Electrosynthesis of azopyrazoles via the oxidation of N-alkylaminopyrazoles on a NiO(OH) anode in aqueous alkali – A green method for N-N homocoupling

A nickel oxyhydroxide [NiO(OH)] anode was exploited to develop a new synthetic route for the electrocatalytic N-N homocoupling of N-alkylaminopyrazoles in an alkaline aqueous medium. The advantages of this green electrochemical methodology include low cost, atom economy and high yields.     

Gewald-type reaction of double activated 2,3-diarylcyclopropanes with elemental sulfur for synthesis of polysubstituted 2-aminothiophenes

A new synthetic procedure for the polysubstituted 2-aminothiophenes was developed via Gewald type ring-opening reaction of 1,1-dicyano-2,3-diarylcyclopropanes with elemental sulfur in N,N-dimethylformamide in the presence of morpholine as base.     

Synthesis of polyfunctionalized methylphosphine oxides

N,N-Dialkylamino(diphenylphosphoryl)chloromethanes, a new type of organophosphorus compounds, were synthesized. On dissolving in polar and low polar solvents, N,N-dialkylamino(diphenylphosphoryl)chloromethanes dissociate spontaneously with the P??C bond cleavage to form the diphenylphosphinite anion Ph₂PO^?. This was confirmed by the reaction of N,N-dimethylamino(diphenylphosphoryl)chloromethane with electrophilic substrates to form the corresponding addition or substitution products of Ph₂PO^?. The capability of spontaneous generating the diphenylphosphinite anion considers accessible N,N-dimethylamino(diphenylphosphoryl)chloromethane as a synthetic equivalent of the diphenylphosphinite anion.     

N-phosphorylation of pyrroles: An intramolecular migration reaction

A new synthetic method is reported for the N-phosphorylation of pyrroles via intramolecular migration of a phosphonate diester group. The reaction proceeds under mild conditions and produces N-phosphorylated pyrrole derivatives in moderate to good yields.     

Synthesis of new mono-N-tosylated diamine ligands based on (R)-(+)-limonene and their application in asymmetric transfer hydrogenation of ketones and imines

A synthetic procedure leading to the preparation of a new family of enantiopure mono-N-tosylated-1,2-diamines derived from (R)-(+)-limonene is described. (+)-Limonene was transformed into the appropriate N-tosyl derivative using N-tosylaziridination based on chloramine-T trihydrate. Subsequent ring opening by sodium azide afforded the corresponding isomeric azides. Finally, reduction of the azide function gave enantiomerically pure mono-N-tosylated-1,2-diamines. The ligands obtained proved to be effective in the asymmetric transfer hydrogenation protocol on aromatic ketones and imines.     

Joined use of oxazolidinone and desymmetric amino protection: a new strategy for protection of glucosamine

Joined use of N-benzyl oxazolidinone and N-benzyl-N-benzyloxycarbonyl (N-BnCbz) desymmetric amino-protecting function is reported. The new synthetic approach enables the facile preparation of type 1 and type 2 LacNAc disaccharides in satisfactory yields. One-pot deprotection of N-BnCbz and O-benzyl ether is achieved by hydrogenolysis under mild conditions.     

Chemistry of indoles carrying a basic function. Part 8: A new approach to the ergoline skeleton

Starting from N-pivaloyl-Uhle's ketone a new synthetic approach to the ergoline skeleton has been elaborated. Ring D of the tetracyclic skeleton was formed by an intramolecular Dieckmann-condensation of a diester, obtained in a Reformatsky reaction of a properly substituted derivative of N-pivaloyl Uhle's ketone followed by elimination of water.     

New synthetic technology for the construction of N-hydroxyindoles and synthesis of nocathiacin I model systems

A new synthetic method providing expedient access to a wide range of polyfunctionalized N-hydroxyindoles (IV) is reported. These unique constructs are assembled by nucleophilic additions to in situ generated α,β-unsaturated nitrones (III) through carbon-carbon and carbon-heteroatom bond formation. The new synthetic technology was applied to the synthesis of nocathiacin I (1) model systems (2 and 3a-c) containing the N-hydroxyindole structural motif.     

