Vol. 41 No Journal of Jiangxi Normal University Natural Science Mar. 2017

Transcript

1 41 2 Vol 41 No Journal of Jiangxi Normal UniversityNatural Science Mar * * α- 3 1 H NMR 13 C NMR O A DOI /j cnki issn CuI TB- HP 1 H NMR 13 C NMR α- 1-3 α- α- α- 1 α- α- 1 α- α- 4 α α β- 6 α- Ohaus Instrument Bruker Avance 400 MHz TMS α-cdcl ~ α- 1 0 mmol 5 0 mmol α- 20% 3 equiv CXTD wborganic@ 163 com cl changlin@ yahoo com

2 CDCl 3 δ h ae ml 3 32% 1 H NMR400 MHz CDCl 3 δ8 32 ~ 8 29m 2H7 48 ~ 7 45m 2H7 0br s 1H 5 89br s 1H 13 C NMR 100 MHzCDCl 3 δ v v = af 5 48% 1 H NMR 400 MHzCDCl δ8 95 s aa 4 94% 1 H NMR400 MHz CDCl 3 δ7 92d J = 7 2 Hz 2H7 62t J = 7 6 1H7 49t J = 8 Hz 1H3 75Br s 4H3 61t J = 5 2 Hz 2H t J = 5 2 Hz 2H 13 C NMR100 MHz CDCl 3 δ ba 13 90% 1 H NMR400 MHz CDCl 3 δ 8 37d J = 8 8 Hz 2H ~ m 2H Br s 4H3 72 ~ 3 70 m 2H 3 44 t J = 4 8 Hz 2H 13 C NMR 100 MHzCDCl 3 δ ca 12 86% 1 H NMR400 MHz CDCl 3 δ7 83 d J = 8 8 Hz 2H7 66d J = 8 4 Hz 2H3 78 Br s 4H 3 65 t J = 5 2 Hz 2H 3 38 t J = 4 8 Hz2H 13 C NMR 100 MHzCDCl 3 δ ac 11 81% 1 H NMR400 MHz CDCl 3 δ7 95 d J = 8 4 Hz 2H 7 66 ~ 7 62 m 1H7 52 t J = 7 6 Hz 2H3 71 Br s 2H 3 29 t J = 5 6 Hz 2H1 70t J = 2 8 Hz 4H1 55d J = 5 2 Hz 2H 13 C NMR 100 MHzCDCl 3 δ N N ad 4 58% 1 H NMR400 MHz CDCl 3 δ 7 97d J = 7 6 Hz 2H7 67t J = 7 6 Hz 1H 7 54t J = 7 2 Hz 2H3 60q J = 7 2 Hz 2H 3 28q J = 7 2 Hz 2H1 32t J = 7 2 Hz 3H 1 19 tj = 7 2 Hz 3H 13 C NMR 100 MHz 1H8 46 ~ 8 38t J = 11 5 Hz 2H 7 76 ~ 7 62 m 1H7 51t J = 7 8 Hz 2H7 40t J = 7 9 Hz 2H 7 20 t J = 7 4 Hz 1H 13 C NMR 100 MHz CDCl 3 δ N ag 4 44% 1 H NMR400 MHz CDCl 3 δ8 36 ~ 8 35m 2H7 65 ~ 7 61m 1H7 51 ~ 7 47m 2H7 11 s 1H 2 98 d J = 4 8 Hz 3H 13 C NMR100 MHz CDCl 3 δ ee 5 72% 1 H NMR400 MHz CDCl 3 δ7 82 d J = 7 6 Hz 2H7 29d J = 7 6 Hz 2H3 68 Br s 2H3 026t J = 5 2 Hz 2H2 41s 3H 1 67s 4H1 53d J = 5 2H 3H 13 C NMR100 MHz CDC1 3 δ fa 13 86% 1 H NMR400 MHz CDCl 3 δ7 84 d J = 7 2 Hz 1H7 67d J = 7 2 Hz 1H7 51 ~ 7 43m 2H 3 84 ~ 3 80 m 4H 3 76 d J = 4 0 Hz 2H 3 60 t J = 4 4 Hz 2H 13 C NMR 100 MHz CDCl 3 δ gb 11 75% 1 H NMR400 MHz CDCl 3 δ7 85 d J = 8 4 Hz 2H7 62t J = 8 4 Hz 2H3 62 t J = 6 4 Hz 2H 7 62 t J = 6 4 Hz 2H 1 93 m 4H 13 C NMR 100 MHz CDCl 3 δ a

3 a 1 Entry catalyst Oxidant Solvent T / Yield /% d 1 7 CuI TBHP dioxane CuI TBHP MeOH % Entry 1 Table 1 10 CuI CuI TBHP TBHP toluene neat CuI DTBP neat 50 n d 12 CuI H 2 O c 2 neat 50 n d Entries 1-5 Table 1 13 CuI DDQ neat 50 n d 14 CuI TEMPO neat 50 n d THF 15 CuI TBHP neat dioxane MeOH toluene 16 CuI TBHP neat Entries 6-9 Table 1 17 CuI TBHP neat e 78% 18 CuI TBHP neat f 19 CuI TBHP neat CuI TBHP neat h 21 CuI TBHP neat i 94% Entry 10 Table 1 1a1 0 mmol 2a5 0 mmol DTBP H 2 O 2 20% 3 20 hn d DDQ TEMPOEntries Table b TBHP 70% c 1 30% d e 10% f 30% g 1 h 2 1 i 4 50 Entry 10 Entry 15 Entry % Entry 10 Entry 17 Entry 2 18 Table 1 3 mmol Entry 10 Entries Table 1 1 mmol 5 mmol 0 2 mmol 3 mmol 50 3aa 94% Entry mmol h Entry catalyst Oxidant Solvent T / Yield /% d CuI TBHP b MeCN CuCl 2 TBHP MeCN 50 n d 3 Cu 2 O TBHP MeCN 50 n d 4 CuBr TBHP MeCN CuBr 2 TBHP MeCN CuI TBHP THF α- 3

