2-Bromo-3-thiophenecarboxylic acid

Light yellow crystalline powder

An oven-dried 100 mL round bottom flask was charged with compound 1 (2.00 g, 15.6 mmol) and tetrahydrofuran (THF; 30 mL). The solution was cooled to -78.0 °C and 2.50 M n-butyllithium in hexane (12.6 mL, 31.5 mmol) was slowly added dropwise. The reaction mixture was stirred for 30 min at -78.0 °C and bromine (0.86 mL, 16.4 mmol) was added dropwise. Stirring was continued for 1 h at -78.0 °C and the mixture was heated to room temperature. After stirring the mixture overnight, a small amount of dilute 1M HCl (50.0 mL) was added to quench the reaction and the solution was then concentrated. After extracting the resultant mixture using ether and water, the organic layer was dried with Na2SO4. The compound was recrystallized twice using a H2O/ether mixture to furnish the compound as faint yellow needles (2.13 g, yield 66.0percent; 1H NMR (500 MHz, DMSO‑d6, d (ppm)): 7.63-7.62 (d, J 5.8 Hz, 1H), 7.32-7.31 (d, J 5.8 Hz, 1H)).The reaction temperature was -78 , the reaction time was 2h, the yield was about 50percent. In a 50 ml pear-shaped flask were placed 8 ml of deionized water, 0.6 g of NaOH (15 mmol) and 1.9 g of 2-bromo-3-thiophenecarboxaldehyde(190 g mol-1, 10 mmol), 1.58 g of KMnO4 (158 g mol-1, 10 mmol) and stirred in a 50 ° C water bath for 2 hours.Hot filtration, extraction and separation, the aqueous phase was concentrated hydrochloric acid filtration to obtain a white solid, yield: 70percent.An oven-dried 100 mL round bottom flask was charged with compound 1 (2.00 g, 15.6 mmol) and tetrahydrofuran (THF; 30 mL). The solution was cooled to -78.0 C and 2.50 M n-butyllithium in hexane (12.6 mL, 31.5 mmol) was slowly added dropwise. The reaction mixture was stirred for 30 min at -78.0 C and bromine (0.86 mL, 16.4 mmol) was added dropwise. Stirring was continued for 1 h at -78.0 C and the mixture was heated to room temperature. After stirring the mixture overnight, a small amount of dilute 1M HCl (50.0 mL) was added to quench the reaction and the solution was then concentrated. After extracting the resultant mixture using ether and water, the organic layer was dried with Na2SO4. The compound was recrystallized twice using a H2O/ether mixture to furnish the compound as faint yellow needles (2.13 g, yield 66.0%; 1H NMR (500 MHz, DMSO-d6, d (ppm)): 7.63-7.62 (d, J 5.8 Hz, 1H), 7.32-7.31 (d, J 5.8 Hz, 1H)).The reaction temperature was -78 , the reaction time was 2h, the yield was about 50%. In a 1 L two-necked flask, 24.5 g of 3-methylthiophene (98 g mol-1, 24.5 g, 250 mmol) was added and 400 mL of chloroform / glacial acetic acid (V: V = 1: / L, Favoring the inhibition of the bis-brominated product), 44.5 g of NBS (178 g mol-1, 44.5 g, 250 mmol) were added in portions in an ice-water bath.After the addition of NBS to continue stirring for 2-3 hours, TLC monitoring. After treatment: deionized water to quench the reaction, liquid separation, the organic phase was NaOH solution, washed with water, dried, concentrated vacuum pump with fractional distillation.At low temperature (-78C), n-BuLi (24.99 g, 390.16 mmol) was slowly added dropwise to a solution of diisopropylamine (39.48 g, 390.16 mmol) in tetrahydrofuran (250 mL). After completion of addition, the reaction solution was slowly warmed up to 0C, stirred for half an hour and then cooled to -78C. A solution of thiophene-3-carboxylic acid (25 g, 195.08 mmol) in tetrahydrofuran (100 mL) was added dropwise. After completion of dropwise addition, the reaction solution was slowly warmed up to 20C with stirring for half an hour, and added with CBr4 (64.69 g, 195.08 mmol) with stirring for 1h. TLC showed complete reaction, the reaction solution was quenched with saturated NH4Cl (20 mL), then added with 1N HCl (300mL) to acidize, and extracted with DCM (300 mL * 3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was recrystallized in 50% ethanol (500 mL) to give the title compound (40 g, crude), which was used directly in the next step. 1H NMR (400MHz, DMSO-d6) delta = 7.64 - 7.60 (m, 1H), 7.31 (d, J=5.8 Hz, 1H).

Molecular Weight:207.05
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:205.90371
Monoisotopic Mass:205.90371
Topological Polar Surface Area:65.5
Heavy Atom Count:9
Complexity:128
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes