A preparative microwave method for the isomerisation of 4,16-dibromo[2.2]paracyclophane into 4,12-dibromo[2.2]paracyclophane

4,16-Dibromo[2.2]paracyclophane (4) is isomerised to 4,12-dibromo[2.2]paracyclophane (1) by the application of microwaves in DMF solution.     

From N,N-diphenyl-N-naphtho[2,1-b]thieno[2,3-b:3′,2′-d]dithiophene-5-yl-amine to propeller-shaped N,N,N-tri(naphtho[2,1-b]thieno[2,3-b:3′,2′-d]dithiophene-5-yl)-amine: syntheses and structures

Three unique propeller-shaped helicenyl amines compounds: N,N-diphenyl-N-naphtho[2,1-b]thieno[2,3-b:3′,2′-d]dithiophene-5-yl-amine (1), N-phenyl-N,N-di(naphtho[2,1-b]thieno[2,3-b:3′,2′-d]dithiophene-5-yl)amine (2), and N,N,N-tri(naphtho[2,1-b]thieno[2,3-b:3′,2′-d]dithiophene-5-yl)amine (3) were efficiently synthesized by Wittig reaction and oxidative photocyclization. The crystal structures of 1, 2 and molecular configuration optimization (DFT-B3LYP/6-31+G(d)) of 3 reveal that the steric hindrance from the moiety of trithia[5]helicene effectively forces the nitrogen atom and the three bonded carbon atoms to coplanar and the interplanar angles of the facing terminal thiophene ring and benzene ring becoming larger when the helical arm increased from 1 to 3. Electrochemical properties and UV–vis absorption behaviors of 1, 2, 3 were primarily determined by the moiety of trithia[5]helicene.     

Substituted coumarin amidines: useful building blocks for the preparation of [1]benzopyrano[4,3-b]pyridin-5-one and [1]benzopyrano[4,3-d]pyrimidin-5-one derivatives

The synthesis of [1]benzopyrano[4,3-b]pyridin-5-ones 4a-f and 4g-j starting from 3-formylcoumarin and 3-cyanocoumarin N-functionalized amidines 3a-f and 3g-j, respectively, was reported. The ring-closure reaction mechanism, under basic or acidic media, was proposed. Furthermore, the reaction of 3-formylamidines 3a,c-f with ammonium acetate gave good yields of 2-substituted [1]benzopyrano[4,3-d]pyrimidin-5-ones 7.     

Synthesis and self-assembly of novel calix[4]arenocrowns: formation of calix[4]areno[2]catenanes

A series of novel calix[4]arenocrowns 1a-c were efficiently synthesized by a one-pot reaction of calix[4]monohydroquinone diacetate 5 with ditosylate 6 and its analogues in the presence of sodium hydroxide. It was found that the calix[4]arenocrowns could form stable pseudorotaxane-type complexes 2a-c with paraquat, and further self-assemble into calix[4]areno[2]catenanes 3a-c with dicationic salt 8 and p-bis(bromomethyl)benzene.     

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Novel dipyrido[1,2-a;3′,4′-d]imidazoles 7a-d, dipyrido[1,2-a;4′,3′-d]imidazoles 8a,c and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives 9a-d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2-a]pyridines 11.     

Solid-state and solution photocycloadditions of 4-acyloxy-2-pyrones with maleimide

Solid-state photosensitized reactions of 4-acyloxy-2-pyrones (1b,c) with maleimide (2) afforded endo-endo double-[4+2] cycloadducts (3b,c) with high stereoselectivity. Sensitized photoreactions of 1a-d with 2 in solution gave exo-endo double-[4+2] cycloadducts (4a-d). 2-Pyrones 1a-d were photolyzed to give carboxylic acids (5a-d) via their valence isomerization in the solid state and in solution. Such kinds of photoreaction of the 4-acyloxy-2-pyrones were dramatically different from regio- and stereoselective [2+2] cycloadditions of 4-alkyloxy-2-pyrones. The photoreaction mechanisms of 1 with 2 and 1 itself were analyzed by powder X-ray diffraction analysis and MO calculations.     

