Synthesis
General procedure for the synthesis of 2-amino-3-cyano-5-methylthiophene from propionaldehyde and malononitrile: 0.070 g of 4-propylcyclohexanone (0.5 mmol), 0.030 g of malononitrile (0.5 mmol), 0.019 g of powdered sulphur (0.6 mmol), and 0.1 cm3 of NaOH (4 mol/dm3 aqueous solution) in a 1 cm3 choline chloride The mixture/urea was stirred at 60°C for 2-3 hours. The progress of the reaction was monitored by TLC and when the reaction was complete, 5 cm3 of water was added. The solid product was separated by filtration and recrystallized with ethanol if necessary to obtain the pure target compound.
References
[1] Monatshefte fur Chemie, 2017, vol. 148, # 4, p. 711 - 716
[2] Research on Chemical Intermediates, 2018, vol. 44, # 3, p. 2195 - 2213
[3] Patent: WO2008/50341, 2008, A2. Location in patent: Page/Page column 32; 33
[4] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 7, p. 1953 - 1956
[5] Journal of Pharmaceutical Sciences, 2001, vol. 90, # 3, p. 371 - 388
