7-Hydroxy-3-phenoxy-8-formylchromones, analogs of natural flavonoids

Abstract

UDC 547.814.5 7-Hydroxy-3-phenoxy-8-formylchromones were synthesized using the Duff reaction and were reacted with 2,4-dinitrophenylhydrazine to produce hydrazones and with an excess of hydrazine hydrate to produce the pyrazole recyclization products. Derivatives of α-pyrono[2,3-f]chromones were synthesized using the Knoevenagel condensation with 2-azahetarylacetonitriles and the Perkin reaction.Few 7-hydroxy-8-formylchromones (isounonal 1) and their partially hydrogenated derivatives, lavinal (2), and 4,7-dihydroxy-6-methyl-5-methoxy-8-formylflavan (3) have been discovered within the broad class of natural flavonoids. The first two occur together in plants of the family Annonaceae [1-6] such as Dasymaschalon rostratum [1], Desmos chinensis Lour [2], Desmos cochinchinensis [3], and Unona lawii Hook. f. & Thoms [4]. The last is found in roots of Desmos cochinchinensis [3]. A mixture of all three flavonoids isolated from D. cochinchinensis [3] exhibited antimalarial activity whereas lavinal itself was viewed as a potential AIDS agent [7]. Phenoxychromones are also found in nature [8]. This enabled us to combine these two classes into one in order to study properties different from those of each class individually but characteristic of the system as a whole.The classical method for synthesizing 7-hydroxy-8-formylchromones is the Duff reaction [9-15]. Starting 7-hydroxy-3-phenoxy-8-formylchromones 4-10 were synthesized using the Duff reaction by heating chromones 11-17 with urotropine in acetic acid with subsequent work up of the reaction mixture by HCl solution. PMR spectra of these compounds in DMSO-d 6 showed a singlet for the formyl group near 10.5 ppm and a broad singlet for the hydroxyl proton that was shifted to weak field relative to the resonance of the hydroxyl in the starting chromone by 1.6-1.7 ppm as a result of the formation of an intramolecular H-bond.The presence of the formyl group was also confirmed by formation of the 2,4-dinitrophenylhydrazone 18 upon reaction of 8 with 2,4-dinitrophenylhydrazine. The PMR spectrum of 18 exhibited resonances for aromatic protons characteristic of starting chromone 8; 1H doublets for H-5′′ and H-6′′ at 8.39 and 7.89 ppm, respectively; and a singlet for H-3′′ of the 2,4-dinitrophenyl group at 8.90 ppm.The reaction of 8-formylchromone 6 with an excess of hydrazine hydrate did not stop at the formation of the hydrazone but led to recyclization of theγ-pyrone ring to form pyrazole 19. This was confirmed by a broad singlet typical of the pyrazole NH proton at 12.90 ppm, singlets for two hydroxyls at 11.78 and 12.07, and a 2H singlet at 6.69 for the hydrazone amino group in the PMR spectrum recorded in DMSO-d 6 .

Synthesis of Chromone-Related Pyrazole Compounds

“…The excess of hydrazine hydrate used in the reaction of 8-formyl-7-hydroxy-2-methyl-3-phenoxychromone 116 in refluxing ethanol led to the isolation of a unique structure 117 ( Scheme 39 ) containing a hydrazone moiety, formed from the reaction of hydrazine with the 8-formyl group, but also the pyrazole ring, resulted from the reaction of hydrazine and recyclization of the γ-pyrone ring of the starting chromone [ 90 ].…”

“… Reaction of 8-formyl-7-hydroxy-2-methyl-3-phenoxychromone 116 with an excess of hydrazine hydrate [ 90 ]. …”

The synthesis of angular heteroarenochromones based on 7-hydroxy-8-carbonylchromones

“…Naturally abundant furo [2,3-h]flavones, such as lancheolatin B (5), pongoglabol (6), pongaglabol methyl ether (7), pongaglabrone (8) and karanjin (9) which are the major constituents of the Pongamia genus are known to possess antibacterial, antifungal and cytotoxic activity [18,19] (Figure 1). …”

“…[9,20], -pyrono [2,3-f]flavones [5] and -pyrono [2,3-f]isoflavones [50], while condensation with diethyl malonate, ethyl acetoacetate and cyanoacetic ester under the Knoevenagel conditions gave 9-carbethoxy, 9-acetyl and 9-cyano-4Н,8Н-pyrano [2,3-f]chromen-4,8-diones 21, respectively [20,43] (Scheme 9). 9-Carbethoxy derivatives 21…”

Synthesis and biological activity of chromones annelated at the C(7)–C(8) bond with heterocycles (review)

“…By the condensation of 8-formyl-7-hydroxychromones 98 with hetarylacetonitriles, it is possible to insert a heterocyclic substituent at position 9 of the 4H,8H-pyrano[2,3-f]chromene-4,8-dione system [48][49][50][51]. …”