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.     

One-pot synthesis of oxygen and nitrogen-bridged calix[2]arene[2]triazines

A simple and powerful one-pot reaction method was developed for the synthesis of heteracalixaromatics. In the presence of a base, one-pot macrocyclic condensation reaction between cyanuric chloride and 1,3-phenylene diols and diamines proceeded effectively under very mild conditions to afford a number of functionalised oxygen and nitrogen-bridged calix[2]arene[2]triazines in 33–54% yields. The method was applied in a multigram-scale (14.4 g) preparation of tetraoxacalix[2]arene[2]triazine.     

Synthesis of mesoionic[1,2,3]triazolo[5,1-d][1,2,5]triazepines

Intramolecular cyclization of 1-amino-3-phenacyl-4-carbohydrazido-1,2,3-triazolium-5-olates has been shown to take place via selective interaction of the carbonyl group with the terminal amino function of the hydrazido group to form a 1,2,5-triazepine ring. Minor products, resulting from the interaction of the α-nitrogen atom of the hydrazido group with the carbonyl function, having a N-amino-pyridazine structure were also detected and isolated. A general method for the synthesis of novel mesoionic 2-amino-7-aryl-4-oxo-2,4,5,8-tetrahydro[1,2,3]triazolo[5,1-d][1,2,5]triazepin-9-ium-3-olates was developed.     

Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis,Anti-Viral In Vitro Study and Target Validation Activity

This study of the interaction system of binucleophilic 3-substituted 4-amino-4H-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4H-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.     

Construction of a hetero pseudo[2]rota[2]catenane

A novel ammonium template containing three ammonium sites was synthesized. Two ammoniums located on the linear component served as template for cucurbit[6]uril to form the CB-based pseudo[2]rotacane while another one located on the macrocyclic component played a role of template for clipping reaction. As a result of a ‘‘threading-followed-by-clipping' approach, a novel hetero pseudo[2]rota[2]catenane was successfully constructed.     

Simple NMR method for assigning relative stereochemistry of bridged bicyclo[3.n.1]-2-enes and tricyclo[7.n.1.0]-2-enes

The stereochemistry of syn and anti-forms of bridged bicyclo[3.n.1]-2-ene, tricyclo[7.n.1.0]-2-ene (n=1-3) and bicyclo[4.3.1]dec-7-ene derivatives can be assigned from the ¹³C chemical shift difference of the double bond. Both syn-9-R-bicyclo[3.3.1]non-2-enes and syn-13-R-tricyclo[7.3.1.0^2,7]tridec-2(7)-enes have a large shielding difference between sp² carbons, while the corresponding anti-forms have a smaller one. In contrast, 8-R-bicyclo[3.2.1]oct-2-enes and 12-R-tricyclo[7.2.1.0^2,7]dodec-2(7)-enes have an inverse correlation. The reason of this specificity is the influence of the γ-gauche effect on the chemical shift of C(2) atom. The GIAO theory has been applied to investigate the ¹³C chemical shifts. The conformational equilibrium in the formamide group of 13-formylamino-tricyclo[7.3.1.0^2,7]tridec-2(7)-enes has been studied.     

Synthesis of naphtho[b]cyclobutenes from 1,2-bis(3-propynol)benzenes

We have demonstrated that the reaction of benzene-bridged bis(propargyl alcohol)s with chlorodialkylphosphines exclusively afforded 3,8-bis(dialkylphosphinyl)naphtho[b]cyclobutenes via the [2+2] cycloaddition of 1,2-bis(α-phosphinylallenyl)benzenes. Dephosphinylation of the product has also been achieved.     

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.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Probing the spatial requirements for [60]fullerene-[60]fullerene π-stacking and the syn addition of [60]fullerenes across acenes

The reaction between 2 equiv of [60]fullerene and 6,8,15,17-tetraphenylheptacene-7,16-quinone leads to both cis and trans-bis[60]fullerene adducts. This result contrasts sharply with the highly diastereoselective syn additions of [60]fullerenes across 6,13-diphenylpentacene and 6,8,15,17-tetraphenylheptacene. The importance of spatially dependent [60]fullerene-[60]fullerene π-stacking interactions in promoting a syn addition of [60]fullerenes is discussed.     

Formation of the same pyrimido[1,2-a]indoles from 1-(oxiran-2-ylmethyl)-1H-indole or [1,3]oxazolo[3,2-a]indole derivatives in its reactions with aromatic amines

Reactions of two isomers—2-chloro-1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde or 2-(chloromethyl)-2,3-dihydro[1,3]oxazolo[3,2-a]indole-9-carbaldehyde with aromatic amines lead to the same products in both cases—hydrochlorides of pyrimido[1,2-a]indole derivatives containing two fragments of an amine per one part of the indole nucleus. Its structure was confirmed by X-ray analysis of the crystals base, obtained by alkali treatment of the reaction product (when aryl is 4-MeOC₆H₄).     

