SN1 - Substitution Nucleophilic Unimolecular
II. B)
Example:
CH3
CH3
O
C
CH3
O
C
(Wade 6-13, 6-14)
CH3
Cl
CH3
CH3
C
6-5
O
O
C
CH3
Cl
CH3
Could this be an SN2 mechanism?
Still a substitution, but a different mechanism (stepwise).
SN1 Mechanism: two key steps (but usually three total steps)
Step 1
Loss of the
leaving group
Cl
Step 2
Addition of
nucleophile
SN1 Kinetics Rate = k [t-BuCl]
- rate-determining step involves E+ only (unimolecular reaction)
- rate is independent of [Nu:]
- a more stable carbocation will be formed faster
Rate of SN1 (by type of RX):
SN1 Energy vs. Progress of Reaction Diagram
Structure of first Transition State, TS-1
E
Structure of TS-2?
POR
6-6
Stereochemistry of the SN1 Mechanism
carbocation intermediate
racemization
SN1 results in racemization (loss of stereochemistry) due to the achiral carbocation intermediate.
Cl
H
(R)
(SN1)
NaI
acetone
(solvent)
Rate (by RX type)
SN1 Summary
- stepwise mechanism via carbocation
benzyl/allyl/3˚
>
2˚
>>
1˚, methyl
- more stable carbocation =
- racemization occurs
- requires: 1) stable carbocation (not 1˚ or methyl)
2) weak Nu: (usually the solvent, H2O or ROH, is the nucleophile = "solvolysis")
Solvolysis: SN1 Mechanism is three steps (6-13, 6-14)
Example:
Br
CH3OH
OCH3
- Nu: is H2O or ROH
- final deprotonation step required
HBr
6-7
Predict the Major Product(s) (SN2 or SN1 mechanism? See Wade 6-16)
Include stereochemistry, where appropriate. Write N.R. if no reaction is expected.
6-7
KOH
CH3Cl
O
I
CH3
C
ONa
NaI
Br
Which would be the faster reaction (A or B)? Explain. (Consider first: SN2 or SN1 mechanism?)
A
B
H2O
Br
H2O
Br
OH
II. C)
OH
Leaving Groups (Wade 6-11, 11-5)
- weak bases make good leaving groups
- more stable = less reactive, weaker base
- typical leaving group? halide (X-)
(all have strong conj. acids: HCl, HBr, HI)
Leaving groups
F
Cl
<
Br
<
I
Is the Forward or Reverse reaction favored?
Best substitution reaction has best LG leaving (gives more stable products so ΔH < 0 and ΔG < 0)
CH3OH
NaCl
CH3Cl
NaOH
Hydroxide, HO-, is a poor leaving group BUT we can make it better. There are two methods.
6-8
1. Add a strong acid (acid protonates the alcohol to make a great LG, H2O)
ROH
HCl / HBr / HI
CH3OH
NaCl
CH3OH
HCl
RCl / RBr / RI
H2O
mechanism:
2. Make a tosylate LG (see Wade 11-5)
TsCl
CH3OH
base
O
CH3
CH3OTs
S
Cl
O
tosyl chloride, TsCl
Nu:
CH3Nu
OTs
tosylate
CH3OH
base
(- HCl)
O
CH3
S
Nu:
O CH3
O
O
CH3
S O
O
TsO
(tosylate LG)
why is this more stable than HO-?
Synthesis/"Transform" Problem - Provide the reagents needed to transform the given
starting material into the desired product. More than one step may be required.
OH
II. D)
I
Nucleophilicity (Nucleophile strength) (Wade 6-10)
II. D)
Nucleophilicity (Nucleophile strength) (Wade 6-10)
1. More electron-rich, better Nu:
CH3OH2
CH3OH
2. Periodic Trends:
CH3O
across row:
decreasing nucleophilicity
NH3
down a family:
H2O
generally increasing nucleophilicity (BUT this trend depends on solvent!)
I
Cl
Good Nucleophiles (Nu:)!
!!!
