分子重排

+
CH3 CH3 C C CH3 +OH CH3
H+
CH3
The stable cation formed superior
+ H Ph2C Ph2C CH2 + OH OH
CH2 OH
Ph2CH CH +OH
CH Ph CH 2 H+ O
Phenyl group move first
PhHC CHPh OH OH
C2H5 C CH2C2H5 CH3CONH H
5 Baeyer-Villiger Rearrangement
O CH3 C Ph
CH2Cl2
CF3CO3H
O CH3 C OPh
O CF 3CO3H
CH3COOEt
O O
O CF3COOH
OH CH Cl 2 2 CH3 C Ph
+
CH3
OH C Ph
第三步 要满足迁移始点外层8电子结构,一般与亲核 试剂结合或通过-消除完成重排过程.
H 3CH2C C CH3 H
H+
CH3-CH=CH-CH3
* 但在实际反应中有时是两步,甚至三步同时发生, 如
O R C N Br
O C N R + Br-
* 重排过程中,往往发生邻基的参与而形成桥式中 间体或过渡态,迁移基团与迁移始点和迁移终点相结 合,与环丙烷正离子相似.
O+H CH3
CH3
C H
Ph
-N2
CH3
C+
Ph C
NH2
N2+
OH H CH3
Ph C
C H
Ph
-H+
Ph C O
C
H
Ph
Under HNO2, the amino alcohol rearranges as that of pinacol
NH2 OH CH2NH2 OH
HNO2
CHO
HNO2
PCl5
O C N
C6H4OCH3
Et2O, -10℃
OH mp 147℃
UV light Ph C N HO C6H4OCH3
Ph H mp 171℃
PCl5 Et2O, -10℃
Ph H
C N
O C6HHale Waihona Puke BaiduOCH3 -p
mp 117℃
mp156℃
O2N
Ph N Br OH PCl5
O2N
O NHPh H2O Br
O
频哪醇重排的立体化学特征:
H3C C2H5 HO C H
C H H
+
H3C C2H5
H C+
C H
C2H5 H3C
H C+
C H
OH
OH
-H+
OH
-H+
H H3C C2H5 H迁移速度慢, Ph迁移速度快 C
H
C
H O
+
H C
C
C2H5 H3C
O
Racemic mixture
*Ph HO Ph C
C Ph
H+
CH3 H3C C
O C Ph + Ph
CH3 C O
C Ph
OH OH
Ph
CH3
主要产物
次要产物
-氨基醇在亚硝酸作用下生成重氮盐, 然后脱氮生 成碳正离子之后的重排反应, 与频哪醇重排反应 是相似的, 一般叫半频哪醇重排.
Ph Ph C OH CH3
C H
HNO2
Ph Ph C OH
O OH Ph C C O Ph
-
Final deprotonation of the carboxylic acid drives the reaction forward.
O OH O O OH R C C OR C C R R
O OH R C C O R
-
OH OR C C O R
O O C C
H2O
CH3CH=CHCH3
亲核重排反应机理:
第一步 缺电子中心的创建
CH3CH2CH 2CH2OH H+ CH3CH 2CH2CH 2OH 2 H 2O CH 3CH2CH 2CH2+
第二步 迁移基团带着一对电子迁移到缺乏电子中心
H H3CH2CHC CH2 H H3CH 2C C CH 2 H
远距离的重排:
Me HO D OH H+ H2O Me D OH Me D OH Me D OH -H+ O Me D OH Me D
Note: 远程迁移中, 烷基迁移是很难的, 氢容易迁移.
几种重要的亲核重排反应
1 Wagner-Meerwein rearrangement ( Carboncation rearrangement )
Z A B
所形成的中间体为两电子三中心体系, 属于非经 典离子中间体或过渡态. 从成键情况分析它具有 三个轨道,一个成键轨道和两个简并的反键轨道, 两个电子在基态时处于能量最低成键轨道.
1) 重排中常常是通过生成桥式中间体的途经进行.
Br C C H3 C C C H C C
C
C
2) 迁移基团往往是从离去基团的背面进攻迁移终点, 因此, 从立体化学来看, 发生的常常是反式重排. 3) 对迁移的终点而言, 可以是SN1类型, 也可以是SN2 类型的同步反应. 一般迁移终点为叔碳或至少连有 一个芳基时为SN1历程, 其它的则为SN2历程.
the electron property of the moving group,
such as
1. Nucleophilic rearrangement, 2. Electrophilic rearrangement, 3. Radical rearrangement, etc.
1. Nucleophilic rearrangement
I Classification of Rearrangement Reactions
Molecular Rearrangements: it refers those reactions in which the carbon skeleton or the position of functional group changed.
