Synthesis of hexahydro[2]benzopyrano[4,3-c]pyridines as serotonin 5-HT2C receptor agonists via intramolecular hetero Diels-Alder reactions

Hexahydro[2]benzopyrano[4,3-c]pyridines were synthesized by an intramolecular hetero Diels-Alder reaction. The reaction was applicable to a range of substrates and the products could be easily converted into serotonin 5-HT_2C receptor agonists.     

Application of 2-(2-chloroaroyl)methyleneimidazolidines in domino and multicomponent reaction: new entries to imidazo[1,2-a]pyridines and benzo[b]imidazo[1,2,3-ij][1,8]naphthyridines

A new strategy for the synthesis of tetrahydroimidazo[1,2-a]pyridines and unusual tetrahydrobenzo[b]imidazo[1,2,3-ij][1,8]naphthyridines has been successfully developed by cascade reactions including Knoevenagel condensation, aza-ene reaction, imine-enamine tautomerization, cyclocondensation/oxidation, and intramolecular S_NAr of precursors 2-(2-chloroaroyl)methyleneimidazolidines as new heterocyclic ketene aminals (HKA), which represent a class of polyfunctional scaffolds with four active reaction sites with aromatic aldehydes and malononitrile or ethyl 2-cyanoacetate under mild conditions. In this domino reaction, nine different active sites are involved, and two C-C bonds, two C-N bonds, and two new rings are constructed with all reactants efficiently utilized in the chemical transformation.     

A straightforward preparation of benzo[f]naphtho[b][1,4]oxazepines from TNT

2,4,6-Trinitrotoluene readily reacts with 1-nitroso-2-naphthol to afford 9,11-dinitrobenzo[f]naphtho[2,1-b][1,4]oxazepine. The nitro groups of the latter undergo displacement by O- and S-nucleophiles with preferential substitution of the 11-NO₂ (peri-nitro group). The structures of the substitution products are confirmed by X-ray diffraction and ¹H NMR NOE experiments.     

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).     

Synthesis of layered cathode material Li[CoxMn1−x]O2 from layered double hydroxides precursors

Cathode materials Li[Co_xMn_1−x]O₂ for lithium secondary batteries have been prepared by a new route—precursor method of layered double hydroxides (LDHs). In situ high-temperature X-ray diffraction (HT-XRD) and thermogravimetric analysis coupled with mass spectrometry (TG-MS) were used to monitor the structural transformation during the reaction of CoMn LDHs and LiOH·H₂O: firstly the layered structure of LDHs transformed to an intermediate phase with spinel structure; then the distortion of the structure occurred with the intercalation of Li⁺ into the lattice, resulting in the formation of layered Li[Co_xMn_1−x]O₂ with α-NaFeO₂ structure. Extended X-ray absorption fine structure (EXAFS) data showed that the Co-O bonding length and the coordination number of Co were close to those of Mn in Li[Co_xMn_1−x]O₂, which indicates that the local environments of the transitional metals are rather similar. X-ray photoelectron spectroscopy (XPS) was used to measure the oxidation state of Co and Mn. The influences of Co/Mn ratio on both the structure and electrochemical property of Li[Co_xMn_1−x]O₂ have been investigated by XRD and electrochemical tests. It has been found that the products synthesized by the precursor method demonstrated a rather stable cycling behavior, with a reversible capacity of 122.5 mAh g⁻¹ for the layered material Li[Co_0.80Mn_0.20]O₂.     

One-pot three-component reaction for the synthesis of biologically important spiro[benzo[f]quinoline-3,3′-indoline] derivatives

A previously unknown class of highly substituted benzoquinoline–spirooxindole are easily prepared by a novel application of a mild and efficient catalyst SbCl₃ for carbon–carbon and carbon–nitrogen bond formation reaction involving isatin, alkyne (dialkyl but-2-ynedioate) with aromatic amine (2-naphthylamine) in a one-pot three-component reaction. This protocol of one-pot synthesis afforded a library of dialkyl 2′-oxo-4H-spiro[benzo[f]quinoline-3,3′-indoline]-1,2-dicarboxylate derivatives, a potential bioactive compound in very good to excellent yields.     

