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1、本章学习要求,了解碳负离子形成的基本条件 掌握碳负离子引发的缩合反应的基本原理以及它们在有机合成中的应用 掌握Micheal等反应基本原理及其在有机合成中的应用,第三章 碳负离子,浙大,一. 碳负离子结构：,第一节 基本知识,A carbanion contains a carbon surrounded by eight electrons.so it is not electron deficient; rather,it is electron rich and a strong nucleophile.,1. 电子效应,二.稳定碳负离子的因素,中心碳连有强吸电子基时，将使碳负离子的稳定
2、性,中心碳连有供电子基时，将使碳负离子的稳定性,任何使电荷分散的结构因素,chemoffice2004,大连理工,DBCA,2.比较 a-氢酸性,4烯醇含量,1.510-4,7.710-3,7.3,76.5,3.比较稳定性,Keto-enol tautomerism,t:tmrizm,ki:tu,i:nl,中科大,常见位取代基对碳负离子稳定能力的顺序是： -NO2-COR-SO2Cl-COOR-CNCONH2-X-H-R-OR,第二节,Reactions of ketones and aldehydes :nucleophilic addition,Carbonyl condensations
3、 are alpha substitutions where the electrophile is another carbonyl compound. With ketones and aldehydes, protonation of the alkoxide gives the product of nucleophilic addition.,醛酮羰基 a 位 H 的弱酸性和烯醇负离子,（较稳定的共振式）,烯醇负离子,碳负离子,烯醇 (enol),酮 (one),性质分析,羰基氧有弱碱性 可与酸结合,羰基碳有亲电性 可与亲核试剂结合,a碳有吸电子基 a氢有弱酸性,碳与氧相连 氢易被氧
4、化,L:可被亲核试剂取代,羰基：可加成至饱和,a-H：有弱酸性,离去基团 (Leaving group),nju:kliufilik,Esters: nucleophilic substitution,est,Alkyl halides,nucleophiles,Aldehydes & ketones, reactions: Oxidation and Reduction Addition of cyanide氰化物 Addition of derivatives of ammonia Addition of alcohols Cannizzaro reaction Addition of G
5、rignard reagents 8) (Alpha-halogenation of ketones) (Addition of carbanions) addition of Grignard reagents aldol condensation “crossed” aldol condensation,.ksden,.sanad,dirivtiv,mnj,hldnein,.ldul,.kndensen,-C6H5 C6H6 C6H5MgBr,-CH2COX CH3COX(X=R,OR,NR2),R- RM, R2CuLi,-CH2COCH3 CH3COCH2CO2Et,-CH2COOH
6、CH2(CO2Et)2,Synthon,Synthetic Equivalent,.sinetik,.ikwivlnt,一 Aldol condensation,例：,b-羟基醛（酮）,醇 alcohol,醛 aldehyde,Under basic conditions, the aldol condensation involves the nucleophilic addition of an enolate ion to another carbonyl group. Aldol condensations often take place with subsequent dehydr
7、ation to give ,-unsaturated ketones and aldehydes.,nucleophilic attack,alkoxide,protonation,1.Base-promoted aldol condensation,ldul,反应可逆,强碱有利于脱水成不饱和醛,2.合成转换,合成 b-羟基醛(酮) 合成 a, b-不饱和醛(酮),转换成其它相关化合物,1, 3-二羰基化合物 (b-二羰基化合物),1, 3-二醇类化合物,Pd/c H2,NaBH4,H2 /Ni,例: 写出下列转变的机理,b- 羟基 醇,a, b-不饱和酮,分析：两者均与羟醛缩合反应有关,逆
8、向羟醛缩合,羟醛缩合,3.Acid-catalyzed aldol condensation,2010南开,Proposing reaction mechanisms 1).Consider the carbon skeletons of the reactants and products, and decide which carbon atoms in the products are likely derived from which carbon atoms in the reactants.,2).Consider whether any of the reactants is a
