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|  


 

    
|     
    |
i i i i
Nuc ½ C X Nuc C X Nuc C + X

transition state

 ½ !
| "  #
$ |
%& '
| | 
()*+ 

jr CN
+ KCN + Kjr

%|' % '
$()
*+ * *
O
CH2 OH OTs
OCCH3
TsCl
benzyl (jz) -OAc, acetate H CH3 H CH3
jz jz
(S)(-) (S)
[  -33o
CH3 SO2Cl KOAc

p-toluenesulfonyl chloride RO-H


(Ts-Cl) H CH3 H CH3
jz H2O jz
O
CH3 S O R OH OAc
O (R)(+) (R)
a tosylate (ROTs) [  +33o
 ,-. 

 /)+0 

Bz Bz
- - Bz
i i
GTs cG GTs
cG cG GTs
3 3
(S) (R) 3
() +
") ½  
|  )
|++  +
  1   
 %1   '2

R jr + Cl R Cl + jr
3
½ . , 4.. 5.... 6,.
(CH3)3Cjr (CH3)3CCH2jr (CH3)2CHjr CH3CH2jr CH3jr
tertiary neopentyl secondary primary methyl
,  7  778 

Bulkiness o Substrate
$ | )
| )  9+9  
G G G
 3S 3  3 ( 3 )2  3 3
SG acetonitrile  acetone

$  ) 1+   


G 3  )

 3G Br G 3

 3G
   
    + +    
- - - -
CH 3 > NH 2 > OH > F

    + + +  + 


- -
OH < SH
- - - -
F < Cl < jr < I
NH 3 < PH 3

   +     : +


-
NH 2 > NH 3
-
OCH 3 > CH 3 OH
(  )2;  
   
   
(pre erably non-basic)

  

- - - - - - - -
HS > :P(CH 3)3 > CN > I > OCH 3 > OH > jr > Cl > NH 3 > OAc
0 /)+0 
&
 LG   + >|
?   )++  

Sul onates are excellent leaving groups


G G
 3 SG  3SG
G G
tosylate mesylate
<" ="
* /)+0 

      8  (        *   
      
G G
in pyridine
 3G lSR  3GSR l
G G

tosylate R =  3

mesylate R =  3
| 

| 
H H Nuc
Nuc:
R1 C C C C
R1 + jr
R2 jr R2



H
j: R1
R1 C C C C + j-H + jr
R2 R2
jr
rate  k[R-jr[j -
   
 

    

jase ½ H
C C C C + base-H
ï 
jr + jr
ï   

i
jase H

C C
ï 
i
jr
|* 1

>     
|  
 
 3G 2 Gc
wk. base  3  3  2=  3
Br ,..@.@
 3  3
Gt
 3 2G
 3  3  2=  3
str. base
.@-.@
|* 1


> |B

 3 2G
 3 2 2 2Gt  3 2 = 2
str. base
A.@,.@
 3 2 2 2Br
( 3)3G
 3 2 2 2GtBu  3 2 = 2
str. bulky base ,4@ -4@
|* 1

   | 

CN
CH3CH2CH2CH2jr CH3CH2CH2CH2CN
str. nuc.; wk. base
, ,.. |

CN
(CH3)3Cjr CH2C(CH3)2
8 ,..

| 


 !
  

 3G

    Ô  3G
ï
Br Ô Br

ï )++ 
 * * 
3(R),4(R) 3-Bromo-3,4-
dimethylhexane
 2 3

Br  3 aG 3

 3
in  3G
heat
 2 3
     

CH3O H Me Et
Et Me
C C C C
Et ï Me Et
Me (R) (R) jr

OCH 3
H
Me Et Me Et
Et Me
Et Me
jr
(*  
/)+0   
KG( 3)3
GTs Ô KGTs
in V-BuG / Œ

GTs
GTs

GVBu
has no anti-coplanar
Ë)C 

NaOCH 3
+
in CH 3OH
jr 85% 15%
Ë)D  : In an elimination reaction, the
more highly substituted alkene (usually) predominates
=|  
$  
: +
D  1 :*  

,     

C
C C
C

        


& 
 $ ; 
&1   E
 3

aGt in tG
l heat
 ( 3 )2
=   
 3

aGt in tG
l heat

 ( 3 )2

    


