Sulfuric Acid → 4-Formylphenylboronic Acid

Participants

Reaction Conditions

Reaction Steps

Using a method based on that in Liebigs Ann. 1995, 1253-1257, a solution of 120 g of tri-n-butyl borate in 250 g of dry tetrahydrofuran was placed under nitrogen in a dried 2 l flask fitted with a dropping funnel and cooled to -50° C. 535 g of a 26.5% strength solution of 4-diethoxymethylphenylmagnesium bromide in THF are then added dropwise at such a rate that the internal temperature does not exceed −40 to −50° C. The mixture is subsequently stirred at −50° C for another 1 hour. 1 l of methyl t-butyl ether (MTBE) is subsequently added and the mixture is hydrolyzed at 5-10° C. using 650 g of 1M sulfuric acid. The aqueous phase was separated off and extracted three times with 500 ml each time of methyl t-butyl ether. The solvent was distilled off under reduced pressure and the crude boronic acid was once again taken up in 0.5 l of water and 185 ml of 5N aqueous potassium hydroxide (pH 14) at 5° C. The aqueous phase was extracted once with 250 ml of MTBE and subsequently, at 5° C., brought to a pH of 1 using 400 ml of 1M sulfuric acid. The precipitate was filtered off, washed twice with 150 ml of ice water and dried. This gives 66.1 g of 4-formylphenylboronic acid (88% of theory) comprising, according to HPLC, 89% of 4-formylphenylboronic acid, 4% of 4-carboxyphenylboronic acid, 3.8% of 4-hydroxymethylphenylboronic acid.

Provenance & Evidence