Consecutive nucleophilic substitution and aza Diels-Alder reaction—an efficient strategy to functionalized 2,2′-bipyridines

An efficient strategy for the synthesis of functionalized 2,2′-bipyridines is reported. The strategy is based on readily available 3-pyridyl-1,2,4-triazine 4-oxides and uses a reaction sequence of nucleophilic substitution of hydrogen and aza Diels-Alder reaction.     

Functionalized 2,2'-bipyridines and 2,2':6',2' '-terpyridines via stille-type cross-coupling procedures

Stille-type cross-coupling procedures are utilized in order to prepare a variety of functionalized 2,2'-bipyridines and 2,2':6',2' '-terpyridines. Such N-heterocyclic compounds are of great interest as chelating ligands for transition-metal ions in the field of supramolecular chemistry. Various mono- and disubstitued 2,2'-bipyridines were synthesized in high yields and multigram scales using a modular design principle. The terpyridines may be functionalized in one step with different substituents at the outer pyridine rings and at the 4'-position of the centered ring, leading to multifunctionalized compounds. The initially obtained methyl ester and ethyl ester groups can be simply converted into bromomethyl and hydroxymethyl groups which allow further functionalization reactions.     

Facile synthesis and platinum complexes of 4',5,5'-trisubstituted-2,2':6',2'-terpyridines

The synthesis of trisubstituted 4',5,5' terpyridines is described. The strategy begins with synthesis of 2-acetyl-5-bromopyridine (3) from 2,5-dibromopyridine, substitution of the bromine in 3 using a variety of metal-catalyzed reactions and then formation of the terpyridine using the Krohnke reaction. The complexes have been prepared by reaction of [Pt(PhCN)(2)Cl(2)] with the appropriate silver salt followed by addition of the terpyridyl ligand. The crystal structure of two complexes have been determined via X-ray diffraction and the MLCT (metal-to-ligand charge-transfer) emissions determined by UV/Vis spectroscopy.     

Alkylation of 1-alkoxy-3-methyl-1-triazene 2-oxide sodium salts

1-Alkoxy-3-methyl-1-triazene 2-oxide sodium salts react with chloromethyl methyl sulfide to give a mixture of 1-alkoxy-3-methyl-3-(methylthiomethyl)-1-triazene 2-oxides and 3-alkoxy-1-methyl-3-(methylthiomethyl)-1-triazene 2-oxides. The reaction of these triazene oxide sodium salts with 3,3-dialkyl-1-chloromethoxy-1-triazene 2-oxides produces a complex mixture of product bearing the oxytriazene moieties of the starting alkoxy-1-triazene 2-oxides bonded with the methylene group as a key structural fragment.     

Synthesis of Rationally Halogenated Buckybowls by Chemoselective Aromatic C−F Bond Activation

Halogenated buckybowls or bowl‐shaped polycyclic aromatic hydrocarbons (BS‐PAHs) are key building blocks for the “bottom‐up” synthesis of various carbon‐based nanomaterials with outstanding potential in different fields of technology. The current state of the art provides quite a limited number of synthetic pathways to BS‐PAHs; moreover, none of these approaches show high selectivity and tolerance of functional groups. Herein we demonstrate an effective route to BS‐PAHs that includes directed intramolecular aryl–aryl coupling through C−F bond activation. The coupling conditions were found to be completely tolerant toward aromatic C−Br and C−Cl bonds, thus allowing the facile synthesis of rationally halogenated buckybowls with an unprecedented level of selectivity. This finding opens the way to functionalized BS‐PAH systems that cannot be obtained by alternative methods.     

6,6'-Dibromo-4,4'-di(hexoxymethyl)-2,2'- bipyridine: a new solubilizing building block for macromolecular and supramolecular applications

Although brominated bipyridines and terpyridines are highly desirable synthetic building blocks for both ligand design and macro- or supramolecular applications, few such synthetic precursors have been reported that include much-needed solubilizing groups. Reported here is an inexpensive route to 2,6-dibromo-4-(hexoxymethyl)pyridine from citrazinic acid with an overall yield of 44% and its efficient conversion (60%) to 6,6'-dibromo-4,4'-di(hexoxymethyl)-2,2'-bipyridine via oxidative coupling.     

Synthesis of methylene-bis(1-oxy-3,3-dialkyl-1-triazene 2-oxides) and their analogs

Synthetic procedures towards methylene-bis(1-oxy-3,3-dialkyl-1-triazene 2-oxides), the first representatives of a new class of promising exogenous nitric oxide (NO) donors, which can release NO in living organisms, were developed. Synthesis involves the reactions of salts of 1-hydroxy-3,3-dialkyl-1-triazene 2-oxides with either dibromomethane or 1-chloromethoxy-3,3-dialkyl-1-triazene 2-oxides.     

Chloromethyl-, dichloromethyl-, and trichloromethyl-1,2,4-triazines and their 4-oxides: method for the synthesis and tele-substitution reactions with C-nucleophiles

A simple procedure was developed for the synthesis of 1,2,4-triazines and their 4-oxides containing the ClCH₂, Cl₂CH, or CCl₃ group at position 3 by cyclization of 2-aryl-2-hydrazono-1-oximinoethanes with the corresponding chloroacetonitriles. The reaction pathway depends on the number of halogen atoms in the acetonitrile used. The reactions with trichloroacetonitrile, monochloroacetonitrile, and dichloroacetonitrile afford 3-trichloromethyl-1,2,4-triazines, 3-chloromethyl-1,2,4-triazine 4-oxides, and a mixture of the corresponding dichloromethyltriazines and their 4-oxides, respectively. The reactions of 3-trichloromethyl-1,2,4-triazines with indoles and phenols are accompanied by tele-substitution with elimination of halogen from the trichloromethyl group to give 5-indolyl- (or 5-hydroxyphenyl)-3-dichloromethyl-1,2,4-triazines.     

Synthesis of 1-alkoxy-3-methyl-1-triazene 2-oxides and 3, 3´-methylene-bis(1-alkoxy-3-methyl-1-triazene 2-oxides)

Russian Chemical Bulletin - A method for the synthesis of 1-alkoxy-3-methyl-1-triazene 2-oxides and their salts with alkali metals was developed. 3,...     

Synthesis of 1-[(nitroxyalkoxy)methoxy]-1-triazene 2-oxides,new hybrid nitrogen monoxide donors

1-[(Nitroxyalkoxy)methoxy]-3,3-dialkyl-1-triazene 2-oxides were obtained by the reaction of 3,3-dialkyl-1-hydroxy-1-triazene 2-oxide sodium salts with β- or γ-nitroxyalcohol chloromethyl ethers or by the reaction of 3,3-dialkyl-1-(bromoalkoxymethoxy)-1-triazene 2-oxides with silver nitrate. These compounds can be of interest as new hybrid NO donors in living organisms.     

A first one-pot synthesis, isomerization and synthetic utility of mono- and bis Morita-Baylis-Hillman adducts of 1,1′-ferrocenedialdehyde

A one-pot synthesis of mono- and bis-Morita-Baylis-Hillman adducts of 1,1′-ferrocenedialdehyde has been achieved. These adducts undergo a facile and efficient stereoselective isomerization with a number of saturated, unsaturated, aromatic alcohols, phenols and thiophenol with a montmorillonite K10 clay catalyst to afford highly functionalized trisubstituted alkene derivatives of ferrocene. The synthetic utility of isomerized derivatives has been demonstrated by a ferrocene appended novel macrocycle synthesis, a ferrocenyl bis-triazole synthesis and an evaluation of the liquid crystalline property of a cholesterol derivative of ferrocene.     

Synthesis of 1-alkoxy-3-(2-hydroxyethyl)-1-triazene 2-oxides

Synthetic procedure to access the first representatives of a new series of 3-monosubstitued functional derivatives of 1-alkoxy-1-triazene 2-oxides, i.e., 1-alkoxy-3-(2-hydroxyethyl)- and 1-alkoxy-3-(2-acetoxyethyl)-1-triazene 2-oxides, were elaborated. 1-Alkoxy-3,3-bis(2-hydroxyethyl)-1-triazene 2-oxides were used to derive 3-(2-acetoxyethyl)-, 3-(2-bromoethyl)- and 3-(2-cyanoethyl)substituted 1-alkoxy-3-(2-acetoxyethyl)-1-triazene 2-oxides.     

New and versatile syntheses of 3-alkyl- and 3-aryl-1,2,4-benzotriazine 1,4-dioxides: preparation of the bioreductive cytotoxins SR 4895 and SR 4941

Palladium-mediated coupling of 3-chloro-1,2,4-benzotriazine 1-oxide with a variety of stannanes in the presence of Pd(PPh₃)₄ gives 3-alkyl derivatives in good yields. Suzuki reaction of the 3-chloro compound with phenylboronic acids gives 3-aryl-1,2,4-benzotriazine 1-oxides. Oxidation of 1-oxides with trifluoroperacetic acid gives the 1,4-dioxides. This method provides a better route to the potential anti-cancer agents SR 4895 and SR 4941.     

Acylation of 1-methoxy-3-methyl-1-triazene 2-oxide

Chlorides and anhydrides of carboxylic (including dicarboxylic) acids react with salts of 1-methoxy-3-methyl-1-triazene 2-oxides to give the corresponding 3-acyl-1-methoxy-3-methyl-1-triazene 2-oxides.     

