Chemistry of naphthazarin derivatives. 12. Synthesis and investigation of prototropic tautomerism of 3-(alk-1-enyl)-2-hydroxynaphthazarins

Substituted 3-(alk-1-enyl)-2-hydroxynaphthazarins were synthesized. According to data from IR spectroscopy, these compounds exist in organic aprotic solvents as mixtures of tautomeric 1,4-naphthoquinonoid forms. The compositions of tautomeric mixtures were quantitatively determined. The effects of the structure of the alkenyl substituent and the polarity of the solvent on the tautomeric equilibrium were qualitatively estimated.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2519–2525, November, 2004.     

Synthesis and structure elucidation of oxidative coupling products of 2-hydroxy-1,4-naphthoquinones

2,3-Dihydro-3-O-(1,4-naphthoquinon-2-yl)-2-oxo-1,4-naphthoquinones are the products of oxidative coupling of substituted 2-hydroxy-1,4-naphthoquinones (regardless of the presence of peri-hydroxy groups in their structures) under the action of lead dioxide. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 294—298, February, 2006.     

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.     

Synthesis of benz[f]indole-4,9-diones via acetylenic derivatives of 1,4-naphthoquinone

A synthetic route to benz[f]indole-4,9-diones from 1,4-naphthoquinone is described. Effective methods for cross-coupling of 3-acetylamino-2-bromo-1,4-naphthoquinone with terminal acetylenes and cyclization of the resulting 3-acetylamino-2-alkynyl-1,4-naphthoquinones are developed.     

Amidines: synthesis from o-alkenylanilines and cyclization in polyphosphoric acid

Condensation of 2-[(E)-pent-3-en-2-yl]-4-, 2-[(E)-pent-2-en-2-yl]-4-, or 2-(cyclopent-1-enyl)-6-methylaniline with 1-chloro-1-(N-methylimino)- or 1-chloro-1-(N-phenylimino)ethane affords the corresponding amidines. Cyclization of the N-methylimino derivatives in polyphosphoric acid gives 3,4-dihydroquinazolines in high yields.     

Conformational in the IR spectra of 1′-hydroxyethyl derivatives of 1,4-benzo-and 5,8-dihydroxy-1,4-naphthoquinones: A DFT study

Detailed conformational analysis of the molecule of ′-hydroxyethyl-1,4-benzoquinone (3) by the B3LYP/cc-pVTZ method revealed predominance of rotamers with the free 1′-OH group in the gas phase. B3LYP/cc-pVTZ calculations with inclusion of solvent (cyclohexane) effect in the framework of the polarizable continuum model predict an increase in the percent-age of such rotamers compared to the corresponding gas-phase values. The results obtained are in qualitative agreement with the experimentally observed pattern of v(OH) bands in the IR spectrum of compound 3 in cyclohexane (hexane) solution. Conformational analysis, including tautomerism and rotamerism, of 2-ethyl-1′,5,8-trihydroxy-1,4-naphthoquinone (2) was performed by the B3LYP method with the 6-31G(d), 6-311G(d), 6-311G(d,p), and cc-pVDZ basis sets. The most abundant tautomeric form of compound 2 is form A in which the substituent bearing 1′-OH group is in the quinonoid nucleus. In the gas phase, the percentage of all rotamers in form A is about 86% (among them, the proportion of rotamers with the free 1′-OH group is more than 60%). The main reason for splitting of the v(OH) bands in the IR spectra of compounds 2 and 3 in solutions in nonpolar solvents is the equilibrium between rotamers with a relatively weak intramolecular hydrogen bond between the 1′-OH group and the carbonyl group and those having no this bond.     

Synthesis of benzo[<Emphasis Type="Italic">g</Emphasis>]quinoline-5,10-diones

Addition of HCl to 2-amino-3-(4-methyl-3-oxopentynyl)-1,4-naphthoquinone in CHCl₃ at 20 °C is followed by its cyclization to 4-chloro-2-isopropylbenzo[g]quinoline-5,10-dione. Chlorine atom in this compound can be easily replaced by dialkylamino group upon treatment with secondary amines. 4-Dialkylamino-2-isopropylbenzo[g]quinoline-5,10-dione is also formed by the direct reaction of the starting ketone with secondary amines. Syntheses of 2-amino-3-(4-methyl-3-oxopentynyl)-1,4-naphthoquinone from 2-bromo-and 2-amino-3-iodo-1,4-naphthoquinones are also described. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2381–2385, December, 2007.     

An unexpected reaction of 2-(cyclopent-2-enyl)aniline hydrochloride with dimethyldioxirane

An unusual direction of the reaction of 2-(cyclopent-2-enyl)aniline hydrochloride with dimethyldioxirane was found: the formation of two isomeric products,viz., 3- and 6-chloro-2-(cyclopent-2-enyl)anilines, was observed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1654–1655, August, 1998.     

Synthesis and efficiency of photolysis of methylated 2-dialkylamino- and 2-piperidino-1,4-naphthoquinones

2-Dialkylamino- and 2-piperidino-1,4-naphthoquinones with a methyl group in position 3 or 5(8) of the naphthoquinone were synthesized by reacting dimethyl- and diethylamines and piperidine with 2- and 5-methyl-1,4-naphthoquinones. The quantum yields of photoconversion of the synthesized compounds in benzene were determined. A 1.2- to 6.5-fold increase of the quantum yield over that of 2-dimethylamino-1,4-naphthoquinone was established. A comparison of the quantum yields with the calculated charges on the reaction centers in the excited (T ₁) state showed that there is not a linear relationship between them.Institute of Organic Chemistry, Russian Academy of Sciences, Siberian Branch, 630090 Novosibirsk. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 707–714, March, 1992.     

