Synthesis and Transformations of 2-Hydroxy-2-(benzotriazol-1-yl)-1,4-naphthoquinone

2-Hydroxy-3-(benzotriazol-1-yl)-1,4-naphthoquinone reacts with o-phenylenediamine and 4-chloro-2-aminophenol to give cyclization products: 5-oxo-6-(benzotriazol-1-yl)-5,6H-benzo[a]phenazine and 5-oxo-6-(benzotriazol-1-yl)-10-chlorobenzo[a]phenoxazine; the reaction with aniline yields the quaternary anilinium salt, and benzoyl chloride and benzenesulfonyl chloride acylate the nitrogen atom of the benzotriazolyl moiety.     

1,4-Disubstituted and 1,4,5-Trisubstituted 2-[(Benzotriazol-1-yl)methyl]pyrroles as Versatile Synthetic Intermediates

The CH(2)Bt substituent, unlike previously used CH(2)X substituents, enables (i) the synthetic elaboration of pyrroles with unsubstituted ring positions and (ii) electrophilic as well as nucleophilic substitutions to give pyrroles of type pyrrolyl-2-CHENu. Thus, 1,4-disubstituted (7) and 1,4,5-trisubstituted 2-[(benzotriazol-1-yl)methyl]pyrroles (15) were easily prepared from the reaction of 5-(benzotriazol-1-yl)-1,2-epoxy-3-pentynes 4 or 14 with primary amines in i-PrOH. The 2-(benzotriazol-1-yl)methyl side chains of compounds 7 and 15 were elaborated by nucleophilic substitution and also by initial alkylation followed by replacement or elimination of the benzotriazolyl moiety to afford a variety of 1,2,4-trisubstituted (6, 8-9, 11-13) and 1,2,4,5-tetrasubstituted pyrroles (18, 20-22).     

Novel routes to 1-aryl-1,4-dihydro-3(2H)-isoquinolinones and 2-substituted or 2,3-disubstituted benzofurans by intramolecular cyclizations

N-(α-Benzotriazolylalkyl)arylacetamides, readily available from an arylacetamide, an aldehyde and benzotriazole, undergo intramolecular cyclization under acidic conditions to give 1-aryl-1,4-dihydro-3(2H)-isoquinolinones in good to excellent yields. Similarly, 2-(benzotriazol-1-yl)-2-(o-hydroxyphenyl)ethanols, obtained by lithiation of 2-(benzotriazol-1-ylmethyl)phenols followed by quenching with aldehydes or ketones, eliminate a molecule of water and a molecule of benzotriazole yielding 2-substituted and 2,3-disubstituted benzofurans.     

Reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone derivatives and the properties of the obtained products

N′-(4-Oxo-1,4-dihydronaphthalen-1-ylidene)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides and N′-(3-methyl-4-oxo-1,4-dihydronaphthalen-1-ylidene)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides were synthesized by reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone or 2-methyl-1,4-naphthoquinone. The alkylated analogues of the above products were obtained using ethyl iodide. The interaction of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 2,3-dichloro-1,4-naphthoquinone was followed by formation of N′-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides. All these compounds were characterized using ¹H, ¹³C NMR, IR and mass spectra. Some of the new compounds were tested for the antimicrobial and antifungal activity.     

A Short and Efficient Synthesis of Novel N-(2,3-dihydro-2-oxo-5-phenyl-1 H -1,4-benzodiazepin-3-yl)-2-carboxamides

 Several novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides were prepared by acyl coupling of 2-aminobenzophenones with α-(benzotriazol-1-yl)-N-acylglycines followed by displacement of the benzotriazole ring with ammonia and cyclization of the resulting monoacyl aminals. In addition to high yields and shorter reaction sequences due to avoiding deprotection and acylation of the protected 3-amino-1,4-benzodiazepin-2-one intermediates, the present approach did not involve the use of toxic and odoriferous materials as is the case with other methods.     

Reactions of 1,4-naphthoquinone and 5-hydroxy-1,4-naphthoquinone with ninhydrin

Russian Chemical Bulletin - 1,4-Naphthoquinone and 5-hydroxy-1,4-naphthoquinone react with ninhydrin to give 2-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)naphthalene-1,4-dione and 8-hydroxy-...     

A Short and Efficient Synthesis of Novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides

Summary.  Several novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides were prepared by acyl coupling of 2-aminobenzophenones with α-(benzotriazol-1-yl)-N-acylglycines followed by displacement of the benzotriazole ring with ammonia and cyclization of the resulting monoacyl aminals. In addition to high yields and shorter reaction sequences due to avoiding deprotection and acylation of the protected 3-amino-1,4-benzodiazepin-2-one intermediates, the present approach did not involve the use of toxic and odoriferous materials as is the case with other methods. Received September 20, 2000. Accepted (revised) November 29, 2000     

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.     

