Facile synthesis of spiro[benzo[e]indole-2,2′-piperidine] derivatives and their transformation to novel fluorescent scaffolds

The reaction of azaheterocyclic enamines with acrylamide was employed for the preparation of novel fluorescent scaffolds possessing a benzo[e]indoline moiety. Reaction of 3-substituted 2-methylidene-1H-benzo[e]indole with acrylamide gave rise to spiro[benzo[e]indole-2,2′-piperidin]-6′-ones. Ring opening reactions of the latter spiro compounds were investigated. Benzo[e]indoline derivatives possessing 2-(3-carbamoylpropyl), 2-[3-(ethoxycarbonyl)propyl] and 2-(4-aminobutyl) side chains were synthesised. The optical properties of the benzo[e]indoline derivatives were studied by UV-vis and fluorescence spectroscopy.     

Synthesis of new benzo[b]thieno fused ring systems via transition metal-mediated cyclisations

The compact synthesis of a new ring fused benzo[b]thieno derivative with an embedded nine-membered ring system via ring closing metathesis methodology is described. The preparation of the novel 11H-benzo[b]thieno[2,3-c]pyrrolo[2,3-a]indol-11-one via palladium-mediated oxidative cyclisation of benzo[b]thien-2-oyl indole derivatives is also reported.     

Solvent-free reaction between acenaphthoquinone, various benzils and ammonium acetate: synthesis of 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones

A simple synthesis of benzo[d,e]imidazo[2,1-a]isoquinolines is described. Heating a mixture of acenaphthoquinone, a benzil, and ammonium acetate under solvent-free conditions afforded 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones in good to excellent yields.     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.     

Synthesis of dihydropyrano[3,2-e]indoles as rotationally restricted phenolic analogs of 5-hydroxyindole—thermal Claisen approach versus gold catalysis

The Claisen rearrangement/cyclization of 5-propargyloxyindoles (2) to afford dihydropyrano[3,2-e]indoles (3) as direct precursors to tetrahydropyrano[3,2-e]indoles (1, a rotationally restricted phenolic analog of 5-hydroxyindole) was examined using either refluxing bromobenzene (156 °C) or Au⁺¹ catalysis in refluxing dioxane (101 °C). This transformation was best effected using Au⁺¹ catalysis (i.e., tris[triphenylphosphinegold(I)] oxonium tetrafluoroborate) because this method required a lower reaction temperature and gave better yields when compared to the simple thermal reaction conditions (156 °C).     

New long alkyl side-chain benzo[a]phenoxazines as micellisation probes

Several novel fluorescent benzo[a]phenoxazinium chlorides possessing a long aliphatic chain substituent at the 5-amino function of the heterocycle were efficiently synthesised. All compounds obtained absorbed and emitted at longer wavelengths with moderate to good fluorescent quantum yields. The photophysics of N-[10-methyl-5-(octylamino)-9H-benzo[a]phenoxazin-9-ylidene]ethanaminium chloride and N-[10-methyl-5-(dodecylamino)-9H-benzo[a]phenoxazin-9-ylidene]ethanaminium chloride was studied in Triton^® X-100 and in cetyltrimethylammonium bromide micellar media, demonstrating the capability of these fluorophores in detecting the micellisation process.     

Novel synthesis of benzo[b]carbazoles

A new method was adopted for the synthesis of benzo[b]carbazoles by Claisen condensation followed by Fischer indole cyclization. Newly synthesized benzo[b]carbazoles were treated with ethanol amine in the presence of polyphosphoric acid which leads to the formation of pyrazino carbazoles. All the synthesized compounds were characterized by all spectral means.     

Synthesis and rotational barriers of atropisomers of 1,2-bis[5-(11H-benzo[b]fluorenyl)]benzenes and related compounds

Several 1,2-bis[5-(11H-benzo[b]fluorenyl)]benzenes and related compounds were synthesized via a cascade reaction sequence of the corresponding benzannulated enyne-allene precursors. The X-ray structures showed that the two benzo[b]fluorenyl moieties attached via the C5 carbons to the adjacent carbon atoms of the central benzene ring are oriented essentially perpendicular to the central benzene ring. The rates of rotation around the carbon-carbon single bonds attaching the benzo[b]fluorenyl moieties to the central benzene ring are relatively slow, allowing several anti and syn atropisomers to be separated at ambient temperature.     

2-Oxobenzo[h]chromene: a novel entry for the synthesis of functionalized angular polycyclic azaarenes

An efficient and short synthesis of (5,6-dihydrobenzo[h]pyrido[2,1-b]quinazolin-2-ylidene)acetonitriles, (5,6-dihydrobenzo[h]pyrazino[2,1-b]quinazolin-2-ylidene)acetonitriles and (5,6-dihydrobenzimidazo[1,2-b]benzo[f]isoquinolin-7-yl)acetonitriles in good yields is delineated through base catalyzed ring transformation of 4-(piperidin-1-yl)-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 2-amino-pyridine, 2-aminopyrazine and (imidazo-2-yl)acetonitrile.     

l-Proline catalyzed one-step synthesis of 4,5-diaryl-2H-1,2,3-triazoles from heteroaryl cyanostilbenes via [3+2]cycloaddition of azide

Use of a novel reagent has been established for the synthesis of a series of 4,5-diaryl-2H-1,2,3-triazoles (6a–i and 9a–e) from cyanostilbene analogs of benzo[b]thiophene, benzo[b]furan, and indole, catalyzed by l-proline via Lewis base-catalyzed one-step [3+2]cycloaddition of azide. This method provides an efficient, simple, and environmentally benign procedure that affords good yields and relatively short reaction times.     