Synthesis of the common propellane core structure of the hasubanan alkaloids

The racemic synthesis of the common propellane core structure found in various hasubanan alkaloids is reported. The successful completion hinged upon the stereocontrolled construction of the cis-substituted heterobicycle as a precursor for the intramolecular Dieckmann condensation. A novel strategy is introduced for the facile hydrolysis of a sterically demanding carboxamide under a mild condition. The 2-nitroanilide obtained by the Goldberg arylation of a carboxamide with 2-iodonitrobenzene was readily converted to the corresponding ester derivative by way of N-acylbenzotriazole. We expect that the reported synthetic route will allow the synthesis of a series of hasubanan alkaloids starting from the correspondingly functionalized 2-tetralone derivatives.     

2,2′:6′,2″‐Terpyridines Functionalized with Thienyl Substituents: Synthesis and Applications

This review deals with the synthesis and applications of 2,2′:6′,2″‐terpyridines which are functionalized with thiophene ring, directly linked to the terpyridine core or via a spacer. Two main methodologies were used, ring closure of diketo‐derivatives and cross coupling reactions. The obtained compounds find applications in various fields especially in material sciences such as solar cells or macromolecular sciences.     

Synthesis of a β-strand mimetic based on a pyridine scaffold

A synthetic route to a 2,4-disubstituted pyridine as a potential β-strand mimetic has been developed and applied in the synthesis of a tripeptidomimetic of Leu-Gly-Gly. The pyridine scaffold replaces the central glycine, and is substituted with analogues of leucine and glycine in positions 4 and 2, respectively. 2-Fluoro-4-iodopyridine was chosen as the functionalized scaffold and was substituted with protected leucinal in position 4 via a Grignard exchange reaction using iso-propyl magnesium chloride. The glycine moiety was introduced in position 2 via a nucleophilic aromatic substitution reaction (S_NAr) facilitated by microwave irradiation. The synthetic sequence involved 12 steps with an overall yield of 7%.     

Rapid and stereocontrolled synthesis of racemic and optically pure highly functionalized pyrrolizidine systems via rearrangement of 1,3-dipolar cycloadducts derived from 2-azetidinone-tethered azomethine ylides

This work describes a convenient procedure for the straightforward preparation of polyfunctionalized enantiopure pyrrolizidine systems. The methodology capitalizes on a HCl(g)-promoted reaction of the 1,3-dipolar cycloadducts derived from 2-azetidinone-tethered azomethine ylides, smoothly affording different types of highly functionalized bi- and tricyclic systems in racemic and optically pure forms. This process involves a selective bond cleavage of the four-membered ring, followed by a rearrangement under the reaction conditions. The synthetic route employed was shown to be compatible with a variety of 4-oxoazetidine-2-carbaldehydes, alpha-amino esters, or dipolarophiles, offering a versatile entry to pyrrolizidine systems.     

Unprecedented Strong Lewis Bases—Synthesis and Methyl Cation Affinities of Dimethylamino‐Substituted Terpyridines

A versatile method for the synthesis of functionalized 2,2′:6′,2′′‐terpyridines by assembly of the terminal pyridine rings is presented. The cyclization precursors—bis‐β‐ketoenamides—are prepared from 4‐substituted 2,6‐pyridinedicarboxylic acids and acetylacetone or its corresponding enamino ketone. Treatment with trimethylsilyl trifluoromethanesulfonate induces a twofold intramolecular condensation providing an efficient access to 4,4′′‐di‐ and 4,4′,4′′‐trifunctionalized 6,6′′‐dimethyl‐2,2′:6′,2′′‐terpyridines. Using this method, hitherto unknown 4,4′′‐bis(dimethylamino)‐ and 4,4′,4′′‐tris(dimethylamino)terpyridines have been prepared that show remarkably high calculated Lewis basicities.     

Synthesis of 2-(2-methyltetrazol-5-yl)-2,2-dinitroacetonitrile and its reaction with substituted nitrile N-oxides

A procedure of synthesis of 2-(2-methyltetrazol-5-yl)-2,2-dinitroacetonitrile has been developed and its reaction with substituted nitrile N-oxides has been investigated, proceeding by the mechanism of 1,3-dipolar cycloaddition and affording 2-methyl-5-[(1,2,4-oxadiazol-5-yl)(dinitro)methyl]-2H-tetrazoles. The latter react with KOH in ethanol forming the potassium salt of 2-methyltetrazol-5-yldinitromethane and substituted 5-hydroxy-1,2,4-oxadiazoles.