Chapter 5

homolytic rxn ;
heterolytic rxn ;
B A A B
A B B A
C B A A C B
C B A A C B B A A B
A B B A
(mainly in gas phase)
(mainly in solution)
cI) homolysis , heterolysis
nucleophilic (aliphatic) substitution



Which chemical rxn occurs ?
a matter oI relative rates oI competing rxns



ex) halogenation

What happens? Where does it happen? Does it happen?


alkyl halide
alcohol
R X
R OH
Iunctional group ; deIine the structure
determine the property
characteristic rxns occur
primary
secondary
tertiary



IUPAC name Ior halide p168


alkyl halide ; van der Waals Iorce or weak dipole-dipole interaction

relatively low m.p & b.p
soluble in non-polar solvents
insoluble in H

O
denser than H

O (not Ior mono-chlorides)

How to prepare R X ; R OH R X
R X R I
HX
or PX
3
NaI
acetone
(X ; Cl, Br)
substitution
elimination
organometallic
Irom alkane (mixture, not practical)


CH
3
Br OH

CH
3
OH Br

nucleophilic substitution
substrate
nucleophile leaving group
heterolytic
anion or neutral (containing an unshared pair oI electrons)
basic
compete with elimination p173 p174



R W

Z R Z W

solvent
substrate
nucleophile leaving group
strong base
weaker base
better nucleophile
better leaving group
true only Ior the related sets
ex) -OTs, -OH, -OMe
basicity ; a matter oI
equilibrium.
Ior proton.
basicity is only one oI
the Iactors involved

nucleophilicity ; a matter oI
rate.
Ior carbon.


R X
OH

R OH

H
2
O R X X

ROH
2

ROH H

(hydroxide) (alcohol)
(methoxide) (ether)
(cyanide) (nitrile)
(iodide) (alkyl iodide)
CH
3
OH ROCH
3
NH
3
RNH
2
R OCH
3
OCH
3
R CN
R I I
CN

halide as leaving group other leaving group ; R OS Ar
O
O


rate
collision
Iriquency
energy
Iactor
probability
Iactor
an increase
in concn
at a const T
no change increase no change
increase in rate
CH
3
Br OH

CH
3
OH Br rate k |CH
3
Br| |OH |

rate const ; l/mle sec

second-order kinetics


C
CH
3
CH
3
Br
CH
3
OH C
CH
3
CH
3
OH
CH
3
Br rate k |RBr|
sec
-1
Iirst-order kinetics

methyl, primary halides ; second-order
tertiary halides ;
Iirst-order
secondary halides ; borderline
2nd order
1st order
nucleophilic aliphatic
substitution can proceed
by two diIIerent mechanisms
Eig 5-1
reactivity Ior OH
CH
3
X
3
o
2
o
1
o

S
N
2, S
N
1
S
N
2
S
N
1
RX CH
3
, 1
o
, 2
o
, 3
o


CH
3
Br OH

CH
3
OH Br

rate k |CH
3
Br| |OH |

OH

C Br HO C Br


need a collision between
CH
3
Br and OH

Br

HO C
at the Iace most remote Irom Br
with suIIicient energy
the rxn occurs transition state
partially bonded
C OH
C Br
OH ; diminished negative charge
Br ; developed a partial
negative charge
partially Iormed
partially broken
C OH
C Br
all bond angles ; 120
o


S

2, mechanism (substitution nucleophilic bimolecular) what evidence?

inversion oI
conIiguration
NaOH
optical purity x
optical purity x
C H
CH
3
Br
C
6
H
13
C
H
C
6
H
13
HO
CH
3
occurs in a single step
bond-making &
bond-breaking
occur simultaneously
in a concerted Iashion
consistent with the kinetics
stereochemistry oI the pdts


RBr Cl RCl Br
DME
(S
N
2)
CH
3
Br CH
3
CH
2
Br
CH
3
CH
3
CHBr CH
3
C
CH
3
CH
3
Br

relative
rate
37 1.0 0.02 0.0008
reactivity
Cl

R Br
R Br Cl

Cl R Br

transition state is diIIerent
Irom the structures oI
the reactants and the pdts.
the Iactors to stablilize
them are not expected
to stabilize the
transtion state
the polar eIIects oI the
substituent groups are
not expected to be
important due to nearly
no charge on carbon in
the trasition state
shape the diIIerent rates are
mainly due to steric Iactors
Eig 5.3 & 5.4
p188 (relative rate)

