Thieno[3,4-c]pyrrole-incorporated quinoidal terthiophene with dicyanomethylene termini: synthesis, characterization, and redox properties

Synthesis, characterization, molecular structure, and redox properties of a new quinoidal terthiophene incorporated with a thieno[3,4-c]pyrrole moiety (5) are described. Although an electrochemical reduction of 5 formally produces the non-classical thieno[3,4-c]pyrrole moiety, 5 showed a reversible reduction wave on cyclic voltammogram, indicating that the thieno[3,4-c]pyrrole moiety can be stabilized by delocalized 10π-conjugated system in the dianion state of 5. However, the reduction potential was largely affected by incorporation of the thieno[3,4-c]pyrrole and shifted cathodically by 0.4 V compared to that of the parent quinodial terthiophene (1).     

The acid-mediated intramolecular 1,3-dipolar cycloaddition of derived 2-nitro-1,1-ethenediamines for the synthesis of novel fused bicyclic isoxazoles

The discovery of a novel synthesis of new fused bicyclic isoxazoles, for example, N-methyl-3-phenyl-5,6-dihydro-4H-isoxazolo[3,4-c]azepin-8-amine (2a), N-methyl-3-phenyl-4,5-dihydroisoxazolo[3,4-c]pyridin-7-amine (2b) and N-methyl-3-phenyl-4H-pyrrolo[3,4-c]isoxazol-6-amine (2d) in high yield is reported. We speculate that the reaction proceeds via acid-mediated intramolecular 1,3-dipolar cycloaddition from 2-nitro-1,1-ethenediamines 1a,b,d.     

Microwave-assisted synthesis of fused heterocycles incorporating trifluoromethyl moiety

4,4,4-Trifluoro-1-(thien-2-yl)butane-1,3-dione (1) reacts with 5-aminopyrazole, 1,2,4-aminotriazole and 2-aminobenzimidazole derivatives, in the presence of triethylorthoformate under pressurized microwave irradiation to afford the corresponding trifluoromethyl derivatives of pyrazolo[1,5-a]pyrimidine, 1,2,4-triazolo[1,5-a]pyrimidine, and pyrimido[1,2-a]benzimidazoles. Also, compound 1 couples readily with azole diazonium salts to give pyrazolo[5,1-c]triazine, benzimidazo[5,1-c]1,2,4-triazine, and triazolo[3,4-c]1,2,4-triazine derivatives incorporating trifluoromethyl group.     

Rearrangement of furo[2,3-c]quinoline-2,4(3aH,5H)-diones to furo[3,4-c]quinoline-3,4(1H,5H)-diones

Thermally assisted base-catalyzed rearrangement of furo[2,3-c]quinoline-2,4(3aH,5H)-diones 1 to the corresponding furo[3,4-c]quinoline-3,4(1H,5H)-diones 2 is reported, and a mechanism of the transformation is proposed.     

Intramolecular nitrilimine cycloadditions onto β-lactams bearing an alkenyl dipolarophile: synthesis of novel tricyclic β-lactams

A five-step synthesis of novel tricyclic β-lactams has been exploited by stereoselective intramolecular cycloadditions of appropriate nitrilimines 6 and 12. These labile intermediates were generated in situ from the corresponding hydrazonoyl chlorides giving rise to the hitherto unknown azeto[3′,4′:1,2]hexano[3,4-c]pyrazole and azeto[3′,4′:1,2]heptano[3,4-c]pyrazole skeletons.     

Preparation of novel pyridine-fused tris-heterocycles; pyrido[4,3-e]pyrrolo-/pyrido[4,3-e]furano[2,3-c]pyridazines and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole

Three novel pyrido-fused tris-heterocycles have been prepared based on a Suzuki coupling and subsequent cyclisation approach. Pyrido[4,3-e]pyrrolo[2,3-c]pyridazine (3b, 77%) and pyrido[4,3-e]furano[2,3-c]pyridazine (5b, 76%) were obtained by intramolecular diazocoupling. Successful diazocoupling of furan (5b) is thus reported for the first time by NOBF₄ generation of the diazonium intermediate. N-TIPS-pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (TIPS-4b) was synthesised by thermal cyclisation of pyridyl nitrene in considerably higher yield (71%) than previously experienced from similar cyclisations, due to TIPS-activation.     