Synthesis of benzotriazolylsuccinimides in melt

N-Phenyl-3-(benzotriazol-1-yl)pyrrolidine-2,5-dione was synthesized by condensation of N-phenylmaleimide with benzotriazole in melt. The adducts of 2 moles of benzotriazole to different bismaleimides, namely, bis[3-(benzotriazol-1-yl)pyrrolidine-2,5-diones] were obtained under analogous conditions. These adducts, according to the data from ¹H and ¹³C NMR spectroscopy, contain also (benzotriazol-2-yl)succinimide and residual maleimide fragments.     

Luminescent heteroleptic copper(I) complexes with polydentate benzotriazolyl-based ligands

Transition Metal Chemistry - Bis(benzotriazol-1-yl)phenylmethane CHPh(btz)2 and tris(benzotriazol-1-yl)methane CH(btz)3 were used as N-donor ligands to prepare luminescent heteroleptic copper(I)...     

Unusual deoxygenation and reactivity studies related to O6-(benzotriazol-1-yl)inosine derivatives

New and unusual developments related to the chemistry of O6-(benzotriazol-1-yl)inosine derivatives are reported. First, a simple, scalable method for their syntheses via the use of PPh3/I2/HOBt has been developed and has been mechanistically investigated by 31P(1H) NMR. Studies were then conducted into a unique oxygen transfer reaction between O6-(benzotriazol-1-yl)inosine nucleosides and bis(pinacolato)diboron (pinB-Bpin) leading to the formation of C-6 (benzotriazol-1-yl)purine nucleoside derivatives and pinB-O-Bpin. This reaction has been investigated by 11B(1H) NMR and compared to pinB-O-Bpin obtained by oxidation of pinB-Bpin. The structures of the C-6 (benzotriazol-1-yl)purine nucleosides have been unequivocally established via Pd-mediated C-N bond formation between bromo purine nucleosides and 1H-benzotriazole. Finally, short and extremely simple synthesis of 1,N6-ethano- and 1,N6-propano-2'-deoxyadenosine are reported in order to demonstrate the synthetic versatility of the O6-(benzotriazol-1-yl)inosine nucleoside derivatives for the assembly of relatively complex compounds.     

New NH-substituted 1,4-naphtho- and 1,4-benzo- quinones: Synthesis,characterization and potential antiproliferative effect against MDA-MB-231 cells

Abstract

Eleven new alkyl and aryl amino quinones were synthesized from quinones (2,3-dibromo-1,4-naphthoquinone 1, 2-bromo-1,4-naphthoquinone 2, p-benzoquinone 3 or 2,6-dichloro-1,4-benzoquinone 8) with primary amines. The structures of all compounds were characterized by spectroscopic technics and elemental analysis. The structure of 2-((6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)methylamino)-3-bromonaphthalene-1,4-dione (5a) was established by single crystal diffraction. 2-(2-(Ethylthio)ethylamino)naphthalene-1,4-dione (6b) was found to have noteworthy antiproliferative effect against MDA-MB-231 cells.     

O6-(benzotriazol-1-yl)inosine derivatives: easily synthesized, reactive nucleosides

A novel class of O6-(benzotriazol-1-yl)inosine as well as the corresponding 2'-deoxy derivatives can be conveniently prepared by a reaction between sugar-protected or -unprotected inosine or 2'-deoxyinosine nucleosides and 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). The reaction appears to proceed via a nucleoside phosphonium salt, and in the absence of any additional nucleophile, the released 1-hydroxybenzotriazole undergoes reaction with the formed phosphonium salt leading to the requisite O6-(benzotriazol-1-yl)inosine or 2'-deoxyinosine derivatives. Isolation and characterization of the phosphonium salt as well as analysis by 31P{1H} NMR appear to be consistent with this reaction pathway. The resulting O6-(benzotriazol-1-yl)inosine derivatives are effective as electrophilic nucleosides, undergoing facile reactions with a variety of nucleophiles such as alcohols, phenols, amines, and a thiol. Unusual and challenging nucleoside derivatives such as an aryl-bridged dimer, a nucleoside-amino acid conjugate, and a nucleoside-nucleoside dimer have also been synthesized from the O6-(benzotriazol-1-yl)-2'-deoxyinosine derivative. Finally, a fully protected DNA building block, the O6-(benzotriazol-1-yl)-2'-deoxyinosine 5'-O-DMT 3'-O-phosphoramidite, has been prepared and a preliminary evaluation of its use for DNA modification has been performed. Results from these studies indicate several important facts: A single, simple methodological approach provides a class of stable, isolable ribo and 2'-deoxyribonucleoside derivatives that possess excellent reactivity for SNAr chemistry with a wide range of nucleophiles. Also, a benzotriazolyl nucleoside phosphoramidite appears to be a suitable reagent for incorporation into DNA for purposes of site-specific DNA modification.     