9、 strong enough electrophile to react without being activated. If not, consider how one of the reactants might be converted to a strong electrophile by protonation of a lewis basic site(or complexation with a lewis acid).,electrophile,酸催化，酮式转化成烯醇式,3).Consider how a nucleophilic site on another reacta
10、nt can attack the strong electrophile to form a bond needed in the product. Draw the product of this bond formation.,nucleophile,electrophile,烯醇对质子化的酮亲核加成，得到质子化的-羟基酮,5）.Draw all the steps of the mechanism,using curved arrows to show the movement of electrons.,4).Consider how the product of nucleophi
11、lic attack might be converted to the final product.or reactivated to form another bond needed in the product.,经过质子转移消除水得到产物,酸催化与碱催化的羟醛缩合对比,酸催化,碱催化,不对称酮,主要产物,主要产物,二.,不含 a H的羰基化合物先与催化剂混合，,克莱森-施密特反应（Claisen-Schmitt）,Slowly add the carbonyl compound having an hydrogen to this mixture. Why?,碳负离子一边生成，一边发生
12、加成反应可得单一产物：,酮的酰基化机理,酮与酯的a - 氢酸性比较：,优先?,半缩醛（酮）,缩醛（酮）,逆向为缩醛的水解机理,三.缩醛机理,复旦,作业,Acetals hydrolyze under acidic conditions, but they are stable to strong bases and nucleophiles. Acetals are easily made from the corresponding Ketones and aldehydes and easily converted back to the parent carbonyl compounds
13、.,This easy interconversion makes acetals attractive as protecting groups to prevent ketones and aldehydes from reacting with strong bases and nucleophiles.,本发明涉及一种丁醛乙二醇缩醛的制备方法，在装有分水器、回流冷凝管、温度计的三口烧瓶中，依次加入丁醛、乙二醇，催化剂和带水剂环己烷。加热回流搅拌至无水分离出来。反应结束后，待反应物冷却至室温后，过滤除去催化剂。分离出粗广物，依次用水、饱和食盐水洗涤，用无水硫酸镁干燥。在常压下蒸馏，收集馏
14、分，得无色透明液体具有果香味的丁醛乙二醇缩醛。所用催化剂为固体超强酸，该方法具有收率高，易于操作等特点。,专利号：201010575486,申请（专利权）人：尹华芳,特点： 1、对碱、氧化剂（碱性）、还原剂（Na+ROH）金属氢化物(LiAlH4、NaBH4)、催化氢化、Grignard试剂、亲核试剂等稳定，酸性条件下不稳定。 2、稀酸脱保护，甚至很弱的草酸、酒石酸或离子交换树脂都能有效的脱保护基。 3、常用的保护试剂是乙二醇、1,3-丙二醇,南大,2) Grignard试剂与醛、酮；环氧乙烷的反应,1o 醇,2o 醇（R = H）,3o 醇,3o 醇,1o 醇（R = H）,2o 醇,制备,
15、AlCl3,CH3CH2MgX,无水醚,H+ H2O,+,3oROH可用酮来制备,Restrictions on the use of Grignard reactions,BrCH2CH2CH2CHO,HOCH2CH2OH,干 HCl,Mg 无水醚,1）CH3COCH3,2）H+ H2O,H2,Ni P,3）,复旦,四.分子内羟醛缩合反应,复旦,1. a, b-不饱和醛酮与亲电试剂的亲电加成反应,五. a、 b-不饱和醛酮,有羰基，类似醛酮亲核加成,有双键，类似烯烃亲电加成,结构和性质分析：,卤素、HOX不发生共轭加成，只在碳碳双键上发生亲电加成。,X2,a, b-不饱和醛酮与亲核试剂的亲核加成反应,1, 2 加成为主（Nu : 强亲核试剂，如 RLi, 炔基钠， LiAlH4等）,例：,机理,1, 4 加成为主（Nu : 一些较弱的亲核试剂）,产物为b-位取代的饱和酮 形式上为3, 4-加成（亲核部分总是加在4 位）,HCN、NH3及RNH2 ,R2CuLi与,-不饱和醛酮的加成,3 其它（ 1, 4 和 1, 2 加成兼有）,H Me t-Bu,1, 2加成(
