Chap.

5 Reactive intermediates
Energy surface
The plot of energy (potential
and kinetic) as a function of 3N-
6 coordinates of the chemical
system (reactants, intermediates,
products)

Reaction Coordinate diagram:The reaction coordinate is a one-

dimensional slice of a 3N-
Transition state 6+1dimensional potential surface.
E It goes through a maximum, but
A+B C+D along a valley (potential minimum)
with respect to motion perpendicular
Reaction to the reaction coordinate
Intermediate & Transition State

Transition state
Experimental evidences
show the diradical as intermediate
intermediate

Hammond Postulate
If two states, as for example, a transition state and an unstable
intermediate, occur consecutively during a reaction process and
have nearly the same energy content, their inter conversion will
involve only a small reorganization of the molecular structure.
(→ close in energy, close in structure )

endothermic rxn thermoneutral rxn exothermic rxn

T.S.

Closer in energy, closer in structure.

Factors stablize the intermediate will stablize the T.S.

Reactivity 3°>2°>1°
§ Carbocations
intermediates with formal charge of +1 on a carbon atom, or
a collection of carbon atoms

(and those with three center-two

electron bonding)

H
H H
H H

planar

formation of carbenium 3° > 2° > 1°

1. alkyl gps are electron-donating. (Inductive effect )
VB description
2. hyperconjugation
PMO description
QMOT version

methyl cation with 6 valence electrons is planar

A shorter C-C bond and longer C-H bond expected

stabilization of methyl cation by alkyl substitution is

a result of orbital mixing

Bridged ethyl cation

Detection of carbocation, by NMR
25.2 ppm 330.0 ppm ( in SO2ClF-SbF5 )(from TMS)
H3C C CH3

CH3
large shift due to deshielding
with low electron density
X X δ13C
OCH3 219
CH3 243
H 255
more shielded
CF3 269
stabilized
by e--donor

However,
H
H3C CH3
-125.0 ppm from CS2
C
charge density +0.611
CH3
CH3 -135.4 ppm from CS2
H3C C charge density +0.692

Rearrangement of carbocation

CH3CH2CHCH2 CH3CH2CHCH3

H
1° 2°
NMR shows singlet for 1H at -70° in super acid
13C one peak that couple to 9 H →
9 H become equivalent by fast rearrangement.
ESCA shows 4 uncharged carbon and one positively charged
carbon
The contradiction is due to different time scale
of NMR and ESCA
Rearrangements possible from 2° → 1°
The H can scramble in isopropyl cation,
Carbon-atom also scramble.

edge-protonated
at -78℃ , t1/2 = 1hr, 13C scramble to all C
corner-proronated (methyl bridged)

at -110℃ , 2 sets of peak

at -40℃ , one peak only
H H H
H H
H
CH3
H H
H
H H
H H
corner-protonated
cycloprotane

SbF5
FSO3H H
SO2ClF H H
Cl H H
H H
stable at -75℃ H

above -30℃ at -65℃

H3C
H3C
CH2
H2SO4
H2C CH2 OH

CH2
D2SO 4 CH2DCH2CH2OH + CH3CH2CHDOH + CH3CHDCH2OH
H2C CH2 0.46 0.38 0.17

D scrambled to all carbons

corner-protonated
CH2D CHD CHD
H
CH2 + + +
+ H2C CH2 H2C CH2 H2C CH3
D +
H2C CH2
edge-protonated SOH
CH2 D
+ CHD

H2C CH2 CH2DCH2CH2OS +

H2C CH2
+ H
SOH
CH3CH2CHDOS
SOH
CH2DCH2CH2OS

CH3CHDCH2OS

H H
CH3 CH3 CH3
0~-40oC +
CH3
+ +
Cl SO 2ClF - SbF5
H
CH3 CH3
+
+
Nonclassical Ion
Bridged structure with delocalized σ bond
→ a pair of e- shared by three nuclei.
rate 1
HOAc

OBs
KOAc 350
OAc
exo
：
HOAc
KOAc
OAc
1
OBs

2 Optically active exo → racemic exo

3 Optically active endo → 93% racemic exo
4 For chiral exo S.M., recovered S.M. partially
racemized.
5 For chiral endo S.M., recovered S.M. did not
racemized.
7

