Synthesis of fluorescent water-soluble functionalised benzo[a]phenoxazinium salts

In order to develop long-wavelength functionalised oxazine dyes with good water solubility and high photostability for biological applications, a series of novel side-chain functionalised benzo[a]phenoxazinium salts were synthesised and characterised. These polycyclic cationic compounds showed strong fluorescence in ethanol and water (pH 7.4), with an emission wavelengths higher than 637 nm, as well as high quantum yields and moderate Stokes’ shifts. The photostability of the fluorophores synthesised, under irradiation at 419 nm, was good to excellent in ethanol and moderate in water at physiological pH.     

Serendipitous stereoselective synthesis of brand-new fluorescent dyes: (1Z)-3-(alkylimino)-1-[(chromone-3-yl)methylene]-1,3-dihydro-9H-furo[3,4-b]chromen-9-one-type fluorophores with blue fluorescence emission properties

The reactions of 3-formylchromones with alkyl isocyanides in dry dichloromethane at room temperature lead to new types of organic fluorophores (1Z)-3-(alkylimino)-1-[(chromone-3-yl)methylene]-1,3-dihydro-9H-furo[3,4-b]chromen-9-one, which exhibited strong blue emission in solution. The reactions involve a [4+1] cycloaddition followed by an activated electrophilic aromatic substitution at the furan ring and dehydration sequence.     

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.     

Synthesis and fluorescence properties of difluoro[amidopyrazinato-O,N]boron derivatives: a new boron-containing fluorophore

New boron-containing fluorophores, difluoro[amidopyrazinato-O,N]boron (APB) derivatives, were prepared from amidopyrazines. The fluorescence properties of APB were successfully modulated by an aryl substitution at the C8 position.     

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.     

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.     

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 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.     

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.     

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.     

An efficient synthesis of spiro[dibenzo[b,i]xanthene-13,3′-indoline]-pentaones and 5H-dibenzo[b,i]xanthene-tetraones

Spiro[dibenzo[b,i]xanthene-13,3′-indoline]-pentaones and 5H-dibenzo[b,i]xanthene-tetraones are synthesized from the condensation of 2-hydroxynaphthalene-1,4-dione with isatins or aldehydes.     

Cyclisation of 3-alkenylpyrido[1,2-a]pyrimidines to furo[2,3-d]pyrido[1,2-a]pyrimidines

3-Alkenylpyrido[1,2-a]pyrimidines react under mild conditions to give novel tricyclic furo[2,3-d]pyrido[1,2-a]pyrimidines in high yields. The cyclisation takes place in the presence of an acid catalyst. The product yield is affected by the type and the strength of the acid used. Exceptionally high yields were obtained when an organic acid like trifluoromethanesulfonic acid and trifluoroacetic acid were used. On the other hand, sulfuric acid gave the best results of the inorganic acids examined.     

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.     

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.     

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.     

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.     

Chemical reactivity of [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts

The chemical reactivity of the [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts towards morpholine, water and sodium methoxide have been studied. Among others, new 1-aza and 2-azabutadienes substituted by a [1,2,3]-triazole ring were obtained in the course of the opening of the positively charged pyrimidine ring.     

Synthesis of 9-nitro-5H-spiro[benzo[b]tetrazolo[1,5-d][1,4]oxazepine-4,2′-oxirane] via an unusual ring-expansion

Attempted cyclization of (4-(hydroxymethyl)-8-nitro-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-4-yl)methyl 4-methylbenzenesulfonate 2 did not give the expected spirooxetane product 1, but instead provided 9-nitro-5H-spiro[benzo[b]tetrazolo[1,5-d][1,4]oxazepine-4,2′-oxirane] 3via an unusual ring-expansion process. The structure of compound 3 was confirmed by single-crystal X-ray crystallography. The spiroepoxide (oxirane) in compound 3 could be ring-opened with a variety of nucleophiles to give products of potential interest to medicinal chemists.     

Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.