yqChapter 17 Ketones and Aldehydes II.ppt

1、Chapter 17Ketones and Aldehydes II,Aldol Reaction,Reaction at the - Carbon of Carbonyl Compounds 羰基取代反应和缩合反应,General Nucleophilic Additions to the C=O,Hydrogens of Carbonyl Compounds,1. Keto-Enol Tautomerism?,Enol (an alkene + an alcohol),Reaction at the - Carbon of Carbonyl Compounds,Some Represent

2、ative Enol Percents,Enol form of 2,4-pentanedione,103 pm,133 pm,134 pm,141 pm,124 pm,166 pm,H3C,C,C,C,CH3,H,O,O,H,C=C and C=O are conjugated,Intramolecular hydrogen bond,1、 KetoEnol Tautomerism (互变异构) 酸和碱均可催化这一互变异构平衡的达到 碱性条件下，碱夺取a -H形成烯醇负离子,酸催化条件下，羰基氧首先质子化，吸电子作用进一步增强，然后脱去a H形成烯醇,1、 KetoEnol Tautomer

3、ism,2、Formation of Enolate 烯醇负离子由于羰基的共轭作用得以稳定 弱碱如NaOH，RONa作用下，反应只能达到一定的平衡 强碱如LDA作用下，可以定量地转化为烯醇负离子, low temperature, give kinetic enolate high temperature, give thermodynamic enolate,动力学控制产物,热力学控制产物,2、Formation of Enolate,强碱有利于形成动力学控制的少取代烯醇负离子。 酸性条件则有利于形成热力学控制的多取代烯醇。 弱碱条件下，影响因素会更多，选择性不高。,2、Formation

4、of Enolate 酸性条件下将形成烯醇，而不是烯醇负离子,Examples 预测下列每组化合物，哪一个烯醇负离子是主要的（动力学控制产物）,预测下列每组化合物中，哪一个烯醇结构较稳定，即为热力学控制烯醇？,Racemization,Racemization at an a-carbon is catalyzed by acid,3. The -Carbon Atom and its Hydrogens,羰基C=O的吸电子作用使得a-H具有明显的酸性，在碱性条件下可以离解，生成烯醇负离子，从而成为亲核试剂，进攻羰基碳或卤代烃，发生亲核加成反应、亲核取代反应。,1,2,3,烯醇中的C-C双键接

5、受亲电试剂进攻，发生a 卤代反应；醛酮、羧酸和酰卤可以发生该反应 烯醇负离子作为亲核试剂，进攻卤代烃的缺电子碳，则发生亲核取代反应；进攻羰基碳则发生亲核加成反应；,烯醇负离子作为亲核试剂，发生亲核加成的产物可以脱水缩合形成a, b-不饱和羰基化合物；烯醇负离子还可以与a, b-不饱和羰基化合物反应生成1, 5-二羰基化合物。 1, 5-二羰基化合物进一步发生分子内缩合就形成环状结构。,烯醇或烯醇负离子具有C=C双键，可以接受亲电试剂进攻，发生亲电取代反应。酸碱催化机理有所不同。,4、a Halogenation,比较I和II，由于卤素的吸电子作用，II中羰基氧上的电子云密度降低，因此质子化能力

6、降低，反应多停留在一卤代阶段,质子化相对容易,Mechanism of Acid-catalyzed：,比较I和II，由于卤素的吸电子作用，II中连卤素碳上氢的酸性增强，更容易形成烯醇负离子，反应难以停留在一卤代阶段，将进一步发生多卤代反应。 如果原料是甲基酮，则将发生进一步反应，并断键生成卤仿。,Mechanism of base-catalyzed：,4、a Halogenation,Acid-catalyzed： monosubstituent; reactivity:RCOCHR2 RCOCH2R RCOCH3 Base-catalyzed： multisubstituent reac

7、tivity: RCOCH3 RCOCH2R RCOCHR2 RCOCH3 and RCH(OH)CH3发生卤仿反应,碘仿反应：用于鉴别甲基酮和能氧化为甲基酮的醇,4、a Halogenation,羧酸及酰卤 Hell-Volhard-Zelinski reaction (HVZ reaction),4、a Halogenation,完成下列转化,-卤代酮在NaOH水溶液中发生重排成为含有相同C数的羧酸，如果是-环状卤代酮则导致环变小。,法沃斯基重排,5. Alkylation Reactions,1) From enolate,Lithium Enolates,The extent to w

8、hich an enolate anion forms depends on the strength of the base used.,One very useful strong base for converting ketones to enolates : Lithium diisopropylamide - (i-C3H7)2N-Li+,Regioselective Formation of Enolate Anions,Lithium Enolates in Directed Aldol Reactions,通过enolate的方法，还会得到二烷基化和氧烷基化的产物,2) Fr

