CHAPTER 21 ESTER ENOLATES SOLUTIONS TO TEXT PROBLEMS 21.1 Ethyl benzoate cannot undergo the Claisen condensation, because it has no protons on its a-carbon atom and so cannot form an enolate. Ethyl pentanoate and ethyl phenylacetate can undergo the Claisen condensation 1. NaOCH( 2CH,CH, CH,CH,COCH, CH 2.H2O CHa CH, CH,CH,CCHCOCH2 CH3 CH,CH, CH Ethyl pentanoate Ethyl 3-ox0-2-propylheptanoate 2C.H CH, COCH, CH2 CHCHCCHCOCH,CH 21.2 (b) The enolate formed by proton abstraction from the a-carbon atom of diethyl 4-methylhep- anedioate cyclizes to form a six-membered B-keto ester LOCHICH3 OCHCH CH CHCH OCCH CH CHCH. CH COCH, CH, NaccHlCH3, Ch,Ch o H,C CHCH3 Diethyl 4-methy lheptanedioate Ethyl (5-methyl-2-oxocyclohexane)- carboxylate 576 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
CHAPTER 21 ESTER ENOLATES SOLUTIONS TO TEXT PROBLEMS 21.1 Ethyl benzoate cannot undergo the Claisen condensation, because it has no protons on its -carbon atom and so cannot form an enolate. Ethyl pentanoate and ethyl phenylacetate can undergo the Claisen condensation. 21.2 (b) The enolate formed by proton abstraction from the -carbon atom of diethyl 4-methylheptanedioate cyclizes to form a six-membered -keto ester. CH3CH2OCCH2CH2CHCH2CH2COCH2CH3 CH3 O O CH3CH2O NaOCH2CH3 OCH2CH3 CH3 O O C Ethyl (5-methyl-2-oxocyclohexane)- carboxylate Diethyl 4-methylheptanedioate OCH2CH3 O O C C H2C CHCH3 CH2 CH2 CH 2C6H5CH2COCH2CH3 O Ethyl phenylacetate Ethyl 3-oxo-2,4-diphenylbutanoate C6H5CH2CCHCOCH2CH3 O O C6H5 1. NaOCH2CH3 2. H3O 2CH3CH2CH2CH2COCH2CH3 O Ethyl pentanoate Ethyl 3-oxo-2-propylheptanoate CH3CH2CH2CH2CCHCOCH2CH3 O O CH2CH2CH3 1. NaOCH2CH3 2. H3O 576 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ESTER EN。 LATES 577 (c) The two a carbons of this diester are not equivalent Cyclization by attack of the enolate at C-2 gives NaOCH. CH CH CHOC CHa CH,OCCHCH2 CH,CH,COCH,CH3 H3 yclopentane) This B-keto ester cannot form a stable enolate by deprotonation. It is present in only small amounts at equilibrium. The major product is formed by way of the other enolate OCHCH CH,CH,OCCHCH, CH,CH,COCH, CH3 NaOCH, CH, O CH3 Site of this carbon This B-keto ester is converted to a stable enolate on deprotonation, causing the equilibrium to shift in its favor 21.3(b) Both yl groups of diethyl oxalate are equivalent. The enolate of ethyl phenylacetate attack of them C6HSCHCOCH, CH3 CHa CH,O-CCOCH2CH3 C6HSCHCCOCH,CH Diethyl 2-0X0-3- phenylbutanedioate (c) The enolate of ethyl phenylacetate attacks the carbonyl group of ethyl formate O C6HSCHCOCH,CH3 HC--OCH, CH3 C6HSCHCH OCH, CH3 21. 4 In order for a five-membered ring to be formed c-5 must be the carbanionic site that attacks the H3C CHCH CH CH CHO Enolate of ethyl 4-oxohe Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ESTER ENOLATES 577 (c) The two carbons of this diester are not equivalent. Cyclization by attack of the enolate at C-2 gives This -keto ester cannot form a stable enolate by deprotonation. It is present in only small amounts at equilibrium. The major product is formed by way of the other enolate. This -keto ester is converted to a stable enolate on deprotonation, causing the equilibrium to shift in its favor. 21.3 (b) Both carbonyl groups of diethyl oxalate are equivalent. The enolate of ethyl phenylacetate attacks one of them. (c) The enolate of ethyl phenylacetate attacks the carbonyl group of ethyl formate. 