Efficient synthesis of 2- and 3-substituted-2,3-dihydro [1,4]dioxino[2,3-b]pyridine derivatives

A versatile new approach for the synthesis in three steps of 2-substituted-2,3-dihydro[1,4]dioxino[2,3-b]pyridines B via a Smiles rearrangement using easily available reagents is described. A study illustrating the influence of experimental conditions on the progress of the reaction is reported.     

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.     

An unusual synthesis of tetrahydrobenzo[f]isoquinolines

A facile and short synthesis of 2-oxo-4-sec-amino-2,3,5,6-tetrahydrobenzo[f]isoquinoline-1-carbonitriles has been delineated through base catalyzed ring transformation of 5,6-dihydro-2-oxo-4-sec-amino-2H-benzo[h]chromene-3-carbonitrile by cyanoacetamide in excellent yields.     

p-Toluenesulfonic acid-catalyzed one-pot synthesis of 2-amino-4-substituted-1,4-dihydrobenzo[4,5]imidazolo[1,2-a]pyrimidine-3-carbonitriles under neat conditions

A simple, efficient, and green procedure for the preparation of 2-amino-4-substituted-1,4-dihydrobenzolo[4,5]imidazolo[1,2-a]pyrimidine-3-carbonitriles has been developed by multi-component condensation of 2-aminobenzimidazole with aldehydes and malononitrile in the presence of a catalytic amount of p-toluenesulfonic acid, affording excellent yields under neat conditions. The protocol avoids the use of expensive catalysts, toxic solvents, and chromatographic separation. We believe that this new environmentally metal-free procedure, combined to a solvent-free reaction, would be of importance in the search of green laboratory-scale synthesis.     

Synthesis and Diels-Alder reactions of the benzo[4,5]thieno [2,3-c]pyrrole ring system

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-c]pyrrole ring system and its derivatives, as well as their Diels-Alder reactions with DMAD and N-phenylmaleimide are reported. A new synthesis of the benzo[4,5]thieno[2,3-d]pyridazine ring system is also described.     

Substituted chromones in [3+2] cycloadditions with nonstabilized azomethine ylides: synthesis of 1-benzopyrano[2,3-c]pyrrolidines and 1-benzopyrano[2,3-c:3,4-c′]dipyrrolidines

Chromones bearing electron-withdrawing substituents at the 2- or 3-position react with nonstabilized azomethine ylides to produce 1-benzopyrano[2,3-c]pyrrolidines in good yields. Reactions of 3-cyanochromones proceed diastereoselectively to give 1-benzopyrano[2,3-c]pyrrolidines and tetrahydro-1H-spiro[chromeno[2,3-c]pyrrol-9,5′-oxazolidine]-9a-carbonitriles, depending on the reactant ratio, as a result of a 1,3-dipolar cycloaddition of the azomethine ylide at the double bond and carbonyl group of the chromone system. The latter undergoes demethylenation and recyclization into a novel hexahydrochromeno[2,3-c:3,4-c′]dipyrrole tetracyclic system on heating with hydrochloric acid.     

Synthetic studies of pestalotiopsin A: asymmetric synthesis of the 2-oxabicyclo[3.2.0]heptane substructure

A functionalized 2-oxabicyclo[3.2.0]heptan-3-one derivative, possessing all the skeletal carbons of pestalotiopsin A, has been synthesized. For the preparation of intermediary cyclobutane derivatives in enantioenriched form, the Lewis acid-catalyzed [2+2] cycloaddition of N-propiolated Oppolzer’s camphorsultam with dimethylketene bis(trimethylsilyl) acetal followed by a stereoselective 1,4-hydride addition/protonation, has been developed.     

Theophylline as a new and green catalyst for the one-pot synthesis of spiro[benzo[a]pyrano[2,3-c]phenazine] and benzo[a]pyrano[2,3-c]phenazine derivatives under solvent-free conditions

A green, convenient, high yielding and one-pot procedure for the synthesis of novel spiro[benzo[a]pyrano[2,3-c]phenazine] derivatives by domino multi-component condensation reaction between 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamines, ninhydrine, and malononitrile in the presence of a catalytic amount of 1,3-dimethyl-7H-purine-2,6-dione (theophylline) as an expedient, eco-friendly and reusable solid base catalyst under thermal, microwave irradiation and solvent-free conditions. This procedure has also been applied successfully for the synthesis of benzo[a]pyrano[2,3-c]phenazines.