New nitro-benzo[c]phenanthridine and indolopyridoquinazoline alkaloids from Zanthoxylum atchoum

The first phytochemical investigation of the roots of Zanthoxylum atchoum has led to the isolation of two new nitro-benzo[c]phenanthridine alkaloids 6-nitronitidine (1) and 6-nitro-8-methoxy-7,8-dihydronitidine (2), two new salts of indolopyridoquinazoline alkaloids 3-hydroxy-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (3) and its zwitterionic form 3-phenolate-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (4) along with 18 (5–22) known compounds. Their chemical structures were elucidated by spectroscopic analysis including 1D and 2D NMR and MS techniques. This is the first report of the nitro group on the biosynthesis of the natural benzo[c]phenantridine alkaloids. Compound 2 exhibited potent antibacterial activity against Staphylococcus aureus of MIC₅₀ = 4 μg·mL⁻¹.     

The behaviour of the natural pyranonaphthoquinone pentalongin in alcoholic solvents

Pentalongin, the major constituent of the roots of the East African medicinal plant Pentas longiflora Oliv., undergoes degradation reactions when dissolved in alcoholic solvents. Although these reactions were thought initially to be of a photochemical nature, it is proven that degradation occurs also in the dark. These degradation reactions result in four new derivatives of pentalongin, which were elucidated as 3,4-dihydro-3-methoxypentalongin 4, 3,4-dihydro-trans-3,4-dimethoxypentalongin 5, 10b-hydroxy-3-methoxy-2a,3,6,10b-tetrahydro-2H,5H-furo[2,3,4-ed]naphtho-[2,3-c]pyran-6-one 6 and 3,4-dihydro-trans-3,4-diethoxypentalongin 7.     

Synthesis and alkylation of pyrazolo[3,4-c]isoquinolines and hexahydrocyclohepta[d]pyrazolo[3,4-b]pyridines

The condensation of 1-acyl-2-(morpholin-4-yl)cycloalkenes with 3-amino-1-phenyl-1H-pyrazol-5(4H)-ones gave the corresponding 2,3,6,7,8,9-hexahydropyrazolo[3,4-c]isoquinoline and 3,6,7,8,9,10-hexahydrocyclohepta[ d]pyrazolo[3,4-b]pyridine derivatives. Alkylation of 2,3,6,7,8,9-hexahydropyrazolo[3,4-c]-isoquinolines with alkyl halides occurred at the nitrogen atom in the 3-position. The structure of 7-methyl-2,5-diphenyl-2,3,6,7,8,9-hexahydro-1H-pyrazolo[3,4-c]isoquinolin-1-one was proved by X-ray analysis.     

Synthesis of 2H-3,1-pyrazolo[3,4-e]oxazines via a new conversion of Friedländer reaction

2H-3,1-Pyrazolo[3,4-e]oxazines (5a–c) and tacrine analogies (6a–c) were designed and prepared using 5-amino-4-cyanopyrazole (7) and cycloketones (2a–c) as reactants. The study demonstrated that the new conversion existed in the Friedländer reaction of o-aminocyanopyrazole with cycloketones.     

Aminol initiated Prins cyclization for the synthesis of octahydro-1H-pyrano [3,4-c]pyridine and hexahydro-1H-furo[3,4-c]pyrrole derivatives

Various aldehydes undergo smooth coupling with a branched homoallylic alcohol appended N-tosyl amine (1 & 3) in the presence of 10 mol % BF₃·OEt₂ at room temperature to afford a novel class of 1,8-disubstituted octahydropyrano[3,4-c]pyridine and 1,6-disubstituted hexahydrofuro[3,4-c]pyrrole derivatives in good yields, respectively.     

