Synthesis of 2-Amino-4-(3-amino-5-hydroxy-4H-pyrazol-4-ylidene)-4H-chromene-3-carbonitriles

Abstract

A simple and efficient protocol was developed for the synthesis of 2-amino-4-(3-amino-5-hydroxy-4H-pyrazol-4-ylidene)-4H-chromene-3-carbonitriles by the potassium phosphate-catalyzed reaction of salicylaldehydes, malononitrile, and 2-cyanoacetohydrazide in ethanol. The method offers advantages such as a simple workup procedure and good yields. When the method was extended to two equivalents of 2-cyanoacetohydrazide instead of malononitrile, the unexpected formation of a salicylaldehyde azine was observed, leading to a novel route for the synthesis of salicylaldehyde azines.

Key words

pyrazoles - chromenes - cyclization - multicomponent reactions - azines

• References

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• 17 2-Amino-4-(3-amino-5-hydroxy-4H-pyrazol-4-ylidene)-4H-chromene-3-carbonitriles 4a–f; General Procedure A mixture of the appropriate salicylaldehyde 1 (1 mmol) and malononitrile (2; 1 mmol) in EtOH (2 mL) in a 25 mL round-bottomed flask was stirred at r.t. in the presence of K₃PO₄ (20 mol%) for 10–20 min. 2-Cyanoacetohydrazide (3; 1 mmol) was added, and the mixture was stirred under reflux in an oil bath for the appropriate time (Table 2) while the progress of reaction was monitored by TLC. When the reaction was complete, the mixture was poured into ice-cold water, and the precipitate was collected by filtration and washed with EtOH. 2-Amino-4-(3-amino-5-hydroxy-4H-pyrazol-4-ylidene)-4H-chromene-3-carbonitrile (4a) Yellow powder; yield: 200 mg (75%); mp 270 °C. IR (KBr): 3400 (OH), 3359–3282 (NH₂), 2206 (CN), 1615 (C=N), 1496, 1353, 760 cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 5.66 (s, 2 H, NH₂, D₂O exchangeable), 6.89–6.98 (m, 2 H, Ar), 7.15–7.18 (m, 1 H, Ar), 7.28–7.34 (m, 1 H, Ar), 8.31 (s, 2 H, NH₂, D₂O exchangeable), 10.02 (s, 1 H, OH, D₂O exchangeable). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 75.83, 88.0, 115.86, 116.50, 116.76, 119.40, 122.41, 129.56, 131.63, 154.30, 156.92, 158.56, 159.75. MS (EI): m/z (%) = 267 (100) [M⁺], 250, 238, 210, 181, 126, 88, 63, 51.