4
5 3 HOAc assisted by the C1-C6
KOAc
6
1
2
OBs -
OBs bond to give bridged
nonclassical intermediate
≣

C6：pentacoordinate
H H

The rate enhancement was due to proper anti-alignment of

the C(1)-C(6) bond and the leaving gp at C(2).
The stereochemical outcome is due to a symmetric intermed.
No backside assistance in endo compound

HOAc
KOAc +

OBs
?
The endo S.M. undergoes a classical ion intermediate then
nonclassical ion

HOAc
KOAc
+ +
OBs
Classical ion Non-classical ion

Two steps, the classical ion may be intercept by solvent to retain configuration
, depending on the nuceophilicity of the solvent.
Thus, in acetone, → 87% racemization
HOAc, → 93% racemization
HCOOH → 97% racemization

Observation in recovered S.M. is due to internal return of symmetrical

Intermediate for exo S.M.

HOAc
KOAc + OAc
OBs OAc
82±15%
retention of Optically active
configuration

H
classical, achiral chiral ,non-classical
Alternative interpretation by H.C. Brown
fast equilibrium
of classical ions
rate enhancement：release of torsional strain of leaving gp
e.g. and neighboring gps.

OBs OBs
rate 14 ： 1
high exo/endo ratio：steric hindrance
e.g.
kexo/kendo=140
OPNB

OPNB
classical ions
product stereoselectivity：steric hindrance

aq. acetone only

Cl OH

ψ classical ψ

little involvement
of C1-C6 bond
Cl Cl Cl
ψ
ψ
rate 1 3.9 3.9×107
potential energy for stable and unstable bridged ion
a transition state between
classical structure
A an intermediate in rearr.
between two
B

C the only stable structure

Direct Observation of Norbornyl cation by NMR: Olah
7

13C NMR in SO2-SbF5 (super acid ) 4

5 3

at -70℃, 101.8 ppm C-1,2,6 H

6 1H at -60 ℃,
162 ppm C-3,5,7
1 2
5.35 ppm (4H)
H
3.15 ppm (1H)
156.1 ppm C-4
7 2.20 ppm (6H)

at -150℃ and → 5°K

4
5 3
H 6
H
78.5 ppm C-1,2
171.4 ppm C-6 1 2

160.4 ppm C-4

7
145.8 ppm C-3,7
165.8 ppm C-5 5
4

3
6

H
at -150℃, the hydride shift frozen 1
H
2

→ the NMR confirm the existence of

norbornyl cation as non-classical.
or a equilibrating intermediate with
barrier < 0.2kcal

Summarize：
Nonclassical or bridged structure are readily attainable
intermediate or transition state for many cations.
For norbornyl cation, the bridged structure is an intermediate.
tertiary cation is nearly always classical cation.
primary cation can rearrange to more stable secondary or
tertiary carbocation, with bridged structure as T.S..
§ Carbanions:
intermediates with formal charge of –1 on carbon, 8 valence electrons
H
H H
C
C
H H
H 1-2 kcal

less than 109.5o

R R
C C stability inc.
R (higher S-character at carbon)

C C
Metal-carbon bond can be polar-covalent, such as C-Li
Organometallic species can be associated species(oligomeric)

The barrier of inversion at carbanion carbon can be increased

by incorporation of small ring, attaching electronegative
substituent,
cyclopropyl anion is stable pyramidal
Inversion barrier for NH3 ~5kcal, for NF3 ~50kcal

Ph CH3 BuLi Ph CH3

CO2 Ph CH3

Ph Br Ph Li Ph CO2H

100% retention of
conformation
Substituent that allows π-delocalization favors planar structure
Ph CN
Ph CN MeI

Ph Li Ph Me

racemic a fast inverting tetrahedral

stabilized by resonance
less interaction with metal ion carbanion center is indicated
Generation of carbanion
→reduction of carbon-halogen bond by metal
→deprotonation (acid/base rxn) by strong base
→reduction/addition of alkene
→…….

Stability of carbanion
Acidity 3º < 2º < 1º in solution
(due to destabilization of e-donating alkyl groups?)

But in gas phase, measured acidity:

Ethene<propane(2º-H)<methane<isobutane(3º-H)
The solution acidity is complicated by solvation

The order of acidity of alcohol

In gas phase
t-butyl > isopropyl>ethyl>methyl
In aqueous solution
methyl>ethyl>isopropyl>t-butyl

The alkyl group can polarize the electron away

from the center of negative charge and stabilize it.
§ Free Radicals
Structure with unpaired electron and zero formal charge
7 valence electrons (for neutral radical )

They are paramagnetic, attracted by magnetic field.

N -e- N
cation radical：

anion radical： O + Na O Na

Ph H t-BuOK
Ph3CCl + Zn Ph3C
Ph CPh3
Ph
Ph Ph
C CH Ph
Ph C Ph
Ph Ph
Ph
Ph

Radicals are in general reactive intermediate, but can be

stablized via delocalization of the radical：such as

Ph Ph

Ph Ph

Ph

Cl
or by steric hindrance
Cl Cl

(H3C)3C Cl Cl
Cl Cl
C C(CH3)3
Cl Cl
H

Cl Cl Cl Cl
Cl Cl
PMO & EHMO description of ethyl radical

on p

on methyl gp ( the one with

π-symmetry )
EHMO

hyperconjugation
( VB )

Structure and bonding

alkyl radical
P-
H
or C H is planar
2
sp H

Evidence of planar geometry

Methyl radical is planar, with very small barrier
for pyramidalization. All other radicals are non-
planar. Electronegative substituent shifts the
shape to pyramidal.

staggered
bridgehead radical are less strained, as compare to planar carbonium ion

stability of radical

methyl < 1° < 2° < 3°

due to hyperconjugation
§ carbenes
6 valence electrons on a CR2

Ground state multiplicity affects reactivity (e.g. singlet has

ambiphilic character; triplet reacts as diradical)
Large σ-pπ separation => singlet ground state
Smaller σ-pπ separation => triplet ground state.
The substituents affect the ground state multiplicity

Ground state for simple carbene

136° 105°

higher energy
lower energy
The substituents affect the ground state multiplicity
Inductive effect: (inductively stabilize σ by increasing
its S-character)
σ-withdrawing group favors singlet
σ-donating group favors triplet

C F C
Li C Li H H
104o
129o F
triplet singlet
Resonance Effect:
X: +R (-F, -Cl, -Br, -I, -NR2, -PR2, -OR, -SR)
Z: -R (-COR, -CN, CF3, -BR2, -SiR3, -PR3+)
(X,X) –carbene => bent singlet

C C
½ σ+ ½ σ+
X X X X
e.g, dimethoxycarbene, dihalocarbene
(Z,Z) – carbene => linear singlet carbene

Z C Z Z C Z
½ σ+ σ_ ½ σ+
e.g. diborylcarbene, dicarbomethoxycarbene

(X,Z) – carbene => linear singlet e.g. phosphinosilylcarbene

X C Z X C Zσ-
σ+
Steric effect:
increasing steric bulkness -> increase the bond angle =>
favor triplet
Dimethylcarbene, di(t-butyl)carbene diadamantylcarbene
Bent singlet, 111° triplet, ° triplet, 152°

To stabilize a carbene:
two π-donor, σ-attractor substituents ( push push resonance, pull pull
inductive substituent) NR2

R2N

Two π-attractor, σ-donor substituents (pull pull resonance, push push

inductive substituent)
R2B BR2

A π-donor, π-acceptor (push pull resonance substituent)

R2P SiR3
Reaction of Carbene
triplet carbene behaves as diradical
singlet carbene behaves as both carbocation and carbanion.

Addition Singlet carbene inserts

stereospecifically
R R
triplet carbene inserts
R R non-stereospecifically
Singlet
one
step

R R R R
Triplet

Insertion

CH3
CH3 H3C
+ CH2 + + +

10% 25% 25% 40%

Rearrangement