A facile method for the synthesis of 3,1-benzooxazines from N-acyl-2-(alk-2-enyl)anilines

Electrophilic addition of HCl or Br₂ to N-acyl-2-(alk-2-enyl)anilines is accompanied by intramolecular cyclization of these amides to give 3,1-benzooxazine hydrochlorides or hydrobromides in high yields.     

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.     

Intramolecular cyclization ofN-acetyl-6-(cyclopent-1-enyl)-2-methylaniline

N-Acetyl-6-(cyclopent-1-enyl)-2-methylaniline underwent intramolecular cyclization in the presence of HCl in CH₂Cl₂ at 20°C to form 2,8-dimethylspiro[cyclopentane-1,4′-4′H-3,1-benzooxazine] in quantitative yield. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 398–400, February, 1999.     

Reaction of 2-chloro-3-(4-N,N-dimethylaminoanilino)-1,4-naphthoquinone with cyclic amines (piperidine,morpholine, and pyrrolidine)

It was shown that the reaction of 2-chloro-3-(4-N,N-dimethylaminoanilino)-1,4-naphthoquinone with piperidine in the absence of a solvent gives not only a product of replacement of the chlorine atom by a piperidino group, 3-(4-N,N-dimethylaminoanilino)-2-piperidino-1,4-naphthoquinone, but also 2-(4-N,N-dimethylaminoanilino)-1,4-naphthoquinone and 2-(4-N,N-dimethylaminoanilino-2-piperidino)-1,4-naphthoquinone. The latter compounds are the only reaction products formed in dimethyl sulfoxide. The reaction with morpholine occurs in a similar way, whereas that with pyrrolidine gives only a product of replacement of the chlorine atom by hydrogen.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2451–2454, December, 1995.     

Photolysis of 2-dialkylamino-3-amino(or alkylamino)-1,4-naphthoquinones

Using¹H and¹³C NMR spectroscopy, naphthodihydroimidazolediols were identified as the primary products of photolysis of 2-dialkylamino-3-amino(alkylamino)-1,4-naphthoquinones. Their further non-photochemical (thermal) transformations depend on their structure and on the photolysis conditions.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 358–362, February, 1993.     

Synthesis of 2-(3-amino-2-oxoindolin-3-yl)-3-hydroxynaphthalene-1,4-dione derivatives via a one-pot,three-component reaction under catalyst-free conditions

A concise, facile and straightforward synthetic method has been described for the synthesis of 2-(3-amino-2-oxoindolin-3-yl)-3-hydroxynaphthalene-1,4-dione derivatives by a one-pot, three-component reaction of isatins, 2-hydroxy-1,4-naphthoquinone and ammonium acetate under catalyst-free conditions in ethanol. This protocol becomes highly efficient due to its mild reaction conditions, operational simplicity, and overall good to excellent yields (80–99%).     

Synthesis, spectral and electrochemical characterization of novel 2-(fluoroanilino)-1,4-naphthoquinones

The preparation of novel 2-(fluoroanilino)-1,4-naphthoquinones is presented. It takes place under mild conditions by reacting the corresponding fluoroaniline and 1,4-naphthoquinone in the presence of a Lewis acid catalyst with strong oxidation properties such as CeCl₃·7H₂O. This preparation was also investigated under microwave irradiation. All 1,4-naphthoquinone derivatives were characterized by UV-Vis, IR, ¹H and ¹⁹F NMR, MS and cyclic voltammetry, to investigate the effect of the fluoro-substituents on their electronic properties.     

Synthesis of substituted benz[<Emphasis Type="Italic">g</Emphasis>]indole-6,9-diones and benzo[<Emphasis Type="Italic">h</Emphasis>]quinoline-7,10-diones by heterocyclization of 6-alkynyl-5-amino-1,4-naphthoquinones

Substituted benz[g]indole-6,9-diones were synthesized by intramolecular cyclization of 6-alkynyl-5-amino-3-diethylamino-1,-4-naphthoquinones. A method was developed for the preparation of 2-aryl(or alkyl)-4,9-bis(dialkylamino)benzo[h]quinoline-7,10-diones, which involves the addition of a secondary amine to 6-acylethynyl-5-amino-3-diethylamino-1,-4-naphthoquinone followed by cyclization of the resulting adduct.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–418, February, 2005.     

Effect of 5-hydroxy- and 5,8-dihydroxy-1,4-naphthoquinones on the hydrolytic activity of <Emphasis Type="Italic">α</Emphasis>-galactosidase

The effect of natural and synthetic polyhydroxy-1,4-naphthoquinones on the hydrolytic activity of α-galactosidase from marine bacteria was studied. It was shown that the inhibiting properties relative to the enzyme depended on the nature of the substituents, their number, and their position in the structure of these compounds. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 59–63, January–February, 2009.     

虾青素的合成

以α-紫罗兰酮为起始原料, 采用2C₁₅＋C₁₀→C₄₀路线合成了虾青素. 并经过选择性环氧化三甲基硅基烯醇醚双键的关键步骤, 设计并完成了关键中间体C₁₅部分——6-羟基-3-(3-羟基-3-甲基-1,4-戊二烯)-2,4,4-三甲基-2-环己烯-1-酮的合成.     

A DFT study on regioselectivity in the [2 + 2] photocycloaddition of 6-amino-2-(3′-thienoyl)-1,4-benzoquinone and ethylene

DFT-B3LYP studies have been used to understand the realm of [2 + 2] photocycloaddition reactions that lead to the formation of four-membered cyclobutane derivatives. Regioselectivity in these reactions has been explored for the typical system 6-amino-2-(3′-thienoyl)-1,4-benzoquinone and ethylene. The results favor initial attack of ethylene on quinonoid carbon C5 rather than any other position.