)* 
=        

l
 3 
( 3
3)2 (
l 3)2

stable
stable and reactive
lip aGt

 ( 3)2  3  3

aGt

l
 3  ( 3)2  ( 3)2
reactive

 
%  '   8  
I
aG  3
2 3
 3   2 3  
in ethanol Œ
 3  3  2 3

(R,R) GR
 2 3
 2=   2 3
GR  
 3  3  3
| ( 
) 
I
CH2CH3 H CH3CH2
H C CH3
CH3 C CC
H CH3 CH3
%  ' OEt

I
CH3CH2 CH3

H CH3
H

 F 
>   +Ë (  

Br  3
Br
 3  
n 3 3
 
(R) (R)  
 3 Br  3 Gc
Br
anti con ormation only 2  forms
å   |   

  |, 
,

 3  3  3
in warm  3G
 3  Br  3  G 3 Ô = 2
 3  3  3 Ô Br

|,
,
 
, 
|,  (Wade)

,   +
$ (Wade)
|,|
  C$ 
A Related species that are close in energy are close in
structure.
A In an endothermic reaction, the transition state is
similar to the product in structure and stability.
A In an exothermic reaction, the transition state is
similar to the reactant in structure and stability.
A i.e. the structure of the transition state resembles
the structure of the most stable species.
ndo- transition state looks like product
xo- transition state looks like reactant
|,<|
|,| )


 3  3
RG
 3  l  3  GR Ô l

 3  3

tG 40% 2G / 60% tG 80% 2G / 20% tG 2G

react.: ,,..,5...,.....
<+ 1   )
$   B|,
*| 
+     1+
*| 

CH3 H
CH3 C > CH3 C  CH 2CH CH2  CH2 > CH 3CH 2
CH3 CH3
          B    

 B
* +
,   |
Br G
2G
 3    3  3    3 Ô Br
 3  3
* +
, = |
ydride shift

ydride
shift

o o
2 3
Ring xpansion

a
a
c
c
b
b
o o
2 2
Rings ontract, too

hydride
a
shift
b

ring
a
contraction
b

,=

, |,* 
a) b)
OTs
CH3OH / ΠOCH3
+
CH3 CH3 CH3
Zaitsev
a) CH3OH

H
CH3
CH3
b) CH3OH
|* C+ 
Br

 3G

 3G
 3G  3G
 3G
+
=
| 3    +
via
Br hydride shift
c

b  3G
a
b c
a via
ring expansion

i hydride shift
i
>   
,
OH
H
H2SO4 (aq) cat.
+ H 2O

H
regenerated
H H HSO4
O or H2O
-H2O H
= |;
/ G

G  3
 3
 3
 3
2SG4 (aq)
 Ô  3
3 distill
Ô 2G
major minor
$) =

H OCH3 CH3O H
jr
OCH3
CH3OH, warm
+ +

+ Hjr
(or CH 3OH2)
G 3  3G
Br
G 3
 3G , warm
Ô Ô
a) b) c)
 Br Ô Br
3G a)
b) G 3 (or  3G 2)

ring expansion
(squiggly bond = both isomers)
 3G  3G
G 3

hydride shift
  ! +  E
No >es

no reaction     


o o
1 3
o
2
nuc. hindered, strong base? strong base? >es 
nuc. a strong base?
No
>es No
>es No
>es ,H
polar solvent?
 good nuc., non-basic? ,
 good nuc., nonbasic?
>es No
(some S N2) >es
No

 %   '
solvent polar?
>es ,H
 ,
* S N1 is favored over E1 unless high temp. and trace amounts of base are used.
0)=:$ I
$ =

OH
6M H 2 SO 4
120 o C, distill
CH 3
G
6 2SG 4
120 o, distill
 3
,  3
NaNH 2 in liq. NH 3

OTs
NaNH 2 in liq. NH 3

OTs
H
Kjr
CH3 CH2CH3
OTs in acetone, 20 oC
H
Kjr jr
C H3 C H2 CH 3 C H3 C H2 CH 3
O Ts in acetone, 20 o C H
| 
Br 1% gG3
in  3 2G
jr 1% AgNO3 CH3CH2O
in CH3CH2OH + Agjr
| ,
 3 2 2G
Br warm
CH 3CH 2CH 2OH
jr warm OCH2CH 2CH3
| ,J,

+
 3
aS 2 3
in  3
Br
CH3
NaSCH2CH3 CH3

in CH3CN
jr SCH2CH3
| 
I
H 2O
(phase transfer cat.)
I G
2G
(phase transfer cat.)
|,%
,' Ô
I
NaOCH 2CH 3
CH3
in refluxing ethanol
CH3
I
NaOCH 2CH3
CH3 CH3
in refluxing ethanol
CH3  CH3
NaOCH 3
CH 3CH 2CH 2CH 2CH 2Cl
in methanol, room temp.
NaOCH3
CH3CH2CH2CH2CH2Cl
in methanol, room temp. O
| 
& =  

 E

( 3)2 I ( 3)2 I

 
     
V I

( I
3)2
)  
 ( 3)2

2 I

( 3)2 reacts more rapidly

)I