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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。
The (+) - camphor was used as the raw material, and the (+) - π-bromocamphor was reduced by secondary bromination and then the π-oxide camphor was synthesized through esterification, hydrolysis and oxidation. The optimum reaction conditions were as follows: (1) Bromination reaction: n [(+) - camphor ]:n (Br2) = 1: 1.4, glacial acetic acid as solvent and reaction at 80 ℃ for 6h, (+) - α-bromocamphor]: n (Br2) = 1: 1.1, and chlorosulfonic acid was used as assistant to react for 2 h at room temperature. The yield of dibromo-camphor was 80.1%. (2) Reduction reaction: n (+) - α, π-dibromo-camphor]: n Yield 66.3%. (3) Esterification-hydrolysis reaction: n (+) - π-bromocamphor]: n (CH 3 COOK) = 1: 1.5 and glacial acetic acid as solvent. After reaction at 190 ℃ for 30 h, ): V [w (KOH) = 55% aqueous solution] = 1: 9 hydrolyzate, refluxing for 2.5 h, the yield of (+) - π-hydroxycamphor was 78.1%. (4) Oxidation reaction: use pyridinium chlorochromate (PCC) as oxidant, n (PCC): n [(+) - π-hydroxy camphor] = 2: h, π-oxide camphor yield 95.5%. The total target product yield of 35%. The intermediates and the structure of the target product were confirmed by IR, GC-MS and 1H NMR.