21.4 In order for a five-membered ring to be formed, C-5 must be the carbanionic site that attacks the ester carbonyl. O O H3C CH3CH2O Enolate of ethyl 4-oxohexanoate CH2 CH2 C C CH3CH2O O O H3C CH HC OCH2CH3 O C6H5CHCOCH2CH3 O Ethyl 3-oxo-2- phenylpropanoate C6H5CHCH O COCH2CH3 O C6H5CHCOCH2CH3 CH3CH2O CCOCH2CH3 O OO C6H5CHCCOCH2CH3 COCH2CH3 OO O Diethyl 2-oxo-3- phenylbutanedioate CH3CH2OCCHCH2CH2CH2COCH2CH3 NaOCH2CH3 O O CH3 Site of carbanion Enolate attacks this carbon. Ethyl (3-methyl-2- oxocyclopentane)- carboxylate O CH3 OCH2CH3 O C CH3CH2OCCHCH2CH2CH2COCH2CH3 NaOCH2CH3 O O CH3 Site of carbanion Enolate attacks this carbon. Ethyl (1-methyl-2- oxocyclopentane)- carboxylate O O CH3CH2OC H3C Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
578 ESTER EN。 LATES H3C- H. +“ OCH.CH CH3CH 21.5 The desired ketone, cyclopentanone, is derived from the corresponding B-keto ester. This key intermediate is obtained from a Dieckmann cyclization of the starting material, diethyl hexanedioate. COCH. CH CHaCH,O, C(CH,), CH First treat the diester with sodium ethoxide to effect the Dieckmann cyclization L. NaOCHCI COCHCH CH, CH,OCCH, CH, CH, CH,COCH Ch3 2Hao Diethyl hexanedioate Ethyl (2-oxo Next convert the B-keto ester to the desired product by saponification and decarboxylation. COCHCH 3. heat Ethyl (2-oxocyclopentane)- 21.6(b) Write a structural formula for the desired product; then disconnect a bond to the a-carbon CH,3CH,CCH CH CHCCH Derived from alkyl halide Therefore 1. NaOCH, CH -CH Br+CH, CCH,COCH- CH, 2.HO",H,0 CH,CH,CCH3 4. heat Benzyl bromide Ethyl acetoacetate pheny l-2-butano Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
578 ESTER ENOLATES 21.5 The desired ketone, cyclopentanone, is derived from the corresponding -keto ester. This key intermediate is obtained from a Dieckmann cyclization of the starting material, diethyl hexanedioate. First treat the diester with sodium ethoxide to effect the Dieckmann cyclization. Next convert the -keto ester to the desired product by saponification and decarboxylation. 21.6 (b) Write a structural formula for the desired product; then disconnect a bond to the -carbon atom. Therefore CH2CH2CCH3 O Benzyl bromide 4-Phenyl-2-butanone CH2Br Ethyl acetoacetate CH3CCH2COCH2CH3 O O 1. NaOCH2CH3 2. HO, H2O 3. H 4. heat CH2 CH2CCH3 O Required alkyl halide CH2 X Derived from ethyl acetoacetate CH2CCH3 O COCH2CH3 O O Ethyl (2-oxocyclopentane)- carboxylate O Cyclopentanone 1. HO, H2O 2. H 3. heat CH3CH2OCCH2CH2CH2CH2COCH2CH3 O O 1. NaOCH2CH3 2. H3O COCH2CH3 O O Ethyl (2-oxocyclopentane)- carboxylate Diethyl hexanedioate CH3CH2O2C(CH2)4CO2CH2CH3 O COCH2CH3 O O O O H3C OCH2CH3 O O H3C CH3CH2O 2-Methyl-1,3- cyclopentanedione Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ESTER EN。 LATES 579 (c) The disconnection approach to retrosynthetic analysis reveals that the preparation of 5-hexen- 2-one by the acetoacetic ester synthesis requires an allylic halide H,C=CHCH,$CH, CCH3 H,C=CHCH, CH,CCH Derived from alkyl halide H_C=CHCH2Br CHaCCHCOCH CH3 2.HO-HO .NaoCHCH3 HC=CHCH, CH, CCH 4. heat Allyl bromide hyl 21.7(b) Nonanoic acid has a CH3(CH,)CH attached to the CH, COH synthon CH,(CH),,+-CH, COH> CH,CH,),CH,X+: CH,COH Required alkyl halide Derived from Therefore the anion of diethyl malonate is alkylated with a l-haloheptane CH3(CH2)5 CH2 Br CH2(COOCHCH3)2- cthanol CH3(CH2)sCH CH(COOCH2CH3) Diethyl malonate Diethyl 2-heptylmalonate CHa(CH2)5CH,CH,CO,H Nonanoic acid (c) Disconnection of the target molecule adjacent to the a carbon reveals the alkyl halide needed to react with the enolate derived from diethyl malonate. CH,CH, CHCH, CH, COH CHCH,CHCH,X CH, COH Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(c) The disconnection approach to retrosynthetic analysis reveals that the preparation of 5-hexen- 2-one by the acetoacetic ester synthesis requires an allylic halide. 