A QUICK REVIEW OF TWO SUBSTITUTION REACTIONS

SN1 / SN2

RECALL FROM LAST LECTURE

RBr + NaOH ROH + NaBr
Two similar reactions, different kinetics.

1) First Case

CH3 Br + NaOH
primary

80% ethanol 20% water 55oC

CH3 OH + Br

SN2

rate = k2 [RBr] [NaOH]

RECALL FROM LAST LECTURE

2) Second Case

CH3 H3C C Br + NaOH CH3

tertiary
80% ethanol 20% water

CH3
55oC

H3C C OH + Br

CH3

SN1

rate = k1 [RBr]

QUESTION SN1
rate = k1 [RBr]

SN2
rate = k2 [RBr] [NaOH]

Is this difference significant, or is it just a mathematical illusion of some kind?

THE WORK OF HUGHES AND INGOLD

HUGHES AND INGOLD ca. 1940

It was found experimentally that : Most primary compounds undergo SN2 reactions with second order kinetics. Most tertiary compounds undergo SN1 reactions with first order kinetics. Most nucleophilic substitution reactions fit one or the other of these two patterns. Is this significant, or is it just a mathematical illusion of some kind?

2-BROMOOCTANE
A STUDY IN STEREOCHEMISTRY Lets use an optically-active compound.

2-BROMOOCTANE
CH3CH2CH2CH2CH2CH2 CH CH3 Br

R = C6H13
abbreviation

* CH

chiral

CH3
can react both SN1 and SN2

Br
secondary

DIFFERENT KINETICS AT DIFFERENT BASE CONCENTRATIONS

SN1
H R C CH3 Br
low conc [ OH- ] < 0.1 M

k1[RBr]

H R C CH3 +

SN2
H

high conc [ OH- ] >1M

1) H2O 2) -H+

R C CH3
k2[RBr][OH]

OH

The two mechanisms compete.

SN1

SN2
TOTAL

Total Rate = k1 [RBr] + k2 [RBr] [OH-]

dominates at low [OH-]

SN2 k2 [RBr] [OH-]

dominates at high [OH-]

Rate SN1 k1 [RBr]

[ OH- ] [RBr] constant

STEREOCHEMICAL RESULTS
CH3CH2CH2CH2CH2CH2 CH CH3 Br

2-Bromooctane is chiral ..... What if we start with an enantiomerically pure compound (one enantiomer only)? Is the stereohemical result the same in each case : SN1 and SN2 ?

STEREOCHEMISTRY CHANGES
R-(-)-2-bromooctane [a]D = -36.0o

R CH3 Br

SN2 conditions high [OH-]

R HO H

complete inversion

CH3

SN1 conditions low [OH-]

S-(+)-2-octanol [a]D = +10.3o

R
CH 3
complete racemization

R
+

R OH HO H

S
CH3
[a]D = 0o

enantiomers racemic mixture

THE MECHANISMS
Can we explain the stereochemical results with our proposed mechanisms for SN1 and SN2 reactions? Lets Try .......

SN1

SN1 MECHANISM
R CH 3 H Br
(R) sp2 50%

+
C

R H

planar carbocation

CH 3

-O H
attacks top and bottom 50% equally

RACEMIZATION

OH + H
(S)

OH R H CH 3
(R)

CH3

enantiomers racemic mixture

SN2

SN2 MECHANISM
nucleophilic attack
(R)-config

.. : H O .. CH3
attacks back lobe

C
H

.. : Br : ..

R
.. : H O ..
(S)-config

C CH3 H

INVERSION

CONCEPTUAL ANALOGY 1

LIKE POOL OR BILLIARDS

2) forceful shot directly on axis
Nu X 1) two balls at rest and touching
Similar in concept to an attack from the back forcing the nucleophile to leave.

Nu

3) straight-on collision

4) momentum transfer

Nu

CONCEPTUAL ANALOGY 2

INVERSION OF AN UMBRELLA IN THE WIND

Inversion of the umbrella is similar in concept to the inversion of an SN2 atom.

THE INVERSION PROCESS

sp2

R C

2p

HO

HO

Br

partial bonding

CH3 H .. H O ..: R
sp3

activated complex is trigonal planar (sp2 )

configuration is inverted

C CH3 H

: Br
Ea

sp3

HO :

(R)-configuration

CH3

(S)-configuration

ACTIVATED COMPLEX FOR SN2

MIDPOINT OF THE REACTION

trigonal planar (sp2)

forming

R C CH3 H

breaking

HO

Br
5 bonds to Carbon but the bonds to Br and OH are only half-formed and are not full bonds. NOT A STABLE SPECIES