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2 h,(+)-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30 h,除去溶剂后用V(CH3CH2OH)∶V〔w(KOH)=55%的水溶液〕=1∶9的水解液,回流反应2.5 h,(+)-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2 h,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1HNMR确证。
π-Oxocamphor in a 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 were ascertained as follows：（1）Bromination：n（（＋）-camphor）∶n（bromine）=1∶1.4,glacial acetic acid as solvent,reaction time being 6 h at 80 ℃,the yield of（＋）-α-bromination camphor was 88.5%;n（（＋）-α-bromination camphor）∶n（bromine）=1∶1.1,chlorosulfonic acid as adjuvant,reaction time being 2 h 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 for 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 being 30 h at 190 ℃.Then,the solvent was removed,and the reaction took place at reflux temperature in the hydrolysate（V（CH3CH2OH） ∶V（mass fraction 55% potassium hydroxide）=1∶9） for about 2.5 h to give the（＋）-π-hydroxyl camphor in a yield of about 78.1%.（4）Oxidation：chlorine pyridine chromium acid salt（PCC） as oxygenant,n（PCC）∶n（（＋）-π-hydroxyl camphor）=2∶1,CH2Cl2 as solvent,under the protection of nitrogen,the reactants reacted for 2 h at room temperature,and the yield of π-oxocamphor was 95.5%.The structure of the intermediates and the target products was confirmed by IR,GC-MS and 1HNMR.
出处
《精细化工》
EI
CAS
CSCD
北大核心
2012年第4期361-365,共5页
Fine Chemicals
关键词
π-氧化樟脑
强心药
医药与日化原料
π-oxocamphor
cardiotonic drug
drug and cosmetic materials
