Ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate

Yellow solid

Synthesis of ethyl 2-amino-4, 5-dimethylthiophene-3-carboxylate. Into a mixture of butan-2-one (20 g, 0.28 mol, 1.0 eq), ethyl 2-cyanoacetate (31.4 g, 0.28 mol, 1.0 eq), and sulphur (8.9 g, 0.28 mol, 1.0 eq) in 100 mL of ethanol was added diethyl amine (21 g, 0.28 mol, 1.0 eq). The mixture was stirred for 8 h at room temperature. The reaction mixture was diluted with water and the precipitate was collected by filtration and recrystallized from ethanol to afford ethyl 2-amino-4, 5-dimethylthiophene-3-carboxylate as yellow solid (41 g, 75percent).General procedure: For the synthesis of 4, 5-alkyl-2-aminothiophenes (2a–2j), the general procedures are the same as those of compound 2i. A mixture of N-benzyl-4-piperidone (1i, 380 mg, 2 mmol), malononitrile (132 mg, 2 mmol), sulfur (64 mg, 2 mmol), and basic ionic liquid (bmIm)OH (380 mg, 2.4 equiv.) was heated to 60°C for 2 h. The reaction mixture was cooled to room temperature and washed with diethyl ether or ethyl acetate (340 mL), and the organic layers were concentrated under vacuum to obtain an oily crude product. The crude product was dissolved in ether/hexane (3:1, 50 mL) mixture, insoluble material was decanted, and the organic layer was concentrated to 1/4 of the volume and kept in a refrigerator. The precipitate that formed was filtered and dried.General procedure: Diethylamine (0.1mol) was added dropwise for 30min to a suspension of the appropriate ketone (0.1mol), ethyl cyanacetate 0.1mol (11ml) and 3.2g sulfur in 30ml ethanol and the reaction mixture was stirred at room temperature for about 75min. When the synthesis was completed the mixture was cooled. The obtained 2-aminothiophene crystalized in the form of yellow powder. The precipitate was filtrated, washed with water and recrystallized from ethanol to give the 2-aminothiophene derivatives [27]. 6.1.1 General procedure: A mixture of 1 (1 mmol), 2 (1 mmol), elemental sulfur (1 mmol)and BSA (20 mg) was added to 1 mL of DMF. The reaction was incubatedat 50 C and 200 rpm. After the required time, the BSA wasfiltered off to terminate the reaction. For the products with highyields, the solid crude products precipitated in water, and then followedby filtration and drying. For the products with low yields, the crude residues were purified by flash column chromatographyon silica gel using petroleum/ethyl acetate.General procedure: To a mixture of ketone (1 eq.), ethyl cyanoacetate (4) (1 eq.), and elemental sulfur (1 eq.) in absolute ethanol (1.7 mL/mmol eq.) was added triethylamine (1.5 eq.), and the mixture was refluxed for 24 h. The reaction mixture was then concentrated and the residue was partitioned between water (10 mL/mmol eq.)and ethyl acetate (10 mL/mmol eq.). The organic layer was separated, dried over MgSO4, and concentrated, and the crude product was purified by crystallization from EtOH/H2O unless otherwise stated.#10;

Molecular Weight:199.27
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:199.06669983
Monoisotopic Mass:199.06669983
Topological Polar Surface Area:80.6
Heavy Atom Count:13
Complexity:198
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes