0522講課稿件

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應用應用4 1,2-二官能團化合物的合成二官能團化合物的合成1,

3、5二羰基化合物：麥克加成二羰基化合物：麥克加成,含活潑氫的羰化物含活潑氫的羰化物,需添酯基，保證活潑氫酸性足夠大需添酯基，保證活潑氫酸性足夠大 三乙03中科院中科院08南開南開作業(yè)作業(yè)106復旦復旦先羥醛縮合容易關環(huán)先羥醛縮合容易關環(huán)use of-halo esters or ketones in alkylation應用應用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團為coch3試劑: ch3cocl引入基團為ch2coch3試劑: ch3coch2cl或 用i2偶合試劑:(ch2)nxx1.3二羰基二羰基(氧氧) 化合物化合物 酯縮合酯縮合三乙三乙1.4二羰基二羰基(氧氧)化合物化合物 羰基負離子羰基負離子+鹵代物鹵代物1.5二羰基二羰基(氧氧)化合物化合物 羰基負離子羰基負離子+不飽和物不飽和物 不飽和化合物不飽和化合物 羥醛縮合羥醛縮合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復旦復旦(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復旦復旦復旦復旦作業(yè)作業(yè)20101中科大中科大512etooetoo1) naoetx2) x (ch2)netooetoox(ch2)nnaoetetooetoo(ch2)n1) oh2) h+, hoo(ch2)n -鹵代酸的直接氨化鹵代酸的直接氨化 gabriel合成法合成法 strecker合成法合成法ohorx2

13、nh3ohornh2+nh4xcnh2cncnh2coohconacnnh4clh3ooch3orxoornh3nkoonoorooch3h3o 復習、氨基酸的制備方法復習、氨基酸的制備方法鄰苯二甲酰亞胺與氫氧化鉀的乙醇溶液作用轉變?yōu)猷彵洁彵蕉柞啺放c氫氧化鉀的乙醇溶液作用轉變?yōu)猷彵蕉柞啺符}，此鹽和鹵代烷反應生成二甲酰亞胺鹽，此鹽和鹵代烷反應生成n-烷基鄰苯二甲烷基鄰苯二甲酰亞胺，然后在酸性或堿性條件下水解得到一級胺和鄰酰亞胺，然后在酸性或堿性條件下水解得到一級胺和鄰苯二甲酸，這是制備純凈的一級胺的一種方法。苯二甲酸，這是制備純凈的一級胺的一種方法。 應用五、應用五、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業(yè)作業(yè)鄰苯二甲酰亞氨基丙二酸二乙酯鄰苯二甲酰亞氨基丙二酸二乙酯07中科院中科院作業(yè)作業(yè)3pcc氧化劑也稱為沙瑞特（氧化劑也稱為沙瑞特（sarrett）試劑，）試劑， pyridinium chlorochromate全名：全名：pyridinium chlorochromate pcc是吡啶是吡啶和和cro3在鹽酸溶液中的絡合鹽，是橙紅色晶體。它溶于在鹽酸溶液中的絡合鹽，是橙紅色晶體。它溶于ch2cl2，使用很方便，在室溫下便可將伯醇氧化為醛，而，使用很方便，在室溫下便可將伯醇氧化為醛，

15、而且基本上不發(fā)生進一步的氧化作用。且基本上不發(fā)生進一步的氧化作用。而且對分子中存在而且對分子中存在的的c=c、c=o、c=n等不飽和鍵不發(fā)生破壞作用。等不飽和鍵不發(fā)生破壞作用。 pcc絡合鹽結構絡合鹽結構氯鉻酸吡啶嗡鹽氯鉻酸吡啶嗡鹽 c5h5n.hcro3cl naoetlialh4h2o , h+, co2cooh浙江大學浙江大學04 作業(yè)作業(yè)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絲氨酸絲氨酸3?；狨シ；狨シㄗ鳂I(yè)作業(yè)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