The chemistry of naphthazarine derivatives

Based on IR and¹H and¹³C NMR spectroscopic studies, the oxidation product of echinochrome with Ag₂O was assigned the structure of 2,3-epoxy-7-ethyl-2,3-dihydro-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone. For part 4, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1607–1609, August, 1999.     

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.     

New 7-substituted quinolone antibacterial agents. The synthesis of 1-ethyl-1,4-dihydro-4-oxo-7-(2-thiazolyl and 4-thiazolyl)-3-quinolinecarboxylic acids

A series of 1-ethyl-1,4-dihydro-4-oxo-7-(4-thiazolyl)-3-quinolinecarboxylic acids and 1-ethyl-1,4-dihydro-4-oxo-7-(2-thiazolyl)-3-quinolinecarboxylic acids were prepared. Also prepared was 10-[2-(aminomethyl)-4-thiazolyl]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid. Analogs with basic amine substituents on the thiazole moiety were found to have antibacterial activity.     

Synthesis of 1,4-benzothiazin-2-yl derivatives of 1,3-dicarbonyl compounds and benzothiazinone spiro derivatives by the reaction of 2-chloro-1,4-benzothiazin-3-ones with ‘push-pull’ enamines

The reaction of 2-chloro-3-oxo-3,4-dihydro-2H-1,4-benzothiazines with ‘push-pull’ enamines was investigated. The reaction with the enamines occurs at the β-carbon atom in the presence of a small excess of triethylamine. As a result, a set of 3-oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl derivatives of 1,3-dicarbonyl compounds and benzothiazinone spiro derivatives was prepared. On acidic hydrolysis of ethyl 2-ethyl-3-(methylimino)-2-(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl)butanoate, a new rearrangement affording ethyl 11-ethyl-2,3-dimethyl-4-oxo-2,3,4,5-tetrahydro-1H-2,5-methano-6,1,3-benzothiadiazocine-11-carboxylate was discovered. A plausible mechanism and factors influencing the course of the reaction are discussed.     

Reduction of nitronate adducts from RMgX and 1-hethoxy-4-nitronaphthalene to oximes or amines by trivalent phosphorus reagents

The reduction of nitronate adducts from 1-methoxy-4-nitronaphthalene and Grignard reagents (CH₃ MgX, PhCH₂CH₂HgX, i-C₃H₇ MgX, c-C₆H₁₁MgX and t-C₄H₉MgX) with hexamethyl phosphorous triamide and phosphorous trichlorlde is reported. With the former reagent the reaction is chemio and stereoselective and only the E-oxime is recovered being the E-2-alkyl-4-methoxy-1(2H)naphthalenone oximes and the E-2-alkyl-2,3-dihydro-1,4-naphthoquinone-1-oximes obtained after quenching with NH₄Cl and HCl respectively. Oxime stereochemistry is assigned by LIS values caused by Eu(dpm)₃ on ¹³C signals of 2-methyl-4-methoxy-1-(2H)naphthalenone oxime and 2-methyl-2,3-dihydro-1,4-naphthoquinone-1-oxime. Complete reduction to amines is obtained with phosphorous trichloride.     

Photoinduced Molecular Transformations. Part 142. One-step syntheses of 1H-benz[f]indole-4,9-diones and 1H-indole-4,7-diones by a new regioselective photoaddition of 2-amino-1,4-naphthoquinones and 2-amino-1,4-benzoquinones with alkenes

The 2,3-dihydro-1H-benz[f]indole-4,9-diones 3a–d , h were formed in a one-step reaction in 13–82% yield by an unprecedented [3 + 2] regioselective photoaddition of 2-amino-1,4-naphthoquinone ( 1 ) with various electronrich alkenes 2 (Scheme 1, Table). The [3 + 2] photoadducts derived from 1 with vinyl ethers and vinyl acetate gave 1H-benz[f]indole-4,9-diones 4e , f , i , in 33–72% yield, by spontaneous loss of the corresponding alcohol or AcOH from the resulting adducts; 4i has a kinamycin skeleton. The [3 + 2] photoaddition also took place on irradiation of the differently substituted amino-1,4-benzoquinones 6 , 7 , and 12 and excess alkenes 2 in benzene, giving 1H-indole-4,7-dione derivatives 13 and 14 (Scheme 3), 15a and 16 (Scheme 4), and 18 (Scheme 4), respectively. The initial products in these photoadditions were proved to be hydroquinones, the air oxidation of which yielded the heterocyclic quinones; 2,3-dihydro-2-methoxy-2-methyl-5-phenyl-1H-indole-1,4,7-triyl triacetate ( 19 ) was isolated after treatment of the crude photoaddition mixture obtained from 2-amino-5-phenyl-1,4-benzoquinone ( 7 ) and 2-methoxyprop-1-ene ( 2f ) with Ac₂O and pyridine under N₂. A pathway leading to the annelated hydroquinones involving ionic intermediates arising from an electron transfer in these photoadditions is proposed (Scheme 5).     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

Synthesis of carbamate derivatives of 2,3-dihydro-4<Emphasis Type="Italic">H</Emphasis>-1,4-benzoxazine

Alkylation of methyl 2-hydroxyphenylcarbamates with 1,2-dibromoethane in acetone in the presence of K₂CO₃ gave the corresponding methyl 6(7)-R-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylate. Alkylation of methyl 2-hydroxyphenylcarbamates with chloromethyloxirane was accompanied by recyclization of the oxirane ring with formation of methyl 6(7)-R-3-hydroxymethyl-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylates.     

Synthesis of lomazarin and norlomazarin, pigments from Lomandra hastilis

5,8-Dihydroxy-2,3,6-trimethoxy-7-ethyl-1,4-naphthoquinone (1) was used to synthesize in high yield 5,8-dihydroxy-7(1′-hydroxyethyl)-2,3,6-trimethoxy-1,4-naphthoquinone (lomazarin, 3), a pigment from Lomandra hastilis. Alkaline hydrolysis of lomazarin produced mainly 5,6,8-trihydroxy-2,3-dimethoxy-1,4-naphthoquinone (9) through a retro-aldol decomposition of the 6-keto-form of 5,6,8-trihydroxy-7(1′-hydroxyethyl)-2,3-dimethoxy-1,4-naphthoquinone (13b) formed during the reaction. 2,5,8-Trihydroxy-7(1′-hydroxyethyl)-3,6-dimethoxy-1,4-naphthoquinone (norlomazarin, 4a), a pigment of L. hastilis, and its 3,5,8-trihydroxy-7(1′-hydroxyethyl)-2,6-dimethoxy isomer 4b were formed as a difficultly separable mixture in addition to quinone 9. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 581–584, November–December, 2008.     

Interaction of a lithiated nitronyl nitroxide with polyfluorinated 1,4-naphthoquinones

A 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl lithium derivative was found to react with 2-methoxypentafluoro-1,4-naphthoquinone to form a product of addition at the carbonyl function: radical 2-(3,5,6,7,8-pentafluoro-1-hydroxy-2-methoxy-4-oxo-1,4-dihydronaphthalen-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl. The yield of the addition product increased with temperature and reached 84% at 0?°C. The reaction of the lithium derivative with hexafluoro-1,4-naphthoquinone gave rise to a product of addition at both carbonyl groups, namely, nitronyl nitroxide diradical 2,3,5,6,7,8-hexafluoro-1,4-bis(4,4,5,5-tetramethyl-3-oxide-1-oxyl-4,5-dihydro-1H-imidazole-2-yl)-1,4-dihydronaphthalene-1,4-diol in a 16% yield. The structures of both mono- and diradical were solved by X-ray diffraction analysis, which revealed formation of an intramolecular H-bond between the OH group and nitroxide oxygen. According to electron paramagnetic resonance (EPR) spectroscopy, the obtained mono- and dinitroxide are prone to spontaneous deoxygenation in a toluene solution to give corresponding iminonitroxides. In water, they are much more stable.     

A new type of palladium(0) complex having both electron-withdrawing and -donating sites in a ligand: 5,8-dihydro- and 5,8,9,10-tetrahydro-1,4-naphthoquinone complexes

A new type of palladium(0) complex, (5,8-dihydro-1,4-naphthoquinone)Pd(PPh₃)₂ and (5,8,9,10-tetrahydro-1,4-naphthoquinone)Pd(PPh₃)₂, having both olefin and quinone or dihydro-quinone sites in a ligand molecule was prepared. IR and ¹H NMR spectroscopic studies of these complexes suggested that it is the quinone or dihydro-quinone CC bond which is complexed to Pd. Ligand exchange reactions showed that the stability order of the olefinic quinone complexes was as follows: (1,4-naphthoquinone)Pd(PPh₃)₂ > (5,8-dihydro-1,4-naphthoquinone) Pd(PPh₃)₂>(5,8,9,10-tetrahydro-1,4-naphthoquinone)Pd(PPh₃)₂.     

Deep eutectic solvent-mediated expedient multicomponent synthesis of oxazine scaffolds

A simple, efficient, and eco-friendly protocol for the synthesis of 1,3-oxazine derivatives, viz. 7-aryl-7,8-dihydro-6H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-e][1,3]oxazines and 3-aryl-3,4-dihydro-2H- naphtho[2,3-e][1,3]oxazine-5,10-diones, involving one-pot multicomponent condensation reaction of various amines and formaldehyde with sesamol/2-hydroxy-1,4-naphthoquinone, respectively, catalyzed by a choline chloride–oxalic acid deep eutectic solvent has been developed. The method offers several advantages, including mild reaction conditions, simple operating procedure, recyclable and biodegradable catalyst, short reaction times, and excellent yields of the target products.

     

Reaction of 2-bromomethyl-1,3-thiaselenole with thiourea: en route to the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines

The regioselective reaction of 2-bromomethyl-1,3-thiaselenole 1 with thiourea is accompanied by rearrangement, expanding the ring to afford the corresponding six-membered isothiuronium salt, 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide 2, a synthon of the 2,3-dihydro-1,4-thiaselenin-2-ylthiolate anion. The latter was used for the synthesis of the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines 3a–g, bis(2,3-dihydro-1,4-thiaselenin-2-yl) disulfide 5 and 1,6-bis(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)hexane 6.     

A new base-induced ring transformation of pyrido[2,3-d]pyrimidines

8-Substituted 5,8-dihydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates ( 3 ) rearranged to 8-substituted 7,8-dihydro-5-hydroxy-7-oxopyrido[2,3-d]pyrimidine-6-carboxaldehydes ( 5 ) when treated with sodium ethoxide in an aprotic polar solvent at room temperature. The 6-cyano analogue ( 18 ) also underwent ring transformation under the same mild conditions giving 7-amino-8-ethyl-5,8-dihydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxaldehyde ( 21 ). However, the ring transformations of the pyrido[2,3-d]pyrimidine bearing no N₈-substituent ( 12 ), ethyl 1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine- ( 14 ) and -quinoline-3-carboxylates ( 16 ) failed to occur. A mechanism is discussed.     

Synthesis of 2-aryl-2,3-dihydro-4-styrylpyrimidodiazepines in the reaction of 4,5,6-triaminopyrimidine and 2,4,5,6-tetraaminopyrimidine with diarylidenacetones

New 6-amino and 6,8-diamino-2-aryl-2,3-dihydro-4-styryl-1H-pyrimido[4,5-b][1,4]diazepines were obtained in the reaction of 2,4,5,6-tetraaminopyrimidine 1a and 4,5,6-triaminopyrimidine 1b with one equivalent of the diaryli dene acetones 2 in absolute ethanol with acetic acid as the catalyst. Structure analysis of 6-amino and 6,8-diamino-2-aryl-2,3-dihydro-4-styryl-1H-pyrimido[4,5-b][1,4]diazepines 3a-i, determined by detailed nmr measurements, reveals a high regioselectivity of this reaction.     

Synthesis of benzo[b]xanthene-triones and tetrahydrochromeno[2,3-b]xanthene tetraones via three- or pseudo–five-component reactions using Fe3O4@SiO2/PEtOx as a novel,magnetically recyclable,and eco-friendly nanocatalyst

In this study, poly(2-ethyl-2-oxazoline) (PEtOx) immobilized on Fe₃O₄ nanoparticles (Fe₃O₄@SiO₂/PEtOx) has been constructed as a new, heterogeneous, efficient, and recyclable nanocatalyst. The prepared nanocatalyst was characterized by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) analysis, and vibrating-sample magnetometer (VSM) techniques. Nanocatalyst was employed to synthesize benzo[b]xanthene-triones and tetrahydrochromeno[2,3-b]xanthene tetraones via one-pot three- or pseudo–five-component reaction between 2-hydroxy-1,4-naphthoquinone or 2,5-dihydroxy-1,4-benzoquinone, aldehyde, and dimedone or 1,3-cyclohexanedione under reflux condition in ethanol. The catalyst could be easily separated and recycled several times without considerable loss of activity. Clean methodology, easy work-up, mild reaction condition, short reaction time with good-to-excellent yields, and simple preparation of the catalyst are some advantages of the presented work.     

