1、Chapter 15 Enols and Enolates （烯醇与烯醇负离子）,15.1 The acidity of the hydrogens ofcarbonyl compounds: enolate ions 15.2 Keto and Enol tautomers 15.3 Halogenation of aldehydes and ketones 15.4 The Haloform Reaction 15.5 The Aldol Condensation（羟醛缩合） 15.5.1 Mechanism for the aldol addition 15.5.2 The featur
2、es of aldol addition 15.5.3 Mixed aldol condensationClaisen-Schmidt condensation,15.6 Nucleophlic addiotion to -unsaturatealdehydes and ketones 15.6.1 1,2 addition and 1,4 addition 15.6.2 The Micheal reaction 15.6.3 Conjugate addition of organocopperreagents 15.7 Alkylation of enolate ions,Hydrogens
3、 are acidic:,When a carbonyl compound loses an proton, the anion called enolate isproduced:,The acidity of the hydrogens ofcarbonyl compounds: enolate ions,Pka: 19-20 25,A,B,Enolates (烯醇负离子）,Enolate is stabilized by resonance,P358,p-conjugation,Lithium diisopropylamide (二异丙基氨基锂) (LDA),Sodium hydride
4、 (氢化钠),P361,Keto and enol form are called tautomers,Aldehydes and ketones containing - hydrogen are in equilibrium with their enol isomers,Keto and Enol tautomerism (酮式与烯醇式互变异构）,The bond of C=O is stronger thanC=C,P353,In -dicarbonyl compounds, two carbonyl groups are separated by oneCH2group,Resona
5、nce stabilization of the enol form,Halogenation of aldehydes and ketones,Aldehydes and ketones react with halogens by substitution of one of the hydrogen,Features of the reaction: Acid catalyzed Regiospecific Aldehydic hydrogen isnt affected,P356 11.3,Mechanism of halogenation of aldehydesand ketone
6、s,Step 1 Acid-catalyzed formation of an enol,Step 2 Reaction of the enol with halogen,Ch.P349,The Haloform (卤仿)Reaction,A methyl ketone react with a halogen in the present of base, multiple halogenations occur at the carbon of -CH3,The dissociation of the trihalomethylketone in aqueous base, to prod
7、uce carboxylate （羧酸盐）and the haloform,CHI3 is yellow Precipitate (沉淀）,15.5 The Aldol Condensation(羟醛缩合),2 Molecules of aldehydes,Dilute sodium hydroxide,To form hydroxy aldehyde,aldehyde + alcohol = aldol,Aldol addition , aldol reaction or aldol condensetion,15.5.1 Mechanism for the aldol addition:,
8、Step 1 Base-catalyzed formation of enolateion:,Enolate ion,P366 11.8,Step 2 The nucleophilic addition of enolate to carbonyl group:,Step 3 The alkoxide ion abstracts a proton from water to form aldol:,- conjugation,15.5.2 The features of aldol additions: Carbon-carbon bond formation between the-carb
9、on atom of one aldehyde and the carbonyl group of another.,2. Dehydration of addition product,The addition product ( aldol + OH）is heated,hydration occurs to form ,- unsaturated aldehyde:,3. Reversible reaction. the equilibrium ofaldol reation for ketones is unfavorable.,Intra-molecular aldol conden
10、sation:,1.6-Cyclodecanedione（1,6-环癸二酮）,Bicyclo5.3.0dec-1(7)- en-2-one(96%) （二环5.3.0-1-癸烯-2-酮）,4. The product with two functional groups:,Insect repellent,15.5.3 Mixed aldol condensation,Only one of the reactant can form an enolate. One of the reactant is more reactive toward nuelophilic addition tha
11、n other.,Claisen-Schmidt condensation,Ketones react with aromatic aldehydein the presence of base, to give mixed aldolcondensation product:,The enolate of ketone as a nucleophile attacks the carbonyl group of aromatic aldeyhyde.,2-Hydroxymethyl- 3-methylbutanal (3-甲基-2-羟甲基丁醛),Claisen, Ludwig Born: K
12、ln (Germany), 1851 Died: Godesberg near Bonn(Germany), 1930,http:/www.chemsoc.org/networks/ enc/fecs/Claisen.htm,15.6 Conjugation addition to ,-unsaturated aldehydes and ketones,The nucleophilic addition of ,- unsaturated aldehydes or ketones may be in two way:,1,2-addition Direct addition （直接加成）,1,
13、4-addition Conjugate addition（共轭加成）,The resonancestructure:,15.6.1 1,2 addition and 1,4 addition,General roles: When the nucleophile is stronger base, 1,2 addition is often observed: RMgX, RLi, LiAlH4.,2. When the nucleophile is weaker base, conjugate addition is observed:,(95%),3. 1,2 additionKinet
14、ic control1,4 addtionThermodynamic control,1,2 addition product retains C=C bond, 1,4 addition product retains C=O bond. carbon-oxygen double bonds are more stable than carbon-carbon double bonds,15.6.2 The Micheal Reaction,Conjugate additions of enolate ions (or carbanions)to ,-unsaturate carbonyl
15、compoundsMicheal addition(迈克尔加成) or Micheal reaction.,Enolate ions or carbanions: derived from - dicarbonyl compounds.,Ch.P413,Robinson annulation,(65%),Intramolecular Aldol addition product,Micheal addition of stabilized anions,3-oxocyclohexylacetic acid (3-氧代环己基乙酸),Problem:,Sir Robert Robinson Uni
16、ted Kingdom University of Oxford Oxford, United Kingdomb. 1886 d. 1975,http:/www.nobel.se/chemistry/laureates/1947/robinson-bio.html,The Nobel Prize in Chemistry 1947,Robinson received the 1947 Nobel Prize in Chemistry for his work on the synthesis of natural products, especially the alkaloids. His
17、1917 landmark one-step synthesis of tropinone from three simple precursors at room temperature in dilute aqueous solution was the forerunner of modern biomimetic syntheses. He did structural and synthetic work on other alkaloids (strychnine, morphine, brucine), on steroids (cholesterol), on wood dye
18、s (brazilin, haematoxylin), and on the coloring matter of flowers (anthocyanins). In connection with steroid synthesis, he developeda general method for constructing a six-membered ring onto a ketone with an enolizable hydrogen (Robinson annulation).In the mid-1920s, Robinson introduced his electron
19、ic theory of organic reactions, and used it to rationalize orientation in electrophilic aromatic substitution. The curved arrow used by chemists to represent electron displacements was first used in this way by Robinson (1924). Robinson wrote over 500 papers and several books on natural products but
20、 in addition he wasan avid chess player who wrote “The Art and Science of Chess:A Step-by-Step Approach“.,http:/poohbah.cem.msu.edu/Portraits/PortraitsHH_Detail.asp? HH_LName=Robinson,15.6.3 Conjugate addition of organo-copper reagents,Organocopper reagents (CuLiR2) undergo conjugate addition to,-un
21、saturated carbonyl compounds:,98% 2%,Lithium dialkylcuprates adds predominantly in the less-hindered way to give the product with the alkyl groups trans to each other.,15.7 Alkylation of enolate ions,Enolate ions derived from - dicarbonyl compounds react with alkyl halide by SN2 mechanism :,Enolate ions of - dicarbonyl compounds are more stables than aldehydes or ketones.,p- conjugation,2. Alkyl halide: CH3X,RCH2X,P362 11.6,
