71845-20-0

1694-20-8

71845-20-0

GENERAL METHODS: All anilines required for the synthesis of the indigo analogs are commercially available except for 10c, 10d and 10i. Sodium (105 mmol) was reacted in small portions in ethanol (109 mL) over 2 hours. The resulting mixture was mixed with a solution of diethyl 4-ethyl-3-nitrobenzylphosphonate (11a, 11b, 100 mmol) and benzaldehyde (12, 100 mmol) or cinnamaldehyde (14, 100 mmol) dissolved in ethanol (164 mL) at room temperature, and the reaction lasted for 1.5 hours. After continued stirring for 20 h, a thick yellow precipitate was collected by vacuum filtration and washed sequentially with 40 mL of ethanol and 40 mL of petroleum ether. The resulting nitrofunctionalized intermediates 13a, 13b and 15 (yields 69-71%) were used in subsequent reactions without further purification. The nitro derivatives (25 mmol) were suspended in 400 mL of methanol and the reaction flask was purged with argon. Pd/C (10%) of 3% by weight of the nitro derivative was taken, pre-wetted with 2 mL of water and added to 10 mL of methanol and this mixture was carefully added to the reaction system. After replacement with hydrogen atmosphere, the reaction solution was stirred at room temperature for 24 h. The reaction solution gradually changed to a clarified solution. The catalyst was removed by filtration through a bed of diatomaceous earth and the methanol solvent was removed by evaporation under reduced pressure. The resulting aniline derivative was dissolved in CH2Cl2 (70 mL) and converted to the corresponding hydrochloride salt. 150 mL of diethyl ether can be added to the acidic CH2Cl2 solution to promote precipitation of the salt (41-95% yield). The melting points of 10c, 10d, and 10i hydrochlorides were measured to be 203-210 °C (decomposition), 164-181 °C, and 174-180 °C, respectively.