4 α- 4 1Fusetani NMatsunaga SMatsumoto H et al Bioactive marine metabolites 33 cyclotheonamides potent thrombin inhibitors from a marine sponge theonella sp J Journal of the American Chemical Society Sheha M Mahfouz N Hassan H et al Synthesis of di- and tripeptide analogues containing α-ketoamide as a new core structure for inhibition of HIV-1 protease J European Journal of Medicinal Chemistry Maryanoff B Greco M Zhang H et al Macrocyclic peptide inhibitors of serine proteases Convergent total synthesis of cyclotheonamides A and B via a late-stage primary amine intermediate Study of thrombin inhibition under diverse conditions J Journal of the American Chemical Society a1 0 mmol 2a5 0 mmol CuI 4Li DengkeWang Min Liu Jie et al Cu Ⅱ-catalyzed 20% 3 50 decarboxylative acylation of acyl C-H of formamides with 20 h α-oxocarboxylic acids leading to α-ketoamides J Chemical Communications Mupparapu NVishwakama RAhmed Q Iodine-DMSO promoted C-H SP3functionalization approach to α-ketoamides J Tetrahedron Papanikos A Rademann J Meldal M α-ketocarbonyl peptidesa general approach to reactive resin-bound Intermediates in the synthesis of peptide isosteres for protease inhibitor screening on solid support J Journal of the American Chemical Society Semple J Edward Owens T Nguyen K et al New synthetic technology for efficient construction of α-hydroxy-β-amino amides via the passerini reaction J Organic Letters Buckley T Rapoport H Mild and simple biomimetic conversion of amines to carbonyl compounds J Journal of 2 the American Chemical Society Ozawa F Soyama H Yanagihara H et al Palladium-catalyzed double carbonylation of aryl halides to give α-keto amides Mechanistic studies J Journal of the American α- Chemical Society Wang Hua Guo Lina Duan Xinhua Copper-catalyzed oxidative condensation of α-oxocarboxylic acids with for- mamidessynthesis of α-ketoamides J Organic & Biomolecular Chemistry Mupparapu N Khan S Battula S et al Metal-free oxida-

5 2 149 tive amidation of 2-oxoaldehydesA facile access to α-ketoamides J Organic Letters Kotha S Sekar G Metal free synthesis of α-keto amides from 2-hydroxy acetophenones through domino alcohol oxidation-oxidative amidation reaction J Tetrahedron Letters Du Bingnan Jin Bo Sun Peipei The syntheses of α-ketoamides vianbu 4 NI-catalyzed multiple sp3c-h bond oxidation of ethylarenes and sequential coupling with dialkylformamides J Organic & Biomolecular Chemistry Dutta S Kotha S Sekar G Metal free one-pot synthesis of α-ketoamides from terminal alkenes J RSC Advances Kumar M Devari S Kumar A et al CopperII-triflatecatalyzed oxidative amidation of terminal alkynesa general approach to α-ketoamides J Asian Journal of Organic Chemistry Meena S Singh R Vishwakarma R A et al se0 2 mediated efficsyunthesis of amides and α-ketoamides of secindary amies with wide substrate scope J Tetrahedron Letters Guo shiyu Fang zheng Yang zhao et al I2-promotef aerobic oxidative coupling of acetophenes with amines under metal-ferr conditionsfacile access toα-ketoamides J RSC Advances Sharma R k Sharma S Gaba G et al Coordinated copper Ⅱsupported on silica nanospheres applied to the synthesis ofα-ketoamides Via oxidative amidatio of methyl ketines J Jourual of Materials Science Du F Ji J Copper-catalyzed direct oxidative synthesis of α- ketoamides from aryl methyl ketones amines and molecular oxygen J Chemical Science Zhang XWang L TBHP /I2-promoted oxidative coupling of acetophenones with amines at room temperature under metal-free and solvent-free conditions for the synthesis of α-ketoamides J Green Chemistry Zhao Q Miao T Zhang X et al Direct use of formamides as amino group sources via C-N bond cleavagea catalytic oxidative synthesis of α-ketoamides from acetophenones and formamides under metal-free conditions J Organic & Biomolecular Chemistry Kumar Y Shaw M Thakur R et al CopperII-mediated aerobic oxidation of benzylimidatessynthesis of primary α-ketoamides J Journal of Organic Chemistry One Pot Synthesis of α-ketoamides LIU Fuyan LIN Chang * WANG Bo * College of Materials and Chemical Engineering Hainan University Haikou Hainan China AbstractA one-pot synthetic protocol of α-ketoamides from aryl methyl ketones using copperiiodide as catalyst and tert-butyl hydroperoxide as oxidant is reported in this paper The method has the advantages of mild reaction condition high yield and good atom economy Most of the aryl methyl ketones and amines can be successfully converted to their corresponding α-ketoamides with 3 equivalents of oxidant tert-butyl hydroperoxide The crude product was purified by column chromatography and the product was characterized by 1 H NMR 13 C NMR Key wordsα-ketoamidesaryl methyl ketonescopperiiodidetert-butyl hydroperoxide