Synthesis of chiral 2′,3′-pyranone(pyrrolidinone)-fused tryptamines

Chiral pyrano- and pyrrolidino-fused tryptamines were prepared by a diasteroselective trimolecular condensation between indole, Garner's aldehyde and Meldrum's acid, followed by selective functional group transformations.     

An efficient one-pot three-step domino synthesis of substituted bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones)

A convenient and efficient one-pot three-step domino approach to bis(pyrazinothienopyrimidinones) from ethyl 3-(triphenylphosphoranylideneamino)-thieno[2,3-b]pyrazine-6-carboxylate 1 has been developed. In this method, treatment of phosphazene 1 with a mixture of isocyanates, nitrogen, sulfur, and oxygen bis(nucleophiles) and K₂CO₃ in refluxing THF regioselectively furnishes the corresponding bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones) in satisfactory to good yields. This methodology is highly versatile and efficient for the generation of these functionalized bis(triheterocyclic) compounds that are not readily available by other synthetic methods.     

Efficient one-pot preparation of bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-yl)benzenes based on an aza-Wittig/mediated annulation strategy

Aza-Wittig mediated annulation provides a highly facile and straightforward one-pot strategy for the synthesis of bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-yl)benzenes 5 and 7. A tandem aza-Wittig reaction of iminophosphorane 2 with 1,4- or 1,3-phenylene diisocyanate, followed by intramolecular heteroconjugate addition annulation after addition of a nucleophilic reagent (amine, phenol, thiophenol or ROH), in presence of catalytic K₂CO₃ or NaOR, gives selectively the functionalized bis(pyrazinothienopyrimidinones) 5 and 7.     

Synthesis of tetrahydropyrido- and pyrido-[1′,2′:1,2]imidazo[4,5-b]pyrazine derivatives

Reactions of tetrafluoropyridazine with iminopiperidine and 2-aminopiccoline gave novel tetrahydropyrido- and pyrido-[1′,2′:1,2]imidazo[4,5-b]pyrazine heterocyclic frameworks respectively in high yields.     

Synthesis of pyrido[2′,1′:2,3]imidazo[4,5-b]quinoline and pyrido[1′,2′:1,2]imidazo[4,5-b]quinoline and their benzo and aza analogs via tandem catalysis

In this paper we report regioselective tandem metal-catalyzed aminations on dihaloquinolines (2-chloro-3-iodoquinoline and 2,3-dibromoquinoline) with amino(benzo)(di)azines. Eight new heterocyclic scaffolds of the dipyridoimidazole type could be synthesized. By controlling the reaction temperature selective C-2 intermolecular Pd-catalyzed amination on 2,3-dibromoquinoline with amino(benzo)(di)azines can be achieved.     

First synthesis of 4-aminopyrido[2′,3′:4,5]furo[3,2-d]pyrimidines

This Letter describes for the first time the synthesis of pyrido[2′,3′:4,5]furo[3,2-d]pyrimidines substituted by a primary or secondary amino group on position 4 of the pyrimidine ring. Application of microwave irradiation technology allowed fast and convenient procedures.     

A practical one-pot procedure for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinones by a tandem aza-Wittig/heterocumulene-mediated annulation strategy

A simple one-pot and efficient method is described for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 6 via a tandem aza-Wittig/heterocumulene-mediated annulation process. The iminophosphorane 3 reacted with aryl isocyanates, followed by heterocyclization on addition of secondary amines to give the corresponding guanidine intermediates 5, which were cyclized in the presence of a catalytic amount of potassium carbonate to tricyclic compounds 6. Similarly, iminophosphorane 3 reacts with phenols, thiophenol, or ROH to give 2-aryl(alkyl)oxy(thio)pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 7 in good yields. The corresponding carbodiimide 4c and guanidine-type intermediate compounds 5 could be isolated and characterized, thus confirming the suggested reaction pathway. However, two isomeric pyrazinothienopyrimidinones 8 and 9 may be produced in the reaction of iminophosphorane 3 with aromatic isocyanates and subsequent reaction with primary amines in the presence of a catalytic amount of potassium carbonate. The effects of the nucleophiles and isocyanates on the regioselectivity of the cyclization have been investigated.     

Cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines): synthesis, structure and mechanism of their formation

Reactions of 3-alkylamino-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones with cyclohexyl- and cycloheptylamines in the presence of AgPy₂MnO₄ produce novel cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines). Detailed information concerning the scope and mechanism of these transformations is discussed.     

Synthesis of pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolines via a one-pot,three-component reaction

A one-pot, three-component reaction for the synthesis of pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolines starting from 2-aminopyridines, phthalaldehyde, and trimethylsilyl cyanide in good to high yields is described.     

Synthesis of new fluorescent 2-(2′,2″-bithienyl)-1,3-benzothiazoles

Bithienyl-1,3-benzothiazole derivatives were synthesised by reacting various 5-formyl-5′-alkoxy- or 5-formyl-5′-N,N-dialkylamino-2,2′-bithiophenes with ortho-aminobenzenethiol in good to excellent yields. Evaluation of the fluorescence properties of these compounds was carried out. They show strong fluorescence in the 450-600 nm region, as well as high quantum yields and large Stokes’ shifts.     

Syntheses and properties of complexes with bis(2,2′-bipyridyl)ruthenium(II) moieties coordinated to 4,4′:2′,2′′:4′′,4′′′-quaterpyridinium ligands

Eleven new complexes of the form cis-[Ru^II(bpy)₂(L^A)]⁴⁺ (bpy = 2,2′-bipyridyl; L^A = a pyridinium-substituted bpy derivative) have been prepared and isolated as their PF₆⁻ salts. Characterisation involved various techniques including ¹H NMR spectroscopy and MALDI mass spectrometry. The UV-Vis spectra show intense intraligand π → π^∗ absorptions and metal-to-ligand charge-transfer (MLCT) bands with two distinct maxima in the visible region. Small shifts in the MLCT bands correlate with the electron-withdrawing strength of the ligand L^A. Cyclic voltammograms show quasi-reversible or reversible Ru^III/II oxidation waves, and two or more ligand-based reductions with varying degrees of reversibility. The variations in the redox potentials correlate with changes in the structure of L^A, and also with the MLCT energies. Differential pulse voltammetry allows the first reduction process for two of the complex salts to be resolved into two peaks. Single-crystal X-ray structures have been solved for three of the new complex salts and also for a pro-ligand salt. Two carboxylate-functionalised compounds have been tested as photosensitizers on TiO₂-coated electrodes, but show only negligible efficiencies, in accord with expectations.     

Dipyrido[1,2-a;3′,4′-d]imidazole systems

Novel tricyclic dipyridoimidazole derivatives can be readily synthesised in one pot processes from various highly fluorinated pyridine systems such as pentafluoropyridine and relatively nucleophilic 2-aminopyridine derivatives. Further nucleophilic aromatic substitution reactions of the novel tricyclic scaffolds allow the regioselective synthesis of various nitrogen, oxygen, carbon and sulfur-functionalised dipyridoimidazole products.     

Synthesis of substituted dipyrido[3,2-a:2′,3′-c]phenazines and a new heterocyclic dipyrido[3,2-f:2′,3′-h]quinoxalino[2,3-b]quinoxaline

Three new α,α′-diimine ligands were synthesized based on condensation of 1,10-phenanthroline-5,6-dione with 1,2-phenylenediamine derivatives using different approaches. All compounds were fully characterized by IR, ¹H and ¹³C NMR, UV-visible, and MS spectroscopies. We report the first example of a dipyrido[3,2-f:2′,3′-h]quinoxalino[2,3-b]quinoxaline, which exhibits a strong absorption at 430 nm and an interesting electrochemical behavior. These new molecules may have biological potential and are of synthetic and technological importance.     

