Chem 161
Nov 21, 2006
Stereospecific reactions: stereochemistry of starting material determines
stereochemistry of product. All concerted reactions are stereospecific but not all
stereospecific reactions are concerted. Examples of concerted stereospecific rxns include:
- E2 – elimination reaction
- SN2 – substitution reaction
i)
SN2 reaction:
Nu
C L
L
Nu C
L = leaving group – partially negative ( eg. TsO (tosylate, a sulfonate) , Cl, Br, I)
Nu = Nucleophile – a substance (molecule) that seeks a positive center (usually carbon)
H
H C I
H
H 2O
H
H C I
H
No reaction
H
H C OH
H
Na OH
+
NaI
Making NaOH from H2O : Demo
Nao
+
NaOH
H OH
+
Stereospecific addition reaction: (see reactions of alkenes)
Eg. Epoxidation:
same molecules
O
O
cis-2-butene
O
O
H
H
H
O
H
H
achiral - meso compounds
(plane of symmetry)
H-H
O
O
O
H
H
HO
H
O
H
trans-2-butene
H
O
O
H
H
H
(S, S)
(R, R)
- both starting materials are achiral (not chiral), but each of the products can be chiral
- however they are formed as a 1:1 mixture of enantiomers – racemic mixture
Generally get pure (or partially pure) chiral products only if one of the reagents is chiral
Substitution Reactions:
1) SN2 reaction:
S = Substitution
N = nucleophilic
2 = bimolecular reaction (rate of reaction depends on 2 reagents)
H
H
!
C
H
Na Cl
H
!
I
Cl
H
C
+
NaI
H
methyl iodide
- stereochemistry of product is inverted (attack from the opposite side as leaving group)
- WALDEN INVERSION
Proton
1H
2H
1H
!
C
3
Deuterium H
Tritium
!
I
NaCl
Cl
C
2H
+
NaI
3H
stereochemistry inverted
SN2 Reaction:
- concerted reaction – all bonds break and form at the same time
- stereospecific – inversion of configuration
- rate depends on [Cl-] & [CH3I] – bimolecular process (two molecules are
involved)
Influences on SN2 reaction:
- works best if 1o carbon attached to leaving group
- with 2o carbon the reaction goes okay, with 3o carbon fails (too bulky)
- with reactive nucleophile reaction goes best
- for leaving group – best if the leaving group is electron withdrawing (solvation
factor also affects leaving group ability)
- solvent – polar-aprotic solvents are best, such as DMF, DMSO
- aprotic – no hydrogen (proton) attached to oxygen in the molecule
O
H
O
S
N
dimethylsulfoxide (DMSO)
dimethylformamide (DMF)
- leaving groups:
O
RO S OO
>
I-
>
Br-
>
very good
Cl-
>>
F-
The order of halide leaving group
ability is due to solvation
poor
- groups that could never be leaving group in substitution reaction:
OH, -OR, -NHR
H
H C I
H
Nao
+ H3COH
H3CO- Na+
H
H
H C O C H
H
H
H3CO- Na+
+ H2
- in the reaction to form dimethyl ether shown above, the reverse reaction would not
occur, since –OCH3 is a very poor leaving group
H
H C I
H
H
H C NH2
H
Na+ -NH2
+ NaI
CH3
H3C C OH
CH3
CH3
H3C C I
CH3
+ NaI
3o carbon, so no SN2 reaction
Na+ -OH
2) SN1 Reaction:
S = Substitution
N = Nucleophilic
1 = unimolecular reaction – rate of the reaction depends on only one reagent
- nucleophilic substitution reaction
- rate depends on one reagent’s concentration
- step-wise reaction (not concerted)
- carbocation intermediate is observed
- favoured if leaving group is at 3o carbon center
- non-stereospecific
- best if leaving group is attached to 3o carbon center
- never occurs if 1o carbon is attached to leaving group
eg.
! !
C I
H-OH
C
I-
H
O H
C
O H
C
sp2 hybridization
planar geometry
- the carbocation intermediate may undergo elimination in the presence of base:
H
CH2
H 3C C
CH3
B-
H3C
C CH2
H 3C
Sample questions:
! !
H NH2
!
!
CH3CH2-Br
NH2
CH3CH2
H3C C
CH3
HBr
! !
H-OH
CH3
H 3C ! !
H3C C Br
CH3
+
H3C ! !
H3C C OH
CH3
Br-
O
!
!
CH3CH2-I
+Na -S
O
CH3
H3CCH2S
CH3
+
NaI
+
HBr