C
CH
3
Br
CH
3
CH
3

OH
C
CH
3
OH
CH
3
CH
3
Br

rate k |tBuBr|
C
CH
3
CH
3
CH
3
Br C
CH
3
CH
3
CH
3

Br

slow ; rate-determing step

require energy
C
CH
3
CH
3
CH
3

OH

C
CH
3
CH
3
CH
3
OH
Iast ; release energy
S
N
1 (substitution nucleophilic unimolecular)




C
CH
3
CH
3
CH
3

; carbocation
(carbonium ion)
a carbon atom has
six electrons and
a positive charge
CH
3
CH
3
CH
2
CH
3
CHCH
3

(CH
3
)
3
C

C
R
R
R
RE R

H
2
O
ROH
(Eig 5.6)
very reactive
very strong Lewis acid
SbE
5 SbE
6




What evidence Ior S
N
1 ? Iirst-order kinetics.
the stereochemistry oI pdts.



R : X R X R ,, X R X
intimate
ion pair
solvent-
separated
ion pair
Iree ions
completely
racemized pdt
backside attack
due to the
shielded Irontside
C
Me
Et
R W CH
3
OH
C
Me
Et
R OMe
decreased optical
activity

inverted pdt
decreased optical activity
optically active



relative stability
oI carbocation
p197
3
o
2
o
1
o
CH
3

heterolytic bond
RCl
R

SbE
5
Cl SbE
5
the diIIerences in stability
are much the same
How about in soln?
phase
dissociation in gas
the greater the number oI alkyl groups,
the more stable the carbocation
alkyl groups should release
electrons to disperse the
positive charge on carbon
inductive eIIect ; the intrinsic tendency oI a substituent to release
or withdraw electrons
resonance eIIect ; delocalize electrons ( electrons)
not clear Ior alkyl groups.
may be an inductive eIIect.
may be a resonance eIIect.
(overlap oI bonds with the
empty p orbital ; hyperconjugation)
may be a combination oI the two



relative reactivity Ior S
N
1
3
o
2
o
1
o
CH
3
W (p200)
rate oI Iormation carbocations
carbocation
stability
3
o
2
o
1
o
CH
3

the more stable the carbocation,

the Iaster it is Iormed.
R : X R X

R X
reactant trasition state
product
carbon has partly gained
the positive charge.
electron-releasing groups disperse
the partial positive charge
Iaster rxn
lower E
stabilize the transition state
Eig 5-10
+



C
CH
3
CH
3
CH
3
CH
2
Br
EtO
EtOH
C
CH
3
CH
3
CH
3
CH
2
OEt
C
CH
3
OEt
CH
3
CH
2
CH
3
no rearrangement
rearrangement
C
CH
3
CH
3
CH
3
CH
2
Br
C
CH
3
CH
3
CH
3
CH
2
C
CH
3
CH
3
CH
2
CH
3
C
CH
3
OEt
CH
3
CH
2
CH
3

carbocation was
proposed Ior the
rearrangement.

in the rearrangment,
a less stable carbocation
is converted into a more
stable
C
H
H
CH
3
CH
2

C
H
CH
3
CH
3
C
CH
3
H
CH
3
CH
2

C
CH
3
CH
3
CH
3

C
CH
3
CH
3
CH
3
CH CH
3

C
CH
3
CH
3
CH CH
3

CH
3
H shiIt
(hydride shiIt)
CH
3
shiIt
(alkyl shiIt)
1,2-shiIt
:
:

S
N
2
S
N
1
second-order kinetics
complete stereochemical inversion
no rearrangement
Iirst-order kinetics
racemization
rearrangement
3
o
2
o
1
o
3
o
2
o
1
o
CH
3
W CH
3
W
which mechanism will predominate Ior a given substrate
under a given set oI conditions?
a matter oI relative rates oI competing rxns

1) substrate
leaving group ; the bond to the leaving group is broken in r.d.s.
a better leaving group speeds up rxn by both mechanisms
to about the same degree.
little eIIect on which mechanism is predominant

alkyl group ; steric eIIect
the ability to stabilize a positive charge

a proIound eIIect on which mechnism is predominant.
2) nucleophile
S

2 ; involved in r.d.s.
S

1 ; involved aIter r.d.s.

|Nu| rate oI S
N
2
rate oI S
N
1 no eIIect
high |Nu| Iavors S
N
2.
low |Nu| Iavors S
N
1.
stronger Nu ; rate oI S
N
2 is Iaster strong Nu Iavors S
N
2.
weak Nu Iavors S
N
1. no eIIect on S
N
1



alcoholic AgNO
3
is used Ior the detection oI alkyl halides.
reactivity
3
o
2
o
1
o
via carbocation
allylic & benzylic halides are very reactive.
vinyl & aryl halides are unreactive.
R X
R I R Br R Cl

Ag R AgX