5-Methyl-2-thiophenecarboxaldehyde

CLEAR YELLOW TO BROWN LIQUIDMay be synthesized from thiophene (or its derivatives) and formamide in the presence of POCl3; from N-(2-thenyl)formaldimines.

Pale yellow, gold, orange or dark brown liquid; roasted, nutty odour

5-Methyl-2-thiophenecarboxaldehyde is a member of thiophenes.

General procedure: To a solution of 0.99 M EtMgCl (0.61 mL, 0.6 mmol) in THF were added dicyclohexylamine (0.01 mL, 0.05 mmol), and 2-methylthiophene (1a, 0.048 mL, 0.50 mmol) dropwise under an nitrogen atmosphere. After stirring at 60 °C for 24 h, 1.4 mL of THF and N, N-dimethylformamide (0.5 mL, 6.46 mmol) were successively added and stirring was continued for further 1 h. The mixture was quenched by saturated aqueous solution of ammonium chloride (1.0 mL) and the solution was poured into the mixture of diethyl ether/water to result in separation into two phases. Aqueous was extracted with diethyl ether twice and the combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to leave a crude oil, which was purified by column chromatography on silica gel (hexane/EtOAc = 20/1) to afford 62.3 mg of 2-formyl-5-methylthiophene (1a-CHO, colorless oil, 99percent).Reference General procedure: To a stirred solution of 9ha–9hd (200 mmol) in dried DMF (43.86 g, 600 mmol) cooled in anice-water bath was added dropwise POCl3 (46.00 g, 300 mmol). The resulting mixture was stirred atthis temperature for 30 min and then at 100 °C for another 5 h. After cooling to room temperature, the reaction mixture was poured carefully into ice-water (300 mL). The mixture thus obtained wasextracted with CH2Cl2 (300 mL × 3), and the combined extracts were washed successively with 5percentbrine (200 mL), 10percent aqueous K2CO3 (200 mL) and 5percent brine (200 mL), dried (Na2SO4) and evaporatedon a rotary evaporator to afford a residue, which was purified by column chromatography to yield10ha–10hd.General procedure: To a 50 mL of Schlenk tube were added 1 or 3 (0.2 mmol, 1.0 equiv), Pd(OAc)2 (10 molpercent), dppf (10 molpercent) under air, followed by K3PO4·3H2O (0.3 mmol, 1.5 equiv) and Ag2CO3 (0.3 mmol, 1.5 equiv) . The mixture was then evacuated and back filled with N2 (3 times). Bromodichoromethane (0.4 mmol, 2.0 equiv), Ac2O (2 mmol, 190 uL) and CH3CN (1 mL) were added subsequently. The Schlenk tube was screw capped and put into a preheated oil bath (60 °C). After stirring for 24 hours, the reaction mixture was cooled to room temperature, diluted with CH2Cl2 and Ethyl Acetate, then filtered with a pad of silica gel. The isolated yield was given by a hydrolysis pathway, in which the concentrated reaction mixture was diluted with 5 mL CH2Cl2 and 10 mL 3 N HCl and stirred over night. The reaction mixture was extracted with dichloromethane (3 times) and the solvent was removed under rotary evaporation. The residue was then purified by a preparative TLC to give product 2 or 4.

Molecular Weight:126.18
XLogP3:1.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:126.01393598
Monoisotopic Mass:126.01393598
Topological Polar Surface Area:45.3
Heavy Atom Count:8
Complexity:92.5
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes