7-溴-2,3-二氢-1-茚酮的合成新方法研究
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摘要
本文以邻溴苯甲醛为原料,经亲电加成反应、氧化反应以及分子内Friedel-Crafts烷基化反应合成了7-溴-2,3-二氢-1-茚酮。研究发现,分子内Friedel-Crafts烷基化是影响总收率的关键步骤,探讨了反应溶剂、反应温度、反应时间等条件对反应的影响。同时,对氧化反应步骤中氧化剂及反应溶剂进行了筛选,结果发现,在以丙酮为溶剂琼斯试剂为氧化剂的条件下,产物收率最高。所有产物经NMR和MS进行确证。
7-bromo-2,3-dihydro-1-indanone was synthesized from o-bromobenzaldehyde by electrophilic addition reaction,oxidation reaction and intramolecular Friedel-Crafts alkylation.It is found that intramolecular Friedel-Crafts alkylation is a key step affecting the overall yield.The effects of reaction solvent,reaction temperature and reaction time on the reaction are discussed.At the same time,the oxidant and the reaction solvent in the oxidation reaction step were screened.The results showed that the yield of the product was highest under the condition that the dichloromethane reagent was used as the oxidant.All products were confirmed by NMR and MS.
7-bromo-2,3-dihydro-1-indanone was synthesized from o-bromobenzaldehyde by electrophilic addition reaction,oxidation reaction and intramolecular Friedel-Crafts alkylation.It is found that intramolecular Friedel-Crafts alkylation is a key step affecting the overall yield.The effects of reaction solvent,reaction temperature and reaction time on the reaction are discussed.At the same time,the oxidant and the reaction solvent in the oxidation reaction step were screened.The results showed that the yield of the product was highest under the condition that the dichloromethane reagent was used as the oxidant.All products were confirmed by NMR and MS.
引文
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[3] Patel V M,Bhatt N,Bhatt P,et al.Synthesis and pharmacological evaluation of novel 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one derivatives as potential antimicrobial agents[J].Med Chem Res,2014,23:2133-2139.
[4] Saravanan V S,Selvan P S,Gopal N,et al.Synthesis and pharmacological evaluation of some indanone-3-acetic acid derivatives[J].Asian J Chem,2006,18 (4):2597-2604.
[5] Tang M L,Zhong C,Liu Z Y,et al.Discovery of novel sesquistilbene indanone analogues as potent anti-inflammatory agents[J].Eur J Med Chem,2016,113:63-74.
[6] Hammen P D,Milne G M.2-Aminomethyleneindanone analgesic agents:US,4164514[P].1979-08-14.
[7] Albrecht R,Kessler H J,Schroder E.Antimicrobial indanones:US,3671520[P].1972-06-20.
[8] Finkieisztein L M,Castro E F,Fabian L E,et al.New 1-indanone thiosemicarbazone derivatives active against BVDV[J].Eur J Chem,2008,43:1767-1773.
[9] Omran Z,Cailly T,Lescot E,et al.Synthesis and biological evaluation as AChE inhibitors of new indanones and thiaindanones related to donepezil[J].Eur J Med Chem,2005,40:1222-1245.
[10] Sheng R,Xu Y,Chunqi H,et al.Design,synthesis and AChE inhibitory activity of indanone and auronederivatives[J].Eur J Med Chem,2008,20:1-11.
[11] Sindelar R D,Mott J,Barfknecht C F,et al.2-Amino-4,7-dimethoxyindan derivatives:synthesis and assessment of dopaminergic and cardiovascular actions[J].J Med Chem,1982,25(7):858-864.
[12] Gomez N,Santos D,Vazquez R,et al.Synthesis,structural characterization,and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes:potential as Antileukemic agents[J].Chem Med Chem,2011,6:1485-1494.
[13] Charris J E,Lobo G M,Camacho J,et al.Synthesis and antimalarial activity of (E) 2-(2-chloro-3-quinolinylmethylidene)-5,7-dimethoxyindanones[J].Lett Drug Des Discov,2007,4:49-54.
[14] Shih D G,Zhou Y D,Park P U,et al.A new indanone from the marine cyanobacterium Lyngbyamajuscula that inhibits hypoxia-induced activation of the VEGF promoter in Hep3B cells[J].J Nat Prod,2000,63:1431-1433.
[15] Van der Hoeven J C M,Lagerweij W J,Posthumus M A,et al.Aquilide,A new mutagenic compound isolated from bracken fern (Pteridiumaquilinum (L.) Kuhn)[J].Carcinogenesis,1983,4:1587-1590.
[16] Yang Y,Philips D,Pan S.A concise synthesis of paucifloral F and related indanone analogues via palladium-catalyzed a-arylation[J].J Org Chem,2011,76:1902-1905.
[17] Hao X D,Chang J,Qin B Y,et al.Synthesis,estrogenic activity,and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives[J].Eur J Med Chem,2015,102:26-38.
[18] L G Chem Ltd,Seoul.Compound and organic electronic element comprising same:WO,2017/086713[P].2017- 05-26.
[19] 常熟浸大科技有限公司.一种7-卤-1-茚酮的新合成方法:CN ,108164408[P].2018-06-15.