination reactions.
High temperatures favor elimination, both E2 and E1, over substitution. Polar aprotic
solvents such as dimethyl sulfoxide (DMSO or CH3 SOCH 3 ) strongly accelerate SN2
reactions.
3.
From your knowledge of the mechanism, predict and interpret experimental results for the
SN1, SN2, E1, and E2 reactions. Be prepared to draw mechanisms with arrows that show
electron movement. For a summary of important factors that influence reaction rates, see
the study guide on the next page.
4.
Given a reaction coordinate diagram, identify transition states and reactive intermediates, and
calculate activation energies and enthalpies of reaction.
5.
Propose syntheses using these reactions and those learned earlier.
(For a summary of the factors that affect the rates of these reactions see the next page.)
58
Factors Affecting The Rates Of Reactions:
Alkyl group (in the substrate): SN2 reactions are fastest in CH3 substrates; rates are: CH3 > 1˚ >
2˚ >> 3˚ (this is a steric effect; larger groups interfere with the approaching nucleophile). SN1 and
E1 reactions are faster in 3˚ substrates (because the more stable the carbocation, the faster the
reaction; this means 3˚ > 2˚ >> 1˚ > CH3 ). E2 reactions are also faster in 3˚ substrates. Vinylic
(R2 C=CR—) and aromatic substrates are unreactive in all four reaction types.
Leaving groups: All of these reactions are faster when the leaving group is a weak base. For the
alkyl halides as leaving groups, the resulting order is I– > Br– > Cl– >> F–.
Nucleophile: SN2 and E2 reactions are usually faster when a strong base/nucleophile is used (there
are some solvent effects on this). Base/nucleophile identity and concentration has no effect on the
rates of SN1 and E1 reactions.
Temperature: High temperatures increase the rates of all reaction types by increasing both the
collision frequency and the energy factor.
Solvent: Polar protic solvents give faster SN1 and E1 reactions; polar aprotic solvents such as
DMSO give faster SN2 reactions.
Reactant concentration: The reaction rate is directly proportional to substrate concentration for all
reaction types. For SN2 and E2 reactions, the rate is also proportional to the nucleophile/base
concentration. For SN1 and E1 reactions, base/nucleophile concentration has no effect on reaction
rate at all.
59
A STUDENT WHO HAS MASTERED THE OBJECTIVES ON THE PREVIOUS PAGES
SHOULD BE ABLE TO SOLVE THE FOLLOWING PROBLEMS AND RELATED ONES:
1.1
Identify the substrate, the nucleophile, and the leaving group in each of the following
reactions.
a) CH3 CH2 Br + CH3 S– ---> CH3 CH2 SCH 3 + Br–
b) (CH3 )2 CHCH 2 OSO 2 F + NH3 ---> (CH3 )2 CHCH 2 NH 3 + + FSO3 –
1.2
Characterize each of the following reactions as proceeding with retention, inversion, or
racemization. What reaction type is each (SN1, SN2)?
a)
H
H
CH3
Br
+ NH 3 ---> Br
+
H
H3 N
CH3
H
(CH3 )2 CH
(CH3 )2 CH
(CH3 )2 CH
CH3
CH3
OH
C I
+ H2 O ---> HI +
C
OH + C
CH3
|
|
|
CH2 CH3
CH2 CH3
CH2 CH3
b)
c)
1.3
+ OH - ---> Cl- +
H
H
CH3
CH2 CH2 CH2 Cl
H
CH3 CH2 CH2 CH2 OH
Which of the following is a protic solvent?
a) CH3 CH2 CH2 CH2 CH3 b) CH3 SOCH 3
2.
