Synthesis and structure characterization of unsymmetrical oxacalix[2]benzene[2]pyrazines

The synthesis of two unsymmetrically linked oxacalix[2]benzene[2]pyrazines (1 and 2) is described. X-ray single crystal structure analysis revealed a highly distorted 1,3-alternate conformation of compound 1 (containing ortho- and meta-diphenol components) and a distorted boat conformation of compound 2 (containing meta- and para-diphenol components). Oxacalix[2]benzene[2]pyrazine containing both ortho- and para-diphenol components was not obtained via similar synthetic strategy.     

p-Sulfonatocalix[7]arene: synthesis, protolysis, and binding ability

Water-soluble p-sulfonatocalix[7]arene 1 has been synthesized in good yield through standard procedures and its conformational preferences have been investigated by Monte Carlo conformational searches. The acid-base properties of 1 were investigated by means of potentiometric titration, obtaining pK_a values in agreement with those reported for other p-sulfonatocalix[n]arene homologs. The binding ability of 1 toward organic quaternary ammonium cations such as Diquat (2), Paraquat (3), and Chlormequat (4) was investigated by means of ¹H NMR titrations in D₂O at pD=7.3, DOSY NMR measurements, and 2D ROESY NMR spectroscopy. Spectrofluorimetry proved to be a useful method for the determination of trace amounts of 2 and 3 in aqueous solution by using Acridine Orange bound to 1 as a chemical indicator.     

Synthetic studies of benzo[b]pyrrolo[4,3,2-de][1,10]phenanthroline

6,11-Dihydrobenzo[b]pyrrolo[4,3,2-de][1,10]phenanthroline-5,8-dione (6), which possesses a unique heterocyclic ring system similar to that in plakinidines A-D (1-4), was synthesized from 2-acetyl-3′-nitrodiphenylamine (16) in nine steps.     

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.     

Synthesis of terpyridine-substituted calix[n]arenes

Calix[n]arenes (n = 4,5) comprising 4-(2,2′:6′,2″-terpyridyl)-phenyl substituents at the upper rim were synthesized for the first time, employing Suzuki-type coupling reactions. All calix[n]arene derivatives were prepared as cone conformers. The single crystal X-ray structure of cone-5,11,17,23-tetra{4-(2,2′:6′,2″-terpyridyl)-phenyl}-25,26,27,28-tetrabutoxycalix[4]arene 4 is analyzed in terms of structural rigidity and potential use of these ligands as novel synthons of cage-type metallosupramolecular assemblies.     

A general synthesis of water soluble upper rim calix[n]arene guanidinium derivatives which bind to plasmid DNA

The reaction of O-alkylated p-aminocalix[n]arenes (n=4, 6, 8) with N,N′-di(tert-butoxycarbonyl)thiourea in the presence of HgCl₂ and subsequent removal of the protective groups with hydrochloric acid led to the new water soluble calix[n]guanidinium derivatives (p-guanidiniumcalix[n]arenes) 20-23. With the exception of tetraoctyl-p-guanidiniumcalix[4]arene 21, which forms a macroscopic gelatinous aggregate even at very low concentration, all the synthesised guanidinium calixarenes show good solubility in water and sharp NMR signals. Moreover, these compounds are not cytotoxic and bind to plasmid DNA.     

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.     

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.     

Lower rim arylation of calix[n]arenes with extended perfluorinated domains

Exhaustive O-arylation of p-tert-butylcalix[n]arenes 2 (n = 4-8) with an excess of 3-pentadecafluoroheptyl-5-pentafluorophenyl-1,2,4-oxadiazole 3 and K₂CO₃ in refluxing acetonitrile provides an easy entry to a new family of perfluorinated calix[n]arenes 1. The cyclic tetramer furnishes a mixture of cone, partial cone, and 1,2-alternate conformers, while the larger macrocycles afford single products. The structures of all new compounds are substantiated by NMR techniques and MALDI-TOF mass spectral data. Single-crystal X-ray diffraction studies on the pentamer derivative 1b reveal a distorted cone-in conformation of the calixarene cup.     

