Synthesis of imidazole derivatives from β-lapachone and related compounds using microwave and supported reagents

Abstract

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...

Synthesis and biological evaluation of N-alkyl naphthoimidazoles derived from β-lapachone against Trypanosoma cruzi bloodstream trypomastigotes

“…β-Lapachone (1, 2 mmol) was dissolved in a minimum quantity of dichloromethane (2 mL) and added to the beaker and the solvent was evaporated at room temperature. 16 The reaction mixtures were subjected for 15 min to irradiation in a domes-tic microwave oven (Panasonic, model NN-S42BH) adjusted to potency 1 corresponding to 84.1 W from calibration runs. 25 The crude product was extracted from the support by washing the mixture with ethyl acetate.…”

“…Also using microwave activation, 10 (BLI-H), the simplest imidazole derivative of 1, was obtained by the reaction of 1 with paraformaldehyde, using the same procedure mentioned above (ammonium acetate supported on basic alumina and microwave activation). 16 In sequence, 10 was treated with a base and 8 linear alkylating agents, leading to two series of derivatives, N1-n-alkyl and N3-n-alkyl (11-26, Scheme 2).…”

Recent advances in 1,4-benzoquinone chemistry

“…13 Wide applications of quinones can also be found in the field of synthetic organic chemistry. [14][15][16][17][18][19][20] Coordination chemistry of quinones is also quite rich from the perspective of designing magnetic materials 21 and understanding photophysical properties. 22 The studies of quinonoid compounds have focused on a broad spectrum of topics viz occurrence in nature, 2 syntheses, 23 cycloaddition reactions, 24 photochemistry and pulse radiolysis, 1,25,26 computational chemistry, etc.…”

“…El-Feraly and co-workers 52 isolated five new alkylated benzoquinones (16)(17)(18)(19)(20) as methyl ether derivatives from a complex mixture of alkylated hydroxy benzoquinones obtained from the fruits of Maesa lanceolata.…”

Irradiação de micro-ondas aplicada à síntese orgânica: uma história de sucesso no Brasil

“…A síntese de derivados imidazólicos através de catalisadores suportados também foi estudada por diferentes grupos de pesquisa. Ferreira e colaboradores 49 estudaram a síntese de derivados imidazólicos a partir da b-lapachona sob irradiação de micro-ondas (aparelho domestico) e catálise por resinas básicas de alumina. Os resultados obtidos mostram que a utilização de irradiação de micro-ondas leva a rendimentos superiores aos encontrados na literatura (Esquema 5).…”