Studies on 4-Hydroxycoumarins. V. The Condensation of α,β-Unsaturated Ketones with 4-Hydroxycoumarin¹

Abstract

Vol. 66 lated: 0.31 g. of VIII (63%); 0.19 g. of II (35%); 0.20 g. of salicylic acid and traces of carbomethoxysalicylic acid. One gram of the ester under the same conditions yielded 0.18 g. of VIII after refluxing for five minutes.3,3' -Methylenebis -(4 -hydroxycoumarin) dibenzoate (1.12 g.) in 12 ml. of absolute ethanol was refluxed with 2 moles of sodium ethoxide for fifteen hours. Two moles of 1 N hydrochloric acid was added and the combined precipitate of II and VIII was filtered off and II separated from VIII by means of its solubility in dilute NaOH. VIII (0.13 g.) m. p. 318-320°and II (0.56 g.) m. p. 290°w ere obtained. One mole of NaHCOs was added to the filtrate and after concentration to dryness in vacuo, the residue was acidified and extracted with ether. The acid fraction yielded 0.12 g. of benzoic acid, m. p. 118-120°, and the neutral solution yielded 0.02 g. of ethyl benzoate, b. p. 206-207°.3,3'-Methylenebis-(4-hydroxycoumarin) Disalicylate.-The di-(o-benzyloxybenzoate) of I (3.9 g.) in 200 ml. of dioxane was hydrogenated at 1900 pounds pressure and 100°for three hours over Raney nickel. The catalyst was filtered off and the filtrate concentrated to dryness in vacuo.The residue was taken up in a small volume of hot dioxane and the insoluble residue of II was filtered from the hot solution. This process was repeated three times. After a final recrystallization from acetic acid the disalicylate.of II melted at 223-225°, yield 0.7 g.

Carbon-13 Nuclear Magnetic Resonance Spectroscopy. Structure of the Anticoagulant Warfarin and Related Compounds in Solution

“…The rationale for structures 1 and 2 assigned to warfarin and its sodium salt, respectively, has come from chemical synthesis (1) and spectroscopic methods (2). These structures have been assumed to be correct for many years, although no rigorous structural proof has as yet been presented in the literature.…”

Dihydropyran ring conformations. I. Structures of 2-methoxy- and 2-hydroxy-2,4-dimethyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-ones

“…Warfarins are made by the Michael-type addition of unsaturated ketones with 4-hydroxycoumarin (Ikawa, Stahmann & Link, 1944). Using 3-penten-2-one, the racemic hemiketals (2-hydroxy) of the title series were obtained.…”

Structures of (±)-cis-2-hydroxy-4-(2-phenylethyl)- (I) and cis-4-phenyl-2-methyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-one (II)

“…The Michael-type addition of a, fl-unsaturated ketones to 4-hydroxycoumarin is a useful path to a variety of warfarin analogs (Ikawa, Stahmann & Link, 1944). Thus 6-phenyl-3-buten-2-one produces (I) on formation of the cyclic © 1989 International Union of Crystallography C21H200 4 AND C19Hl60 3 hemiketal.…”