1、Chapter 19 Synthesis and reactions of-dicarbonyl compounds:More chemistry of enolate anions19.1 introduction dicarbonyl compounds:Compounds having two carbonyl groups separated by an intervening carbon atom.Specific enol equivalent from 1,3-dicarbonyl compoundsWhy donot enols formed from 1,3-dicarbo
2、nyl compounds react immediately with themselves by the aldol reaction?i)These enols are very stable.ii)The carbonyl groups in the unenolized fraction are poorly electrophilic ester and ketone groups.19.2 Crossed aldol reaction of active hydrogen compounds with aldehydes and ketones-the Knoevenagel c
3、ondensation.Mechanism:E1cBMore examples:More about the base:secondary amine R2NHThe electrophile could be the iminium ion19.3 Claisen condensation:the synthesis of-keto estersmechanismA wrong mechanismDouble-headed curly arrowNotice:When planning a reaction with an ester and an alkoxide anion,it is
4、important to use an alkoxide that has the same alkyl group as the alkoxyl group of the ester.Esters having only one hydrogen do not undergo the usual Claisen condensation.However,they can be converted to-keto esters by reactions that use very strong bases.Dieckmann condensation intramolecular Claise
5、n condensationIn general,the Dieckmann condensation is useful only for the preparation of 5-and 6-membered rings.19.3A Crossed Claisen condensationsCrossed Claisen condensations are possible when one ester component has no hydrogens and,therefore,is unable to form an enolate ion and undergo self-con
6、densation.Reactive esters that cannot enolize19.3B Acylation of other carbanions19.4 The acetoacetic ester synthesis:synthesis of methyl ketones(substituted acetones)Q:How to synthesis the following compound?The third routeAcetoacetic ester synthesisA second alkylation is also possibleAcetoacetic es
7、ter synthesis in practice 1)Monosubstituted acetone2)Disubstituted acetoneEthyl acetoacetate serves as the synthetic equivalent of the enolate from acetone.3)4-oxopentanoic acod4)-diketones5)Acylation of acetoacetic ester anion6)Phenylation of acetoacetic esterDianion of acetoacetic ester19.5 The ma
8、lonic ester synthesis:synthesis of substituted acetic acidsdialkylacetic acid1.Synthesis of glutaric acidDihaloalkanes in malonic ester synthesis:2.Synthesis of cyclic carboxylic acidSummaryWhile.19.6 Further reactions of active hydrogen compoundsActive hydrogen compounds:compounds that have two ele
9、ctron-withdrawing groups attached to the same carbon atom.pKa 3-1319.7 Direct alkylation of esters and nitriles19.8 the Perkin reaction Recall back the Knoevenagel condensationThe-unsaturated acid can also be synthesized by Perkin reaction:mechanism19.9 Michael additionsRobinson annulation(conjugate
10、 addition followed by aldol cyclization)Conjugate addition followed by Claisen ester cyclization gives cyclic diketonesAcetoacetic ester synthesis?,-unsaturated nitriles are ideal for conjugate additiontropinone synthesis I(Michael addition)tropinone synthesis II(Mannich reaction)Mechanism:19.10 Sto
11、rk enamine reactions19.1 recall backEnamine in Aldol reaction19.2 Acylation,alkylation and Michael addition reaction of enaminesThe products of N-acylation are unstable salts and N-acylation is reversible.Enamines in Michael addition:For enamine alkylation,less reactive alkylating agents react to a
12、significant degree at N rather than at C.Heating the N-alkylated product often converts it to a C-alkyl compound.Asymmetric synthesis19.11 BarbituratesThe first two barbiturates used in medicine(as soporifics)How nature makes fatty acidsFatty acidsFatty acids are made in living things by Claisen ester style condensations of acetic acid derivatives.
