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.     

Convenient synthesis of fused pyrano[3,2-h]- and furo[3,2-h]benzo[f]coumarins from naphthalene-2,3-diol

The treatment of 8-propargyloxy-benzo[f]coumarin with boron trifluoride diethyl etherate in N,N-dimethylformamide under reflux or MW irradiation resulted in pyrano[3,2-h]benzo[f]coumarin, while the furo[3,2-h]benzo[f]coumarin is received from the treatment with N-methylformamide under MW irradiation.     

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs containing benzo[b]thiophene/benzo[b]pyrrole

The synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating benzo[b]thiophene/benzo[b]pyrrole units is described.     

Synthesis and characterization of benzo[c]thiophene analogs incorporating benzo[b]thiophene/1-hexylindole/benzo[b]furan

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating heterocycles such as benzo[b]thiophene/1-hexylindole/benzo[b]furan and thiophene units is described. Optical and electrochemical studies of the benzo[c]thiophene analogs are also reported.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

Access to N-protected or N-free imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives as potential antiviral compounds was achieved in good yields from N-protected 7-amino-8-halo-2-methylimidazo[1,2-a]pyridines by catalytic coupling of terminal acetylenes under mild conditions using [PdCl₂(PPh₃)₂] or [Cu(Phen)(PPh₃)₂]NO₃.     

Synthesis of novel fluorescent benzo[a]pyrano[2,3-c]phenazine and benzo[a]chromeno[2,3-c]phenazine derivatives via facile four-component domino protocol

An efficient and practical route to novel fluorescent benzo[a]pyrano[2,3-c]phenazine framework has been developed by one-pot, four-component reaction of 2-hydroxynaphthalene-1,4-dione, 1,2-phenylenediamines, aromatic aldehydes, and Meldrum’s acid in glacial acetic acid at 70 °C. Photophysical studies of these compounds have been reported. Reactions involving cyclohexane-1,3-dione/5-methylcyclohexane-1,3-dione/dimedone in the place of Meldrum’s acid yielded corresponding benzo[a]chromeno[2,3-c]phenazine derivatives. Crystal structure of 3k established the regioisomer formed. Mild reaction conditions, good yields, short reaction time, and easy separation are some of the salient features of the present protocol.     

Synthesis and characterization of fluorene tethered benzo[c]thiophene/benzo[c]selenophene analogs

Synthesis of 9,9-dialkyl/diarylfluorene based benzo[c]thiophene/benzo[c]selenophenes is presented. The synthesis of benzo[c]thiophene analogs is also realized with fluorene containing one or two thiophene units. The optical and electrochemical studies of fluorenyl benzo[c]heterocycles are correlated with their structures.     

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.     

First straightforward synthesis of 2,4-disubstituted benz[g]isoquinoline-3,5,10(2H)-triones, 1,2,3,5-substituted naphtho[3,2,1-de]isoquinoline-4,7-diones, and 6-substituted benzo[h]pyrido[3,4,5-kl]-1,2,3,4-tetrahydroacridine-5,8-diones

Structural modifications to the benz[g]isoquinoline skeleton of N-substituted benz[g]isoquinoline-3,5,10(2H)-triones were envisaged in order to make future SAR studies possible for this type of bioactive compounds. Several N-substituted benz[g]isoquinoline-3,5,10(2H)-triones were converted to novel 2,4-substituted benz[g]isoquinoline-3,5,10(2H)-triones, new tetracyclic 1,2,3,5-substituted naphtho[3,2,1-de]isoquinoline-4,7-diones, and 6-substituted benzo[h]pyrido[3,4,5-kl]-1,2,3,4-tetrahydroacridine-5,8-diones. All the synthesized target compounds represent new heterocyclic systems, which were previously undescribed in the literature.     

Synthesis and self-assembly of dibenzo[jk,mn]naphtho[2,1,8-fgh]thebenidinium derivates

A novel synthetic method toward nitrogen containing positively charged dibenzo[jk,mn]naphtho[2,1,8-fgh]thebenidinium (DBNT, 1) salts was developed. In this method, the undehydrogenated precursor of DBNT, 14-phenyl-14-dibenzo[a,j]acridinium salt (6), was produced directly from the reaction between 14-phenyl-14-dibenzo[a,j]xanthenylium (2) and amine/aniline in reasonable yield. Various DBNT salts with different alkyl and alkylphenyl chains were synthesized in this two-step method. The self-assembly behavior of two alkylated DBNT salts, 1c and 1f, was studied in this work. Due to the different substituents and counterions, compound 1c formed nanoscale wirelike fibers, and helical aggregates were obtained from 1f, in their methanolic solutions.     

A new strategy for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines

A series of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of aldehyde N-(1,3-diphenylpyrazolo[3,4-d]pyrimidin-4-yl)hydrazones. Dimroth rearrangement of such a series yielded pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines.     

[H3tren] and [H4tren] fluoride zirconates or tantalates

Four new [H₃tren]³⁺ or [H₄tren]⁴⁺ fluoride zirconates and two new [H₃tren]³⁺ fluoride tantalates are evidenced in the (ZrF₄ or Ta₂O₅)-tren-HF_aq.-ethanol systems at 190 °C: the structurally related phases [H₄tren]·(Zr₂F₁₂)·H₂O and α-[H₄tren]·(Zr₂F₁₂) (P2₁2₁2₁), β-[H₄tren]·(Zr₂F₁₂) (P2₁/c), [H₃tren]₄·(ZrF₈)₃·4H₂O (I23), β-[H₃tren]₂·(Ta₃O₂F₁₆)·(F) (R32) and its monoclinic distortion α-[H₃tren]₂·(Ta₃O₂F₁₆)·(F) (C2/m). α and β-[H₄tren]·(Zr₂F₁₂) and [H₄tren]·(Zr₂F₁₂)·H₂O are built up from (Zr₂F₁₂) dimers of edge sharing ZrF₇ polyhedra while isolated ZrF₈ dodecahedra are found in [H₃tren]₄·(ZrF₈)₃·4H₂O. Linear (Ta₃O₂F₁₆) trimers build α and β-[H₃tren]₂·(Ta₃O₂F₁₆)·(F); they consist of two (TaOF₆) pentagonal bipyramids that are linked to two opposite oxygen atoms of one central (TaO₂F₄) octahedron. A disorder affects the equatorial fluorine atoms of the trimers and eventually carbon or nitrogen atoms of [H₃tren]³⁺ cations.     

Synthesis, structure, and conformation of ortho-linked oxacalix[n]arene[n]hetarenes

ortho-Linked oxacalix[n]arene[n]hetarenes (n=2, 3) were prepared by one-step cyclooligomerization of catechol and meta-dichlorinated nitrogen containing heterocycles or via a two-step reaction process. Solid state structure of the ortho-linked oxacalix[n]arene[n]hetarenes (n=2, 3) has been determined by X-ray crystallography. 1,3-Alternate and 1,3,5-alternate conformations were found for ortho-linked oxacalix[2]arene[2]pyrazine (1) and oxacalix[3]arene[3]pyrazine (2), respectively. However, a core conformation with C₃ symmetry was found for ortho-linked oxacalix[3]arene[3]pyrimidine (4), which is completely different from that of its isomer, compound 2.     

