5-Formyl salicylaldehydes, preparation

The Vilsmeier-Haack reaction (herein, Vilsmeier reaction ) provides an effective method for the formylation of aromatic systems. The combination of phosphoryl chloride with V-methylaniline or dimethylformamide generates an iminium phosphorus derivative or chloro-iminium cation that is the active electrophile in an electrophilic substitution reaction. The resulting substitution product is an iminium salt 1, which is hydrolyzed on workup with alkali to give the carbaldehyde product 2 (Scheme l).1,2 The method is particularly useful with activated arenes or electron-rich heterocycles, such as pyrroles, furans, thiophenes, and indoles. We had a special interest in the preparation of indole-7-carbal-dehydes, namely, their properties as isosteres of salicylaldehyde. Thus, we became involved in a wide-ranging investigation of 4,6-dimethoxy-... 

The salicylaldehyde and hydroxynaphthaldehyde intermediates are often prepared by introducing a formyl group or an equivalent synthon next to the OH group (blocked, if necessary) of the corresponding phenol or naphthol many formylation methods are known. Salicylaldehydes can easily undergo the common electrophilic substitution reactions, thus affording, for example, nitrated, haloge-nated, and chloromethylated products suitable for further transformations. 

In attempts to prepare 3-acyl-substituted BIPS (113), various salicylaldehydes were condensed with l,3,3-trimethyl-2-formylmethyleneindoline (Fischer s aldehyde). In alcohol, dimethylformamide, tetrahydrofuran, Y-mcthylpyrrolidonc. and hexamethylphosphoramide as the sole solvents, decarbonylation occurred and the only products were the BIPS compounds. However, in dimethyl sulfoxide, 5-nitro-and 3-bromo-5-nitrosalicylaldehydes gave 11 and 5.6% of the desired 3-formyl-BIPS, respectively. The structures were assigned from their IR and NMR spectra. 

Enantioselective epoxidation. This effective catalyst (1) is readily prepared in a 70-100 kg scale from the resolved diamine (with tartaric acid), the salicylaldehyde (from formylation of the phenol by Duff reaction), and manganese acetate, followed by anion exchange by treatment with aqueous NaCI. 

Through a domino oxa-Michael-aldol condensation reaction, a range of 2-substituted 3-formyl-2E/-chromenes were prepared from salicylaldehydes and a,p unsaturated aldehydes catalyzed by a diphenylperhydro indoUnol... 

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