Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Organoboron luminophores with extremely strong dual–phase emissions

Developing efficient dual–phase emission emitters upon organoboron luminophores remains a formidable challenge due to the ubiquitous self–absorption and deleterious π-π interactions from aromatic structure. Here, a new family of benzothiazole–enolate–based organoboron luminophores (HN1–4) with effective dual–phase emission was constructed. HN4 showed almost the highest quantum yield (QY) among this type of compound so far. The three-ring–fused rigid skeleton and moderate intramolecular charge transfer (ICT) effect ensured that HN4 could give rise to extremely strong emission in any solution (QY up to 99%). X-ray crystallographic analysis showed that the twisted core structure constructed by the boronic coordination of two penta-fluorobenzene of HN4 was responsible for intense emission in the solid state (QY up to 68%). Besides, HN4 exhibited a unique response to mechanical force accompanied by a reversible change of the QY. We believe that this strategy provides beneficial inspiration and methodology to design materials with high emissive quantum yield that can be used in a variety of luminescent events.     

Microwave assisted synthesis of 3-aminoindole-2-carbonitriles from anthranilonitriles via N-unprotected 2-(cyanomethylamino)benzonitriles

Anthranilonitrile 3a, 4,5-dimethoxyanthranilonitrile 3b and 5-nitroanthranilonitrile 3c, react with paraformaldehyde, KCN and ZnCl₂ in acetic acid under acid catalysis (H₂SO₄) in a sealed tube at ca. 55 °C to give the corresponding 2-(cyanomethylamino)benzonitriles 4a-c in 96, 86 and 57% yields, respectively. Thorpe-Ziegler cyclisation of the N-unprotected 2-(cyanomethylamino)benzonitriles 4a-c with K₂CO₃ in EtOH at elevated temperatures and pressures using either microwave heating or conventional heating in a sealed tube gives 3-amino, 3-amino-5,6-dimethoxy, and 3-amino-5-nitroindole-2-carbonitriles 2a-c in moderate to good yields. All new compounds are fully characterised.     

Meerwein arylation with 3-fluorobutenone

3-Fluorobutenone (7) reacts with aryl triazenes in the presence of zinc iodide to give 4-aryl-3-fluoro-3-iodo-2-butanones (9a-9f) in moderate yields. The products arise from a free radical process that terminated by iodination of an alkyl radical. The process yields unusual geminal iodo-fluoro compounds.     

An efficient potassium cyanide-promoted synthesis of 2-arylbenzoxazoles from [4.3.0]boron heterobicycles

The 2-arylbenzoxazoles 3a-f were produced in moderate to excellent yields merely by stirring a potassium cyanide (3 equiv)-containing methanol solution of the borobicyclic compounds 1a-f at room temperature. These compounds were fully characterized spectroscopically [IR, ¹H, and ¹³C NMR and X-ray analysis (3a)] and by elemental analysis.     

Photophysical and electrochemical properties of π-extended molecular 2,1,3-benzothiadiazoles

The reaction of 4,7-dibromo-2,1,3-benzothiadiazole with arylboronic acids (phenyl, 1-naphthyl, 4-methoxyphenyl, 4-chlorophenyl and 4-trifluoromethylphenyl) in the presence of catalytic amounts of a NCP-pincer palladacycle affords photoluminescent π-extended 4,7-diaryl-2,1,3-benzothiadiazoles 4a-e in high yields. These 4,7-diaryl-2,1,3-benzothiadiazoles exhibit high fluorescent quantum yields, high electron affinities and adequate band gap values for testing as OLEDs. The 4,7-bis-naphthyl-2,1,3-benzothiadiazole 4b presents two different lifetimes (bi-exponential decay) due to the presence of two atropisomers. The Sonogashira coupling reaction of 4,7-diethynyl-2,1,3-benzothiadiazole 6 with the corresponding halo-aryl compounds (iodobenzene, 1-bromonaphthalene, 4-iodoanisole, 4-bromo-N,N-dimethylaniline and 2-bromopyridine) afforded the photoluminescent π-extended 4,7-bis-alkynylaryl-2,1,3-benzothiadiazoles 7a-e, also in high yields. These 4,7-diethynyl-2,1,3-benzothiadiazoles also present high fluorescent quantum yields, high electron affinities and adequate band gap values for testing as OLEDs. The 4,7-disubstituted-2,1,3-benzothiadiazoles 4a-e and 7a-e exhibit different electrochemical behavior. The presence of two ethynyl spacers in 2,1,3-benzothiadiazoles 7a-e shifts the reduction potentials to less cathodic values and also results in two well-defined and distinct reduction processes.     

Applied biological and physicochemical activity of isoquinoline alkaloids: oxoisoaporphine and boldine

The aim of this study was to determine the electronic influence of substituent groups and annelated rings such as oxazole-oxazinone on the physicochemical and photoprotection, antioxidant capacity, toxicity and singlet oxygen photosensitization biological properties of isoquinoline alkaloid frameworks. Thus, oxoisoaporphine derivatives 1-5 and 3-azaoxoisoaporphine (6), some of them with phenolic structures, did not present any antioxidant capacity, possibly either by formation of keto-enol tautomerism species or the formation of unstable free radicals. Due to the singlet oxygen quantum yields (F_D) near to unity, and greater photostability than phenalenone, oxoisoaporphines 4-6 may be considered as photosensitizers for singlet oxygen production and can be used as new universal study tools. The biological application as antibacterial agents is an important and possible tool in the study of compounds with low cytotoxicity and high reactivity in antineoplastic chemotherapy. On the other hand, when boldine and its annelated derivatives B1-4 are irradiated, a photoprotector effect is observed (SPF = 2.35), even after 30 minutes of irradiation. They also act as photoprotectors in cell fibroblast cultures. No hemolysis was detected for boldine hydrochloride and its salts without irradiation. In solutions irradiated before incubation (at concentrations over 200 ppm) photoproducts were toxic to the nauplii of Artemia salina.     

Optical properties of oligo(2,3-dioxyfunctionalized)naphthalenes

The properties of two series of oligo(2,3-dioxyfunctionalized)naphthalenes which are connected at the 1,4-positions, that is, methoxy derivatives 1-4 and derivatives that possess two pyrene groups on the central scaffolding oxygen functions 5-8, are described. In 1-4, the fluorescence quantum yields increased by about 20-80% as the number of naphthalene units increased. The intramolecular energy transfer quantum yields of 5-8 were around 20% regardless of the number of naphthalene units.     

An efficient synthesis of benzofurans and their application in the preparation of natural products of the genus Calea

The intramolecular cyclization of the β-substituted olefins methyl 2-aryloxy-3-dimethylaminopropenoates 3a-3f catalyzed by Lewis acids leads to a short and novel synthesis of benzofurans 2a-2f. When the olefins 4-dimethylamino-3-aryloxy-3-buten-2-ones 4a-4f were used, the cyclization process was faster and provided the corresponding substituted 2-acetylbenzofurans 1a-1f. Among the latter, naturally occurring compounds calebertin (1a), caleprunin A (1b), and caleprunin B (1c) were prepared in good overall yields. These benzofurans were also obtained by direct treatment under MW irradiation of the precursors 1-aryloxypropan-2-ones 7a-7c with DMFDMA, followed by addition of the catalyst, resulting in a route that was one step shorter.     

Diazonamides C-E, new cytotoxic metabolites from the ascidian Diazona sp.

Three new macrocyclic peptides, diazonamides C-E (1-3), were isolated together with the previously reported diazonamides A (4) and B (5) from samples of the marine ascidian Diazona sp. collected in Indonesia. Their structures were assigned on the basis of detailed analysis of the 1D and 2D NMR and mass spectral data as well as Marfey’s analysis of the aminoacid residues. All the new compounds isolated displayed moderate cytotoxicity against a panel of three human tumor cell lines.     

Novel pyrazoline and pyrazole porphyrin derivatives: synthesis and photophysical properties

2-Vinyl-5,10,15,20-tetraphenylporphyrinatozinc(II) reacts with nitrile imines, generated in situ from ethyl hydrazono-α-bromoglyoxylates, affording the corresponding pyrazolines in good to excellent yields. Treatment of pyrazoline derivatives with DDQ affords the corresponding pyrazole derivatives with moderate to excellent yields. When the hydrolysis of ester group in the pyrazoline derivatives was considered, it was observed the concomitant oxidation of the heterocyclic unit, which allowed directly obtaining porphyrin-pyrazole derivatives with a carboxylic group, in very good yields.The photophysical properties of the pyrazoline and pyrazole porphyrin derivatives show that the influence of the heterocyclic substituents is limited by the tendency of these molecules to aggregate. All other properties and especially the triplet kinetics remain unaffected. The adducts with low tendency to aggregate showed very high singlet oxygen yield, which makes these compounds interesting for their use as photosensitizers for PDT.     

