1、Chapter 5,Rearrangement Reaction,第五章 重排反應(yīng),1,精制課件,重排反應(yīng) 1. 碳原子到碳原子重排 （1） Wagner-Meerwein重排 （2） Pinacol重排 （3）二苯乙醇酸重排 （4） Favorski重排 （5） Wolff重排及Aendt-Eistert反應(yīng),2,精制課件,重排反應(yīng) 2. 碳原子到雜原子重排 （1）Beckmann重排 （2）Hoffman重排 （3）Curtius重排 （4）Schmidt重排 （5）Bayer-Villiger反應(yīng),3,精制課件,重排反應(yīng) 3. 雜原子到碳原子重排 （1）Stevens重排 （2）Somm

2、elet-Hauser重排 （3）Wittig重排 4. s鍵遷移重排 （1）Claisen重排 （2）Cope重排 （3）Fischer吲哚合成,4,精制課件,分子重排反應(yīng) 分子重排反應(yīng)就是化學(xué)鍵的斷裂和形成發(fā)生在同一分子中，引起組成分子的原子的配置方式發(fā)生改變，從而形成組成相同、結(jié)構(gòu)不同的新分子的反應(yīng)。 重排反應(yīng)中鍵的斷裂和形成的方式有異裂、均裂和環(huán)狀過渡態(tài)三種。,5,精制課件,Radical rearrangement,Usually, the rearrangement was classified by the electron property of the moving grou

3、p,Nucleophilic rearrangement,Electrophilic rearrangement,第一節(jié) 重排反應(yīng)機理,6,精制課件,2020/6/29,1. Nucleophilic rearrangement,7,精制課件,2020/6/29,2. Electrophilic rearrangement,8,精制課件,2020/6/29,3. Radical rearrangement,9,精制課件,1. 反應(yīng)通式,第一節(jié) 碳原子到碳原子重排,一、Wagner-Meerwein重排,10,精制課件,11,精制課件,2. 反應(yīng)機理,12,精制課件,3. 影響因素 （1）碳正離

4、子形成方式：鹵代烴與Lewis酸作用、醇與酸作用、烯烴質(zhì)子化、胺與亞硝酸作用。 （2）the stereochemistry of themigrating group is retained, which is in accordance of the Woodward-Hofmann rules.,13,精制課件,4.應(yīng)用特點 （1）醇類的Wagner-Meerwein重排,2020/6/29,Addition of a nucleophile,Loss of a proton,14,精制課件,2020/6/29,15,精制課件,（2）鹵代烴的Wagner-Meerwein重排,Stabl

5、e cation,16,精制課件,2020/6/29,Stable cation,Migratory order of the migration groups,17,精制課件,（3）胺類化合物的Wagner-Meerwein重排,2020/6/29,18,精制課件,2020/6/29,19,精制課件,二、Pinacol Rearrangement,1. 反應(yīng)通式,20,精制課件,X = Cl, Br, I, SR, OTs, OMs, N2+,21,精制課件,2. 反應(yīng)機理,22,精制課件,（1）碳正離子的穩(wěn)定性 the product is usually formed via the m

6、ost stable carbocation intermediate when the glycol substrate is unsymmetrical;,3. 影響因素,23,精制課件,（2）立體化學(xué)因素,24,精制課件,(3) besides protic acids, Lewis acids (e.g., BF3OEt2, TMSOTf) are also used; various conformational effects and neighboring group participation in cyclic systems are complicating factors

7、.,25,精制課件,（4）遷移能力及推廣的重排,. HPh321 .,26,精制課件,.,27,精制課件,28,精制課件,-二酮在濃堿作用下發(fā)生重排，生成安息香酸的重排反應(yīng)稱為二苯乙醇酸重排。,三、二苯乙醇酸重排,1. 反應(yīng)通式,29,精制課件,2. 反應(yīng)機理,30,精制課件,3. 影響因素,（1）用苛性堿得到羥基酸，用醇鹽則生成酯；,31,精制課件,（2）環(huán)狀二酮生成環(huán)狀羥基酸,32,精制課件,四、Favorski重排,1. 反應(yīng)通式,33,精制課件,2. 反應(yīng)機理,34,精制課件,催化劑的影響,3. 影響因素,35,精制課件,Different - chloroketone form sa

8、me rearrangement product:,Same intermediate,36,精制課件,由鹵代酮制備羧酸衍生物,4. 應(yīng)用特點,37,精制課件,五、 Wolff重排及Arndt-Eistert反應(yīng),Wolff rearrangement,1. 反應(yīng)通式,38,精制課件,2. 反應(yīng)機理,39,精制課件,40,精制課件,(1) the reaction can be initiated thermally, photolytically, or by transition metal catalysis; (2) freshly prepared silver(I)oxide or

9、 silver(I)benzoate are best suited for the reaction; (3) if the migrating group has a stereocenter, the stereochemistry remains unchanged (net retention of configuration) after the migration;,3. 影響因素,41,精制課件,Examples,42,精制課件,Arndt-Eistert synthesis,1. 反應(yīng)通式,43,精制課件,2. 反應(yīng)機理,44,精制課件,羧酸同系化C+1,3. 應(yīng)用特點,45