H
O
||
c) CH3 CH2 OH d) HC-N(CH3 )2
Predict the major organic product of each of the following reactions.
a) CH3 CH2 CH2 Br + CH3 NH 2 --->
b) CH3 I + (C6 H5 )3 P --->
60
2. Predict the product (continued)
(CH3 )3 COH
c) (CH3 )3 CBr + (CH3 )3 COK ---------------->
alcohol, heat
d)
3.1
Br + KOH
Provide curved mechanism arrows for each of the following reactions.
a) CH3
H
H +
C
C
CH3
Br
b) CH3 CH2
OH
SN2
OH ------>
H
H
+ Br
CH3
SN1
C CH2 CH2 CH3 -------> CH3 CH2
CH3
+ Br
CH2 CH2 CH3
C
Br
CH3 CH2
C
CH3
CH3
O
+ CH3 OH --->
CH2 CH2 CH3
C
CH3 CH2
CH3
O
C
CH3 CH2
c) CH3
H
Br
H
|
CH2 C
CH3
E1
------>
CH3
O
C
CH2 CH2 CH3
CH3
CH3
C CH3
CH3
+ CH3 OH --->
CH3 CH2
C
61
CH2 CH2 CH3
CH3
+ CH3 OH 2
CH2 CH2 CH3
CH3
CH3
+ Br
CH3
+ CH3 OH ---> CH2
CH3
H
C
CH3
CH3
+ CH3 OH 2
H
|
d) CH2
CH3
C CH3 +
E2
OC(CH3 )3 ------> CH2
CH3
C
CH3
+ HOC(CH3 )3
+ Br
Br
3.2
water
Consider the reaction CH3 CHBrCH 3 + NH3 ----------> CH3 CHOHCH3 + Br– .
ethanol
What is the effect on the rate of the reaction if each of the following changes is made? Possible
answers: increases, decreases, remains the same.
IF THE RXN.
IS SN1
CHANGE
|
|
|
Use CH 3 CHICH 3 instead of CH3 CHBrCH 3 |
|
–
Use NH2 instead of NH3
|
|
Increase the concentration of CH3 CHBrCH 3 |
|
Decrease the concentration of NH3
|
|
|
|
|
|
|
|
|
|
|
|
|
Use CH 3 CH2 Br instead of CH3 CHBrCH 3
4.1
IF THE RXN.
IS SN2
|
|
|
|
|
|
|
|
|
|
|
In the reaction coordinate diagram shown: (a) What point(s) represent(s) transition states?
(b) What point(s) is(are) reactive intermediates?
B
D
C
A
E
Energy
Reaction coordinate
62
4.2
Answer the following questions using
the reaction coordinate diagram shown.
50
a) What is Eact of A ---> B?
40
b) What is Eact for B ---> A?
c) What is ∆ H for A ---> B?
Potential
Energy, 30
Kj / mole
20
10
d) What is ∆ H for B ---> A?
0
5
A
B
Reaction coordinate
Propose syntheses of each of the compounds shown, from the given starting materials and
any other needed reagents.
a) CH3 CH2 NH 2 from CH3 CH2 Br
b)
OCH 2 CH3 from CH3 CH2 Br
c) CH3 CH2 NH 2 from CH3 CH3
63
ANSWERS TO THE PROBLEMS:
1.1
a) CH3 CH2 Br is the substrate, CH3 S– is the nucleophile, Br– is the leaving group
b) (CH3 )2 CHCH 2 OSO 2 F is the substrate, NH3 is the nucleophile, FSO3 – is the
leaving group.
1.2
a) Inversion (at the reacting C, retention at the other stereocenter); SN2
b) Racemization, SN1
c) Retention (at the stereocenters, reacting carbon inverts); SN2
1.3
Compound (c) is a protic solvent.
