Novel access to 1-substituted-benzimidazoles via benzotriazole-mediated synthesis Augusto Rivera * , Mauricio Maldonado, Jaime Ríos-Motta, Miguel Angel Navarro, Diego González-Salas Departamento de Química, Universidad Nacional de Colombia, Ciudad Universitaria, Carrera 30 No. 45-03, Bogotá DC, Colombia article info Article history: Received 21 August 2009 Revised 16 October 2009 Accepted 19 October 2009 Available online 23 October 2009 abstract A one-pot good-yielding synthesis of 1-(alcoxymethyl)-1H-benzimidazoles and 1-((1H-benzimidazol-1- yl)methyl)-1H-benzotriazole from N 1 ,N 2 -bis((1H-benzotriazol-1-yl)methyl)benzene-1,2-diamine (3) and alcohols is described. The synthesis of 3 from macrocyclic aminal 6H,13H-5:12,7:14-dim- ethanedibenzo-[d,i][1,3,6,8]tetraazecine (DMDBTA, 1) and benzotriazole is also described. Both these methods are simple, isolation of the products from the reaction mixtures is easy, and the yields are good. Ó 2009 Elsevier Ltd. All rights reserved. 6H,13H-5:12,7:14-Dimethanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA, 1), which was prepared for the first time by the end of the 19th-century by condensation of o-phenylenediamine with formaldehyde, 1 belongs to a class of nitrogen-containing heterocy- cles having a cage-adamanzanes-type structure. Now, it is worth pointing out that during our continuous research program about the reactivity of 1, 2–4 the reaction between 1 and benzotriazole in dioxane yielding bis-1,3(benzotriazol-yl-methyl)-2,3-dihydro- benzil imidazole (2) resulted in moderate yield. 4 In order to im- prove the yield of 2 we used ethyl acetate as a solvent instead of dioxane due to the major stability of 1 in this solvent. Under these conditions an unexpected compound called N 1 ,N 2 -bis((1H-ben- zotriazol-1-yl)methyl)benzene-1,2-diamine (3) was obtained in good yields. 5 It should be noted that 3 is an interesting compound because it possesses two benzotriazolyl groups, and it is structur- ally related to compounds such as N-(a-amino substituted)-benzo- triazoles (4) which constitute an interesting class of aminals that react by nucleophilic substitution of the benzotriazolyl group with a variety of O-, S-, and C-nucleophiles. 6 The molecular structure of 3, which to the best of our knowl- edge is previously unreported, became evident from NMR spectral measurements in DMSO-d 6 . The 1 H NMR spectrum of 3 5 showed two set of signals for the aromatic protons which were unequivo- cally assigned to protons of the benzotriazolyl and o-phenylenedi- amine rings, based on their chemical shifts and correlation in the 2D-COSY spectrum. An X-ray analysis confirmed the structure of 3. 7 The molecular diagram is shown in Figure 1, and relevant bond lengths and angles are given in Table 1. 4 1 N N N N R 1 R 2 N N N N N N N N 2 HO OH 5 H N H N N N N N HN NH N N N N N N 3 R R Single-crystal X-ray diffraction analysis 7 revealed that 3 is com- posed of discrete monomeric molecules with the two benzotriazol- yl moieties arranged in a face-to-face manner. The bond angles around the benzylic carbon are close to normal tetrahedral bond angles. The bond angles around atoms N4 and N5 are close to sp 2 -hybridization [ P a ffi 360°]. Interestingly, the two benzotriaz- olyl–methylene bonds are different (C20–N3 and C19–N6, Table 1). This observation is explained in terms of a strong anomeric ef- fect of the n N5 ?r  C19—N6 . Such stereoelectronic interactions might cause a lengthening of the C19–N6 bond. 8 Next, our attention was initially focused on the presumption that 3 can undergo double amino-alkylation with phenols to give the corresponding di-Mannich bases 5. However, attempts to pre- pare target compounds 5 by treating 3 with phenols in 2-propanol 0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2009.10.094 * Corresponding author. Tel.: +57 1 3165000x14464; fax: +57 1 3165220. E-mail address: ariverau@unal.edu.co (A. Rivera). Tetrahedron Letters 51 (2010) 102–104 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet