(+)-1,2,3,4-四氢罂粟碱的合成

New Method for Preparation of (+)-1,2,3,4-Tetrahydropapaverine

以Merrified树脂固载的BINOL衍生磷酸催化3,4-二氢罂粟碱不对称转移氢化反应制备了(+)-1,2,3,4-四氢罂粟碱。对催化剂进行了筛选并将最优催化剂在Merrified树脂上进行了负载。考察了溶剂、反应温度、Hantzsch酯结构等对产物收率和对映选择性的影响。以甲苯作为溶剂,温度40℃,2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸甲酯为氢源时,产物的收率达95%,e.e.值达98%。负载手性磷酸催化剂可以方便的分离和回收利用。催化剂反复利用7次后,催化活性略有降低,活性降低的催化剂可以经氯化氢-乙酸乙酯溶液简单洗涤再生。

Merrified resin-bound BINOL-derived phosphoric acid was employed for the catalytic transfer hydrogenation of 3,4-dihydropapaverine to synthesize（ ＋）-1,2,3,4-tetrahydropapaverine. Several catalysts were selected and the excellent catalyst was bounded on Merrified resin. The effects of solvent type,reaction temperature and structure of Hantzsch ester on yield and e. e. value of（ ＋）-1,2,3,4-tetrahydropapaverine were investigated in detail. Under the optimal conditions（ toluene as solvent,40 ℃and dimethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate as hydride source）,the（ ＋）-1,2,3,4-tetrahydropapaverine was obtained in 95% yield and 98% e. e.. The catalyst could be easily separated and recycled. After reused seven times,the activity of catalyst was observed a small drop in e. e.,but could be regained by simple cleaning in hydrogen chloride-ethyl acetate solution.