0522讲课稿件

1、acylation of enolate ionsthe enolate ions from acetoacetic esters react with acylating reagents such as acyl chlorides and acid anhydrides. because these reagents react with ethanol and ethoxide ion, the syntheses typically use sodium hydride (nah) as a base to form the enolate ions in aprotic soven

2、ts such as dimethylformamide (dmf) or dimethyl sulfoxide (dmso).example:o=oeto=nahaproticsolvent-na+o=oeto=acylationo=oeto=r(1) dil naoh/heat(2) h3o+hydrolysisacidification100 ocdecarboxylationrclooo=oho=rorooa -diketoneacylation of enolate ions1,3-dicarbonyl compound应用应用4 1,2-二官能团化合物的合成二官能团化合物的合成1,

3、5二羰基化合物：麦克加成二羰基化合物：麦克加成,含活泼氢的羰化物含活泼氢的羰化物,需添酯基，保证活泼氢酸性足够大需添酯基，保证活泼氢酸性足够大 三乙03中科院中科院08南开南开作业作业106复旦复旦先羟醛缩合容易关环先羟醛缩合容易关环use of-halo esters or ketones in alkylation应用应用5an example of an extended synthesishere is an example of a classic synthesis of 2-alkylcyclopentanones:h3coc2h5oo naoetr xh3coc2h5oooh3

4、coc2h5oo naoetch3coch3coch2ch3coch2ch3coch2ch3coch2ch3coch2(ch2)n-二羰基化合物-二羰基化合物引入基团为coch3试剂: ch3cocl引入基团为ch2coch3试剂: ch3coch2cl或 用i2偶合试剂:(ch2)nxx1.3二羰基二羰基(氧氧) 化合物化合物 酯缩合酯缩合三乙三乙1.4二羰基二羰基(氧氧)化合物化合物 羰基负离子羰基负离子+卤代物卤代物1.5二羰基二羰基(氧氧)化合物化合物 羰基负离子羰基负离子+不饱和物不饱和物 不饱和化合物不饱和化合物 羟醛缩合羟醛缩合ch2coonacl ch2coonacnch2(c

5、ooc2h5)2c2h5ohh2so4nacnohch2coonacl ch2coonacnch2(cooc2h5)2c2h5ohh2so4nacnohch2coonacl ch2coonacnch2(cooc2h5)2c2h5ohh2so4nacnohch2coonacl ch2coonacnch2(cooc2h5)2c2h5ohh2so4nacnoh the malonic ester synthesis of substituted acetic acids2.the enolate can be used as the nucleophile in an sn2 reaction wi

6、th a 1o or ch3 alkyl halide.5. by a similar sequence of alkylation, hydrolysis, and decarboxylation, substituted acetic acids may be prepared from diethyl malonate.the malonic ester synthesis of substituted acetic acidsby a similar sequence of alkylation, hydrolysis, and decarboxylation, substituted

7、 acetic acids may be prepared from diethyl malonate.etocch2coeto=o=r-ch2coohdiethyl malonatealkylated acetic acidmalonic ester synthesismalonate alkylation using dihaloalkanes复旦复旦(ch2)nhoohoo1) oh2) h+, 2xx (ch2)n1) 2naoetetooetoo2)michael additions of 1,3-dicarbonylsthe addition of 1,3-dicarbonyls

8、to,-unsaturated carbonyl compounds under base-catalyzed conditions are referred to as michael additions.michael additions of 1,3-dicarbonylsthe addition of 1,3-dicarbonyls to , -unsaturated carbonyl compounds under base-catalyzed conditions are referred to as michael additions.ch3c=chcoetch3ethyl 3-

9、methyl-2-propenoateo=etoocetoocch2+diethyl malonatecatalytic amt.of naoetetoh, 25 occh3c-ch2coeto=ch3ch(co2et)2these additions are understandable in terms of concepts already discussed that describe the formation and reactivity of enolate anions derived from 1,3-dicarbonyl compounds and the mode of