Amination of naphthoquinones with azidotrimethylsilane

A new method for the synthesis of aminonaphthoquinones from 1,2- or 1,4-naphthoquinones and azidotrimethylsilane is described. In a similar manner 2,3-epoxy-2,3-dihydro-1,4-naphthoquinone was transformed into 2-amino-3-hydroxy-1,4-naphthoquinone. The mechanism of these transformations and the formation of by-products are discussed.

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Aminierung von Naphthochinonen mit Azidotrimethylsilan

Zusammenfassung Eine neue Methode zur Herstellung von Aminonaphthochinonen aus 1,2- oder 1,4-Naphthochinonen und Azidotrimethylsilan wird beschrieben. In analoger Weise wurde 2,3-Epoxy-2,3-dihydro-1,4-naphthochinon in 2-Amino-3-hydroxy-1,4-naphthochinon umgewandelt. Eine mechanistische Deutung dieser Umsetzung und die Bildung von Nebenprodukten wird diskutiert.

     

Polyterephthalates of 2,3-disubstituted butanediols-1,4: Effect of aliphatic substituents on Tg and Tm of the polyesters

Poly(2,3-dialkylbutanediol-1,4 terephthalates) with the alkyl substituents CH₃, C₂H₅, n-C₃H₇, iso-C₃H₇, n-C₄H₉, and n-C₁₀H₂₁, andn-C₁₆H₃₃ were synthesized from the corresponding 2,3-dialkylbutanediols-1,4 and dimethyl terephthalate or terephthaloyl chloride. The substituents of the butanediol-1,4 portion of the polyterephthalates influence the ¹³C NMR chemical shifts of the carbon atoms near the branching site, the glass transition (T_g), and the crystallizability. Small alkyl substituents do not change the T_g of the polymers, whereas bulky substituents such as the isopropyl group increase the T_g and long normal alkyl groups as substituents decrease the T_g of the polymers. Crystallinity in these polyterephthalates was found only with CH₃ and C₁₆H₃₃ as the 2,3-dialkyl substituents in the butanediol-1,4 portion of the polyester. This crystallinity of polyterephthalate of 2,3-di-C₁₆H₃₃ substituted butanediol-1,4 could be assigned to side-chain crystallization of the paraffinic groups.     

Chemistry of dioxine-annelated cycloheptatriene endoperoxides and their conversion into tropolone derivatives: an unusual non-benzenoid singlet oxygen source

The chemistry of two bicyclic endoperoxides, obtained by photooxygenation of 2,3-dihydro-7H-cyclohepta[1,4]dioxine and 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one was investigated with the aim of synthesizing the respective tropolone derivatives. The reaction of these endoperoxides with base, thiourea and their thermolysis provided the desired tropolone derivatives in high yield. On the other hand, the thermolysis of the endoperoxide derived from 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one underwent an unprecedented route and formed parent molecule and singlet oxygen instead of the expected troponoids. The formation mechanisms of all products are discussed.     

Regiospecificity in the reaction of 2,3-dichloronaphthazarins with azide anions. Synthesis of echinamine A—a metabolite produced by the sea urchin Scaphechinus mirabilis

It was found that 6-hydroxy- and 6-alkoxy-2,3-dichloronaphthazarins react smoothly with sodium azide in methanol to produce the corresponding 2-azido derivatives as single regioisomers. We have explored the utility of this reaction for the synthesis of echinamine A (3-amino-7-ethyl-2,5,6,8-tetrahydroxy-1,4-naphthoquinone)—the first marine aminated hydroxynaphthazarin, a metabolite of the sea urchin Scaphechinus mirabilis (Agassiz).