Acylation of 2-arylamino-3-chloro-5,8-dihydroxy-1,4-naphthoquinones

2-Arylamino-3-chloro-5,8-dihydroxy-1,4-naphthoquinones reacted with acetic anhydride and benzoyl chloride in pyridine to give in succession the corresponding O-acyl derivatives at both hydroxy groups. The primary acylation products were 8-acyloxy-2-arylamino-3-chloro-5-hydroxy-1,4-naphthoquinones.     

Reaction of 2-(4-alkylpiperazino)-3-chloro-1,4-naphthoquinones with sodium azide

It was shown that 2-(4-alkylpiperazino)-3-chloro-1,4-naphthoquinones react on heating with NaN₃ in DMF to form new heterocyclic quinones — 1,2,3,4-tetrahydro-13-alkyl-3,1-(iminoethano)benzo[g]quinoxaline-5,10-diones as well as the corresponding 2-(4-alkylpiperazino)-3-aminonaphthoquinones and naphthimidazopyrazinediones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2103–2107, September, 1990.     

The condensation products of 2,3,6-trisubstituted-1,4-naphthoquinones with 2-aminothiophenol

The 2,6-disubstituted-, 3,6-disubstituted-5H-benzo[a]phenothiazin-5-one derivatives and 7-substituted-benzo[a] [1,4]benzothiazino[3,2-a]phenothiazine derivatives were prepared by the condensation of 2,3,6-trisubstituted-1,4-naphthoquinones with 2-aminothiophenol. The resulting compounds were subjected to reduction, dehalogenation and condensation with aniline. Some of the condensation intermediates were isolated and the reaction mechanism was also investigated.     

Synthesis of cis- and trans-5,8-dihydroxy-5,6,7,8-tetrahydro-1,4-naphthoquinone

Cis- and trans-5,8-dihydroxy-5,6,7,8-tetrahydro-1,4-naphthoquinone (1a, 1b) were for the first time synthesized from 5,8-dihydroxy-1,4-naphthoquinone (naphthazazine) (6) as a starting material and racemic triol (3) was first synthesized from 7. The configuration of 1a was determined by X-ray analysis.     

Antioxidant activity of 5,8-dihydroxy-1,4-dihydro-1,4-methanonaphthalene

5,8-dihydroxy-1,4-dihydro-1,4-methanonaphthalene (DDMN), a substituted phenol, is synthesized by reduction of a cyclic dione, 1,4,4a,8a-tetrahydro-endo-1,4-methano-naphtha-5,8-dione (THMND). Pulse radiolysis technique has been employed to understand the nature of transient species formed on reaction of radiolytic species of water radiolysis with DDMN.^•OH radicals were observed to react with DDMN with a bimolecular rate constant of 1.5×10¹⁰ dm³ mol⁻¹ s⁻¹. Inhibition of radiation induced lipid-peroxidation by DDMN was studied in rat liver microsomes by assessing the formation of thiobarbituric acid reactive substances (TBARS). It was found to be strongly inhibitory. The results suggest that DDMN has very good antioxidant activity and may possibly emerge as a good radio-protector.     

Reactions of 2-(4-hydroxyanilino)-1,4-naphthoquinones with cerium ammonium nitrate and pyridinium chlorochromate

Reactions of 2-(4-hydroxyarylamino)-1,4-naphthoquinones with cerium ammonium nitrate or pyridinium chlorochromate depending on the structure of initial substrate and the type of reagent led to the formation of 2-chloro-3-(4-cyclohexa-2,5-dienylideneamino)-1,4-dihydronaphthalene-1,4-diones, 2-(4-hydroxy-3-nitrophenylamino)-1,4-naphthaquinones, and also to simultaneous oxidation and chlorination.     