脂环族伯胺在亚硝酸作用下发生的重排反应, 常常 伴随着环的扩大或缩小. 例如:
CH2NH2 NH2 HNO2 N2
CH2
+
+
H2O H+ H+
CH2OH
OH
CH2
CH2NH2 HNO2 N2
CH2+
H2O H
+
CH2OH 32%
H+
H+ 2%
+
H2O H
+
OH 58%
HNO2 NH2 N2
+
+
H2O H+
CH3CH2CH=CH2 H3PO4 CH3CH=CHCH3
CH3
CH3 C CH2OH CH3
H+ H2O
CH3C=CHCH3 CH3
CH2NH2
HNO2
CH2OH
+
HNO2
OH
NH2
CH3
CH3 CH3 C C CH3 OH OH
H H2O
+
CH3
CH3 O C C CH3 CH3
Usually the rearrangement was classified by
Cl
Cl
Cl
Cl
OH H+
+
+
CH3
CH3 CH3 C CHCH3 SN1 CH3 C CHCH3 CH3 Br CH3 CH3 C CHCH3 CH3 CH3
Product
Stable cation
CH3 C CHPh CH3 Br SN1 CH3 C CHPh CH3
CH3
CH3
CH3 C CHPh CH3 CH3
Ph2CH CH +OH
H+
PhHC
+
CHPh OH
H
+
Ph2CH CH O
至于不同取代基中究竟哪个发生迁移, 情况比较复 杂, 除了考虑迁移基团的亲核能力外, 迁移后形成的碳 正离子的稳定性也有关系. 一般说, 主要决定于两个迁 移基团的中心原子的电子云密度. 通常迁移趋势的顺 序为:
Ph- > R- > HCH3 CH3 Ph C
Chap.9 Molecular Rearrangements
I Classification of Rearrangement Reactions
II Nucleophilic Rearrangement
III Electrophilic Rearrangement IV Radical Rearrangement
O2N
COOH PhNH2 Br
O2N
Ph N OH Br PCl5
O2N
O2N NHCOPh H2O
Br
NH2 PhCOOH Br
The shift will keep the stereostructure of chiral center
CH3 C N HO C2H5 C CH2C2H5 H H2SO4 Et2O
C
CH3 H NH2
Ph*
HNO2
Ph C O
C
CH3 H
*Ph C O
C
CH3 H
Ph
88%构型翻转
12%构型保持
3. α-Ethandione Rearrangement
O O NaOH Ph C C Ph EtOH Ph2C COONa H O+ 3 OH COOH Ph2C OH
O OH O O OH Ph C C O Ph C C Ph Ph OH O Ph C C O Ph
频哪醇(Pinacol)在无机酸作用下, 转变为不对称 的甲基叔丁基酮, 这类重排反应称为频哪醇重排,也 称邻二叔醇重排.
CH3 CH3 H+ C C CH3 OH OH
CH3
CH3 CH3 CH3 C C CH3 H2O OH +OH2
CH3 C C CH3 O CH3
CH3 CH3 C C CH3 OH CH3
COOR Ph2C OH
α-Ethandione with α- hydrogen will proceed condensation
CH3 O O C C CH3 CH3 OH H2O
-
CH3 C C O O
CH3
O O C C CH3 CH3 C C O
OH H2O
-
O C C CH3 CH3 C C O
迁移基团带着一对电子转移到缺乏电子的迁移终点.
迁移终点可以带正电荷, 也可以是电中性的, 如碳烯、 氮烯等. 无论带正电荷还是不带电荷, 都必须是一个外 层只有六个电子的原子－缺电子的反应中心.
+ H CH3CH2CH2CH2OH
CH3CH2CH2CH2OH2
H CH3CH2CHCH2
CH3CH2CH+CH3 H+
O OH OH C C O
O
OH C O
OH O C O
-
If NaOH was replaced by NaOMe or t-BuONa, α-hydroxy carboxyester will be produced
COOR O O NaOR H3O+ Ph2C Ph C C Ph ROH O
H2O H
+
CH2=CHCH2OH
H N
NH2 CHO CH N COOEt 12 主产物 H N COOEt 13 F COOEt 13 副产物
COOEt 5
CH N
BF3
CH
N
N BF3 BF3
COOEt 10
COOEt
COOEt
H N CH F COOEt 13 COOEt 12 N H
2 Pinacol Rearrangement
CH3 O O CF 3CO3H CH3 C OC(CH3)3 C C(CH3)3 CH2Cl2
O Ph C
O CF 3CO3H PhO C CH2Cl2
醛在过氧酸作用下, 则发生氢的迁移,而重排为酸.
O R C H O
CF3CO3H
R
C
O H
环酮重排为内酯
O
CF3CO3H
Stable cation
Product
脂肪族伯胺与亚硝酸作用发生脱氮重排, 也是 Wagner-Meerwein重排的扩展, 叫做Demyanov 重排.
CH3 H3C C CH3
CH3 C CH2CH3 H2O H+ CH3
CH2NH2
HNO2
-N2
CH3
CH3 C CH2 CH3
CH3
OH C CH2CH3 CH3
CF 3COOH + O
CH3
+
OH C Ph
CF 3C O O OH
CH3
OH C OPh CF 3COOH +
H+ O C OPh
O C OCH Ph CH3
CH3
O * Ph C CH CH3 PhCO3H CHCl3
CH3
CH3
Group moved as the following order: tertiary alkyl ＞ aryl > secondary alkyl ＞primary alkyl ＞ methyl
CH3 CH3 C CH2OH CH3 H
+
CH3
CH3 C CH2OH2 CH3
Cl
-
H2O
Cl C CH2CH3 CH3
CH3
CH3 C CH2 CH3
CH3
CH3 C CH2CH3 CH3
H+
CH3C=CHCH3 CH3
Wagner-Meerwein重排最早是在双萜类化合物的反 应中发现的.
4 Beckmann Rearrangement
R C N OH R'
HO
H
+
R' C N
O C N R
R' H
R
Ph C N
CH3 OH
PCl5 ethyl ether
O C N Ph
CH3
H
The group opposite to hydroxy will shift
Ph C N
C6H4OCH3 -p