Chemistry 125: Lecture 44 January 27, 2010 Nucleophilic Substitution and Mechanistic Tools: Rate Law...
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![Page 1: Chemistry 125: Lecture 44 January 27, 2010 Nucleophilic Substitution and Mechanistic Tools: Rate Law & Rate Constant This For copyright notice see final.](https://reader030.fdocuments.in/reader030/viewer/2022032800/56649d4b5503460f94a2802a/html5/thumbnails/1.jpg)
Chemistry 125: Lecture 44January 27, 2010
Nucleophilic Substitutionand Mechanistic Tools:
Rate Law & Rate Constant
This
For copyright notice see final page of this file
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F CH2
CH2 H :OH
"E2 Elimination"
ABNABN
AON
Make TwoBreak TwoF
H OH
CH2
CH2
Nucleophilic Substitutionand -Elimination
Chapter 7
F H :OH
F H OH
"Acid-Base"
F CH3 :OH
CH3 OHF
"SN2 Substitution"
ABN
Make & BreakSame
(Cf. Lecture 16)
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All are Nucleophilic SubstitutionWilliamson Ether Synthesis (1852)
O- Na+ EtBr+ OEt Na+ Br-+
Finkelstein Reaction (1910)
Na+ Cl-Na+ I- + RCl RI +also RBr Na+ Br-
Menschutkin Reaction (1890)
Et3N + RI Et3N-R + I-+
ExchangeIons
(Double Decomposition)
CreateIons
DestroyIons
Breaking apartby solvent
Solvolysis
(CH3)3C-BrEtOH
HBr +(CH3)3C-OEt
Generalization
Meerwein Reagent (1940s)
RO- Na+ (CH3)3O BF4+ ROCH3 Na+ BF4 ++ - -
()acetone
*
*
*
*
*
LUMOHOMO
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+ -
Generality of Nucleophilic Substitution
CH3
+
Nucleophile Substrate
Solvent
Nu: R-L Nu-R L(+) (-)
S-Adenosylmethionine
ARGININE
:
H
+
Biological Methylation(Post-Transcriptional Protein Modification, etc.)
Product
ARGININE
LeavingGroup
METHIONINEOH
ADENOSINE
ADENINEH OH
SubstituteNR2
for OH
SubstituteSR2 for “OH”
RIBOSE::
But different mechanisms are involved!
SubstituteNHR2 for SR2
SubstituteBase for NR3
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SN2 Nucleophilic Substitution
Nucleophile Substrate
Solvent
Nu: R-L Nu-R L(+) (-)
the Pragmatic Logicof Proving a Mechanism
with Experiment & Theory
(mostly by disproving all alternative mechanisms)
ProductLeavingGroup
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"It is an old maxim of mine that when you have excluded the impossible,
whatever remains, however improbable,
must be the truth."
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SN2 Nucleophilic Substitution
Nu: R-L Nu-R L(+) (-)
Break bond (Dissociation)
(mostly by disproving all alternative mechanisms)
Make bond (Association)the Pragmatic Logic
of Proving a Mechanism with Experiment & Theory
D then A A then D Simultaneous
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Concerted A/D D/A
PentavalentIntermediate
Nu LC
TrivalentIntermediate
CNu LC
TransitionState
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Nu
Concerted A/D D/A
PentavalentIntermediate
Nu LC
TrivalentIntermediate
CNu LC
PentavalentTransition State
Which is it normally?
Unlikely for exothermic
process(Hammond
implausibility)
Nu
a b
c
a b
c
a b
c
enantiomers
stereochemical proof !
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Tools for Testing(i.e. Excluding) Mechanisms:
Stereochemistry (sec 7.4b)
Rate Law (sec 7.4a)
Rate Constant (sec 7.4cdefg)
StructureX-Ray and Quantum Mechanics
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HCH3
O
OC
STEREOCHEMISTRYKenyon and Phillips (1923)
H
PhCH2
CH3
CH
O Cl SO2 CH3
PhCH2
CH3
CH
O SO2 CH3
+33°+31°
O
PhCH2
CH3
CH
-7°
CH3CO
O
PhCH2
CH3
CH
O CH3C
O
OHPhCH2
CH3
CH
O CH3C
O
OH
-32° Inversion!(R) (S)
Backside Attack in
nucleophilic substitution at S (A/D, A favored by vacant d orbital of S)
nucleophilic substitution at C=O (A/D, A favored by *)
nucleophilic substitution at saturated C.
Same as starting
material?
PhCH
CH3
CH
Why not avoid acetate steps by
using -OH? Becauseit attacks H.
-OH
(only step involving chiral C)
H
H
Proves nothing
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Concerted A/D D/A
Trivalent intermediate could be attacked from either face racemization, not inversion.
PentavalentIntermediate
Nu LC
TrivalentIntermediate
CNu LC
PentavalentTransition State
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Stereochemistry
Rate Law
Rate Constant
StructureX-Ray and Quantum Mechanics
Tools for Testing(i.e. Excluding) Mechanisms:
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NaOEt + EtBr EtOEt + NaBr
[NaOEt] ( fixed [EtBr] )
rate
Second Order (SN2)
d[EtO-]dt = k2 [EtO-] [EtBr]
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Nu enters
Concerted A/D D/A
Initial rate-limiting dissociation in D/A would give a rate independent of [Nu], not SN2.
PentavalentIntermediate
Nu LC
TrivalentIntermediate
CNu LC
PentavalentTransition State
Not D/A
Nu enters
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Analogy
EtO- + H+ EtOH
EtO: + H+ EtOHH
+
H
EtO- + EtBr EtOEt
EtO: + EtBr EtOEtH
+
H
NaOEt + EtBr EtOEt + NaBrEtOH
+ k1 [EtBr]+ k [EtOH] [EtBr]
First Order (D/A?)Pseudo First Order
pKa15.7
-1.7
k2 = 20,000 k
[NaOEt]
d[EtO-]dtra
te = k2 [EtO-] [EtBr]
Second Order (SN2)
~ const
at equilibrium
Is it reasonable to be so different?
Ratio should be much less drastic at
SN2 transition state.1017.4
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Stereochemistry
Rate Law
Rate Constant
StructureX-Ray and Quantum Mechanics
Tools for Testing(i.e. Excluding) Mechanisms:
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Rate Constant Dependance on
NucleophileLeavingGroup
SolventNu: R-L Nu-R L
(+) (-)
Product
145
0.82
0.0078
0.000012
~ 0.0005 ?
Substrate
Something else happens
LUMO
Surface Potential+26 to -25 kcal/mole
[1]
krel
(CH3)2CH
CH3CH2
CH3
(CH3)3CCH2
CH3CH2CH2
R
(CH3)3C
Cf. Table 7.1 p. 275
RBr + I-
acetone / 25°C
(CH3)2CHCH2
0.036
145x
>15x
128x1.2x
3000x
23x
C-Lantibonding
node
~same
H
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Methyl Ethyl iso-Propyl
t-Butyl
-Methylation
Total Density (vdW)
Steric Hindrance
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Methyl Ethyl iso-Propyl
t-Butyl
-Methylation
LUMO at 0.04LUMO at 0.06Total Density (vdW)
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Methyl Ethyl iso-Propyl
t-Butyl
-Methylation
Surface Potential+26 to -25 kcal/mole
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-Methylation
Neopentyl
Ethyl [1] n-Propyl 0.82
iso-Butyl 0.0360.000012
No way to avoid the third -CH3
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increased strain in transition state
Cycloalkyl Halides (Table 7.2)
krelative
[1]
1.6
0.008
<0.0001
0.01
C HCC
Br
I
120° sp2
60°
90°
109°
strain in starting material
~109°
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End of Lecture 44Jan. 27, 2010
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