分子重排 课件

Nucleophilic rearrangement, Electrophilic rearrangement, Radical rearrangement, etc.
Nucleophilic rearrangement
CH3CH2CH2CH2OH H+
H
CH3CH2CH2CH2OH2 H2O
CH3CH2CHCH2
H+
+
Hale Waihona Puke Baidu
2%
NH2
HNO2 N2
+
H2O
H+
H2O H+
OH 58%
+ H2O H+
CH2=CHCH2OH
2 Pinacolic Rearrangement
CH3 CH3 H+
CH3 CH3
CH3 C C CH3 OH OH
CH3 C C CH3 OH +OH2
H2O
CH3
CH3 C C+ CH3 OH CH3
p MeOC6H4C CPh2 28% O C6H4OMe p
Under HNO2, the amino alcohol rearranges as that of pinacol
NH2 HNO2
OH
CH2NH2 HNO2 OH
CHO O
3 α-Ethandione Rearrangement
O O NaOH Ph C C Ph EtOH
COONa Ph2C
OH
H3O+
COOH Ph2C
OH
Ph
O C
O C
Ph OH-
Ph
O C
OH
C O-
Ph
OH O-
Ph C C O
Ph
O- OH
Ph C C O
Ph
OO RCCR
OH-
O OH
R C C O-
OH O-
R
RC C O
R
O- OH
RCCO
R
OO CC
OH-
O OH
C C O-
O- OH
RO O-
COOR PhCH CH2
Ph relative unstable carbon anion
Different α- chloroketone form same rearrangement product:
O
PhCH2 C CH2 Cl
O
PhCH C CH3 Cl
O ROROH Ph
PhCH2 CH2COOR
Molecular Rearrangements:it refers those reactions in which the carbon skeleton or the position of functional group changed.
CH3CH2CH=CH2 H3PO4 CH3CH=CHCH3
PhHC CHPh H+ PhHC CHPh
OH OH
+
OH
Ph2CH CH +OH
H+
Ph2CH
CH O
Phenyl with electron donor group move first
(p MeOC6H4)2C CPh2 H+ OH OH
(p MeOC6H4)2C CPh 72% Ph O
OH
OH CH3 C+ OPh
H+
CF3COOH
O CH3 C OPh
O CH3 C C* H Ph
CH3
PhCO3H CHCl3
O
CH3 C OCH Ph CH3
Group moved as the following order:
tertiary alkyl＞aryl＞H＞secondary alkyl
N
Et2O, -10℃
OH mp147℃
O C6H4OCH3 C
N
Ph H mp171℃
UV light
Ph
C6H4OCH3
PCl5
Ph O C
C N
Et2O, -10℃
N H C6H4OCH3-p
HO mp117℃
mp156℃
O2N
Ph PCl5 O2N
N
O NHPh H2O O2N
COOH PhNH2
Br OH
Br
Br
O2N
Ph
O2N
N OH PCl5
Br
NHCOPh H2O
O2N
Br
NH2 Br
PhCOOH
The shift will keep the stereostructure of
chiral center
CH3 C N
HO
C2H5 C CH2C2H5
H
H2SO4 Et2O
C2H5
C CH2C2H5
Cl
Cl C CH CH2Br Cl
Cl
C
Cl CH
CH2Br
Br2
Cl
Br Cl C CH CH2Br
Cl
Cl
II Nucleophilic Rearrangement
1 Wagner-Meerwein rearrangement ( Carbon cation rearrangement )
CH3 CH3 C CH2OH
CH3CH=CH2 anhydrous AlCl3 PhCH(CH3)2
PhCH(CH3)2
O2
Na2CO3/H2O 100℃
Ph
CH3 C OOH
H+
PhOH
CH3
CH3COCH3
III Electrophilic Rearrangement
Electrophilic rearrangement is not so common
1 favorskii Rearrangement 2 Stevens Rearrangement 3 Wittig Rearrangement 4 Fries Rearrangement
IV Radical Rearrangement
I Classification of Rearrangement Reactions
CH3 PhC O
OH
H+
CH3
H3C
CH3 + C O OH2
_H2O
Ph
CH3
H3C
C
+
O
Ph
H2O
CH3 + H3C C O Ph
CH3+
H3C
CO OHH
Ph
CH3 H3C C O Ph
+OH2
+OH
PhOH + CH3 C CH3 O
CH3 C CH3 + H+
Important industrial reaction for manufacturing phenol and acetone
2 Pinacolic Rearrangement ( ) 3 α-ethandione Rearrangement ( ) 4 Beckmann Rearrangement ( ) 5 Baeyer-Villiger Rearrangement ( )
III Electrophilic Rearrangement ( )
CO
OH O-
CO
α-Ethandione with α- hydrogen will proceed condensation
OO
C CH3
C CH3 CH3
