苯炔参与的N-桥环衍生物的合成

Synthesis of novel N-bridged ring derivatives by the participation of benzyne

本文报道一类N-桥环衍生物(化合物4a~6)的合成方法。以4-溴-2-(溴甲基)苯甲醛(1)为原料,分别和两种胺(甲胺、苄胺)反应,得到两种二烯中间体:5-溴-2-甲基-2H-异吲哚(2a)和2-苄基-5-溴-2H-异吲哚(2b),苯炔前体化合物[5-(甲氧羰基)-2-(三甲基硅)苯基](苯基)碘鎓三氟甲烷磺酸盐(3)再分别与两种二烯中间体(2a)和(2b)反应得到7-溴-11-甲基-9,10-二氢-9,10-环亚胺蒽-2-甲酸甲酯(4a)和7-溴-11-苄基-9,10-二氢-9,10-环亚胺蒽-2-甲酸甲酯(4b),其中,化合物(4b)脱除苄基得到7-溴-9,10-二氢-9,10-环亚胺蒽-2-甲酸甲酯(5),化合物(5)与乙酰氯发生N-酰基化反应得到7-溴-11-乙酰基-9,10-二氢-9,10-环亚胺蒽-2-甲酸甲酯(6)。中间体及产物结构经1H NMR和LC-MS表征。同时以(4a)的合成为模型,考察反应条件对该Diels-Alder反应收率的影响,确定最佳反应条件为:物料摩尔比n(2a)∶n(TBAF)∶n(3)=2.0∶2.0∶1;反应溶剂为二氯甲烷;反应温度为0℃;反应时间为30min。在该反应条件下,产物(4a)和(4b)收率分别达到68.3%和72.5%。

In this paper,the synthesis method of a class of N-bridged ring derivatives(compounds 4a~6)is reported.Using 4-bromo-2-(bromomethyl)benzaldehyde(1)as raw material,two diene intermediates(5-bromo-2-methyl-2H-isoindole 2a and 2-benzyl-5-bromo-2H-isoindole 2b)are obtained by the reaction of 4-bromo-2-(bromomethyl)benzaldehyde with two amines(methylamine and benzylamine)respectively.The benzyne precursor compound(5-(methoxycarbonyl)-2-(trimethylsilyl)phenyl)(phenyl)iodonium trifluoromethane sulfonate(3)reacts with two diene intermediates(2a)and(2b)to give methyl 7-bromo-11-methyl-9,10-dihydro-9,10-epiminoanthracene-2-carboxylate(4a)and methyl 11-benzyl-7-bromo-9,10-dihydro-9,10-epiminoanthracene-2-carboxylate(4b),where compound(4b)removes the benzyl group to give 7-bromo-9,10-dihydro-9,10-cycloiminothrane-2-formate(5),Compound(5)through N-acylated reaction with acetyl chloride to give methyl 11-acetyl-7-bromo-9,10-dihydro-9,10-epiminoanthracene-2-carboxylate(6).The structures of the intermediates and products were characterized by 1H NMR and LC-MS.Taking the synthesis of(4a)as a model,the influence of reaction conditions on the yield of the Diels-Alder reaction was investigated.The optimal reaction conditions were determined as follows:molar ratio is n(2a)∶n(TBAF)∶n(3)=2.0∶2.0∶1;The reaction solvent is dichloromethane;The reaction temperature is 0℃;The reaction time is 30 min.Under these reaction conditions,the yields of(4a)and(4b)were up to 68.3%and 72.5%,respectively.