Preparation of
Preparation of 3-bromo-2-formylthiophene
Ref Acta Chem Scand 22 (1968) 4.1354
2,3-dibromothiophene (14 parts, 0.058 M ex Lancaster
Chemicals) was weighed into a reaction vessel equipped with a rubber septum. Dry diethyl ether (112 mis) was added by syringe through under a nitrogen blanket and cooled to -70°C. n-Butyl lithium (26.8 mis of 2.5 M solution in hexanes ex Aldrich) was slowly added over 20 mins. After stirring at -70°C for M hour, dimethylformamide (6.3 parts) in diethyl ether was added over 5 mins. The reactants were allowed to warm to 20°C, then 100 mis water was added with stirring. The ether solution was then washed with N hydrochloric acid, aqueous bicarbonate and water. The ether solution was then dried over magnesium sulphate and the ether evaporated to leave an orange/brown oil (12.32 parts). This oil was distilled at 0.05 mm Hg and 68°C to give a straw-coloured oil (4.5 parts). This oil was dissolved in dichloromethane and evaporated onto silica. This silica was formed into a column and the product separated by flash chromatography. The silica column was developed by washing with hexane containing increasing amounts of dichloromethane. The product was eluted in fractions containing from 10-30% dichloromethane in hexane.
Yield = 4.05 parts.
Elemental Analysis
Found 32.0% C, 1.8% H, 16.7% S
Theory 31.4% C, 1.6% H, 16.8% S
b) Preparation of 2-(3-bromo-2-thienyl)-1,3-dioxolane
3-bromo-2-formylthiophene (3.89 parts, 0.02 M) was heated at reflux with dry ethyleneglycol (1.6 parts) toluene (25 parts) and p-toluene sulphonic acid (0.1 parts) in a vessel equipped with a Dean and Stark separator for 16 hours. The reactants were then cooled and evaporated into silica. The silica was formed into a column which was then developed by elution with hexane containing increasing amounts of dichloromethane. The product was obtained from fractions containing 10- 60% dichloromethane as a pale straw-coloured oil (4.42 parts).
Elemental Analysis
Found 35.6% C, 3.1% H, 13.6% S
Theory 35.8% C, 3.0% H, 13.7% S c)
Preparation of 2-formyl-3-thiopheneboronic acid
Butyl lithium (7.9 ml of 2.5 M solution in hexanes ex
Aldrich) was slowly added to a solution of the dioxolane from (b) (4.28 parts, 0.018 M) in dry diethylether with stirring at -70°C under a nitrogen blanket. After stirring for 15 mins butyl borate (6 mis ex Aldrich) dissolved in ethylether (20ml) was slowly added at -70°C. The reactants were stirred for a further 4 hours at -70°C and then warmed to 20°C. 25 ml N hydrochloric acid was added and the reactants stirred for 1 hour at 20°C. The ether layer was then separated and extracted with N aqueous sodium carbonate solution (3 x 10ml). This aqueous carbonate solution was slowly acidified whereupon the product separated and was filtered and dried. Yield = 0.89 parts. Elemental Analysis
Found 36.6% C, 3.0% H, 19.6% S
Theory 38.5% C, 3.2% H, 20.5% S d)
Preparation of title compound
The boronic acid from (c) (0.5 parts, 0.0032 M) was dissolved in ethanol and sodium borohydride (30 mg ex Aldrich) added with stirring at 20°C. After 30 mins the reaction mass was evaporated onto silica which was formed into a column and developed with hexane containing increasing amounts of dichloromethane and then dichloromethane
containing increasing amounts of methanol. The product was obtained from fractions of dichloromethane containing 3-4% methanol. After evaporating the solvent, the product was recrystallised from toluene. Yield = 0.13 part mp 203-4°C.
Elemental Analysis
Found 45.5% C, 3.2% H, 23.3% S
Theory 45.8% C, 3.1% H, 26.4% S
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