10、,精制課件,46,精制課件,酮肟在酸性催化劑的作用下重排成酰胺的反應(yīng)稱為貝克曼重排。,H+,R-C-NHR,O,=,第三節(jié) 碳原子到雜原子重排,一、Beckmann重排,1. 反應(yīng)通式,47,精制課件,重排,互變異構(gòu),2. 反應(yīng)機理,48,精制課件,（1）催化劑影響 The reaction is usually carried out under forcing conditions (high temperatures, large amounts of strong Brosted acids) and it is non-catalytic.The applied Brosted ac

11、ids are: H2SO4, HCl/Ac2O/AcOH, etc. 其他催化劑：PPA、POCl3、PCl5、SOCl2、MsCl、TsCl等。,3. 影響因素,49,精制課件,（2）溶劑的影響 用極性小或非極性的非質(zhì)子溶劑，PCl5催化可防止異構(gòu)化,50,精制課件,當溶劑中含有親核性化合物、分子內(nèi)含有親核性官能團、溶劑本身為親核性化合物，碳正離子與其結(jié)合而得不到酰胺 也可用此制備苯并咪唑衍生物,51,精制課件,立體專一性,4. 應(yīng)用特點,52,精制課件,二、Hofmann重排,1. 反應(yīng)通式,53,精制課件,2. 反應(yīng)機理,54,精制課件,55,精制課件,3. 應(yīng)用特點,（1）制備C-1

12、伯胺,56,精制課件,(2) 因親核劑不同而產(chǎn)物各異,57,精制課件,（3） Curtius Rearrangement,58,精制課件,59,精制課件,60,精制課件,Example,61,精制課件,62,精制課件,（4） Schmidt Rearrangement,63,精制課件,64,精制課件,65,精制課件,66,精制課件,（5） Lossen Rearrangement,67,精制課件,68,精制課件,Example,69,精制課件,酮類化合物被過酸氧化，與羰基直接相連的碳鏈斷裂，插入一個氧形成酯的反應(yīng)稱為拜耳-魏立格（Baeyer-Villiger)氧化重排。,+ CH3COOOH

13、,CH3COOC2H5,40oC,+ CH3COOH,常用的過酸有： （1）一般過酸 + 無機強酸（H2SO4） （2）強酸的過酸 ：CF3COOOH （3）一般酸 + 一定濃度的過氧化氫（產(chǎn)生的過酸立即反應(yīng)）,（5）拜耳-魏立格氧化重排,70,精制課件,反應(yīng)機理,H+,O-O鍵斷裂,-RCOO- , -H+,R重排,R3C- R2CH- ,RCH2- CH3-,71,精制課件,3. 從雜原子到碳原子的重排,Stevens重排,72,精制課件,R1 = EWG = Ar, heteroaryl, COR, COOR, CN; Y= CH2, CHR, NH;,base: NaH, KH, RL

14、i, ArLi, RONa, ROK,R4 = CH3, alkyl, allyl, benzyl,CH2COAr,73,精制課件,74,精制課件,75,精制課件,General fetures,(1) the key intermediate of the rearrangement is the nitrogen- or sulfur ylide; (2) the R1 group has to be able to stabilize carbanions, so it is often an electron-withdrawing group;,76,精制課件,General fet

15、ures,(3) depending on the nature of R1, the acidity of the adjacent C-H bond varies so the type of base used for the deprotonation must be chosen accordingly; (4) R2 and R3 groups of ammonium salts cannot contain a hydrogen at their -position, since the Hofmann elimination may compete;,77,精制課件,(5) w

16、hen the migrating group has a stereocenter, it is transferred with retention of configuration at the migrating terminus; (6) when R1=aryl or heteroaryl, the Sommelet-Hauser rearrangement becomes competitive;,78,精制課件,Example,79,精制課件,80,精制課件,Sommelet-Hauser重排,81,精制課件,82,精制課件,Wittig重排,83,精制課件,Example,8

17、4,精制課件,85,精制課件,4. s-鍵遷移重排,Claisen重排,（1）Claisen Rearrange,86,精制課件,87,精制課件,環(huán)狀過渡態(tài),烯丙基苯基醚,鄰烯丙基苯酚,對烯丙基苯酚,互變異構(gòu),互變異構(gòu),環(huán)狀過渡態(tài),3,3遷移,3,3遷移,88,精制課件,89,精制課件,Example,90,精制課件,（2）Amino-Claisen Rearrangement,This reaction occurs best when nitrogen is converted to the ammonium salt.,91,精制課件,(3) Thio-Claisen Rearrange

18、ment,This reaction is often run with a reagent that will convert sulfur to oxygen following the reaction. An advantage of the thio-Claisen rearrangement is that the precursor can be deprotonated and alkylated.,92,精制課件,93,精制課件,(4) The Carroll Reaction,94,精制課件,Johnson-Claisen重排,95,精制課件,Mechanism,96,精制課件,Example,97,精制課件,Eschenmoser-Claisen重排,98,精制課件,Ireland-Claisen重排,The most useful of all Claisen rearrangements. The enolate may be trapped with TMSCl or t