Synthesis of imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridones and imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridines as potential antibacterial agents

Abstract  New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug. Graphical abstract        

Synthesis and properties of cyanomethyl derivatives of imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine,imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine,and imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazole

2-Cyanomethyl derivatives were obtained of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[2,1-b]thiazole, and their reactivity was investigated by an example of imidazo[1,2-a]pyridine: It was subjected to nitration, bromination, azo coupling and nitrosation. Acylation of the methylene group effected by amino acids esters with a subsequent addition of the amino group to the cyano group resulted in the formation of 5-amino-4-imidazo[1,2-a]-pyridin-2-yl-1-phenyl-1,2-dihydro-3H-pyrrol-3-one and 2-amino-1-ethyl-3-imidazol[1,2-a]pyridin-2-yl-4(1H)-quinolinone.     

Synthesis of azepino[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazoles and imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]azepines

Fusion of 4-bromo-1,3-diphenyl-2-buten-1-ones (γ-bromodypnones) with 1,2-dimethyl-1H-benzimidazole and further treatment of the reaction product with a base (morpholine) gives 7,9-diaryl-5-methyl5,10-dihydroazepino[1,2-a]benzimidazol-11-ium bromides. The reaction of γ-bromodypnone with 1-alkyl-2-methyl-1H-imidazoles in benzene at 25 °C gives quaternary azolium salts. Upon heating their solutions in alcohol in the presence of K₂CO₃ the latter cyclize to 1-R-6,8-diaryl-1,5-dihydroimidazo[1,2-a]azepin-4-ium bromides or 1-R-6,8-diaryl-1H-imidazo[1,2-a]azepines depending on the nature of the substituent in the benzene rings and the substituent at the N(1) atom of the imidazole.     

New general synthesis of benzo[4,5]imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine and benzo[4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazoline derivatives

The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under solvent-free conditions unexpectedly afforded benzo[4,5]imidazo[1,2-a]pyrimidine, benzo[4,5]imidazo[2,1-b]-quinazoline, and 2,2′-(benzene-1,2-diyldiimino)bis[pyrimidin-4(3H)-ones]. The described reaction is the first example of synthesis of these heterocyclic systems by fusion of benzimidazole to pyrimidine or quinazoline and is likely to follow ANRORC mechanism.     

Crotonization in the benzo[<Emphasis Type="Italic">a</Emphasis>]acridine series. Synthesis of naphtho[2,1-<Emphasis Type="Italic">j</Emphasis>][1,7]phenanthroline derivatives

8,9,10,11-Tetrahydrobenzo[a]acridin-11-one reacted with aromatic aldehydes to give the corresponding 10-arylmethylidene-8,9,10,11-tetrahydrobenzo[a]acridin-11-ones. Reactions of the latter with malononitrile in the presence of a base catalyst led to the formation of polynuclear partially hydrogenated systems, 2-alkoxy-4-aryl-5,6-dihydronaphtho[2,1-j][1,7]phenanthroline-3-carbonitriles, whose absorption and luminescence spectra in solution and polycrystalline state were studied.     

Fluoro-containing Heterocycles: XIII. Fluoro-containing Derivatives of Thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-, Benzothiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-, and Benzimidazo[3,2-<Emphasis Type="Italic">a</Emphasis>]quinazolinones

Reactions of 2-aminothiazole, derivatives of 2-aminobenzothiazole and 2-aminobenzoimidazole with polyfluorobenzoyl chlorides gave rise to acylation products that at heating in the diphenyl ether formed fluoro-containing derivatives of thiazolo[3,2-a]-, benzothiazolo[3,2-a]-, and benzimidazo[3,2-a]quinazolinone.     

Benzo[4,5]imidazo[2,1-<Emphasis Type="Italic">a</Emphasis>]phthalazines: I. substituted <Emphasis Type="Italic">o</Emphasis>-nitrophenylhydrazines in the synthesis of phthalazin-1(2<Emphasis Type="Italic">H</Emphasis>)-ones

Efficient cyclization procedure was developed for 2-nitro-, 2,4-dinitro-, 2-nitro-5-chloro-, and 4,5-dichloro-2-nitrophenylhydrazines with 2-acylbenzoic acids by heating the reagents in a mixture of of concentrated sulfuric acid and ethanol. A series of new phthalazin-1-ones was obtained with a substituted 2-nitrophenyl group in the position 2 and various substituents in the position 4.     

Reactions of 3-Aroylpyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxaline-1,2,4(5<Emphasis Type="Italic">H</Emphasis>)-triones with 2,3-Dihydrofuran and 3,4-Dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyran

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones reacted with 2,3-dihydrofuran and 3,4-dihydro-2H-pyran to give mixtures of the corresponding hetero-Diels–Alder (furo- and pyrano[3″,2″: 5′,6′]pyrano- [4′,3′: 2,3]pyrrolo[1,2-a]quinoxalines) and Michael adducts (furyl- and pyranylpyrrolo[1,2-a]quinoxalines).     