New ‘2-phenylnaphthalene’-mediated synthesis of benzo[b]naphtho[2,3-d]furan-6,11-diones and 6-oxa-benzo[a]anthracene-5,7,12-triones: first total synthesis of 6-oxa-benzo[a]anthracen-5-ones

We describe here a novel synthesis of benzo[b]naphtho[2,3-d]furan-6,11-diones based on the heteroannulation of 2-(2-bromophenyl)-3-hydroxy-1,4-naphthoquinones. The naphthoquinones were prepared from 3-(2-bromophenyl)naphthalen-2-ols, which were obtained by intramolecular aldol condensation of 2-[3-(2-bromophenyl)-2-oxo-propyl]benzaldehydes. Alternatively, benzo[b]naphtho[2,3-d]furan-6,11-diones were obtained more directly and efficiently by cyclization of 3-(2-bromophenyl)naphthalen-2-ols to benzo[b]naphtho[2,3-d]furans and oxidation of the resulting compounds. Furthermore, the first 6-oxabenzo[a]anthracen-5-one described was similarly obtained from 2-[3-(2-formylphenyl)-2-oxopropyl]benzoic acid and oxidized to 6-oxa-benzo[a]anthracene-5,7,12-trione.     

Synthesis and preliminary evaluation of duocarmycin analogues incorporating the 1,2,11,11a-tetrahydrocyclopropa[c]naphtho[2,3-e]indol-4-one (CNI) and 1,2,11,11a-tetrahydrocyclopropa[c]naphtho[1,2-e]indol-4-one (iso-CNI) alkylation subunits

Efficient syntheses and a preliminary evaluation of 1,2,11,11a-tetrahydrocyclopropa[c]naphtho[2,3-e]-indole (CNI) and 1,2,11,11a-tetrahydrocyclopropa[c]naphtho[1,2-e]indole (iso-CNI), and their derivatives containing an anthracene and phenanthrene variant of the CC-1065 or duocarmycin alkylation subunit are detailed.     

Efficient synthesis of 5,6-dihydro-8H-[1,2,4]thiadiazino[6,5,4-de]phenanthridine 4,4-dioxide and 5,6-dihydro-8H-[1,2,4]-thiadiazino[6,5,4-ij]thieno[2,3-c]quinoline 4,4-dioxide

A new efficient and versatile synthesis to obtain different substituted 5,6-dihydro-8H-[1,2,4]thiadiazino[6,5,4-de]phenanthridine 4,4-dioxide and 5,6-dihydro-8H-[1,2,4]-thiadiazino[6,5,4-ij]thieno[2,3-c]quinolone 4,4-dioxide was developed. The four cyclic systems are achieved by a three-step synthesis proceeding under mild conditions in high yields.     

Conformational analysis of bridgehead-substituted bicyclo[m.m.m]alkanes and bicyclo[8.8.n]alkanes

Conformational analyses of bicyclo[m.m.m]alkanes where m=1-10 and of bicyclo[8.8.n]alkanes where n=1-7 bearing methyl groups on the bridgeheads were carried out using a Monte Carlo search strategy. In the bicyclo[m.m.m]alkane series, greater variability was observed for the inter-bridgehead distance for larger values of m. This suggests that properly substituted bicyclo[8.8.8]hexacosanes or larger ring systems might serve as molecular springs.     

An efficient synthesis of novel estrieno[2.3-b] and [3.4-c]pyrroles

An efficient protocol for the preparation of novel estrieno[2.3-b] and [3.4-c]pyrroles 1 and 2 using Pd(0)-catalyzed amination and Bischler indole synthesis is described.     

Microwave-assisted synthesis of novel N-(4-phenylthiazol-2-yl)-benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides inspired by marine topsentines and nortopsentines

We report the synthesis of novel N-(4-phenylthiazol-2-yl)-substituted benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides, which were inspired by marine topsentines and nortopsentines. Condensation of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) with various ortho-halogenated anilines, aminopyridines and aminophenols gave the corresponding aryliminodithiazoles in good to excellent yields. Copper(I)-mediated or nucleophilic-assisted cyclization of aryliminodithiazoles furnished cyano-functionalized benzo[d]thiazoles, thiazolo[4,5-b]- and thiazolo[5,4-b]-pyridines and benzo[d]oxazoles. The latter were condensed with substituted 4-phenylthiazol-2-amines to furnish twenty seven new polyaromatic carboximidamides in moderate to good yields.