Naftoimidazóis inéditos foram preparados por reação, ativada por microondas, entre paraformaldeído, β-lapachona (ou o-quinonas correlatas) e acetato de amônio suportado em montmorilonita k-10, ou em alumina básica. O uso do suporte básico forneceu os melhores rendimentos, superiores a 80%. Isso foi confirmado para a reação com β-lapachona e piperonal.New naphthoimidazoles were prepared by reaction, activated by microwave irradiation, between paraformaldehyde, β-lapachone (or related o-quinones) and ammonium acetate supported on montmorillonite k-10, or on basic alumina. Use of the basic support gave the best results, with yields above 80%. This was confirmed for the reaction with β-lapachone and piperonal.Keywords: imidazole, microwave, basic alumina, lapachone Introduction β-Lapachone (1a) is an ortho-naphthoquinone present in small amounts in trees of the Tabebuia species (Bignoniaceae), commonly called "ipê" or "pau d'arco" in Brazil. In addition, it can be obtained by the isomerization of lapachol, a quinone that is more abundant and more readily extracted from the same sources. The biological activities of these compounds and simple derivatives, have been investigated since the 1940's (anti-malarial 1 ) up to the present (anti-tumor, 2 anti-microbial, 3 anti-inflammatory 4 and anti-parasitic 5 ) and were recently reviewed. 6 The use of β-lapachone and some semi-synthetic derivatives as chemotherapic agents in the treatment of American trypanosomiasis (Chagas disease) has been investigated, 7 and five imidazole derivatives, prepared from this quinone and aromatic aldehydes, have shown expressive action over the tripamastigote form of Trypanosoma cruzi. 8,9 These imidazole derivatives were prepared by conventional methods. 9 As part of an ongoing study into the use of microwave activation and the use of supported reagents, in this case ammonium acetate, we investigated the preparation of the previously unknown simple imidazole derivatives of β-lapachone and related ortho-quinones with formaldehyde.Microwave activation has provided significant improvement on heterocyclic synthesis, 10 including imidazoles, with [11][12][13] or without support, 14,15 with reduction/ elimination of solvents, decreased reaction times and equal or improved yields.
Results and DiscussionImidazole synthesis from α-diketones has a long history 16 and was initially plagued by low yields and by-products (such as oxazoles). Improvements occurred by the use of acidic conditions, e.g., glacial acetic acid reflux. 17 The availability of microwave technology for synthetic purposes has allowed the efficient preparation of 2,4,5-trissubstituted and 1,2,4,5-tetrassubstituted imidazoles. Further observed benefits, that were occasionally associated with solid supports such as silica, alumina, clays, amongst others, 11-13 included improved yields, and dramatic reductions in reaction time and quantities of solvent used (AcOH). 14,15 Interestingly, the best supports found in these studies were always the acidic in nature.Based on these findings, th...