21.7 (b) Nonanoic acid has a CH3(CH2)5CH2@ unit attached to the synthon. Therefore the anion of diethyl malonate is alkylated with a 1-haloheptane. (c) Disconnection of the target molecule adjacent to the carbon reveals the alkyl halide needed to react with the enolate derived from diethyl malonate. Derived from diethyl malonate CH2COH O Required alkyl halide CH3CH2CHCH2X CH3 CH3CH2CHCH2 O CH2COH CH3 1-Bromoheptane CH3(CH2)5CH2Br Diethyl malonate CH2(COOCH2CH3)2 Diethyl 2-heptylmalonate CH3(CH2)5CH2CH(COOCH2CH3)2 Nonanoic acid CH3(CH2)5CH2CH2CO2H NaOCH2CH3 ethanol 1. HO, H2O 2. H 3. heat Derived from diethyl malonate CH2COH O Required alkyl halide CH3(CH2) CH3(CH2)5CH2 5CH2X O CH2COH CH2COH O Allyl bromide H CHCH2Br 2C 5-Hexen-2-one CHCH2CH2CCH3 O H2C Ethyl acetoacetate CH3CCH2COCH2CH3 O O 1. NaOCH2CH3 2. HO, H2O 3. H 4. heat Required alkyl halide H2C CHCH2 X Derived from ethyl acetoacetate CH2CCH3 O H2C CHCH2 O CH2CCH3 ESTER ENOLATES 579 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
580 ESTER EN。 LATES The necessary alkyl halide in this synthesis is l-bromo-2-methylbutane CH, CH,CHCH,Br +CH,(COOCH, CH,)2-od+ CH, CH, CHCH, CH(COOCH, CH, ) I-Bromo-2-methylbutane Diethyl malonate Diethyl 2-(2-methylbutyl)malonate 1. HO. H-O 3. heat CH, CH,CHCH,CH,COH 4-Methy hexanoic acid (d) Once again disconnection reveals the necessary halide, which is treated with diethyl malonate CsH.CH,&CH,COH CsHCH,X CH,COH Alkylation of diethyl malonate with benzyl bromide is the first step in the preparation of 3-phenylpropanoic acid CGHSCHBr CH2(COOCH2CH3)ethanol C&HS CH CH(COOCH2 CH3)2 H+ CsH,CH, CH, COH Diethyl malonate Diethyl 2-benzylmalonate 3-Phenylpropanoic acid 21.8 Retrosynthetic analysis of the formation of 3-methyl-2-butanone is carried out in the same way as for other ketones CH CCH&CH CH, CCH 2CH,X H3 Derived from The two alkylation steps are carried out sequentially CHaCCH,COCH_CH3-ch.BT CH,CCHCOCH、NocH2 CHICCCOCH2CH3 3 hea CH,CCH(CH3) CH HC Eth Ethyl 2- methyl-3-oxobutanoate 2, 2-dimethyl-3-oxobutanoate Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
The necessary alkyl halide in this synthesis is 1-bromo-2-methylbutane. (d) Once again disconnection reveals the necessary halide, which is treated with diethyl malonate. Alkylation of diethyl malonate with benzyl bromide is the first step in the preparation of 3-phenylpropanoic acid. 21.8 Retrosynthetic analysis of the formation of 3-methyl-2-butanone is carried out in the same way as for other ketones. The two alkylation steps are carried out sequentially. CH3CCHCOCH2CH3 NaOCH2CH3 CH3Br O O CH3 CH3CCH2COCH2CH3 NaOCH2CH3 CH3Br O O Ethyl acetoacetate Ethyl 2-methyl-3-oxobutanoate 1. HO, H2O 2. H CH3CCCOCH2CH3 O O H3C CH3 Ethyl 2,2-dimethyl-3-oxobutanoate CH3CCH(CH3)2 O 3-Methyl-2-butanone 3. heat CH3CCH 2CH3X O O CH3CCH CH3 CH3 3-Methyl-2-butanone (two disconnections as shown) Derived from ethyl acetoacetate Benzyl bromide C6H5CH2Br Diethyl malonate CH2(COOCH2CH3)2 NaOCH2CH3 ethanol Diethyl 2-benzylmalonate C6H5CH2CH(COOCH2CH3)2 1. HO, H2O 3-Phenylpropanoic acid C6H5CH2CH2COH O 2. H 3. heat Derived from diethyl malonate CH2COH O Required halide C6H5CH2 C6H5CH2X O CH2COH Diethyl malonate CH2(COOCH2CH3)2 NaOCH2CH3 ethanol 1-Bromo-2-methylbutane CH3CH2CHCH2Br CH3 1. HO, H2O 2. H 3. heat Diethyl 2-(2-methylbutyl)malonate CH3CH2CHCH2CH(COOCH2CH3)2 CH3 4-Methylhexanoic acid CH3CH2CHCH2CH2COH CH3 O 580 ESTER ENOLATES Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website