Facile synthesis of thiacalix[n]arenes (n=4, 6, and 8) consisting of p-tert-butylphenol and methylene/sulfide alternating linkage and metal-binding property of the n=4 homologue

2,14-Dithiacalix[4]arene 3₄ was conveniently prepared in 16% yield by acid-catalyzed cyclocondensation of 2,2^′-thiobis[4-tert-butylphenol] with formaldehyde. The present method also afforded the first isolation of the analogues with six and eight phenol units, 3₆ (10%) and 3₈ (5%), respectively. Solvent extraction showed that 3₄ had high selectivity toward Cu²⁺ ion at pH 5.5 by coordination of the bridging sulfur with cooperative donation of the adjacent phenolate oxygens.     

Reactions promoted by [hydroxy(tosyloxy)iodo]benzene in pyrazino[1,2-b]isoquinolines

The hypervalent iodine reagent PhI(OH)OTs (HTIB) promoted oxidative demethylation of 1,4-hydroquinone methyl ethers to give quinones in a quantitative conversion. The efficacy of this reaction, that has been applied to simple arene compounds and to heterocyclic systems, such as 2-isopropoxycarbonyl-7,10-dimethoxy-pyrazino[1,2-b]isoquinoline-4-ones and 1,4-diones to get the corresponding 7,10-quinones (compounds 6-8), is similar to those promoted by CAN and does not require the presence of water. Instead of oxidative demethylation, HTIB promoted in 1-methoxy-pyrazino[1,2-b]isoquinoline-4-ones complex multi-step processes to give compounds 9 or 10.     

A novel transformation of 1-exo-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones with sulfoxonium ylide to highly strained 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans

When 1-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones (1) were treated with dimethylsulfoxonium methylide, 1-endo isomers (endo-1) gave 1-substituted 3-aroyl-1,2,4a,9b-tetrahydrodibenzofuran-4-ols (2) exclusively as expected. On the other hand, 1-exo isomers (exo-1) underwent a novel transformation to 1-substituted 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans (3), together with 2.     

New iminophosphorane-mediated synthesis of thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones and 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes

Mono(iminophosphorane) 4 was selectively prepared from the reaction of 3,4-diaminothieno[2,3-b]thiophene 3 with excess triphenylphosphine, C₂Cl₆, and Et₃N due to intramolecular double hydrogen bond formation. Mono(iminophosphorane) 4 reacted with aromatic isocyanates to give stable carbodiimides 8, which were further treated with aliphatic secondary or primary amines to give 2-amino substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 10 or 12 in the presence of a catalytic amounts of EtO⁻Na⁺. However, in the presence of a catalytic amounts of potassium carbonate, the carbodiimides 8 were transformed into previously unreported 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes 13 via direct cyclization in high yields. The reaction of carbodiimides 8 with phenols in the presence of a catalytic amounts of potassium carbonate gave a mixture of 2-aryloxy substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 14 and 13. X-ray structure analysis of 10m supported the structure and the proposed reactivity of amino group.     

CMPO-substituted calix[6]- and calix[8]arene extractants for the separation of An/Ln from radioactive waste

Three calix[6]arene derivatives (1a-c) and two calix[8]arene derivatives (2a,b), with six and eight CMPO residues, respectively, attached to the narrow/lower rim via ether links, were synthesised. Preliminary liquid-liquid extraction studies for Eu(III) and Am(III) from aqueous nitric acid to o-nitrophenylhexyl ether reveal remarkable properties with respect to efficiency and selectivity, especially for the tert-butylcalix[6]arene derivative with a -(CH₂)₃- spacer.     

Preparation of new pyrido[3,4-b]thienopyrroles and pyrido[4,3-e]thienopyridazines

Two new types of pyrido-fused tris-heterocycles (1a,b and 2a,b) have been prepared from 3-aminopyridine in five/six steps. A synthetic strategy for the preparation of the novel pyrido[3,4-b]thieno[2,3- and 3,2-d]pyrroles (1a,b) and pyrido[4,3-e]thieno[2,3- and 3,2-c]pyridazines (2a,b) has been studied. The Suzuki cross coupling of the appropriate 2- and 3-thienoboronic acids (3,4) and 4-bromo-3-pyridylpivaloylamide (9) afforded the biaryl coupling products (10,11) in high yields (85%). Diazotization of the hydrolysed (2-thienyl)-coupling product (12) and azide substitution gave the 3-azido-4-(2-thienyl)pyridine intermediate (72%, 14). 3-Azido-4-(3-thienyl)pyridine (15) was prepared by exchanging the previous order of reactions. The desired β-carboline thiophene analogues (1a,b) were obtained via the nitrene by thermal decomposition of the azido precursors (14,15). By optimising conditions for intramolecular diazocoupling, the corresponding pyridazine products (72-83%, 2a,b) were afforded.     

