582 ESTER EN。 LATES 21.11 The carbonyl oxygen at C-2 of pentobarbital is replaced by sulfur in Pentothal( thiopental) CH3o CH3 CH..CH CH2CHCH2CH、 CH3 CH2 6 CHCH Pentobarbital; prepared from urea, (HNC=O The sodium salt of Pentothal is formed by removal of a proton from one of the N-H groups by odium hydroxide O H3 CH, CHCHCH CH, CHCH、>NNa CH-C CH3 CH2 Pentothal sodium 21.12 The synthesis of phenobarbital requires diethyl 2-phenylmalonate as the starting material NaTCH.C HN C6HS CH(COOCH_ CH3)2 CHCHBr CHSC(COOCH2 CH3)2 H3 CH2 CH- CH3 Diethyl Phenobarbital -ethyl-2-phenylmalonate ethyl 2-phenylmalonate is prepared by a mixed Claisen condensation between ethyl phenyl- acetate and diethyl carbonate. C6H-CH, COCH, CH3+ CH3 CH,OCOCH, CH C6H_CH(COOCH,CH3) Diethyl carbonate Diethyl 2-phenylmalonate 21.13 Like diethyl malonate, ethyl acetoacetate undergoes Michael addition to an a, B-unsaturated ke NaoCH, CH, CHa CCH,COCH,CH3 CH,CH,OH CHCOCHCH Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website21.11 The carbonyl oxygen at C-2 of pentobarbital is replaced by sulfur in Pentothal (thiopental). The sodium salt of Pentothal is formed by removal of a proton from one of the N@H groups by sodium hydroxide. 21.12 The synthesis of phenobarbital requires diethyl 2-phenylmalonate as the starting material. Diethyl 2-phenylmalonate is prepared by a mixed Claisen condensation between ethyl phenyl￾acetate and diethyl carbonate. 21.13 Like diethyl malonate, ethyl acetoacetate undergoes Michael addition to an , -unsaturated ketone. NaOCH2CH3 CH3CH2OH CH3CCH2COCH2CH3 O O O CHCOCH2CH3 O CH3 C O O NaOCH2CH3 Ethyl phenylacetate C6H5CH2COCH2CH3 O Diethyl carbonate CH3CH2OCOCH2CH3 O Diethyl 2-phenylmalonate C6H5CH(COOCH2CH3)2 C6H5CH(COOCH2CH3)2 Diethyl 2-phenylmalonate Phenobarbital C6H5 CH3CH2 O N N O O NaOCH2CH3 CH3CH2Br Diethyl 2-ethyl-2-phenylmalonate C6H5C(COOCH2CH3)2 CH2CH3 H2NCNH2 O H H Pentothal sodium CH3CH2CH2CH CH3CH2 O N N O S CH3 Na CH3CH2CH2CH CH3CH2 O N N O S CH3 Na H H Pentobarbital; prepared from urea, (H2N)2C O CH3CH2CH2CH CH3CH2 O N N H H O O CH3 1 3 4 6 5 2 Pentothal; prepared from thiourea, (H2N)2C S CH3CH2CH2CH CH3CH2 O N N H H O S CH3 582 ESTER ENOLATES Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website