CH3 C C
OO
OH-
H2O
OO C C CH3
CH3 CH3 C C
O
OH-
H2O
O
C C CH3
CH3 C C O
If NaOH was replaced by NaOMe or t-BuONa, α-hydroxycarboxyester will be produced
CH3 Br
CH3
CH3 C CHCH3
CH3 CH3
Stable cation
CH3 CH3 C CHPh
CH3 Br
SN1
CH3
CH3 C CHPh
CH3
Stable cation Product
Product
CH3 C CHPh CH3 CH3
CH3O ＞ R3C
＞
＞ Cl
＞ CH2=CH
＞ R2CH ＞CH3 ＞ H
＞primary alkyl＞methyl
CH3
O C C(CH3)3
CF3CO3H CH2Cl2
CH3
O C OC(CH3)3
Ph
O C
CH2CH3
CF3CO3H CH2Cl2
PhO
O C
OCH2CH3
O Ph C
CF3CO3H CH2Cl2
O PhO C
The cumene hydroperoxide rearrangement is quite resemble the Baeyer-Villiger Rearrangement
CH3
CH3 C C CH3 +OH CH3
H+
CH3
CH3 C C CH3 O CH3
The stable cation formed superior
Ph2C CH2 H+ Ph2C+ CH2
OH OH
OH
Ph2CH CH +OH
H+ Ph2CH
CH O
Phenyl group move first
CH3 CH3 C CH2OH
CH3
H+ H2O
CH3C=CHCH3 CH3
CH2NH2 HNO3 CH2NH2
CH2OH
CH2OH
CH3 CH3 CH3 C C CH3
OH OH
H+
CH3 O
H2O
CH3
C C CH3 CH3
Usually the rearrangement was classified by the electron property of the moving group, such as
H+
CH3
CH3 CH3 C CH2OH2
CH3
H2O
CH3
Cl-
Cl CH3 C CH2CH3
CH3 C CH2 CH3
CH3 C CH2CH3 CH3
CH3 H+ CH3C=CHCH3
CH3
Cl Cl-
Cl-
Cl
OH H+
+ +
CH3
CH3 C CHCH3 SN1
CH3
CH3 C CHCH3
O
O
H C Cl RO-
CC
ROH
C Cl CC
Cl-
O C CC
RO O-
RO-
C
CC
RO O C
CC
RO O
ROH
C
C CH
For asymmetric cycloprapanone, the stable anion form dominantly
O Ph
RO- RO O-
Ph
PhCH CH2COOR stable carbon anion
O C C R KOH
O C C OH
Cl
O
(CH3)2C C Br
CH3
NaOEt EtOH
R
O
(CH3)2C C OEt CH3
O
O
Ph2C C Br
CH3
NaOEt EtOH
Ph2CCH2
C OEt
Cl O C
①NaOH/H2O ② H3O+
COOH C O
Mechanism of Favorskii Rearrangement
Chapter 12 Molecular Rearrangements
I Classification of Rearrangement Reactions( ) II Nucleophilic Rearrangement ( ) 1 Wagner-Meerwein rearrangement( )
CH3CH2CH+CH3 H+
CH3CH=CHCH3
Electrophilic rearrangement
Ph CH2 O CH3 PhLi C6H6
Ph CH O CH3 Li+
Ph
CH3 CH
O-Li+
H2O
CH3 Ph CH OH
Radical rearrangement
Cl
Cl C CH=CH2 Br Cl
CH3CONH
H
5 Baeyer-Villiger Rearrangement
O CH3 C Ph
O CF3CO3H CH2Cl2 CH3 C OPh
O
O
CF3CO3H CH3COOEt
O
O CF3COOH
CH3
+OH C Ph
CH2Cl2
OH CH3 C Ph
CF3COO+H
O
OH
CH3 C Ph CF3C O+ O
O OH
4 Beckmann Rearrangement
R R'
HO R'
C
H+
C
N
N
OH
R
O R' C N
RH
Ph
CH3
C
N
OH
PCl5 ethyl ether
O CH3 C
N
Ph H
The group opposite to hydroxy will shift
Ph
C6H4OCH3 -p
C
PCl5
Intramolecular SN2 attack(structure
CH3
CH3 C CH2OH CH3
HNO2 N2
CH3 CH3 C CH2
CH3
CH3
C CH2CH3 CH3
H2O H+
OH
CH3 C CH2CH3 CH3
CH2NH2
NH2
HNO2 N2
CH2+ +
H2O CH2OH
OH
H+
H+
CH2
CH2NH2 HNO2 N2
CH2+
H2O H+
H+
CH2OH 32%
O O NaOR Ph C C Ph ROH
Ph2C
COOR
O-
H3O+
COOR Ph2C
OH
Usually, ethyloxy anion acts as a reduction reagent.
H Ph C C Ph CH3CH
OO
O-Ph C CH Ph H3O+ Ph C CH Ph
O O-
as nucleophilic rearrangement
Ph
Ph C CH2Cl Ph
Ph
Na Ph C CH2-Na+
Na+ Ph ROH Ph C CH2Ph
Ph
Ph2CHCH2Ph
The transition state is:
Ph C CH2 Ph
1 Favorskii Rearrangement