1. Nucleophilic Substitution Pentavalent Carbon in SN2? E2, SN1, E1
Chemistry 125: Lecture 46 January 31, 2011
Nucleophilic Substitution Pentavalent Carbon in SN2?
E2, SN1, E1
This
For copyright notice see final page of this file

2. Tools for Testing (i.e. Excluding) Mechanisms:
Stereochemistry
Rate Law
Rate Constant
Structure
X-Ray and Quantum Mechanics

3. Problem: Neither Transition State nor Intermediate would hold together long enough to study.
Pentavalent
Intermediate Nu L C
Transition
State

4. Held in place by molecular framework
HOYWAT + Nu L C
Held in place by molecular framework
JACS (2005)

5. Powerful alkylating agent like “Meerwein’s . Reagent”
CH3 O C
OCH3 + +
CH3-O(CH3)2
BF4-
NOT elongated to reflect superposed average of two “bell-clapper” structures.
HOYWAT
Powerful alkylating agent like “Meerwein’s Reagent”
Et3O+ BF4- + :
ARE THERE BONDS HERE?
F3BF -
BF3
2.64 Å
Calcd.
JACS (2005)

6. Pentavalence seemed to be a safe inference BUT without central C+ etc.
shortened by 0.21 Å!
etc.
Eclipsed repulsion
4.96 Å
4.75 Å
4.86 Å
shortened by 0.16 Å
bent in
bent in
Pentavalent C attraction?
125°
113°
125°
114°
5.02 Å

7. Central O only slightly repulsive compared to C+.
SiO2
CF3
Eclipsed repulsion
5.02 Å
4.86 Å
5.08 Å
5.00 Å
124°
116°
125°
113°

8. BF2 does seem to suck in CH3O groups.
Eclipsed repulsion
4.92 Å
4.56 Å
126°
112°

9. Double minimum with stronger nucleophile O-(higher HOMO
and nearby K+
Double minimum with stronger nucleophile O-(higher HOMO
& lower LUMO)
CF3 - O
5.02 Å
4.86 Å
127°
109°
4.84 Å
1.47 Å
2.99 Å
125°
113°
1.88 Å

10. Range Bonded O (or S) seems to “use up” the vacant AO. For F
CH3O
OCH3 +
Bonded O (or S) seems to “use up” the vacant AO.
Range
For F
withdrawal dominates
 donation.
Compared to what?
Higher neighbor HOMOs favor tetravalence.

11. Short & Long X A X Distances
Pressed in
by HCH3
repulsion C+
A-X distances (Å)
No sign of stability
for pentavalent
SN2 “intermediate ”
 transistion state H
nonbond
reference
~ equal
symmetrical
very different
unsymmetrical B
“loose”
like H B
“tight”
Bonded?
 transistion state B
tetracoordinate
(as calculated by q. mech.) A X
Compound

12. For copyright notice see final page of this file
E2, SN1, E1
This
For copyright notice see final page of this file

13. E2 -Elimination (e.g. J&F sec. 7.9)
Rate influenced by:
[base]  attack occurs during (or before) rate-determining-step
nature of leaving group  it leaves during (or before) rds
H isotope (kinetic isotope effect)  C-H broken during rds
Heavier atom, lower ZPE
see Lecture 8: frames 21-22
F CH2
CH H
:OH
"E2 Elimination"
ABN
AON F
H OH
CH2
C H
C H O
H O
kH > kD
ZPE
(kinetic)
but only if bond is weakened in rate-determining transition state D

14. E2 -Elimination (e.g. J&F sec. 7.9)
Anti
Stereochemistry (J&F sec 7.9c)
but not dogmatic
How to test experimentally?
Which should
be better?
CH3 C Ph
OTs H
H3C
syn
(R)
(S)
CH3 C Ph
OTs H
H3C
F CH2
CH H
:OH
"E2 Elimination"
ABN
AON F
H OH
CH2
(eclipsing strain) C Ph
H3C
CH3 H
(Z)
syn R
Maybe (E) is just more stable than (Z).
trans
anti C Ph
H3C H
CH3
OTs R
anti C Ph
H3C
CH3 H
(E)
cis
(S)
(S)
(anti hybrids overlap better)