9、om enamine(烯胺),通过enamine的方法，只得到单烷基化的产物，合成上更有用。,5. Alkylation Reactions,Synthesis Using imine,Alkylation烃基化,6、Aldol加成和Aldol缩合,1) Aldol addition and aldol condensation,Aldol addition Aldol condensation,b-hydroxyaldehyde b-hydroxyketone,a, b -unsaturated aldehyde a, b -unsaturated ketone,Aldol addition

10、s,Aldol condensation,Aldol products easily dehydrate in acid and sometimes in base.,6、Aldol加成和Aldol缩合,Preparation via Aldol Condensation and reduction!,6、Aldol加成和Aldol缩合,Intramolecular aldol addition to form cyclic b-hydroxyketone or a, b unsaturatd ketone,6、Aldol加成和Aldol缩合,Dieckmann cyclization.,例题

11、与习题 完成下列反应,The mixed aldol addition,如果两个反应物都具有a-H，则将 得到四个产物,6、Aldol加成和Aldol缩合,Crossed Aldol Condensations,Reaction of two different aldehydes: One with an -hydrogen (donor) Other with no -hydrogen (acceptor),acceptor,donor,With one excess starting material, one product could be mainly obtained.,How

12、to get the desired product?,采用强碱LDA与一个醛或酮反应，使之定量地转化为烯醇负离子，然后再向该体系中加入另一个醛或酮，则可以得到单一产物。,6、Aldol加成和Aldol缩合,But,Kinetic enolate,Thermodynamic enolate,LiN(i-C3H7)2,Claisen-Schmidt Reactions,When ketons are used as one component, the Crossed Aldol Condensations are called Claisen-Schmidt Reactions,6、Aldol

13、加成和Aldol缩合,Condensations with Nitroalkane,Condensations with Nitriles,6、Aldol加成和Aldol缩合,-不饱和醛酮加成反应的分类,* 共轭不饱和醛酮的加成,C=C亲电加成,C=O亲核加成,1,4-共轭加成,1,2-亲核加成,7. Reaction of a, b -unsaturated carbonyl compound,共轭不饱和醛酮的加成,在碱性条件下加成反应的机制,H+,互变异构,H,在酸性条件下加成反应的机制,Z-,互变异构,H,使用强亲核试剂容易发生1，2加成；而使用弱亲核试剂容易发生1，4共轭加成。与烯烃的

14、共轭加成对比,1,2-Addition,observed with strongly basic nucleophiles Grignard reagents LiAlH4 NaBH4 Sodium acetylide strongly basic nucleophiles add irreversibly,1,4-Addition,observed with weakly basic nucleophiles cyanide ion (CN) thiolate ions (RS) ammonia and amines azide ion (N3) weakly basic nucleophi

15、les add reversibly,Copper catalyzed conjugate addition reactions,7. Addition to a, b -unsaturated carbonyl compound,Conjugate Addition of Organocopper regants,Lithium dialkylcuprates add predominantly in the less hindered way.,7. Addition to a, b -unsaturated carbonyl compound,It is the addition of

16、a a, b -unsaturated carbonyl compound with an enolate as a nucleophile 1, 4 addition to form 1, 5-dicarbonyl compounds,Michael addition,7. Addition to a, b -unsaturated carbonyl compound,The nucleophile can be an enolate generated from compounds other than aldehydes or ketones it can be an ester, a

17、nitro-compound, or a nitrile The best nucleophile are: b-diketones, b-diesters, b-keto esters,b-keto nitriles e.g.,7. Addition to a, b -unsaturated carbonyl compound,Stork enamine reaction Enamines can be used in place of enolates in Micheal reactions.,7. Addition to a, b -unsaturated carbonyl compo

18、und,The Robinson annulation (环合) 1,5-diketones can undergo an intramolecular aldol addition to form cyclic b-hydroxyketones or a, b-unsaturated ketones,7. Addition to a, b -unsaturated carbonyl compound,The Robinson annulation (环合) e.g.,7. Addition to a, b -unsaturated carbonyl compound,Robinson ann

19、ulation (环合) Applied in synthesis e.g.,7. Addition to a, b -unsaturated carbonyl compound,Robinson annulation (环合) Applied in synthesis e.g.,?,?,7. Addition to a, b -unsaturated carbonyl compound,Robinson annulation (环合) Applied in synthesis,-不饱和醛酮发生加成反应时的选择规律,1 卤素、HOX不发生共轭加成，只在碳碳双键上发生1,2-亲电加成。 2 HX, H2SO4等质子酸以及H2O、ROH在酸催化下与,-不饱