A one-pot four-component synthesis of N-arylidene-2-aryl-imidazo[1,2-a]azin-3-amines

N-Arylidene-2-aryl-imidazo[1,2-a]azin-3-amines were synthesized via a one-pot, four-component condensation reaction using a 2-aminoazine, toluene-4-sulfonylmethyl isocyanide (TsCH₂NC), and two equivalents of readily available aromatic aldehydes. The reaction was performed in diethyl ether as the solvent, with p-toluenesulfonic acid (p-TSA) as the catalyst at reflux temperature.     

Nucleophilic cyclization of 3-alkynylquinoxaline-2-carbonitriles into pyrido[3,4-b]quinoxalines

3-Alkynylquinoxaline-2-carbonitriles have been synthesized from 3-chloroquinoxaline-2-carbonitrile via the Sonogashira reaction. Treatment of 3-alkynylquinoxaline-2-carbonitriles with an alkylamine or ammonia has been shown to produce stable enamines, e.g., (Z)-3-(2-aryl-2-aminovinyl)quinoxaline-2-carbonitriles. Their base-induced cyclization gave the previously unknown pyrido[3,4-b]quinoxalin-1(2H)-imines or pyrido[3,4-b]quinoxalin-1-amines. 3-Alkynylquinoxaline-2-carbonitriles were directly transformed into pyrido[3,4-b]quinoxalin-1(2H)-imines by heating with an alkylamine and K₂CO₃ in DMF. The ionization constants, and absorption and fluorescent properties of the resulted pyrido[3,4-b]quinoxalin-1(2H)-imines were measured.     

Pd/C mediated synthesis of 2-substituted benzo[b]furans/nitrobenzo[b]furans in water

An efficient synthesis of 2-alkyl/aryl substituted benzo[b]furans/nitrobenzo[b]furans in water has been accomplished via Pd/C catalyzed reaction of o-iodophenols with terminal alkynes in the presence of PPh₃, CuI and prolinol. This method can tolerate a variety of functional groups present in the alkynes as well as base labile nitro group in the o-iodophenols. The protocol does not require the use of a phase transfer catalyst or water-soluble phosphine ligands and is free from the use of any organic co-solvent.     

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.     

Application of cyclic-1,3-diketones in domino and multicomponent reactions: facile route to highly functionalized chromeno[2,3-d]pyrimidinones and diazabenzo[b]fluorenones under solvent-free conditions

A facile and efficient protocol for the synthesis of chromeno[2,3-d]pyrimidinones and diazabenzo[b]fluorenones has been developed by one-pot three-component cyclocondensation of aldehydes, cyclic-1,3-diketones and 1,3-dimethylbarbituric acid in the presence of InCl₃ or P₂O₅ under solvent-free conditions.     

An efficient synthesis of 5-substituted 1H-tetrazoles via B(C6F5)3 catalyzed [3+2] cycloaddition of nitriles and sodium azide

A simple and efficient protocol is developed for the synthesis of 5-substituted 1H-tetrazole derivatives from various nitriles and sodium azide (NaN₃) via [3+2] cycloaddition reaction using B(C₆F₅)₃ as a catalyst. The present synthetic method displayed significant advantages such as low catalyst loading, mild reaction conditions, low toxicity, easy work-up, high yields, and compatibility with other functional groups.     

Efficient synthesis of 5-nitro-benzo[b]furans via 2-bromo-4-nitro-phenyl acetates

Acetylation/Sonogashira cross-coupling reaction/cyclization has been carried out in one-pot using a Na₂PdCl₄/2-(di-tert-butylphosphino)-N-phenylindole/CuI system in TMEDA to give 5-nitro-2-substituted benzo[b]furans in excellent yields. We also describe the extension of this method to 4-EWG-2-bromo-phenols obtaining 2,5-disubstituted-benzo[b]furans in good yields.     

Highly efficient synthesis of triazolo[1,2-a]indazole-triones and novel spiro triazolo[1,2-a]indazole-tetraones under solvent-free conditions

A new, convenient, and high yielding procedure for the synthesis of triazolo[1,2-a]indazole-triones by the condensation reaction between dimedone, aryl aldehydes, and ueazoles in the presence of a catalytic amount of sulfonated polyethylene glycol (PEG-SO₃H) as a highly stable and reusable eco-friendly degradable polymeric catalyst is described under solvent-free conditions. This procedure has also been applied successfully for the synthesis of novel spiro triazolo[1,2-a]indazole-tetraones.     