The synthesis and properties of ferroceno[1′,2′;1″,2″]bis(1,3-dithiol-2-thione and -2-one) derivatives

The t-butyl and bis(t-butyl) derivatives of hexathia[3.3]ferrocenophane were prepared from the corresponding trithia[3]ferrocenophanes. The former was a mixture of chair-chair and chair-boat isomers, and the latter existed only chair-boat isomer. The hexathia[3.3]ferrocenophanes were led to the tetrathiols with LiAlH₄, which allowed to react with 1,1′-thiocarbonyldiimidazol to give the corresponding ferroceno[1′,2′;1″,2″]bis(1,3-dithiol-2-thione) derivatives. Mono t-butyl and unsubstituted analogs were prepared in a similar manner. The X-ray structural determination showed that these derivatives adopted the conformation in which the 1,3-dithiol-2-thione rings were heaped on top of each other. In the crystal of ferroceno[1′,2′;1″,2″]bis(1,3-dithiol-2-thione), the molecules packed so as to put the axis of molecule in order and to overlap one another above and below. The desulfurizative coupling of the ferroceno[1′,2′;1″,2″]bis(1,3-dithiol-2-thione) derivatives was unsuccessful.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Synthesis and properties of 4′,5′-bis(methylthio)-4,5-bis(2-pyridylethynyl)tetrathiafulvalene and its copper complexes

Synthesis of redox-active bis-pyridine ligand, 4′,5′-bis(methylthio)-4,5-bis(2-pyridylethynyl)tetrathiafulvalene (1) has been carried out in moderate yield starting from the corresponding diiodide. Bis(pyridylethynyl)-TTF 1 forms 1:1 complexes with Cu(I) and Cu(II) salts. Occurrence of the charge transfer from the TTF moiety to the copper atom was found to depend on the environment of copper atom.     

2′,3′,4′,5′-Tetraacetyl-N(3)-carboxymethylriboflavin derivatives: synthesis and fluorescence studies

The hitherto not described 2′,3′,4′,5′-tetraacetyl-N(3)-carboxymethylriboflavin (1) could be prepared starting from 2′,3′,4′,5′-tetraacetylriboflavin by alkylation with tert-butyl α-bromoacetate and benzyl α-bromoacetate, followed by deprotection reaction. The results of fluorescence studies are described.     

Synthesis of pyridino[3′,2′:4,5]pyrrolo[3,2-g]pyrrolo[3,4-e]indolizin-1,3-dione and pyrrolo[3,2-c]pyrazole skeletons

A three step synthesis of an isogranulatimide analogue, in which the imidazole moiety is replaced by a pyrrole unit and the indole heterocycle is replaced by a 7-azaindole moiety is described. Moreover, a novel synthetic pathway to the pyrrolo[3,2-c]pyrazole skeleton is reported.     

Synthesis, properties and molecular structure of a novel dicyanoheptafulvene derivative, 4′-dicyanomethylidenedispiro[cyclohexane-1, 1′-(1′,4′,7′-trihydrocyclopenta[f]azulene)-7′,1″-cyclohexane]

A novel dicyanoheptafulvene 9 annulated by two spiro[4,5]deca-1,3-dienes was synthesized by the reaction of dispirocyclopentaazulenium cation 8 with bromomalononitrile. Although 9 was found to have a nonplanar heptafulvene structure by its X-ray crystallographic analysis, it is still capable of π-conjugation and thus shows appreciable contribution of the dipolar resonance form 9B based on its spectroscopic data. The degree of the contribution was further evaluated for various dicyanoheptafulvenes in terms of the partial sum of atomic charges of the dicyanomethylene group in the calculated structures besides the interplanar angles of the heptafulvene part and the length of the exocyclic double bond in the crystal structures.     

Synthesis and tautomeric structure of 6-arylhydrazono 1H-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazepines

A simple synthetic strategy is described for synthesis of the hitherto unreported 6-arylhydrazono-1,3-diphenyl-7-methyl-1H-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-ones 5a-j. The acid dissociation constants were determined for the series prepared and were correlated by the Hammett equation using the enhanced substituent constants. The results of such a correlation together with the spectral data indicated that the studied compounds exist predominantly in the hydrazone tautomeric form.