HO
!RO!!
HS
RS!
!! !
NH3
!NH2R
R3P!!
! CN
!N3!
!I
Weak Nucleophiles (Nu:)!
!!
H2O
ROH
Summary of Substitution Reactions
Alkyl Group
SN1
SN2
3° (tertiary)
common
rare (N/R)
2° (secondary)
sometimes
sometimes
1° (primary)
rare (N/R)
common
CH3 (methyl)
never (N/R)
common
allyl/benzyl
common
common (if not 3°)
!Br !
6-9
II. E)
SN2 vs. SN1 (Wade 6-16)
6-10
SN2 requires strong Nu: and minimal steric hindrance
SN1 requires a stable carbocation and typically involves a weak Nu:
See page 6-7 for examples, and SN2/SN1 Predict the Product homework for practice problems.
After attempting the homework, let's look more closely at the following problems:
O
Cl CH2 CH2 CH2 C OH
CH3OH
Cl
III. A)
NaOH
Competing Reactions: Carbocation Rearrangements (Wade 6-15)
CH3 OTs
CH3
C
CH
CH3
H2O
CH3
CH3
H
C
CH2 CH3
OH
CH3
CH3
C
CH3
CH
CH3
CH3
H
C
CH3
CH
H
Alkyl groups can also shift
Cl
EtOH
CH3
CH3
H
C
O
CH2 CH3
H
IV.
Solvent Effects (Wade 6-10B, 6-13C)
6-11
Both SN1 and SN2 reactions need POLAR solvents to stabilize charges in the mechanism.
Protic
Aprotic
- has an OH group
- extremely polar
- strongly stabilizes charges
- has no OH group
Solvent Effects on Reaction Rates
if you INCREASE solvent polarity, then SN1 is ______________ and SN2 is ______________
e.g. using a protic solvent instead of an aprotic solvent
e.g. going from an 80:20, EtOH:H2O solvent to 50:50
Why is a more polar solvent GOOD for an SN1 mechanism? (speeds it up)
Cl
H2O
OH
- carbocation will be better stabilized by more polar solvent
- C+ intermediate and transition state are more stable/lower E
-
Ea (lower height of hill),
Cl
polar aprotic
rate of reaction
E
POR
- SN1 is FASTER in a more polar solvent
Why is a more polar solvent BAD for an SN2 mechanism? (slows it down)
Br
OH
HO
Br
polar aprotic
- nucleophile will be better stabilized by more polar solvent
- Nu: is more stable, less reactive
-
Ea (increased height of hill),
rate of reaction
- SN2 is SLOWER in a more polar solvent
E
POR
CHM 314 - Three Types of Reactions Were Studied
6-12
1. Acid-Base Reaction (proton transfer) (Chapter 1)
H A
acid
B:
base
B H
A:
* equilibrium shifts to more stable, weaker acid/base pair
2. Free-Radical Halogenation Reaction (Chapter 4)
Br2
hv
R H
alkane
R Br
alkyl halide
(or Cl2/hv to make R-Cl)
* for bromination, major product comes from the best (most stable) radical
3. Substitution Reactions (Chapter 6)
R
Nu:
LG
Nu R
LG
* SN2 and SN1 mechanisms
* equilibrium shifts to loss of better (more stable) leaving group, LG
For each type of reaction, be prepared to:
- Predict the major product(s)
- Provide detailed reaction mechanisms (curved arrows, etc.)
- Explain stuff (e.g., regiochemistry, stereochemistry,
reaction rates, equilibrium direction, etc.)
These reactions (and all of Chapters 1-6) will be on the cumulative final exam!
III. B)
Competing Reactions: Elimination Reactions (Wade 6-17 - 6-21)
E1 Mechanism - Elimination Unimolecular
involves carbocation (like SN1)
E2 Mechanism - Elimination Bimolecular
one-step mechanism (like SN2) involving a strong base
NaOH
Cl
CHM 315...competition between all FOUR: Substitution (SN1/SN2) and Elimination (E1/E2)!