Carbonyl and thiocarbonyl compounds XX. Reaction of hydroxybenzaldehydes with o‐phenylenediamine; newer aspects in benzimidazole synthesis

Abstract

The nature of the products of the uncatalysed reaction of the o‐hydroxybenzaldehydes 1a‐d with o‐phenylenediamine in boiling ethanol is mainly dependent on the molar ratio of the reactants and the nature of the substituents at the phenyl ring of the aldehyde. In contrast, the m‐ and p‐hydroxy analogues 1e‐g afford exclusively the corresponding 1‐aralkyl‐2‐arylbenzimidazoles 6, regardless of these factors. However, at low temperature, the hydroxybenzaldehydes 1a‐g react with the diamine always giving monoanils (2) regardless of the hydroxy position. The monoanils of the o‐hydroxy aldehydes afford predominantly 2‐arylbenzimidazoles (4) when boiled in n‐butanol. In contrast, those of the m‐ and p‐hydroxy analogues give exclusively 1‐aralkyl‐2‐arylbenzimidazoles (6), whereas, when heated in nitrobenzene, 2‐arylbenzimidazoles (4) are readily obtained. The dianils 5a‐d, upon boiling in butanol, give a mixture of 2‐arylbenzimidazoles (4) and 1‐aralkyl‐2‐arylbenzimidazoles (6), the ratio of which is dependent on the nature of the substituents at the aldehyde. Reaction mechanisms and spectral features of the products are discussed.

2-(1H-Benzoimidazol-2-yl)-6-ethoxyphenol

“…For hydrogen-bond motifs, see: Bernstein et al (1995). For benzimidazole chemistry, reaction mechanisms and bioactivity, see, for example: Latif et al (1983); Craigo et al (1999); Gudmundsson et al (2000); Trivedi et al(2006); Kim et al (1996); Ramla et al (2006). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986).…”

2-[1-(2-Hydroxy-3-methoxybenzyl)-1H-benzimidazol-2-yl]-6-methoxyphenol monohydrate

“…For hydrogen-bond motifs, see Bernstein et al (1995). For the synthesis and bioactivity of benzimidazoles see, for example: Soto et al (2006); Vazquez et al (2006); Latif et al (1983). For related structures, see: Elerman & Kabak (1997); Liu et al (2006); Al-Douh et al (2006, 2007.…”

4-[1-(4-Cyanobenzyl)-1H-benzimidazol-2-yl]benzonitrile

“…For hydrogen-bond motifs, see: Bernstein et al (1995). For benzimidazole chemistry, reaction mechanisms and their bioactivity, see, for example: Latif et al (1983); Craigo et al (1999); Gudmundsson et al (2000); Trivedi et al (2006); Kim et al (1996); Ramla et al (2006). For the stability of the temperature controller used in the data collection, see : Cosier & Glazer (1986).…”

“…Due to these important applications, many synthetic routes towards benzimidazoles have been developed. They can, for example, be synthesized by the reaction of phenolic aldehydes with o-phenylenediamine (Latif et al, 1983). Based on this route the title compound was synthesized and its crystal structure (Fig.…”