Synthesis of 1H-naphth[2,3-d]imidazole-4,9-diones by acid catalyzed cyclization of 2-Acylamino-3-amino-1,4-naphthoquinones

The conversion of 2-acylamino-3-amino-1,4-naphthoquinones (II) to the corresponding 2-substituted 1H-naphth[2,3-d]imidazole-4,9-diones (I) under both alkaline and acid catalyzed conditions has been effected and the results compared. Treatment of 3-(4′-chlorobutanonyl-amino)-3-amino-1,4-naphthoquinone (He) with aqueous ethanolic sodium hydroxide solution gives 1,2-butanonaphth[2,3-d]imidazole-4,9-dione (V); whereas, treatment of lie with refluxing formic acid gave 2-(4′-chlorobutyl)-1H-naphth[2,3-d]imidazole-4,9-dione. Treatment of 2-substi-tuted 1H-naphth[2,3-d]imidazole-4,5-diones in DMF with alkyl halides in the presence of potassium carbonate affords the expected 1,2-disubstituted naphth[2,3-d]imidazole-4,9-diones (VI). The spectral properties of I, II, V and VI as well as those of some 2-acylamino-3-chloro-1,4-naphthoquinones IV are discussed.     

Synthesis and antitumor activity of 6- and 2- （ 1-acyl sulfanylalkyl）-5,8-dimethoxy- 1,4-naphthoquinones

Sixteen novel 6- and 2-（1-acylsulfanylalkyl）-5,8-dimethoxy-l,4-naphthoquinones were designed and synthesized. Their cytotoxicities were evaluated in vitro against BEL-7402, HT-29 and SPC-Al cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selectivity for HT-29 cell line. Compound lab exhibited the most potent antitumor activity among the tested compounds.     

Investigations on the antioxidant activity of 5,8-dihydroxy-1,4-dihydro-1,4-methanonaphthalene (DDMN)

5,8-dihydroxy-1,4-dihydro-1,4-methanonaphthalene (DDMN), a substituted phenol, is synthesized by the reduction of a cyclic dione, 1,4,4a,8a-tetrahydro-endo-1,4-methano-naphtha-5,8-dione (THMND). The pulse radiolysis technique has been employed to understand the nature of transient species formed by the reaction of radiolytic species of water radiolysis with DDMN. ^•OH radicals were observed to react with DDMN with a bimolecular rate constant of 1.5 × 10¹⁰ dm³ mol⁻¹ s⁻¹. The inhibition of radiation-induced lipid-peroxidation by DDMN was studied in rat liver microsomes by assessing the formation of thiobarbituric acid reactive substances (TBARS). It was found to be strongly inhibitory. The results suggest that DDMN has very good antioxidant activity and may possibly emerge as a good radio-protector. Dr. Hari Mohan: since deceased.     

Thermal conversions of 2-azido-3-piperazino-substituted 1,4-naphthoquinones

Conclusions The 2-azido derivatives which are formed when 2-chloro-3-(4-acylpiperazino)-1,4-naphthoquinones are reacted with NaN₃ in DMF are converted during the reaction to the corresponding 2-amino derivatives and the cyclization products-naphthimidazolediones.2. It is shown that the precursors of the naphthimidazolediones are 1-(3-amino-1,4-naphthoquinonyl-2)-1,4,5,6-tetrahydropyrazines, which are products from dehydrogenation of the piperazine ring.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2822–2826, December, 1988.     

Iodinated 1,4-naphthoquinones

Iodination of 5-amino- and 6-amino-1,4-naphthoquinones with I₂ and HIO₃ in aqueous dioxane occurs only at the benzoid ring. Depending on the reaction conditions, either aminoiodo- or aminodiiodonaphthoquinones are produced. Diazotization of these compounds followed by reduction or replacement of the diazo group with iodine affords mono- or polyiodo derivatives of 1,4-naphthoquinone. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1465–1469, June, 2005.     

Solvent effects on the oxidative free radical reactions of 2-amino-1,4-naphthoquinones

Solvent effects on the manganese (III) initiated oxidative free radical reactions of 2-amino-1,4-naphthoquinones are described. This free radical reaction provides a novel method for the synthesis of benzo[f]indole-4,9-diones, benzo[f]indole-2,4,9-triones, benzo[b]carbazole-6,11-diones and benzo[b]acridine-6,11-diones. High chemoselectivity was observed in different solvents.     

Transformations of 2-alkylamino-1,4-naphthoquinones under the action of nitrating mixture in acetic acid

Reactions of 2-alkylamino-1,4-naphthoquinones with a nitrating mixture in acetic acid afforded 2-alkyl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones.     

