7-Hydroxy-8-acetylcoumarin N-1-(Carboxymethyl)pyridinium Chloride Hydrazone

As part of a research programme targeting novel molecules with possible biological activity, derived from o-hydroxyaryl ketone hydrazones [1] we attempted to synthesize a water soluble hydrazone of 7-hydroxy-8-acetylcoumarin. Thus, we used 1-(carboxymethyl)pyridinium chloride hydrazide (Girard’s Reagent P), a well known reagent that produces water soluble ketone derivatives.

7-Hydroxy-8-acetylcoumarin was prepared according to the literature method [2] whereas, commercially available Girard’s Reagent P was supplied by Aldrich. Girard’s Reagent P (0.92 g, 4.9 mmol) was added to a solution of 7-hydroxy-8-acetylcoumarin (1 g, 4.9 mmol) in 1-propanol (25 mL). The reaction mixture was refluxed for 2 hours. It was then allowed to cool at room temperature. Subsequently, it was stored in the refrigerator overnight. Filtration of the precipitate, which was formed, afforded of the desired hydrazone as white crystals (1.73 g, 95 %). The product was identified by its ¹H NMR, ¹³C NMR and MS without further purification and was found to be a mixture of two isomers as shown by ¹H and ¹³C NMR data.

M.p. 248-249 °C.

¹H NMR (400 MHz, DMSO-d₆): 2.22 (s, 3H), 2.37 (s, 3H), 5.79 (s, 2H), 5.82 (s, 2H), 6.16-6.22 (m, 2H), 6.98-7.11 (m, 2H), 7.50-7.56 (m, 2H), 7.91-7.97 (m, 2H), 8.13-8.19 (m, 4H), 8.61-8.66 (m, 2H), 9.02-9.11 (m, 4H), 10.60 (s, 1H), 10.70 (s, 1H), 11.18 (s, 1H), 11.46 (s, 1H).

¹³C NMR (100 MHz, DMSO-d₆): 19.1, 20.0, 62.0, 62.4, 109.7, 111.8, 111.9, 112.0, 112.4, 113.7, 113.8, 113.9, 114.4, 115.5, 128.1, 128.2, 128.3, 129.9, 130.1, 130.3, 145.6, 145.9, 147.0, 147.1, 147.9, 152.9, 153.2, 153.3, 158.8, 159.7, 160.0, 160.8, 161.0, 162.9, 167.1, 167.9.

MS m/z (ESI+): Calcd. for C₁₈H₁₆N₃O₄Cl: 711.19647 [C₃₆H₃₂N₆O₈Cl]⁺, 675.21979 [C₃₆H₃₁N₆O₈]⁺, 338.11353 [C₁₈H₁₆N₃O₄]⁺. Found: 711.19687 [C₃₆H₃₂N₆O₈Cl]⁺, 675.22022 [C₃₆H₃₁N₆O₈]⁺, 338.11320 [C₁₈H₁₆N₃O₄]⁺.