Detosylation of 3-amino-1-tosylindole-2-carbonitriles using DBU and thiophenol

Attempted detosylation of the 3-amino-1-(p-tosylamino)indole-2-carbonitriles 4a-c using either K₂CO₃ in EtOH or DBU in PhH at reflux gives unexpectedly the 3-(N-p-tosylamino)indole-2-carbonitriles 5a-c, respectively in high yields. Nevertheless, treatment of 1-(p-tosylamino)indoles 4a-c with thiophenol and DBU in PhH at reflux gives the detosylated 3-aminoindole-2-carbonitriles 5a-c. Reaction mechanisms supporting the tosyl migration (4→5) and the reductive detosylation (4→2) are proposed. All new compounds are fully characterised.     

Microwave-assisted manganese(III) acetate based oxidative cyclizations of alkenes with β-ketosulfones

The microwave-assisted synthesis of 5-(4-nitrophenyl)-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (5a) was performed via manganese(III) acetate based oxidative cyclization of 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone (3a) with vinylbenzene (4a). This new protocol was applied to four sulfone derivatives (3a-d), using vinylbenzene (4a) and diphenylethene (4b), affording a series of 2,3-dihydrofurans (5a-d, 6a-d) in moderate to good yields (26-55%). Similar methodology, applied on allylbenzene (4c), surprisingly, led to dehydronaphthalene derivatives (7a-d) in moderate yields. The unexpected mechanism and the role of allylbenzene (4c) are herein discussed.     

Synthesis of fluorine containing glycolurils and oxazolines from oxides of internal perfluoroolefins

The reaction of oxides of internal perfluoroolefins 1-3 with urea gave two kinds of novel fluorine containing N-heterocyclic compounds depending on the solvent nature: 1,5-bis(perfluoroalkyl)tetraazabicyclo[3.3.0]octane-3,7-diones 4a-c and 2-amino-5-fluoro-4,5-bis(perfluoroalkyl)-4,5-dihydrooxazol-4-ols 7a-d. Use of polar dimethylsulfoxide, N,N-dimethylacetamide and acetonitrile afforded glycolurils 4a-c in moderate yields. In dioxane, unexpected cyclization occurred resulting in oxazolines 7a-d in high yields. A similar reaction of oxiranes 2, 3 with urea in aqueous dioxane gave mixtures of 4,5-dihydroxy-4,5-bis(perfluoroalkyl)imidazolidine-2-ones 9b, c, glycolurils 4b, c and oxazolines 7b-d. The molecular structure of trans-isomers of oxazoline 7b and imidazolidine 9b has been established by X-ray crystallography.     

Dioxadispiroketal Compounds and a Potential Acyclic Precursor from Amomum aculeatum

Four new compounds having an unusual 1,7-dioxadispiro[5.1.5.2]-12-ene-11-one tricyclic ring system (1-4), their potential precursor, 5R-hydroxy-1-(4-hydroxyphenyl)-eicosan-3-one (5), and two known compounds, aculeatins A (6) and B (7), have been isolated from Amomum aculeatum. All compounds were characterized by spectroscopic methods and the configurations were established by 2D NOE correlations. Compounds 1-4, 6, and 7 showed cytotoxic activity against several human cancer cell lines.     

(N-7-Azaindolyl)oligothiophenes: synthesis, characterization, and photophysical properties

The synthesis of a new series of mono- and oligothiophenes capped by 7-azaindoles such as 2-(N-azaindolyl)thiophene (1), 2-(N-azaindolyl)-5′-(bromo)oligothiophenes (2a-4a), and 2,5′-bis(N-azaindolyl)oligothiophenes (2b-4b) has been investigated. The reaction of 7-azaindole with 2-bromothiophene under the modified Ullmann condensation conditions led to the formation of 1. Simple extension of the same method to the reaction of 2,5′-dibromooligothiophenes in the presence of 4-5 M excess of 7-azaindole led to the formation of 2a-4a and 2b-4b in moderate overall yields (40-55%). All compounds were fully characterized by analytical and various spectroscopic techniques. The structures of 2b, 3b, and 4b were determined by X-ray diffraction analyses. All three compounds show several intermolecular C(π)?H interactions leading to the formation of herringbone packing in the solid-state structure. The UV absorption spectra of 1-4 consist of three characteristic electronic transitions corresponding to n→π^∗ and π→π^∗ transitions arising out of the π-conjugation of the entire molecule as well as local aromatic units. The emission spectra of the same compounds show intense fluorescence bands at the wavelengths between 422 and 495 nm. The length of the thiophene chain and the presence of bromine atom influence the band position of both absorption and emission spectra. While the extension in π-conjugation causes the reduction in the band gap, the bromine atom shifts the electronic transition energy to the blue region. The cyclic voltammetric measurements were performed with 1-4, which show that the compounds exhibit a typical pseudo-reversible redox wave with E_ox in the range 0.6-1.2 V.     

