苯甲酸催化一锅合成3_4_二氢嘧啶_2_1H_酮

化学试剂,2007,29(3),181~183苯甲酸催化一锅合成3,42二氢嘧啶22(1H)2酮于杨,刘迪,刘春生,罗根祥*(辽宁石油化工大学化学系,辽宁抚顺 113001)摘要:介绍了用苯甲酸作催化剂利用Bi gi nelli 反应在无溶剂条件下,一锅合成标题化合物的方法。

和传统的Biginelli 反应条件比较,此法有反应时间短(3~5h)和收率高(70%~97%)的特点。

关键词:苯甲酸;Biginelli 反应;嘧啶酮;一锅合成中图分类号:O626.41 文献标识码:A 文章编号:025823283(2007)0320181203收稿日期:2006208212作者简介:于杨(19792),男,吉林松源人,硕士生,主要从事有机合成方面的研究工作。

二氢嘧啶酮类化合物广泛的生物活性引起了众多的化学工作者的兴趣。

Biginelli 在1893年用芳香醛、乙酰乙酸乙酯和脲在盐酸催化条件下首次得到了此类化合物。

方法虽然简单,但存在着反应时间长(18h)、收率低(20%~50%)等缺点。

近年来,人们不断地寻找新的催化剂和探索新的合成方法,相继报道氯化锆[1]、溴化铟[2]、YB (Ó)2树脂[3]、离子液体[4]、乙酸锰[5]、氯化镧[6]、TFA [7]、硼酸[8]、氯化铈[9]、三氟甲烷磺酸镧[10]、三氟甲烷磺酸铜[11]等作为催化剂催化该反应;在合成方法上有微波辐射、超声合成和固相合成等方法。

这些新的发现大大改善了传统方法的不足,提高了收率、缩短了反应时间。

最近,有关苯甲酸作为协同催化剂[12214]催化醛的烯丙基化的报道,其催化效果显著,这给我们以启迪。

我们通过大量的实验发现,苯甲酸作为催化剂可以高收率地合成3,42二氢嘧啶22(1H )2酮类化合物。

本文考察了不同醛以苯甲酸为催化剂进行Biginelli 反应的情况,合成了一系列的目标物。

反应方程式如下。

1 实验部分111 主要仪器与试剂X 26型显微熔点测定仪(北京泰克仪器有限公司);Perkin Elmer GX 系列傅里叶变换红外光谱仪(KBr 压片);Bruker Avance 600型核磁共振仪(600M Hz,CDCl 3作溶剂,T M S 为内标)。

所用试剂均为国产分析纯或化学纯。

112 合成步骤将醛(25mmol)、1,32二羰基化合物(2715mmol)、脲(3715mmol)和催化剂苯甲酸(5m mol)加入到100mL 的梨形烧瓶中,在无溶剂条件下,90e 水浴加热3或5h,再加入20mL 左右的水2乙醇混合溶液(V B V =1B 1)回流10min 左右,使催化剂进入液相。

稍冷后倒入装有碎冰的烧杯中,充分搅拌使产品析出,静置后真空抽滤得到纯净的产物(4a ~4r)。

选取几种产物进行IR 和1HNM R 谱测试,结果与文献值吻合。

52乙氧基262甲基242(42氯苯基)23,42二氢嘧啶22(1H)2酮(4b):I R(KB r),M ,cm -1:3243,1724,1647,840。

1HNM R (D M SO 2d 6),D :9126(s,1H,N H);7176(s,1H,N H );7139~7125(m,4H,C 6H 4);5114(s,1H,C H );3196(q,2H,J =710Hz,OC H 2CH 3);2124(s,3H,C H 3);1109(t,3H,J =710Hz,OC H 2C H 3)。

52乙氧基262甲基242丙基23,42二氢嘧啶22(1H)2酮(4f):IR (KBr),M ,c m -1:3251,3120,2958,2935,2874,1720,1647。

