Friedel–Crafts Condensations with Maleic Anhydrides. III. The Synthesis of Polyhydroxylated Naphthoquinones

Abstract

The condensation of hydroquinone ethers with an excess of dihalomaleic anhydrides has been found to give particularly good yields of dihalonaphthazarins. The etherification of the latter and the nucleophilic substitution of 2,3-dichloronaphthoquinones have been examined. Finally the structures of the products obtained from the Fries rearrangement of polyacetoxynaphthaIenes have been definitively established.La condensation d'Cthers d'hydroquinones avec un excirs d'anhydrides dihalogCnomalCiques donne des rendements particuliirrement ClevCs en dihalogCnonaphtazarines. La mCthylation de ces substances et la substitution nuclCophile de dichloro-2,3 naphtoquinones ont Ct C Ctudikes. Enfin la structure des produits obtenus lors d e la transposition d e Fries de polyacCtoxynaphtal&nes a CtC Ctablie de f a~o n dCfinitive.Can. J. Chern., 52,838 (1974) Few methods exist for the formation of naphthazarins and none of these are very satisfactory. The syntheses of substituted compounds of this type (whether natural or otherwise), in spite of their apparent simplicity, are therefore usually quite tedious processes. We have attempted to improve the preparation of the basic structure and in principle render its derivatives more readily accessible. The Preparation and Structure of Dihalonaphthazarins and of the Corresponding EthersSince its discovery by Zahn and Ochwat (l), the preparation of naphthazarins by the condensation of hydroquinones (or their ethers) (2) and maleic anhydrides in a molten mixture of aluminum and sodium chlorides has been frequently used. This method remains the most simple way of obtaining many naphthazarins but it suffers the serious inconvenience of giving rather low yields. We have found that the use of excess dichloromaleic anhydride can increase the yield quite spectacularly, in one case to 97%. Stoichiometric amounts of anhydride, dibromomaleic anhydride, and substituted hydroquinones give lower yields. Since the halogens can readily be removed (3), this modification also constitutes a convenient synthesis of some halogen-free naphthazarins.The determination of oxidation-reduction potentials of qninones (4) and the analysis of the n.m.r. spectra of naphthazarins (5) ' have shown that the latter exist mainly in the tautomeric form with the electron-withdrawing groups in the aromatic ring. These results suggest that the predominant tautomer of 2,3-dihalonaphthazarins should be B (Scheme 1). However the n.m.r. spectra of 2a, 2b, and 3 show only one signal at 6 7.33, 7.31, an 7.12, respectively, for ring protons and indicate that these compounds exist mainly with the halogens in the quinoid ring. (The spectrum of 3 could seem ambiguous but is in good agreement with other well established structures such as 6-ethyl-2-hydroxynaphthazarin, F 7.13 (7-CH) (5).) The resonance effects which seem to predominate over other considerations in these cases apparently were not taken into account in earlier works.The etherification of naphthazarins has not been studied extensively. Brass et al. (6) were not abl...

Spectroscopic studies on the formation of molecular complexes of sulfamethoxazole with novel 2,3,5-trichloro-6-alkoxy-1,4-benzoquinones

“…alkoxy substituted 1,4-benzoquinones were synthesized and purified by the reported method [29]. The electron donor sulfamethoxazole was obtained as gift sample from a locally available pharmaceutical company and was used as received.…”

Chemie und Biologie von Alkannin, Shikonin und verwandten Naphthazarin-Naturstoffen

“…Dieses Reaktionsverhalten lieû sich in einer effizienten, in groûem Maûstab durchführbaren, dreistufigen Synthese von Naphthazarin nutzen: Die Friedel-Crafts-Acylierung von 1,4-Dimethoxybenzol 66 mit Dichlormaleinsäureanhydrid 65 verläuft im Unterschied zur Reaktion mit Maleinsäureanhydrid in sehr guten Ausbeuten. [144] Die Reduktion des so erhaltenen 2,3-Dichlornaphthazarins 67 mit Zinn(ii)-chlorid [142] und die anschlieûende Luftoxidation einer alkalischen Lösung des Leukonaphthazarins 68 liefert 64 in sehr guter Gesamtausbeute. [135] Einige Methoden für zweifaches und für reduktives, vierfaches Schützen von Naphthazarin 64 sind in Schema 2 zusammengefaût.…”

“…[144] Es wurde vermutet, daû das Keton 143 eine ideale Vorstufe für beide enantiomeren Verbindungsreihen ist, da Arylalkylketone dieser Art sich im allgemeinen hervorragend als Substrate für viele enantioselektive Reduktionsmittel eignen. [196] Ferner konnte man davon ausgehen, daû Bismethylenacetale vom Typ A (Abbildung 11) der Schlüssel zur Lösung der Probleme bei der Schutzgruppenabspaltung sein könnten.…”

The synthesis of thioglucosides substituted 1,4-naphthoquinones and their conversion in oxathiane fused quinone-thioglucoside conjugates

“…The final part of the study was carried out on the 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin) derivatives 7a,b and 8a,b. It is known that naphthazarin exists in various tautomeric forms that react with the formation of different reaction products 15 .…”