Regioselective rearrangement of 7-azabicyclo[2.2.1]hept-2-aminyl radicals: first synthesis of 2,8-diazabicyclo[3.2.1]oct-2-enes and their conversion into 5-(2-aminoethyl)-2,3,4-trihydroxypyrrolidines, new inhibitors of α-mannosidases

Enantiomerically pure 2,8-diazabicyclo[3.2.1]oct-2-ene derivatives (+)-5 and (−)-5 have been obtained from 2-azido-3-tosyl-7-azabicyclo[2.2.1]heptanes (+)-1 and (−)-2 and their enantiomers, by ring expansion under radical conditions. Compounds (+)-5 and (−)-5 were transformed into hemiaminals 9 ((3S,4R,5R)- and 10 ((3R,4S,5S)-5-(2-aminoethyl)-2,3,4-trihydroxypyrrolidine) that are good inhibitors of α-mannosidases.     

A convenient synthesis of benzofuro[3,2-c]isoquinolines and naphtho[1′,2′:4,5]furo[3,2-c]isoquinolines

A convenient method for the preparation of benzofuro[3,2-c]isoquinoline derivatives is described. The condensation reaction of methyl 2-(chloromethyl)-benzoate with substituted salicylonitriles 7a-c and intramolecular cyclization of the resulting substituted methyl 2-[(2-cyanobenzyl)oxy]benzoates 10a-c using potassium tert-butoxide results in the substituted benzofuro[3,2-c]isoquinolin-5(6H)-ones 1a-c. The same sequence of reactions starting from 2-(chloromethyl)benzonitrile and compounds 7a-c gave substituted 5-aminobenzofuro[3,2-c]isoquinolines 13a-c. In addition, this method is useful for the synthesis of other heterocycles. For example, using 1-cyano-2-naphthol 16, instead of the salicylonitriles 7a-c, gives naphtho[1′,2′:4,5]furo[3,2-c]isoquinolines.     

Short-step syntheses and complexation properties of Z,Z-tribenzodidehydro- and all-Z-tribenzo[12]annulenes

Syntheses of all-Z-tribenzo[12]annulenes (1a-c) and Z,Z-tribenzodidehydro[12]annulenes (2a-c) by the reduction of the corresponding tribenzohexadehydro[12]annulenes 3a-c were carried out using a low valent titanium complex generated from Ti(O-i-Pr)₄ and i-PrMgCl. The unique structure of the first reduction products 2a-c as well as 1a-c was fully characterized. Complexation of these annulenes with silver(I) ions produces the corresponding silver complexes. Among them, the silver complexes of 2a-c exhibit interesting monomer-dimer equilibrium.     

Naphthyridines. Part 3: First example of the polyfunctionally substituted 1,2,4-triazolo[1,5-g][1,6]naphthyridines ring system

Treatment of 1,2,4-triazoles (1) with diethylmalonate in bromobenzene gave 1,2,4-triazolo-[1,5-a]pyridines 2. Chlorination of 2 using POCl₃/DMF (Vilsmeier reagent) led to the isolation of 7-chloro-6-formyl-1,2,4-triazolo[1,5-a]pyridine derivative 4, which reacted with the stabilized ylid 5 to afford 6-ethoxycarbonylvinyl-1,2,4-triazolo[1,5-a]-pyridines 6. Azidation of 6 yielded the corresponding azido compound 7, (Scheme 2). Reduction of 7 with Na₂S₂O₄ gave the corresponding 7-amino compound 8, which cyclized in boiling DMF to give the novel 1,2,4-triazolo[1,5-g][1,6]naphthyridines 9. On the other hand, reacting 7 with one equivalent of PPh₃ (aza-Wittig reaction) in CH₂Cl₂ gave 7-imino-phosphorane derivative 10, and subsequent cyclization in boiling DMF afforded the new 1,2,4-triazolo[1,5-g][1,6]naphthyridine derivative 11 (Scheme 3). However, treatment of 10 with phenyl isothiocyanate in 1,2-dichlorobenzene at reflux temperature gave the new 1,2,4-triazolo[1,5-g][1,6]naphthyridine derivative 14 (Scheme 4). Refluxing 6 with excess of a primary amines 15a,b in absolute. EtOH yielded the corresponding 7-alkyl-amino-1,2,4-triazolo[1,5-a]pyridines 16a,b. These obtained amines 16a,b underwent intramolecular heterocyclization in boiling DMF to give the novel 9-alkyl-1,2,4-triazolo[1,5-g][1,6]-naphthyridines 17a,b, in excellent yields (Scheme 5).     