A convenient route to functionalized 3-amino-N-methylfuro[3,2-b]pyridine-2-carboxamides

The synthesis of novel functionalized 3-amino-N-methylfuro[3,2-b]pyridine-2-carboxamides is described from cyanopyridine intermediates. Based on the difference in halogen reactivity, ethyl [(5-bromo-2-chloropyridin-3-yl)oxy]acetate was functionalized by a palladium-catalyzed reaction, before the cyclization to the desired furo[3,2-b]pyridines.     

Synthesis of substituted imidazolines via [3+2]-cycloaddition of aziridines with nitriles

An efficient synthesis of 2,4-disubstituted 1H-imidazolines from aziridines and nitriles in the presence of BF₃-Et₂O or triethyloxonium tetrafluoroborate has been described. The reaction proceeds via a [3+2]-cycloaddition reaction. Most of the nitriles successfully underwent cycloaddition reactions with aziridines even at room temperature in a very short time.     

Regioselective N-alkylation of imidazo[4,5-b]pyridine-4-oxide derivatives: an experimental and DFT study

Regioselectivities were determined for N-alkylations of imidazo[4,5-b]pyridine-4-oxide and 2-methyl-imidazo[4,5-b]pyridine-4-oxide with benzyl bromide or benzyl iodide at RT using K₂CO₃ in DMF as a base. Experimental attempts have shown that N-1/N-3 ratios slightly varied according to the substitution on C-2 position. This was confirmed by DFT calculations in solvent phase. This computational study has shown first that this N-benzylation reaction passed through a S_N2 mechanism. Moreover, regioselectivity of N-benzylation has appeared essentially governed by ‘steric approach control’. It explained that opposite N-1/N-3 ratios were obtained with imidazo[4,5-b]pyridine-4-oxide and its 2-methyl-substituted analog. Finally, regioselectivities slightly varied with the nature of benzyl halide.     

Convenient synthesis of 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]- and [2,3-b]-1,5-oxazocine-6-ones

A convenient and diversity-oriented method for synthesis of the novel 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]-1,5-oxazocine-6-one skeleton 1 and the very rarely described 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocine-6-one skeleton 2, featuring cyclization using nucleophilic aromatic substitution (S_NAr) and Suzuki coupling, is described.     

Synthesis of annelated [a]aza-anthracenones and thieno[3,2-g]aza-naphthalenones through ring transformation of 2H-pyran-2-one followed by photocyclization

A concise synthesis of some new classes of heterocycles (4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a-diaza-cyclopenta[a]anthracen-6-carbonitriles and 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a-diazabenzo[a]anthracene-7-carbonitriles) has been developed by the ring transformation of suitably functionalized 2H-pyran-2-one with α-oxoketene cyclic aminals to intermediates (8-aroyl-5-aryl-2,3-dihydro-1H-imidazo[1,2-a]pyridine-7-ylidene)-acetonitriles and (9-aroyl-6-aryl-1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-8-ylidene)-acetonitriles) followed by their photocyclization either in CHCl₃ or acetonitrile. This reaction was further explored for the synthesis of methyl 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carboxylate, 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carbonitriles, 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a,10-triazabenzo[a]anthracene-7-carbonitriles, 4-aryl-10-oxo-1,2,3,10-tetrahydro-9-thia-1,3a-diazadicyclopenta[a,g]naphthalene-6-carbonitriles and 5-aryl-11-oxo-1,3,4,11-tetrahydro-2H-10-thia-1,4a-diazacyclopenta[b]phenanthrene-7-carbonitriles from the similar reactions.     

2-Benzyliden-2H-thieto[3,2-b]quinoline: a new heterocycle and its rearrangement to 2-phenylthieno[3,2-b]quinoline

Synthesis of the strained 2H-thieto[3,2-b]quinoline ring system is reported for the first time. Treatment of (Z)-2-benzyliden-2H-thieto[3,2-b]quinoline derivatives of this heterocycle with base, at reflux in ethanol, causes a novel rearrangement to 2-phenylthieno[3,2-b]quinolines. Indeed, the one-pot reaction of 2-aminobenzaldehydes and (Z)-2-benzylidenethietan-3-one in refluxing basic ethanol leads directly to 2-phenylthieno[3,2-b]quinolines in good yields.