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One way a
catalyst can
speed up a
reaction is by
holding the
reactants
together and
helping bonds to
break.
ENZYMES
Enzymes are
catalysts in
biological systems.
The substrate fits
into the active site
of the enzyme much
like a key fits into a
lock.
INFLUENCE OF PH ON REACTION RATE
The hydrolysis of esters is catalysed by both acid and base:
H
OH OH O
H2O acid catalysed
H3C H3C OCH 3 H3C OCH 3
hydrolysis
O CH 3 OH2 OH H
O OH O
H2O base catalysed
H3C H3C OCH 3 H3C + CH3O
hydrolysis
O CH 3 O OH
H
OH
log kobs
7.0
pH
Another example: imine formation:
R NH 2 + H+ R NH 3+
nucleophile inactive
C O + H+ C OH
active
log kobs
H2
R NH 2 + C OH R N C OH
4.5
pH
pH optimum ~ 4.5
H
N C HN C R N C OH2
R R
fast
S + HA SH+ + A
slow
SH+ products
K
E + HA EH+ + A fast
k1 H2O
EH+ products slow (A1 mechanism)
k2
or EH+ + H2O products slow (A2 mechanism)
Reaction rate:
[H 3O+ ][A - ]
[E][HA] since Ka =
ν = k1[EH + ] = k1K [HA]
[A - ]
k 1K
we can now write: ν= [E][H 3O + ] = k'[E][H 3O + ]
Ka
So the rate is only dependent on the pH, not on [HA] !!
SPECIFIC BASE CATALYSIS
x
x
O OH O x
CH 3 base kobs x
2
H3C CH 3 H3C CH 3 x
x
I
[OH-]
OC2H5 O
H+
H3C OC2H5 + H2O H3C + 2 C2H5OH
OC2H5 OC2H5
III
[buffer]
good nucleophile
increases k2
(I.e., the rate)
Nu1 is a
better base
Basicity = Thermodynamic
( STRONGER BOND )
B:- + H+ B-H
strong base
shifts equilib.
DIFFERENT PLACES ON THE ENERGY PROFILE
DETERMINE NUCLEOPHILICITY AND BASICITY
NUCLEOPHILES
Nucleophilicity is
determined here
activation energy
and rate (kinetics)
faster is better
BASES
Basicity is
determined here
strength of bonds
and position of
equilibrium
SN2 REACTIONS
WHAT IS THE IDEAL NUCLEOPHILE ?
SN2 REACTIONS
LARGE
..
:Y
.. : STERIC PROBLEMS
no way ! bad
R
SMALL
.. -
: ..
X: good C : Br
R
R
Smaller
is better !
For an SN2 reaction the nucleophile must find
the back lobe of the sp3 hybrid orbital that the
leaving group is bonded to.
EXPECTED “IDEAL” NUCLEOPHILES
cyanide
ROD OR SPEAR - :C N:
SHAPED - + -
:N N N:
azide
F- Cl- Br - I-
F- gas phase
F- (g) F- (aq)
F-
SOLVATED the ion and the solvent
H H is a type of weak bond.
ION
Energy is released when
H H it occurs.
O H H O Solvation lowers the
water solution potential energy of the
nucleophile making it
less reactive.
HALIDE IONS
IONIC
RADIUS 1.36 A 1.81 A 1.95 A 2.16 A
smallest
ion
F- Cl- Br - I-
Heats of
solvation
in H2O - 120 - 90 - 75 - 65
Kcal / mole
-
X(H2O)n
increasing solvation
larger n smaller n
H H
H O
+ - O O H H
H O - H
M +
H O X-
H
O H
H+ H O
H
H H O
H
polar OH bonds
H H
Water is an example of a “protic” H O
solvent.
+ - O O H H
H O - H +
X -
H
Protic solvents are thoseM H O
thatOhave
H
H +
O-H, N-H H O
H
or S-H bonds. H O
H
H
Protic solvents can form hydrogen bonds and can
solvate both cations and anions.
LARGER IONS ARE BETTER NUCLEOPHILES
IN PROTIC SOLVENTS
THREE FACTORS ARE INVOLVED :
C Br
VERY
HYPOTHETICAL
GROUP IV V VI VII
CHARGED NEUTRAL
APROTIC SOLVENTS
APROTIC SOLVENTS
- O O
-
O H3C CH3
+ +
CH3 S CH3 H C N CH3 N P N
H3C CH3
CH3 N
dimethylsulfoxide H3C CH3
“DMSO” dimethylformamide
“DMF” hexamethylphosphoramide
O “HMPA”
H3C O CH3
-
S O M+ O S X-
- +
H3C O CH3
The nucleophile is
“free” (unsolvated),
CH3 S CH and therefore is small
3 and not hindered by
a solvent shell.
DIMETHYLSUFOXIDE
space-filling
O
S
H H
CH3
H3C N C H
+ O
M X-
O
nucleophile is “free”
H C N CH3 (unsolvated)
CH3
OBSERVED NUCLEOPHILICITY
APROTIC SOLVENTS
GROUP IV V VI VII
ions
R-X rate-determining
R+ + X-
step solvation of both ions
speeds the ionization
Carbocation
SN2 SOLVENTS = NONPOLAR
OR POLAR-APROTIC
SN2 reactions prefer “non-polar” solvents, or
polar-aprotic solvents that do not solvate the
nucleophile.
.. R
: ..
X:
SMALL, C : Br
UNSOLVATED
R
smaller is better ! R
CF3COOH
POLAR POLAR
APROTIC H2O
SOLVENTS
CF3CH2OH
O- HCOOH
+ SN1
CH3 S CH3
O CH3OH
H C N CH3
CH3CH2OH
CH3
O overall
CH3COOH
CH3 C CH3 polarity
SN2 POLAR
CH3CH2 O CH2CH3
PROTIC
CCl4 SOLVENTS
CH3CH2CH2CH2CH3
NONPOLAR
SOLVENTS NONPOLAR
SOLVENT MIXTURES
SOLVENT MIXTURES ARE VERY COMMON
SN2
BETTER NUCLEOPHILES REACT FASTER GIVING MORE PRODUCT
qn qe 2(cn ce)2
E
r E HOM O E LUM O
Electrostatic term: important for interactions of hard acids with hard bases
65
Orbital interaction term: important for interactions of soft acids with soft bases
Bases (nucleophiles)