15. E2 -Elimination (e.g. J&F sec. 7.9)
Anti
Stereochemistry (J&F sec 7.9c)
but not dogmatic H
98% yield
OTs D
RO- Na+
starting material is already eclipsed
Loses syn DOTs, not HOTs
despite kinetic isotope effect. H
OTs
Note that in this rigid, eclipsed case overlap with s*C-OTs is better for eclipsed syn D than for anticlinal H. D

16. E2 -Elimination (e.g. J&F sec. 7.9)
Regiochemistry H
“Saytzeff”
“Hofmann”
NaOCH3
HOCH3 L
(cis + trans) I Br Cl
~4:1
~1:50
Range:
200 x
102.3
3 kcal/mole
(subtle) F
(CH3)3N

17. E2 -Elimination (e.g. J&F sec. 7.9)
E2 vs. SN2
Methyl
Ethyl
iso-Propyl
t-Butyl
Steric Hindrance
favors E2
as does a nucleophile that is weak compared to its basicity (e.g. OH-)

18. Synthesis Games - + Exchange Ions + Create + Destroy MTBE
(e.g. J&F sec. 7.10)
Williamson Ether Synthesis (1852) O-
Na+
EtBr +
OEt
Br-
Exchange
Ions
(Double Decomposition)
Finkelstein Reaction (1910)
Na+
Cl- I- +
RCl RI
also RBr
Br-
Menschutkin Reaction (1890)
Et3N + RI Et3N-R + I-
Create
Destroy
Breaking apart
by solvent
Solvolysis
(CH3)3C-Br
EtOH
HBr
(CH3)3C-OEt
Meerwein Reagent (1940s)
RO-
(CH3)3O BF4
ROCH3
+ Na+ BF4
+ (CH3)3O -
()
acetone C OH
CH3
NaH
-H2 O-
+ CH3Br C Br
CH3 +
CH3 C O
MTBE
CH3OH
CH3O-
NaH
-H2
strong base favors E2
too hindered for SN2
actually made a different way

19. (intramolecular “SN2”)
Synthesis Games
(e.g. J&F sec. 7.10)
Epoxide or Oxirane OH Cl O
+ Cl-
73% yield
NaOH / H2O
25°C 1 hr O- Cl
OH-
Backside Attack
(intramolecular “SN2”)
Nu:
Note: Epoxides are ethers with strain & thus a built-in RO- leaving group for adding C-C-O to a nucleophile. Nu O- O

20. N C and RC C are particularly interesting, as are anions like
Synthesis Games
(e.g. J&F sec. 7.10)
pKa 25
pKa 9
N C and RC C are particularly
interesting, as are anions like
CH3-C-CH-C-CH3 O
because they are nucleophiles that form C-C bonds by attacking C
R-C C-H
R-C C- Na+ + NH3
Na+ NH2-
NH3
pKa 34

21. SN1 NaOH + R-Br HO-R + NaBr -1 1 -2 -3 -4
EtOH/H2O (4:1)
55°C
(0.01 M)
NaOH + R-Br
HO-R + NaBr -1 1 -2 -3 -4
log (fraction of R-Br converted to HOR/min)
Rate extrapolated from lower temperature.
plus ~19% E2
k2 (M-1min-1)
concerted
displacement
slowed by
crowding
(CH3)3C
[OH-]
SN1
k1 (min-1)
D/A
accelerated
by crowding,
(CH3)3C+ cation stabilization,
polar solvent
Depends on [OH-]
CH3
CH3CH2
Hughes Ingold
( )
(CH3)2CH

22. SN1 and E1 Product Determined After Rate
(e.g. J&F sec )
SN1 and E1
Product Determined After Rate
by Competition for Short-Lived Cation
(CH3)3C-Br
(CH3)3C-CN
K+CN-
H2O
+ (CH3)3C-OH
rate determining step
Product ratio depends on [K+CN-]
but the rate does NOT!
HOH
CN-
(CH3)3C+
(CH3)3C-Br
(CH3)3C-OH
(CH3)3C-CN

23. SN1 and E1 Rearrangement Demonstrates Cation Intermediate CH3 C CH2 I
(e.g. J&F sec )
SN1 and E1
Rearrangement Demonstrates Cation Intermediate
CH3 C
CH2 I
CH3 C
CH2 OH
AgNO3
Ag+
H2O

24. End of Lecture 46 Jan. 31, 2011
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