Micelles catalyzed one pot regio- and chemoselective synthesis of benzo[a]phenazines and naphtho[2,3-d]imidazoles ‘in H2O’

An efficient, novel, and concise one pot regio- and chemoselective synthesis of benzo[a]phenazines (4) and naphtho[2,3-d]imidazoles (8) has been accomplished in excellent yields by nucleophilic substitution reaction of 2,3-dichloro-1,4-naphthoquinone (1) with o-phenylenediamine (2) and benzamidines (7) respectively ‘in H₂O’ using base and micelles (SDS) as catalyst. Analog reaction of 2,3-dichloro-1,4-naphthoquinone (1) with 2-aminobenzenethiol (9) under identical conditions led to formation of a mixture of benzo[b]phenothiazine (10), benzo[a]phenothiazine (11), and benzo[a]-1,4-benzothiazino-3,2-phenothiazine (12) in 17%, 23%, and 57% yields, respectively.     

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.     

Studies on uracils: a facile one-pot synthesis of oxazino[4,5-d]-, pyrano[2,3-d]-, pyrido[2,3-d]- and pyrimido[4,5-d]pyrimidines using microwave irradiation in the solid state

N,N-Dimethyl-5-formylbarbituric acid 1 reacts with maleimide 2 and phenyl isocyanate/phenyl isothiocyanate 4 under microwave-assisted conditions in the solid phase to afford pyrano[2,3-d]pyrimidines 3 and oxazino[4,5-d]pyrimidines 5 in excellent yields. Under identical conditions, N,N-dimethyl-6-amino-5-formyluracil 6 reacts with 2 and 4 to give pyrido[2,3-d]pyrimidine derivative 7 and pyrimido[4,5-d]pyrimidines 8 in high yields.     

Generation and spectroscopic properties of syn-1,6:9,14-bismethanodicyclodeca[cd,gh]pentalene dianion

The hydrocarbon precursor, 8,16-dihydro-syn-1,6;9,14-bismethano[cd,gh]pentalene (5), to the title structure, dianion 4, was synthesized from ethyl 4-bromo-1,6-methano[10]annulene-3-carboxylate (6) in three steps, which included a nickel-catalyzed stereoselective homo-coupling, LiAlH₄ reduction of the ester groups, and scandium triflate-catalyzed double intramolecular cyclization of the biarylmethyldiol. Deprotonation of 5 with n-butyllithium in THF-d₈ provided 4, whose structure was confirmed by NMR analysis. Aspects of chemical shifts in the ¹H NMR spectrum and the calculated structure of 4 establish its diatropic nature.     

Easy access to 4-nitrothiochroman S,S-dioxides via ring-enlargement from 3-nitrobenzo[b]thiophene

The (E)-2-aryl-1-[2-(methylthio)phenyl]-1-nitroethylenes 5 can easily be oxidized to the relevant sulfones 6 and effectively subjected to cyclization via an intramolecular Michael addition after metallation with lithium bis(trimethylsilyl)amide in THF. After quenching with ammonium chloride the 3-aryl-4-nitrothiochroman S,S-dioxides 2 are obtained as diastereomeric mixtures in good to excellent yields. Both yields and stereochemistry of the ring-closure step appear to be influenced by steric effects of the 3-aryl moiety. As sulfides 5 derive from an initial ring opening of 3-nitrobenzo[b]thiophene (1), the overall 1 to 2 process can be considered as an effective 5 to 6 ring enlargement of the sulfur heterocycle. A conformational ¹H NMR and molecular-mechanics investigation on the isolated diastereomeric 2 has also been accomplished.