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.     

A convenient synthesis of partially reduced benzo[c]phenanthrenes, its ketals and ketones

A concise and convenient synthesis of various partially reduced 6-sec-amino-1,2,3,4,7,8-hexahydro-, 6-sec-amino-1,2,7,8-tetrahydrobenzo[c]phenanthrene-5-carbonitriles, 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-2-one-5-carbonitrile cycloalkene ketals, pendant with electron donor and acceptor substituents has been described through base catalyzed ring transformation of 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by cyclohexanone, 2-cyclohexen-1-one, 1,4-cyclohexanedione monocycloalkene ketals. The acid catalyzed deketalation of 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-2-one-carbonitrile ketals led to yield 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-3-carbonitrile-2-ones in excellent yield. We also performed the X-ray studies of the molecules 3d and 6a to know the degree of non-planarity.     

Synthesis and ring transformations of 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-ones

Heating 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolinium chloride in the presence of hydrazine bishydrate produces regioselectively the five-membered heterocycle 1-amino-1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-2(9H)-one. The assignment of the structure is based on extensive ¹H, ¹³C and ¹⁵N NMR spectroscopic studies. No ring-chain tautomerism of the 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-one was observed to open-chain hydrazides or the corresponding six-membered 1,2,10,10a-tetrahydro[1,2,4]triazino[4,3-a]indol-3(4H)-one. Further transformations of 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-one were performed by treatment with aromatic aldehydes, acid chlorides and isocyanates giving access to 40 novel hydrazones, N,N′-diacylhydrazines, N-acyl-N′-carbamoylhydrazines and 1,3,4-oxadiazoles.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

A non-catalytic approach to the synthesis of 5,6-dihydrobenzo[h]quinolines

A concise synthesis of highly functionalized 5,6-dihydrobenzo[h]quinoline-3-carbonitriles is delineated through base induced ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with S-methylisothiourea sulfate and 1-carboxamidinepyrazole hydrochloride, separately, in DMF. Under analogous reaction conditions the ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by formamidine acetate provided 4-sec-amino-benzo[h]quinoline-3-carbonitriles in moderate yields, while with benzamidine hydrochloride, the reaction followed the same mechanism to yield 2-phenyl-4-sec-amino-5,6-dihydrobenzo[h]quinoline-3-carbonitriles.     

Microwave-assisted chemoselective synthesis of novel pyrazolo[3,4-b]thieno[3,4-e]pyridines: substitution induced axial chirality

A microwave-assisted chemoselective synthesis of novel pyrazolo[3,4-b]thieno[3,4-e]pyridines has been achieved via tandem Michael addition–cyclization–tautomerization–oxidative aromatization sequence of reactions. Compounds with ortho-substituted phenyl rings exhibited axial chirality due to restricted rotation around C–C single bond.     

Investigation towards an efficient synthesis of benzo[g]isoquinoline-1,5,10(2H)-triones

As part of our research on 2-aza analogues of pentalongin, the active principle of Pentas longiflora Oliv., the first synthesis of 2,3-disubstituted benzo[g]isoquinoline-1,5,10(2H)-triones via 3,4-disubstituted 6-hydroxybenzo[g]furo[4,3,2-de]isoquinoline-2,5(4H)-diones as the key intermediates is reported. The latter compounds have been prepared by treating 2-methoxycarbonyl-1,4-naphthoquinone with N-substituted enaminoesters under acidic conditions. These reagents are easily accessible from readily available 1,4-dihydroxy-2-naphthoic acid, β-ketoesters and primary amines. Finally, a short synthesis of substituted benzo[g]isoquinoline-1,5,10(2H)-triones is achieved by an oxidative addition of N-substituted enaminoesters onto methyl 1,4-dihydroxynaphthalene-2-carboxylate.     

Formation of the same pyrimido[1,2-a]indoles from 1-(oxiran-2-ylmethyl)-1H-indole or [1,3]oxazolo[3,2-a]indole derivatives in its reactions with aromatic amines

Reactions of two isomers—2-chloro-1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde or 2-(chloromethyl)-2,3-dihydro[1,3]oxazolo[3,2-a]indole-9-carbaldehyde with aromatic amines lead to the same products in both cases—hydrochlorides of pyrimido[1,2-a]indole derivatives containing two fragments of an amine per one part of the indole nucleus. Its structure was confirmed by X-ray analysis of the crystals base, obtained by alkali treatment of the reaction product (when aryl is 4-MeOC₆H₄).     

A novel synthetic route for the total synthesis of (±)-uleine

In this study, a new synthetic route for the total synthesis of (±)-uleine is described. The important step in the synthesis of this alkaloid consists of an intramolecular cyclization of the D ring of the azocino[4,3-b]indole skeleton. Reduction of (N-methyl){3-β-ethyl-4-oxo-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide with borane yielded the corresponding (N-methyl){3-β-ethyl-4-hydroxy-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide, which underwent acid-catalyzed ring closure to produce azocino[4,3-b]indole core. Finally, the synthesis of (±)-uleine was completed through several steps from the azocino[4,3-b]indole core.     

2-Oxobenzo[h]chromene: a novel entry for the concise and efficient synthesis of indeno[1,2-c]phenanthrenes

An efficient and concise synthesis of 7-sec-amino-5,13-dihydro-6H-indeno[1,2-c]phenanthrene-8-carbonitriles is described through base catalyzed ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 1-indanone in moderate to good yields.