2.
a) CH3 CH2 CH2 Br + CH3 NH 2 ---> CH3 CH2 CH2 NH 2 CH3 + Br– (SN2)
+
+
b) CH3 I + (C6 H5 )3 P ---> (C6 H5 )3 PCH 3 + I– (SN2)
(CH3 )3 COH
c) (CH3 )3 CBr + (CH3 )3 COK ---------------> (CH3 )2 C=CH 2 + (CH3 )3 COH + KBr
(E2)
alcohol, heat
d)
3.1
Br + KOH
+ KBr + H2 O
Curved mechanism arrows:
a) CH3
H
H +
C
Br
OH
SN2
OH ------>
C
CH3
64
H
H
+ Br
(E2)
b) CH3 CH2
CH3
SN1
C CH2 CH2 CH3 -------> CH3 CH2
CH3
+ Br
CH2 CH2 CH3
C
Br
CH3 CH2
C
CH3
CH3
O
+ CH3 OH --->
CH2 CH2 CH3
C
CH3 CH2
CH3
O
C
CH3 CH2
c) CH3
H
E1
------>
CH3
O
CH2 CH2 CH3
CH3
CH3 CH2
C
CH2 CH2 CH3
CH3
+ CH3 OH 2
C
CH2 CH2 CH3
CH3
CH3
C CH3
CH3
+ CH3 OH --->
H
CH3
+ Br
CH3
Br
H
|
CH2
C
CH3
+ CH3 OH ---> CH2
C
CH3
d)
H
|
CH2
CH3
C CH3 +
E2
OC(CH3 )3 ------> CH2
CH3
+ CH3 OH 2
CH3
C
CH3 + HOC(CH3 )3
CH3
+ Br
Br
3.2
CHANGE
IF THE RXN.
IS SN1
|
|
decreases
|
Use CH 3 CHICH 3 instead of CH3 CHBrCH 3 |
increases
|
Use NH2 – instead of NH3
| remains the same
|
Increase the concentration of CH3 CHBrCH 3 |
increases
|
Decrease the concentration of NH3
| remains the same
|
Use CH 3 CH2 Br instead of CH3 CHBrCH 3
65
IF THE RXN.
IS SN2
|
|
|
|
|
|
|
|
|
|
|
increases
increases
increases
increases
decreases
|
|
|
|
|
|
|
|
|
|
|
4.1
a) B and D are transition states.
b) C is a reactive intermediate.
4.2
a)
b)
c)
d)
5.
a) CH3 CH2 NH 2 from CH3 CH2 Br
Eact for A ---> B = 20 kj/mole
Eact for B ---> A = 30 kj/mole
∆H for A ---> B = -10 kj/mole
∆H for B ---> A = +10 kj/mole
Simple way, on paper: CH3 CH2 Br + NH2 – ---> CH3 CH2 NH 2 + Br– (SN2)
Better way in the lab: CH3 CH2 Br + NH3 ---> CH3 CH2 NH 3 + + Br– (SN2)
then: CH3 CH2 NH 3 + + OH– ---> CH3 CH2 NH 2 + H2 O (acid-base)
b)
OCH 2 CH3 from CH3 CH2 Br
CH3 CH2 Br +
O-
----->
OCH 2 CH3 + Br-
c) CH3 CH2 NH 2 from CH3 CH3
CH3 CH3 + Br2 /light ---> CH3 CH2 Br + HBr
then CH3 CH2 Br + NH2 – ---> CH3 CH2 NH 2 + Br–
(see problem 5a above)
66
Name ___________________________________________________ Sixth Drill Test (Sample)
Organic Chemistry 2210DR
Answer All Questions
1)
Consider the reaction (CH3 CH2 )2 CHCl + CH3 OH ---> (CH3 CH2 )2 CHOCH 3 + Cl – .
What is the effect of each of the given changes on the rate of the reaction? Possible
answers: increases, decreases, remains the same.
| Effect if rxn.
| Effect if rxn.
|
Change
|
is SN2
|
is SN1
|
|
|
|
–
Use CH 3 O , not CH3 OH
|
|
|
|
|
|
Use (CH 3 CH2 )2 CHOH, not (CH3 CH2 )2 CHCl
|
|
|
|
|
|
Increase the concentration of CH3 OH
|
|
|
|
|
|
Use (CH 3 CH2 )3 CCl, not (CH3 CH2 )2 CHCl
|
|
|
|
|
|
2)
Consider the reaction shown.