Stereoselective synthesis of highly functionalised tricyclic β-lactams via intramolecular nitrilimine cycloaddition

The novel azeto[2′,1′:1,2]pyrrolo[3,4-c]pyrazole skeleton has been obtained in both racemic and enantiopure forms by means of intramolecular cycloaddition of nitrilimines 6. Fully stereoselective cycloadditions were obtained, giving tricyclic β-lactams 7 as single diastereoisomers with good overall yields.     

Synthesis of linear and cyclic compounds containing the 3,4-bis(furazan-3-yl)furoxan fragment

Some chemical transformations of 3,4-bis(4-aminofurazan-3-yl)furoxan (1) and 3,4-bis-(4-nitrofurazan-3-yl)furoxan (2) were considered. Compounds 1 and 2 are valuable synthons for the preparation of linear and cyclic compounds containing the 3,4-bis(furazan-3-yl)furoxan fragment. The reaction of compound 2 with a series of N- and O-nucleophiles afforded novel heterocyclic systems: 7-R-7H-difurazano[3,4-b:3′,4′-f]furoxano[3″,4″-d]azepine and difurazano[3,4-b:3′,4′-f]furoxano[3″,4″-d]oxepin.     

[1,2,5]Oxadiazolo[3,4-d]pyridazine 1,5,6-trioxides: efficient synthesis via the reaction of 3,4-bis(hydroxyimino)methyl)-1,2,5-oxadiazole 2-oxides with a mixture of concentrated nitric and trifluoroacetic acids and structural characterization

An efficient synthesis of [1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxides (1) from 3,4-bis(hydroxyimino)methyl)-1,2,5-oxadiazole 2-oxides using a mixture of concentrated nitric and trifluoroacetic acids has been developed. The scope of the unconventional reaction was established. The 4,7-dinitro[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide 1f represents a new high energy compound, unfortunately with low thermal stability. The parent [1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide 1c was studied by single-crystal X-ray diffraction analysis which revealed a planar molecule with an unusually long intracyclic NN bond of 1.668(5)?Å and unexpected exo-cyclic bond angles at the nitroxyl nitrogen atoms. In the crystal, the molecules of 1c are bound to each other by strong π-π stacking and CH?O hydrogen bonding interactions into a three-dimensional framework that results in a high crystal density of 1.833?gcm^?3.     

Synthesis of new heterocyclic systems fused at pyrazolo[3,4-c]-2,7-naphthyridine core

Efficient syntheses of new heterocyclic systems comprising pyrimido[1',2':1,5]pyrazolo[3,4-c]-2,7-naphthyridine, pyrazolo[3,4-c][1,2,4]triazolo[3,4-a]-2,7-naphthyridine and pyrazolo[3,4-c]tetrazolo[5,1-a]-2,7-naphthyridine cores were performed in two simple steps. In the first step, pyrazole ring was fused at the 2-chloro-3-cyanopyridine moiety by treatment with hydrazine. In the second step, pyrimidine part was fused at the thus formed 3-aminopyrazole moiety by heterocyclization with acetylacetone.     

Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles

Lithiated oxazolo[3,4-a]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4-a]benzimidazoles 5a–d in good yields as single diastereoisomers. (R)-Benzimidazol-2-yl carbinols 6a–d were obtained upon hydrolysis under acidic conditions of 1H,3H-oxazolo[3,4-a]benzimidazole derivatives.     

Investigation of hydrazine addition to functionalized furans: synthesis of new functionalized 4,4′-bipyrazole derivatives

The addition of hydrazine to functionalized furans 2a-d leads to a variety of 4,4′-bipyrazoles 4a-c depending on the structure of the starting materials. In one example, compound 2c was first converted to an intermediate, furo[3,4-d]pyridazine 3c which was then transformed into 4,4′-bipyrazole 4c on reacting with hydrazine.     

