π-氧化樟脑的合成
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The Synthesis of π-Oxocamphor
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    摘要:

    以(+)-樟脑为原料,先经二次溴化、还原得(+)-π-溴代樟脑,再经酯化、水解和氧化反应合成了强心药物π-氧化樟脑。确定了较佳工艺条件:(1)溴化反应:n((+)-樟脑):n(Br2) =1:1.4,冰醋酸为溶剂,80℃下反应6h,(+)-α-溴代樟脑收率88.5%;n((+)-α-溴代樟脑): n(Br2)=1:1.1,氯磺酸为助剂,室温下反应2h,(+)-α,π-二溴代樟脑收率80.1%。(2)还原反应:n((+)-α,π-二溴代樟脑):n(Zn)=1:3,冰醋酸为溶剂,冰浴反应3h,(+)-π-溴代樟脑收率66.3%。(3)酯化-水解反应:n((+)-π-溴代樟脑):n(CH3COOK)=1:1.5,冰醋酸为溶剂,190℃下反应30h,除去溶剂后用V(CH3COOH):V(w=55%KOH)=1:9的水解液,回流反应2.5h,(+)-π-羟基樟脑收率78.1%。(4)氧化反应:选用氯铬酸吡啶嗡盐(PCC)作氧化剂,n(PCC):n((+)-π-羟基樟脑)=2:1,CH2Cl2作溶剂,氮气保护下室温反应2h,π-氧化樟脑收率95.5%。目标产物总收率35%。中间体及目标产物结构经IR、GC-MS和1H NMR确证。

    Abstract:

    π-Oxocamphor in total yield of 35% was synthesized by esterification, hydrolysis and oxidation from (+)-π-bromocamphor which was prepared from (+)-camphor by twice bromination and reduction reaction. The optimum reaction conditions was determined: (1) Bromination: n((+)-camphor):n(bromine) = 1:1.4, glacial acetic acid as solvent, reaction time was 6 h at 80℃, the yield of (+)-α–bromi nation camphor was 88.5%; n((+)-α-bromination camphor):n(bromine) = 1:1.1, chlorosulfonic acid as adjuvant, reaction time was 2h at room temperature, the yield of (+)-α,π-dibromination camphor was 80.1%. (2) Reduction: n((+)-α,π- dibromination camphor):n(zinc) = 1:3, glacial acetic acid as solvent, ice bath response with 3 h, the yield of (+)-π-bromination camphor was 66.3%. (3) Esterification –hydrolysis: n((+)-π-bromination camphor):n(potassium acetate)= 1:1.5, glacial acetic acid as solvent, esterification reaction time was 30 h at 190 ℃. Then removed the solvent, and reacted at the reflux temperature in the hydrolysate(V(CH3COOH) : V(w = 55% potassium hydroxide) = 1:9)about 2.5h to give the (+)-π-hydroxyl camphor in about 78.1% yield. (4) Oxidation: choose chlorine pyridine chromium acid salt (PCC) as oxygenant, n(PCC):n((+)-π-oxycamphor)=2:1,CH2Cl2 as solvent, with nitrogen protection reacted 2h under room temperature, the yield of π-oxidation camphor was 95.5%. The structure of the intermediates and target products was confirmed by IR, GC-MS and 1H NMR.

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黄顺,邓旭忠.π-氧化樟脑的合成[J].精细化工,2012,29(4):

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  • 收稿日期:2011-12-05
  • 最后修改日期:2012-01-12
  • 录用日期:2012-02-13
  • 在线发布日期: 2012-03-20
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