Gas-phase pyrolysis of benzimidazole derivatives: novel route to condensed heterocycles

Gas-phase pyrolysis of N-(1H-benzimidazol-2-yl)-N′-arylidenehydrazines 1a-e gave the corresponding arylnitriles 2a-e, 2-aminobenzimidazole 3, 2,4,5-triphenylimidazole 4, 1,3-diphenyl-8H-2,3a,8-triazacyclopenta[a]indene 5, and 5,11-diphenyl-6H,12H-dibenzimidazo[1,2-a];1’,2’-d]pyrazine 6. The kinetics and analysis of the products of reaction are reported and used to elucidate the mechanism of the elimination process.     

Conduramine F-1 epoxides: synthesis and their glycosidase inhibitory activities

Starting from (±)-7-oxanorbornenone ((±)-14), (±)-(1RS,2RS,3SR,6SR)-6-azidocyclohex-4-en-1,2,3-triol ((±)-24) and (±)-(1RS,2RS,3SR,6RS)-6-azidocyclohex-4-en-1,2,3-triol ((±)-26) were obtained. Epoxidation of the latter cyclohexene derivative gave two epoxides (±)-30 and (±)-31 that were converted into (±)-conduramine F-1 epoxides (±)-10 and (±)-11 and N-substituted derivatives (±)-12 and (±)-13. Compound (±)-(1RS,2SR,3RS,4SR,5RS,6SR)-5-({[4-(trifluoromethyl)phenyl]methyl}amino)-7-oxabicyclo[4.1.0]heptane-2,3,4-triol ((±)-12c) is a good, non-competitive inhibitor of β-xylosidase from Aspergillus niger (K_i=2.2 μM), and (±)-(1RS,2RS,3SR,4RS,5SR,6SR)-5-{[(biphenyl-4-yl)methyl]amino}-7-oxabicyclo[4.1.0]heptane-2,3,4-triol ((±)-13d) is a good inhibitor of α-glucosidase from brewer's yeast (K_i=2.8 μM, non-competitive).     

Synthesis, crystal structure analysis, and pharmacological characterization of desmethoxy-sila-venlafaxine, a derivative of the serotonin/noradrenaline reuptake inhibitor sila-venlafaxine

rac-Desmethoxy-sila-venlafaxine (rac-3) is a derivative of the noradrenaline-selective serotonin/noradrenaline reuptake inhibitor rac-sila-venlafaxine (rac-1b), a silicon analogue of the serotonin-selective serotonin/noradrenaline reuptake inhibitor rac-venlafaxine (rac-1a) (rac-1a, rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol; rac-1b, rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-1-silacyclohexan-1-ol). The synthesis and crystal structure analyses of rac-3 and rac-3 · HCl are reported, and the pharmacological properties of rac-1a, rac-1b, rac-2 (a sila-venlafaxine derivative with a silacyclopentanol skeleton instead of a silacyclohexanol framework), and rac-3 are compared (comparison of the pharmacological selectivity profiles with respect to serotonin, noradrenaline, and dopamine reuptake inhibition).     

Quinoxaline-annelated Z-shaped quadruple-bridged orthocyclophanes: synthesis and crystal structures

A three-step synthesis of nineteen Z-shaped quadruple-bridged [6,6] and [6,4]orthocyclophanes comprising two quinoxaline-based sidewalls are described. The synthesis began from the bis-Diels−Alder adducts B1-B3 followed by ruthenium-promoted oxidation of dichloroetheno-bridges in the adducts to generate a bis-α-diketones, which were then condensed with various arene-1,2-diamines (9a-g) to construct sidewalls (phane parts) of Z-shaped quadruple-bridged orthocyclophanes D1-3, D2g, and D3g. Single-crystal structures of six orthocyclophanes (D1a, D2a, D2f, D3f, D2g-α, and D3g-α) were obtained and revealed that the C_Ar−H?π and π?π stacking interactions between N-containing arene rings are the major driving force for molecular assembly and crystal packing, in addition to the interactions involving the polar OCH₃ groups and the solvate molecules.     