1HNM R(D M SO 2d 6),D :8193(s,1H,N H);7132(s,1H,NH);4110~4104(q,3H,J =417Hz,H 24,O CH 2C H 3);2115(s,3H,C H 3);1126~1140(m,4H,C H 2CH 2C H 3);1121~1116(t,3H,J =417Hz,OC H 2C H 3);0187~0183(t,3H,J =619Hz,C H 2CH 2C H 3)。

52甲氧基262甲基242(42氯苯基)23,42二氢嘧啶22(1H)2酮(4i):IR(KBr),M ,c m -1:3366,1716,1636。

1HN M R (D M SO 2d 6),D :9127(s,1H,N H );7174(s,1H,NH);7141~7122(m,4H,C 6H 4);5114(s,1H,C H );3153(s,3H,CH 3O CO);2124(s,3H,CH 3)。

181第29卷第3期于杨等:苯甲酸催化一锅合成3,42二氢嘧啶22(1H)2酮2结果与讨论通过实验得知,用苯甲酸作为催化剂来催化合成3,42二氢嘧啶22(1H)2酮类化合物,与经典的Biginelli法相比,反应时间大大缩短(3~5h),收率大幅提高(70%~97%),特别对脂肪醛也有较好的收率,且反应条件温和,操作简便。

表13,42二氢嘧啶22(1H)2酮的产率、熔点产品序号R1R2反应时间/h产率/%m.p./e实测值文献值4a C6H5OEt384200~202 202~204[15]4b42(C l))C6H4OEt385209~211 209~211[16]4c42(C H3O))C6H4OEt390199~201 198~200[17]4d42(C H3))C6H4OEt384210~212 214~215[17]4e42(NO2))C6H4OEt378206~207 207~208[8]4f C3H7OEt570178~180 179~180[18]4g C2H5OEt577178~180 179~181[18]4h C6H5OMe382212~214 207~209[19]4i42(C l))C6H4OMe395207~209 206~208[11]4j42(C H3O))C6H4OMe394196~198 193~196[19]4k42(C H3))C6H4OMe397201~203 204~206[2]4l2,42(Cl)2)C6H3OMe388254~257 254~255[10]4m42(NO2))C6H4OMe382229~231 230[20]4n C3H7OMe572172~174 174~175[18]4o C6H5Me387228~231 233~236[10]4p42(C l))C6H4Me392229~231 233~235[20]4q42(C H3O))C6H4Me391172~174 168~170[10]4r C6H5C H C H Me381223~225 224~226[20]苯甲酸在无溶剂条件下90e水浴中催化合成3,42二氢嘧啶22(1H)2酮的情况见表1。

可以发现:1)参与该反应的不同的醛都有较好催化效果,大体上苯环上是推电子基的醛(4c、4j)比拉电子基的醛(4e、4m)活性高,即产物收率高,可能是在该反应过程中醛作为亲核体被亲电试剂进攻而导致的;2)在参与该反应的1,32二羰基化合物中,乙酰乙酸甲酯的反应活性较乙酰乙酸乙酯和乙酰丙酮高;3)芳香醛和脂肪醛的反应活性有明显的不同,芳香醛参与反应3h,产物收率可达78%~ 97%,而脂肪醛参与反应5h,产物收率仅达到70%~77%,也就是说脂肪醛参与反应的时间虽然延长了2h,但收率仍达不到芳香醛的程度,可能是在反应过程中芳香醛类化合物可形成稳定的共轭体系过渡态所致。

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n(KI)=1B1B1117B0181,a micro wave pow er of320W and an irradiation time of3min,the yield of2,42dinitrophenol2 benzylether reached89128%.Key words:micro wave radiatio n;benzyl chloride;catalyst;syn2 thesis;2,42dinitrophenolbenzylether183第29卷第3期于杨等:苯甲酸催化一锅合成3,42二氢嘧啶22(1H)2酮。