An inorganic iodine-catalyzed oxidative system for the synthesis of benzimidazoles using hydrogen peroxide under ambient conditions.
An inorganic iodine-catalyzed oxidative system for the synthesis of benzimidazoles using hydrogen peroxide under ambient conditions.
复制标题
DOI：
10.1002/cssc.201100228
复制
发表时间：
2011-08
期刊：
影响因子：
8.4
通讯作者：
Chenjie Zhu;Yun-yang Wei
中科院分区：
文献类型：
--
作者：
Chenjie Zhu;Yun-yang Wei
苯并咪唑是用于开发具有药物或生物学意义的分子的非常有用的结构单元。[1]苯并咪唑衍生物对几种病毒表现出显着的活性，如HIV，[2]疱疹（HSV-1），[3] DNA，[4] RNA，[5]流感，[6]和人巨细胞病毒（HCMV）。[2a]双苯并咪唑类化合物正被开发为具有抗肿瘤活性的DNA小沟结合剂[7]，并且可以作为过渡金属的配体用于模拟生物系统。[8]此外，苯并咪唑是有机反应中非常重要的中间体。[9]苯并咪唑类化合物的合成受到了广泛关注。[10]苯并咪唑的合成一般有两种方法。一种是将羧酸或其衍生物（腈、亚氨酸酯或原酸酯）与苯二胺偶联，这通常在强酸性条件下进行，[11]通常需要高温的苛刻脱水条件，[12]或通过使用磷酸酐等试剂，[13]有时与微波辐射结合。[14]另一种方法是苯胺席夫碱的氧化环化脱氢，它通常由苯二胺和醛的缩合反应原位生成。各种氧化剂，如MnO 2、[15] Pb（0Ac）4、[16] PhI（0Ac）2、[17] Oxone、[18] DDQ、[19] I2、[20] 1，4-苯醌、[21]四氰基乙烯、[22]苯并氧化呋咱、[23] NaHSO 3、[24] Na 2S 2 O 5、[25]（NH 4）2S 2 O 8，[26]和硝基苯或DMF（高沸点氧化剂/溶剂）[27]已被用于实现脱氢步骤。尽管这些方法中有许多是实用的，但有些存在问题，例如使用危险或有毒的试剂，或者在氧化之前醛与苯并咪唑啉进一步反应而形成N-苄基苯并咪唑副产物。鉴于现有路线的缺点和绿色化学的重要性，最近报道了一些苯并咪唑的绿色合成，使用空气，[28] HClO（由H2 O2和HCl原位生成）[29]金属离子[30]和离子液体。[31]然而，从实际的角度来看，即使这些方法仍然具有几个缺点。它们是：（i）需要高温（通常> 100 ℃）和长反应时间（最多44小时）;（ii）使用可能对某些敏感底物有害的强酸性条件;（iii）使用金属离子，除了环境问题之外，通常需要将来自产物的金属与金属离子解络合。
Benzimidazoles are very useful building blocks for the development of molecules of pharmaceutical or biological interest.[1] Benzimidazole derivatives exhibit significant activity against several viruses, such as HIV,[2] herpes (HSV-1),[3] DNA,[4] RNA,[5] influenza,[6] and human cytomegalovirus (HCMV).[2a] Bis-benzimidazoles are being developed as DNA minor-groove binding agents with antitumor activity [7] and can act as ligands with transition metals for modeling biological systems.[8] In addition, benzimidazoles are very important intermediates in organic reactions.[9] The widespread interest in benzimidazole-containing structures has promoted extensive studies on their synthesis.[10] There are two general methods for the synthesis of benzimidazoles. One is the coupling of a carboxylic acid or derivative (nitrile, imidate, or orthoester) with phenylenediamine, which is usually performed under strongly acidic conditions,[11] harsh dehydrating conditions that often require high temperatures,[12] or via the use of agents such as phosphorus anhydrides,[13] sometimes in combination with microwave irradiation.[14] The other method is oxidative cyclo-dehydrogenation of aniline Schiff base, which is often generated in situ from the condensation of phenylenediamine and aldehyde. Various oxidative reagents, such as MnO2,[15] Pb (OAc) 4,[16] PhI (OAc) 2,[17] Oxone,[18] DDQ,[19] I2,[20] 1, 4-benzo-quinone,[21] tetracyanoethylene,[22] benzofuroxan,[23] NaHSO3,[24] Na2S2O5,[25](NH4) 2S2O8,[26] and nitrobenzene or DMF (high-boiling oxidant/solvent)[27] have been employed to effect the dehydrogenation step. Although many of these methods are practical, some have problems such as the use of dangerous or toxic reagents, or the formation of N-benzylbenzimidazole side products resulting from further reaction of the aldehyde with benzimidazoline prior to oxidation.In view of the drawbacks of existing routes and the importance of green chemistry, a few green syntheses of benzimidazoles have recently been reported, employing air,[28] HClO (generated in situ from H2O2 and HCl),[29] metal ions,[30] and ionic liquid.[31] However, even these methods still have several drawbacks from a practical point of view. These are:(i) the need for a high temperature (often> 1008C) and long reaction time (up to 44 h);(ii) the use of strongly acidic conditions that may be detrimental to some sensitive substrates;(iii) the use of metal ions which, in addition to environmental concerns, often requires decomplexation of the metal from the product with the