New reaction of ethenetetracarbonitrile with N-arylisoindolines

N-Arylisoindolines 1a-i react with ethenetetracarbonitrile 2 in aerated benzene by formation of [3-(2-aryl-3-dicyanomethylene-2,3-dihydro-1H-isoindol-1-ylidene)-2-aryl-2,3-dihydro-1H-isoindol-1-ylidene]propanedinitriles 8a-i (20-36%), N-aryl-3-dicyanomethylene-isoindol-2-ones 9a-i (15-21%) and N-arylphthalimides 10a-i (4-9%) as well as 1,1,2,2-tetracyanoethane 11 (35-55%). The structure of 8d has been unambiguously confirmed by a single crystal X-ray structure analysis. A rationale for the formation of products 8-11 is presented.     

Triazolopyridines. Part 24: New polynitrogenated potential helicating ligands

The synthesis of novel 7-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}-[1,2,3]triazolo[1,5-a]pyridines 7, 2-pyridyl-[1,2,3]triazolo[1,5-a]pyrid-7-ylmethanols 11, 3-(6-substituted-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridines 12, and 7,7′-disubstituted-3,3′-[1,2,3]triazolo[1,5-a]pyridine 20, interesting polynitrogenated ligands as potential helicating compounds or luminescent sensors, from [1,2,3]triazolo[1,5-a]pyridines is described.     

3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P-C coupling, structure and conversion to pyrido[b]-anellated PC-N heterocycles

Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a-f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a-f, whereas nickel catalysts, although providing access to related anilido-2-phosphonates, proved inactive. Reduction of the aminophosphonate 2a with LiAlH₄ afforded 3-amino-2-phosphinopyridine (3a), which was cyclocondensed with dimethylformamide dimethyl acetal (DMFA) via phosphaalkene intermediates 4a to the novel pyrido[b]-anellated 1,3-azaphosphole 5a. Reaction of amidophosphonates 2b-f with LiAlH₄ did not result in the expected reductive cyclization, as shown by closely related anilido-2-phosphonates, but led to product mixtures containing N-secondary 3-amino-2-phosphinopyridines 3b-f as the main or major component. The conversion of 3b,d,e with DMFA to 5b,d,e provides first examples of N-substituted pyrido[b]-anellated azaphospholes. Structures were confirmed by multinuclear NMR and X-ray crystallography (for 2c, 3b).     

A Pd[0]-catalyzed Ullmann cross-coupling/reductive cyclization approach to C-3 mono-alkylated oxindoles and related compounds

The Pd[0]-catalyzed Ullmann cross-coupling of o-nitrohaloarenes 1a-e with the brominated heterocycles 2a-f delivers the expected products 3a-j in good to excellent yields. The reductive cyclization of such products, as well as N-acyl derivatives 3k, l, and m, has been investigated and provided the C-3 mono-substituted oxindoles 5a-d, f, g, k, and m, the direct reduction products 4i and j or indole 5l.     

A convenient synthesis of new pyrido[3,2-e][1,4]diazepine-2,5-diones and pyrido[2,3-e][1,4]diazepine-2,5-diones

A convenient synthesis of a series of pyrido[3,2-e][1,4]-diazepine-2,5-diones 8 and pyrido[2,3-e][1,4]diazepine-2,5-diones 9, is reported using the condensation of α-amino acid methyl ester derivatives with 1H-pyrido[3,2-d][1,3]oxazine-2,4-dione and 1H-pyrido[2,3-d][1,3]oxazine-2,4-dione. Compounds 8 and 9 were also synthesized by peptide coupling of α-amino acid methyl ester derivatives with β-amino acids (2 or 3) followed by the cyclisation in tetrahydrofuran with sodium hydride (NaH).     

Absolute configuration of gomadalactones A, B and C, the components of the contact sex pheromone of Anoplophora malasiaca

Absolute configuration of gomadalactones A (1), B (2) and C (3), the pheromone components of the white-spotted longicorn beetle (Anoplophora malasiaca) was assigned as (1S,4R,5S)-1, (1R,4R,5R)-2 and (1S,4R,5S,8S)-3 by comparing their published CD spectra with those of (1R,5R)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]oct-7-ene-2,6-dione (4) and (1S,5R,8S)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]octane-2,6-dione (5) prepared from (R)-(−)-carvone (6).