Reactions of the Formyl Group

This category comprises essentially Claisen or Knoevenagel reactions followed invariably by cyclisation. For example, a stirred mixture of 2-hydroxybenzaldehyde and ethyl cyanoacetate was treated at ambient temperarure with a 3 1 mixture of aluminium phosphate /alumina during 1 hour to give ethyl, 3-ethoxycarbonyl-2-iminobenzopyran, hydrolysis of which with dilute hydrochloric acid at 60°C afforded 3-ethoxycarbonylcoumarin (ref. 68). 

Coumarin was synthesised by the addition of 2-hydroxybenzaldehyde to a stirred mixture of phosphorus oxychloride and N,N-dimethylacetamide at ambient temperature followed by heating at 60-70°C to give the 2-dimethylaminobenzopyrylium salt which was isolated in 98% yield after quenching the reaction mixture in ice and treatment with perchloric acid. Hydrolysis of this at 100°C with 20% sodium carbonate solution until dimethylamine ceased to be evolved afforded coumarin quantitatively (ref.69). 

Preliminary ether formation followed by cyclisation to a benzofuran was achieved by reaction of 2-hydroxybenzaldehyde with a 2-haiogeno-methyl-3-methyiquinoxaline and treatment of the product, 2-(3-methyi-2-quinoxalinylmethoxy)benzaldehyde in ethanol with potassium hydroxide under reflux for 3 hours, to afford in 92% yield, 2-(3-methylquinoxalin-2-yl)benzofuran (ref.71). Alkylation occurs rather than condensation of the 3-methyi group with the o-formyl group. 

2-iso-butenytphenol was obtained in 85% yieid by heating a suspension of the secondary alcohol, derived by a Grignard reaction with 2 moies of iso-propylmagnesium bromide on 2-hydroxybenzaldehyde, in hexane in a sealed tube at 170X until completion of dehydration (ref.72). 

4-hydroxybenzaldehyde oxime hydrate (92% pure) was derived in 63% yieid rather than the phenolic methyl ether by alkylation in aqueous sodium hydroxide 

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