Synthesis and properties of a new fused heterocyclic system 12<Emphasis Type="Italic">H</Emphasis>-benzo[5,6][1,2,4]triazepino[3,4-<Emphasis Type="Italic">a</Emphasis>]isoindol-5(6<Emphasis Type="Italic">H</Emphasis>)-one

12H-Benzo[5,6][1,2,4]triazepino[3,4-a]isoindol-5(6H)-one was synthesized by the condensation of anthranilic acid hydrazide with o-phthalaldehyde. The structure of this compound was established by the X-ray diffraction study of its isopropyl derivative. The mechanism of formation of this compound was suggested and its alkylation reactions were investigated. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 180–185, January, 2008.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

Synthesis,reactions, and antimicrobial activity of some novel fused thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-5<Emphasis Type="Italic">H</Emphasis>-indeno[1,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidine derivatives

Series of novel substituted thioxopyrimidine and thiazolo[3,2-a]pyrimidine compounds that combine various heteroaryl rings have been synthesized via Biginelli one-pot three-component reaction and elucidated with chemical and spectral analysis. Several products were tested for their antimicrobial properties.     

Alkylation of 2-(hydroxyimino)-5<Emphasis Type="Italic">H</Emphasis>-[1,3]thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-pyrimidin-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

Alkylation products were obtained from ethyl 2-(hydroxyimino)-7-methyl-3-oxo-5-aryl-2,3- dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-6-carboxylates at the treatment with alkyl halides, dimethyl sulfate, and diazomethane. Diazomethane alkylated the initial substrate at the oxygen atom of the carbonyl group of the thiazolidine fragment, the other reagents, at the oxygen atom of the hydroxyimino group.     

Synthesis and structures of benzo[<Emphasis Type="Italic">cd</Emphasis>]furo[2,3-<Emphasis Type="Italic">f</Emphasis>]indol-4(5<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A procedure was developed for the synthesis of derivatives of the new heterocyclic system, benzo[cd]furo[2,3-f]indole, based on the cyclodehydration of 6-acylmethyloxy-1-alkyl-benzo[cd]indol-2(1H)-ones. Either 7- or 8-aryl derivatives of benzo[cd]furo[2,3-f]indol-4(5H)-ones can be prepared depending on the reaction conditions. The molecular and crystal structures of 7- and 8-phenylbenzo[cd]furo[2,3-f]indol-4(5H)-ones were established by X-ray diffraction.     

Reactions of ethyl 6,6-dialkyl-8,9-dioxo-5,6,8,9-tetrahydrobenzo[<Emphasis Type="Italic">f</Emphasis>]pyrrolo[2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinoline-10-carboxylates with <Emphasis Type="Italic">N</Emphasis>-nucleophiles

Reaction of enaminoesters, derivatives of 2,2-dialkyl-1,2,3,4-tetrahydrobenzo[f]isoquinoline, with oxalyl chloride leads to the formation of ethyl 6,6-dialkyl-8,9-dioxo-5,6,8,9-tetrahydrobenzo[f]pyrrolo[2,1-a]-isoquinoline-10-carboxylates. At reaction of the latter with ammonia and cyclic amines opening of pyrroledione cycle occurs and the formation of enaminoketoamides, and the reaction with o-phenylenediamine furnishes a fragment of benzimidazole. Hydroxylamine behaves as binucleophile and attacks not only lactam, but also the ester group, affording heterocyclic system of isoxazine-3,4,6-trione.     

Synthesis of derivatives of pyrazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines and imidazo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines proceeding from alkyl 2-benzylidene-3-oxo-3-fluoroalkylpropionates

Methods were developed of the synthesis of alkyl 2-hydroxy-2-fluoroalkyl-4-phenyl-1,2,3,4—tetrahydroimidazo-[1,5-a]pyrimidine-3-carboxylates and alkyl-5-hydroxy-2,7-diphenyl-5-fluoroalkyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-6-carboxylates by regioselective [3+3]-cycloaddition of 5-aminoimidazole or 5-aminopyrazole to alkyl 2-benzylidene-3-oxo-3-fluoroalkylpropionates at the fluoroacylvinyl fragment.     

Synthesis of 6-methyl-8<Emphasis Type="Italic">H</Emphasis>-dibenzo[<Emphasis Type="Italic">a</Emphasis>,<Emphasis Type="Italic">g</Emphasis>]quinolizin-8-imines <Emphasis Type="Italic">via Reissert</Emphasis> compounds

Alkylation of Reissert compounds derived from 3-methylisoquinolines with several 2-cyanobenzylbromides followed by hydrolytic cleavage provided the corresponding 1-benzyl-3-methylisoquinolines. Treatment of the latter with methylmagnesiumiodide caused cyclization to the title compounds rather than formation of 2-acetylbenzylisoquinolines.