Sodium Hydroxide → 4-Bromo-2-thiophenecarboxylic Acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromothiophene-2-carbaldehyde (9.1 g, 48 mmol) in acetone (150 mL) at 0° C. was added Jones' reagent (20 mL of a 2.6 M solution [prepared from CrO3 (26.7 g, 270 mmol) dissolved in H2O (40 mL), and H2SO4 (23 mL)], 52 mmol). After stirring for 30 minutes at 0° C., the ice bath was removed and the reaction was allowed to warm to ambient temperature. After 3 hours stirring at ambient temperature, the reaction was quenched by the addition of 2-propanol. After stirring for 64 hours at ambient temperature, the reaction mixture was diluted with Et2O and filtered through a pad of Florisil. The pad was thoroughly washed with EtOAc, and the filtrate was concentrated under reduced pressure to afford a brown paste. This crude material was dissolved in hot aqueous ethanol, treated with decolorizing carbon and filtered while still hot. Upon cooling an oil separated and formed a suspension. This suspension was treated with solid NaOH (4 g, 100 mmol) and boiled briefly to dissolve the solids. The resulting basic aqueous solution was allowed to cool, and was extracted with Et2O (75 mL). The Et2O extract was discarded. The basic aqueous solution was then acidified by the dropwise addition of concentrated HCl. The acidic aqueous phase was extracted with EtOAc (4×60 mL). The combined EtOAc extracts were washed with brine, and dried over Na2SO4 for 16 hours. The mixture was filtered and concentrated under reduced pressure to afford 4-bromothiophene-2-carboxylic acid as a pale brown solid, which was carried on to the next step without further purification.

Provenance & Evidence