10、addition to conjugated enone systems. a mechanisma mechanismformation of enolate ionnaoet +catalytic amount + etohsmall amount ofenolate ionoetoetoooetoetoo-na+conjugate addition of enolate ionoeto+oetoetoo-enolate ion of esteretoetooooetoproton transfer and regeneration of the base+ etoh+ eto-etoet

11、ooooeto-etoetooooetofinal productfurther synthetic modificationsalkaline hydrolysis and heating to induce decarboxylation of the malonic acid subunit yields 3,3-dimethylglutaric acid.further synthetic modificationsalkaline hydrolysis and heating to induce decarboxylation of the malonic acid subunit

12、yields 3,3-dimethylglutaric acid.(1) dil naoh, heat(2) h3o+heat, 100 oc- co2etoetooooetohohooooho3,3-dimethylglutaric acidhohoooohohoohoo复旦复旦复旦复旦作业作业20101中科大中科大512etooetoo1) naoetx2) x (ch2)netooetoox(ch2)nnaoetetooetoo(ch2)n1) oh2) h+, hoo(ch2)n -卤代酸的直接氨化卤代酸的直接氨化 gabriel合成法合成法 strecker合成法合成法ohorx2

13、nh3ohornh2+nh4xcnh2cncnh2coohconacnnh4clh3ooch3orxoornh3nkoonoorooch3h3o 复习、氨基酸的制备方法复习、氨基酸的制备方法邻苯二甲酰亚胺与氢氧化钾的乙醇溶液作用转变为邻苯邻苯二甲酰亚胺与氢氧化钾的乙醇溶液作用转变为邻苯二甲酰亚胺盐，此盐和卤代烷反应生成二甲酰亚胺盐，此盐和卤代烷反应生成n-烷基邻苯二甲烷基邻苯二甲酰亚胺，然后在酸性或碱性条件下水解得到一级胺和邻酰亚胺，然后在酸性或碱性条件下水解得到一级胺和邻苯二甲酸，这是制备纯净的一级胺的一种方法。苯二甲酸，这是制备纯净的一级胺的一种方法。 应用五、应用五、gabrialgab

14、rial合成法：合成法：1溴化丙二酸酯法溴化丙二酸酯法中科院中科院d,l-苯丙氨酸中科大中科大脯氨酸脯氨酸作业作业邻苯二甲酰亚氨基丙二酸二乙酯邻苯二甲酰亚氨基丙二酸二乙酯07中科院中科院作业作业3pcc氧化剂也称为沙瑞特（氧化剂也称为沙瑞特（sarrett）试剂，）试剂， pyridinium chlorochromate全名：全名：pyridinium chlorochromate pcc是吡啶是吡啶和和cro3在盐酸溶液中的络合盐，是橙红色晶体。它溶于在盐酸溶液中的络合盐，是橙红色晶体。它溶于ch2cl2，使用很方便，在室温下便可将伯醇氧化为醛，而，使用很方便，在室温下便可将伯醇氧化为醛，

15、而且基本上不发生进一步的氧化作用。且基本上不发生进一步的氧化作用。而且对分子中存在而且对分子中存在的的c=c、c=o、c=n等不饱和键不发生破坏作用。等不饱和键不发生破坏作用。 pcc络合盐结构络合盐结构氯铬酸吡啶嗡盐氯铬酸吡啶嗡盐 c5h5n.hcro3cl naoetlialh4h2o , h+, co2cooh浙江大学浙江大学04 作业作业44hcho + ch3chooh-ohohhohobrbrbrbrpbr34naoc2h52ch2(cooc2h5)2cco2c2h5co2c2h5+cc2h5o2cc2h5o2c+brbrbrbrco2c2h5co2c2h5c2h5o2cc2h5o

16、2c1. oh-2. h+, -co2coohhooc季戊四醇季戊四醇00科大科大乙酰氨基丙二酸二乙酯乙酰氨基丙二酸二乙酯丝氨酸丝氨酸3酰基丙二酸酯法酰基丙二酸酯法作业作业2retrosynthetic analysis and malonic ester synthesisif the target molecule is a carboxylic acid, consider it as a “substituted acetic acid” and then identify the alkyl groups that need to be introduced.retrosynthetic analysis and malonic ester synthesisif the target molecule is a carboxylic acid, consider it as