Convenient Synthesis of Julolidines Using Benzotriazole Methodology

Reaction of N,N-bis[(benzotriazol-1-yl)methyl]aniline (2) with 1-vinylpyrrolidin-2-one gives a mixture of diastereomeric 1,7-bis(2-oxopyrrolidin-1-yl)julolidines 3. After reduction of 3 with LAH, the predominant trans diastereomer of 1,7-di(pyrrolidin-1-yl)julolidine (4) is separated. Reaction of 2 with ethyl vinyl ether yields predominantly trans-1,7-di(benzotriazol-1-yl)julolidine (11). Stepwise synthesis from tetrahydroquinoline 15 gives access to julolidines with two different substituents on C-1 and C-7. Reaction of 1-[(benzotriazol-1-yl)methyl]-1,2,3,4-tetrahydroquinoline (25) with enolizable aldehydes gives a mixture of tetrahydroquinolines 26-29 which are converted into single julolidine products upon treatment with sodium hydride, LAH, or phenylmagnesium bromide. Reactions of 1,2,3,4-tetrahydroquinolines with benzotriazole and 2 molar equiv of enolizable aldehydes gives 1,2,3-trisubstituted julolidines 38-41, which with lithium aluminum hydride, sodium hydride, or a Grignard reagent produce single diastereomers of products 42, 43, and 45, respectively.     

Research on photochemical and thermochemical reactions between indole and quinones in the absence of solvent

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho[2,3-a:-2′,3′-c]carbazole-6,11,12,17-tetrone ( 1 ) in addition to 2-(3-indolyl)-1,4-naphthoquinone ( 2 ) which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(1H-indol-3-yl)-9-phenanfhrenol ( 3 ) and 9,10-dihydro-9-(1H-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol ( 4 ) or 10,10-di-1H-indol-3-yl-9(10H)-phenanthrenone ( 5 ), respectively. All of these products were only obtained in trace amount in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(1H-indol-3-yl)-9(10H)-phenanthrenone ( 6 ) obtained in the solution photoreaction. A possible mechanism for formation of 4 and 5 is described in terms of electron pair donor/acceptor complexation.     

Synthesis of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides and their transformations to novel benzotriazol-1-yl-substituted cyclopropanes

Diphenylphosphinous anion reacted with chloromethylbenzotriazole to give (benzotriazol-1-yl)methyldiphenylphosphine oxide, which, after lithiation, was alkylated to give 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides in good yield. Treatment of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides with n-butyllithium followed by condensation with epoxides, afforded benzotriazol-1-yl-substituted cyclopropanes, which underwent further lithiation and subsequent reaction with numerous electrophiles to provide a variety of novel benzotriazol-1-yl-substituted cyclopropane derivatives.     

Syntheses and transformations of substituted benzazolyl- and tetrazolyl(benzotriazol-1-yl)methanes

Condensation reactions of o-hydroxy- and o-mercaptoanilines, and o-phenylenediamine with (benzotriazol-1-yl)acetic acid result in (1,3-benzazol-2-yl)(benzotriazol-1-yl)methanes. Cycloaddition of sodium azide to (benzotriazol-1-yl)acetonitrile leads to (1,2,3,4-tetrazol-5-yl)(benzotriazol-1-yl)methane. The diazolo-substituted benzotriazolylmethanes thus obtained were mono- and di-alkylated at the methylene group and the displacement of the benzotriazole group by nucleophiles was investigated.     

Novel synthesis of bicycles with fused pyrrole, indole, oxazole, and imidazole rings

Reactions of benzotriazol-1-yl(1H-pyrrol-2-yl)methanone 10 and benzotriazol-1-yl(1H-indol-2-yl)methanone 11 with diverse ketones, isocyanates, and isothiocyanates in the presence of base afforded pyrrolo[1,2-c]oxazol-1-ones 1, oxazolo[3,4-a]indol-1-ones 2, pyrrolo[1,2-c]imidazoles 3, and imidazo[1,5-a]indoles 4 by a simple one-step procedure.     

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%).     

Preparation of 1,5-disubstituted pyrrolidin-2-ones

1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5-(benzotriazol-2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2, 5-dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10 react identically with nucleophiles.