What is the mechanism of this
reaction? Use the data at right.
E1
3)
E2
SN1
Br + KOH ---> KBr + H2 O +
SN2
[RBr]
0.01
0.02
0.01
What are the values of
a) ∆H and b) EACT for the
reaction A
B? Use the
reaction diagram shown.
a)
4
3
Energy,
kj/mole
b)
4)
2
1
relative rate
1
2
2
B
A
0
Predict the major organic product or products of each of the following reactions.
a)
CH3 CH2 CH2
Br
H
C
|
CH3
b)
5)
[KOH]
0.01
0.01
0.02
Br
SN2
+ H 2 O ------->
heat
+ KOH ------->
Propose a synthesis of (CH3 )2 CHOCH 2 CH3 from CH3 CH2 Br and any other needed
reagents.
67
Name ___________________________________________________ Sixth Drill Test (Sample)
Organic Chemistry 2210 DR
Answer All Questions
1.
Draw the structure of the product or products of each of the following reactions. You must
show the three-dimensional structure where appropriate.
a)
H
I
CH3
NH 3
|
------->
C
CH2 CH3
b)
(CH3 )3 C
Cl
CH3
(CH3 )2 CHOH
|
------------------->
C
CH2 CH3
CH3 CH2 O–
c) CH3 CH2 CH2 CH2 I ---------------->
2.
For each of the following sets, predict which reaction will be faster.
Set 1 _____
a) (CH3 CH2 CH2 )3 CCl + OH– ----> CH3 CH2 CH2 )3 COH + Cl–
b) (CH3 CH2 CH2 )3 CBr + OH– ----> CH3 CH2 CH2 )3 COH + Br–
Set 2 _____
a) CH3 CH2 CH2 Br + H2 S ----> CH3 CH2 CH2 SH + HBr
b) CH3 CH2 CH2 Br + HS– ----> CH3 CH2 CH2 SH + Br–
Set 3 _____
DMSO
a) CH3 CH2 CH2 F + OH– ------------> CH3 CH2 CH2 OH + F–
b) CH3 CH2 CH2 F +
OH–
CH3 OH
----------> CH3 CH2 CH2 OH + F–
Set 4 _____
DMSO
a) (CH3 CH2 CH2 )3 CCl + OH– ----------> (CH3 CH2 CH2 )3 COH + Cl–
DMSO
b) CH3 CH2 CH2 Cl + OH– ----------> CH3 CH2 CH2 OH + Cl–
68
3.
The reaction shown below was run several times using different concentrations of reagents
and the rate of the reaction was determined each time. The results are shown. From this
information, deduce the mechanism of the reaction. Note: OTs is shorthand for the
p-toluenesulfonate or tosylate group, a leaving group.
(CH3 CH2 CH2 )2 CHOTs + Br– ----> (CH3 CH2 CH2 )2 CHBr + TsO–
[ROTs]
0.02
0.04
0.04
[Br– ]
0.02
0.02
0.04
Relative Rate
1
2
4
Circle the correct mechanism
E1
E2
SN1
SN2
4.
Sketch a reaction coordinate diagram for an E2 reaction. Label the positions for the
reactants, the products, and the transition state, and indicate where the energy of activation
would be measured.
5.
Which of the following is a polar aprotic solvent?
A. CCl4
6.
A. HOCH2 CH2 OH
O
||
C. H-C-N(CH3 )2
D. H 2 O
Characterize both the stereochemistry and the mechanism of the following reaction.
H
H
CH3
CH3
|
CH2 CBr
|
CH3
stereochemistry
at stereocenters
inversion
retention
racemization
H
+ H 2 O --->
H
CH3
mechanism
SN1
SN2
E1
E2
69
CH3
+ HBr
|
CH2 COH
|
CH3