Synthesis and optical behaviors of 2-(9-phenanthrenyl)-, 2-(9-anthryl)-, and 2-(1-pyrenyl)-1-alkylimidazole homologues

Eight 2-(9-phenanthrenyl)-, 2-(9-anthryl)- and 2-(1-pyrenyl)-1-alkyl-benzimidazole compounds, three 2-(9-anthryl)-1-alkylphenanthroimidazole compounds and five 4,5-diphenyl-1-alkyl-2-(9-anthryl)imidazole compounds were synthesized by alkylation reactions of the corresponding benzimidazole, phenanthroimidazole or imidazole compounds. 2-(10-Bromo-9-anthryl)-1-alkyl-benzimidazole compounds were prepared by bromination reaction of 2-(9-anthryl)-1-alkylbenzimidazole compounds. All the synthesized compounds were characterized by elemental analysis, ¹H NMR, ¹³C NMR, MS or HRMS; their absorption coefficients (), maximum absorption λ_amax, fluorescence emission maximum λ_em, Stokes shifts and fluorescence quantum yields (Φ_F) in ethyl acetate were determined; their fluorescent lifetimes (T₁ and T₂) were measured in ethyl acetate and in solid state, respectively. The crystal structure of 2-(9-anthryl)-1-n-butyl-4,5-diphenylimidazole (12a) was determined to be triclinic, space group P-1 types, using single crystal X-ray crystallography technique. The results showed that these compounds exhibited moderate fluorescence-emission abilities and higher solubility in most organic solvents than their corresponding starting materials. The relationships between the optical behaviors and structures for these compounds were discussed.     

Free radical domino reactions in the synthesis of small ring compounds: multiple annulation of cyclopropane-containing polycycles

Free radical approach to fused vinylcyclopropane derivatives is described. Homolytic decomposition of Barton esters 4a–f in the presence of activated alkynes affords bicyclo〚3.1.0〛hex-2-ene derivatives 5a–g in moderate yields (18–52 %). The propagation sequence comprises: intermolecular addition/5-exo-cyclization/3-exo-cyclization/β-elimination, and allows for a one-pot synthesis of bicyclic cyclopropane derivatives starting from two acyclic, unsaturated compounds.     

Tetrahydropyridine (THP) ring expansion under the action of activated terminal alkynes. The first synthesis and X-ray crystal structure of tetrahydropyrimido[4,5-d]azocines

Tetrahydropyridopyrimidines (THPPm) 1-3 underwent tandem cleavage-cyclization piperidine ring enlargement under the action of terminal activated alkynes to produce tetrahydropyrimido[4,5-d]azocines 4-7 in good preparative yields. The latter compounds are representatives of a new heterocyclic system.     

Synthesis of sulfur containing analogues of the soluble guanylate cyclase inhibitor 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one NS2028

Sulfur analogues of the soluble guanylate cyclase (sGC) inhibitor NS2028 1a are synthesized. Treating 8-bromo-2H-benzo[b][1,4]oxazin-3(4H)-one oxime (6) with 1,1′-thiocarbonyldiimidazole (1.1 equiv) gave the carbamothioate 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazine-1-thione (3a) in 83% yield. Alternatively reacting NS2028 1a with P₂S₅ (0.5 equiv) affords the carbamothioate 3a in 80% yield. Similar treatment of 8-aryl substituted NS2028 analogues 1b-d with P₂S₅ gave the carbamothioates 3b-d in 64-91% yields. Although quite stable, the carbamothioates 3a-d could be thermally isomerized in the presence of Cu (10 mol %) to afford the thiocarbamates 4a-d in high yields. Interestingly, in the case of carbamothioate 3a Pd and In metals also facilitated the isomerization. Furthermore, treatment of the thiocarbamates 4a-d with P₂S₅ (0.5 equiv) affords the carbamodithioates 5a-d in 72-89% yields. All new compounds are fully characterized including single crystal X-ray data for carbamothioate 3a and thiocarbamate 4a. Finally, a mechanism is proposed for the carbamothioate to thiocarbamate isomerization.