A new method for the synthesis of 2-hydroxy-3-nitro-1,4-naphthoquinones: application to regiospecific preparation of unsymmetrical nitrobiquinones

Novel 2-hydroxy-3-nitro-1,4-naphthoquinones were synthesized by an improved method utilizing nitronium tetrafluoroborate in high yields. A subsequent conversion to 2-chloro-3-nitro-1,4-naphthoquinones and a substitution of the chlorine by hydroxyquinone anions yielded 3-nitro-2,2'-binaphthoquinones with a complete regiocontrol.     

Isomerization of 4-arylamino-1,2-naphthoquinones to 2-arylamino-1,4-naphthoquinones

4-Arylamino-1,2-naphthoquinones isomerize into 2-arylamino-1,4-naphthoquinones upon refluxing in acetic acid. The isomerization follows two routes via intermediate 2-hydroxy-1,4-naphthoquinone and 2-arylamino-1,4-naphthoquinone 4-N-arylimines.     

Diels-Alder Reactions of 5,8-Ethano-5,8-dihydro-1,4-naphthoquinone with Cyclic Dienes

Diels-Alder cycloadditions of 1,3-cyclohexadiene and cyclopentadiene to π -facially dissymmetric 5,8-ethano-5,8-dihydro-1,4-naphtboquinone (1) were examined. The stereochemical outcome of the reactions, determined by a combination of chemical and spectral methods, indicates that addition of cyclic dienes to 1 occurs preferentially at the face syn to the etheno-bridge of 1. Cycloadducts 7a/7b and 8a/8b obtained from Diels-Alder reactions of 1 with cyclopentadiene and 1,3-cyclohexadiene undergo [2+2]-photocyclization to give caged compounds 9a/9b and 10a/10b , respectively. Stereoselective reduction of the enedione double bond in 7a/7b and 8a/8b with aqueous TiCl₃ in acetone affords cis-bis-bicyclic ring-fused 1,4-cyclo-hexadiones 11a/11b , and 12a/12b , respectively.     

Synthesis of 2-Acetyl-5,8-dihydro-1,4-dihydroxy-3-methyl Naphthalene: A Product from the Isomerisation of Diels-Alder Adducts of Both 5-Methyl- and 6-Methyl-2-acetyl-1,4-benzoquinone with 1,3-Butadiene

2-Acetyl-5,8-dihydro-1,4-dihydroxy-3-methyl-naphthalene was synthesised via Diels-Alder addition of 2-acetyl-3-methyl-1,4-benzoquinone to buta-1,3-diene followed by enolisation. It was identical with material obtained by pyridine-induced acetyl migration from the 1,3-butadiene adducts of both 3- and 6-methyl-2-acetyl-1,4-benzoquinone.     

Thermal decomposition of 2-amino-3-aziridino-1,4-naphthoquinones

The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated. In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline-5,10-diones (IIIa-g) with complete stereospecificity. The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f). In the case of 2-amino-3-(2′-phenyl-3′-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-naphtho-imidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzo[g]quinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzo[g]quinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetra-hydro-2-phenyl-3-ethyl-5-iminonaphtho[1,2-b]oxazin-6-one (IX) also occurred. Hypotheses concerning the mechanism and the steric course of this reaction are given. The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxalines.     

A novel manganese(III) acetate mediated reaction between 2-benzoyl-1,4-naphthoquinones and 1,3-dicarbonyl compounds

A manganese(III)-mediated reaction between 2-benzoyl-1,4-naphthoquinones and 1,3-dicarbonyl compounds is described. This reaction provides an effective method for the synthesis of naphtho[2,3-c]furan-4,9-diones and naphthacene-5,12-diones, and it shows fair to high chemoselectivity depending on the electronic effect of the benzoyl group substituent on the reactants. With ethyl benzoylacetate and 1,3-diketones, the novel naphtho[2,3-c]furan-4,9-diones were produced effectively with high selectivity.     

Synthesis of 2-aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones by reaction of 2-benzylamino-1,4-naphthoquinones with nitric acid

2-Aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones were synthesized by treatment of 2-benzylamino-1,4-naphthoquinones with a mixture of nitric and sulfuric acids in acetic acid.