Cyanoacetanilides intermediates in heterocyclic synthesis. Part 6: Preparation of some hitherto unknown 2-oxopyridine,bipyridine, isoquinoline and chromeno[3,4-c]pyridine containing sulfonamide moiety

Treatment of cyanoacetanilide derivative 1 with tetracyanoethylene (2) in dioxane/triethylamine furnished 2-pyridone derivative 6. Aminopyridine 9 was obtained by cyclization of compound 1 with ketene dithioacetal 7/EtONa. Cyclocondensation of 1 with malononitrile and/or acetylacetone (1:1 M ratio) gave pyridine derivatives 11 and 13. Ternary condensation of compound 1, aliphatic aldehydes and malononitrile (1:1:1 M ratio) yielded the 2-pyridones 20a and b. Bipyridines 22a–c were prepared by refluxing of compound 21 with active methylene reagents. Cyclization of chromene derivatives 24 and 28 with malononitrile produced the novel chromeno[3,4-c]pyridine 26 and pyrano[3′,2′:6,7]chromeno[3,4-c]pyridine 29.     

Substituent dependent regioselective synthesis of pyranopyrandiones and 1,2-teraryls from 2H-pyran-2-ones

The one-pot substituent-directed regioselective synthesis of 1,7-diaryl-2-methyl-4H,5H-pyrano[3,4-c]pyran-4,5-diones 3 as the major and 3,4-diaryl-2-methyl-6-methylsulfanylbenzonitriles 4 as the minor products has been delineated through ring transformation of suitably functionalized 2H-pyran-2-ones 1 with aryl acetones 2. Under similar reaction conditions, 6-aryl-4-sec-amino-2H-pyran-2-ones 5 led, regioselectively, to 3,4-diaryl-2-methyl-6-sec-aminobenzonitriles 6.     

Biphenylenes-xxxi: Condensation of benzocyclobutene-1,2-dione with aliphatic and heterocyclic 1,2-diamines and the synthesis of cis-2-cyano-3-(2'-cyanovinyl)-1,4-diaz

As possible routes to 1,4-diazabiphenylene and its 2,3-disubstituted derivatives we have studied the condensation of benzocyclobutene-1,2-dione (BBD) with various 1,2-diamines. Instead of giving the 1,4-diazabiphenylene ring system, BBD reacted with ethylenediamine, diaminomaleonitrile, 4,5-diaminopyrimidine, 2-aminopyridine, also 2,3- and 3,4-diaminopyridine to give, respectively, 2-o-carboxyphenylimidazolidinium acetate 4, 3,4-dicyano-2,5-dihydro[2,5]benzodiazocine-1,6-dione 10, 4-amino-5a,9b-dihydro-5-,9b-dihydroxybenzo [3',4']cyclobuta[1',2'-4,5]imidazo[1,2-c]pyrimidine 14, 5a,9b-dihydro-5a,9b-dihydroxybenzo[3',4']cyclobuta[1',2'-4,5] imidazo[1,2-a]pyridine 17, the 4-amino derivative 16 of the latter, and the zwitter ion 18 of 4-amino-3(2-carboxy-benzylideneamino) However, BBD reacted with 4,5-diaminobenzotriazole to give the expected 1,2,3,6,11-penta-aza-1-H-indeno [4,5-b]biphenylene 20, which, on amination followed by oxidation, gave a very low yield of cis-2-cyano-3-(2'-cyanovinyl)-1,4-diazabiphenylene 3. In model experiments, 7,8-diphenylfurazano [3,4-f]quinox-aline 28 was reduced to 2,3-diamino-5,6-diphenyl quinoxaline 29, which on oxidation, gave a mixture of cis- and trans-2-cyano-3-(2'-cyanovinyl)5,6-diphenylpyrazine, 30 and 31. The pentacyclic compounds, 1,3,6,II-tetra-aza-2-oxa-2H-indeno [4,5-b]biphenylene 23 and 1,3,5,10-tetra-aza-1-H-indeno[5,6-b] biphenylene 25, were formed from BBD and the appropriate 1,2-diamines but the 5-membered heterocyclic rings could not be cleaved by reduction and hydrolysis respectively) to give tetracyclic diamines which might have undergone oxidation to give derivatives of 1,4-diazabiphenylene. Compounds 14, 16, 20, 23, 25 and 28 are derivatives of new heterocyclic systems.