Towards Asymmetrical Methylene Blue Analogues: Synthesis and Reactivity of 3-N′-Arylaminophenothiazines

The search for new ways to obtain analogues of the well-known Methylene Blue dye is an important synthetic task. Herein, we proposed and developed an approach to the synthesis of 3-N′-arylaminophenothiazines and asymmetrical 3,7-di(N′-arylamino)phenothiazines. This approach included the optimization of synthetic strategy by quantification analysis of the positive charge distribution in the cation of 3-N′-arylaminophenothiazine derivative. The obtained experimental data are confirmed by DFT studies. Two synthetic routes for asymmetrical phenothiazine diarylamino derivatives were suggested and verified. The developed convenient and versatile synthetic approach makes it easy to obtain aromatic Methylene Blue isostructural analogues with various substituents. As a result, a series of novel 3-N′-arylaminophenothiazines and asymmetrical 3,7-di(N′-arylamino)phenothiazines containing ester, tert-butoxycarbonyl, sulfonic acid, hydroxyl and amine groups were obtained in high yields.     

Stereoselective synthesis of azasugars by electrochemical oxidation

A new method using electrochemical oxidation has been exploited for the stereoselective synthesis of 2,3,6-trihydroxylated 5S-piperidine derivatives. The electrochemical method was successively used for the conversion of N-protected piperidines to N-protected 1-methoxypiperidines and for the conversion of 1-methoxy-2,3-didehydropiperidine derivatives to 1,2,3-triacetoxypiperidine derivatives. The method provided a new synthetic route to 2S,3S,6-triacetoxy-5S-methylpiperidine and 2R,3R,6-triacetoxy-5S-methylpiperidine.     

Enantioselective synthesis of (S)-N,N-diethyl-2-formyl-2-(methoxymethoxy)butyramide,a key intermediate for 20(S)-camptothecin analogues,via asymmetric bromolactonization

A new enantioselective synthetic method for enantiomerically pure (S)-N,N-diethyl-2-formyl-2-(methoxymethoxy)butyramide 5, a versatile key intermediate has been developed employing asymmetric bromolactonization using (S)-proline as the chiral auxiliary.     

Selectivity between N-1 and N-7 nucleosides: regioselective synthesis of BMK-Y101, a potent cdk7 and 9 inhibitor

BMK-Y101 is a new pyrrolo[2,3-d]pyrimidine-based potent cdk7 and 9 inhibitor, which is characterized by an intriguing structural feature of N-1 nucleoside, departing from previously reported N-7 nucleoside Cdk inhibitor, xylocydine. Though N-1 nucleosides have appeared in the literature, they have often been considered as kinetic products and thus intermediates of N-7 glycosylation. In the course of the synthetic studies of xylocydine derivatives, we have developed a highly regioselective method to obtain the N-1 nucleoside. The origin of the selectivity is apparently based on the reactivity of the silylated nucleobase and the stability of the resulting N-1 nucleoside. The choice of BSA as a silylating agent was critical in securing the N-1 nucleoside, BMK-Y101. On the other hand, proper selection of reaction conditions promoting transglycosylation provides an efficient route to N-7 nucleosides.     

Expeditious synthesis of sulfoazetidine spiro-C-glycosides from ketose acetals

Pyranoid and furanoid spiro-N-mesyl azetidines, a new type of water-soluble spiro-C-nucleoside, have been prepared from easily available sugar spiroacetals (or glycosyl cyanides). The synthetic pathway involves opening of the acetalic ring with trimethylsilylcyanide, reduction, formation of an N,O-dimesylate, cyclization with sodium hydride in anhydrous DMF, and O-deprotection.     

Behaviour of enaminomalonates and enamidomalonates under various reductive conditions: a novel synthetic approach to N-acetyl-N-aryl β-amino acids

The behaviour of enaminomalonates and their deprotection to amines under various reductive conditions is described. A new synthetic approach to N-aryl-N-acetyl-β-amino acids using heterogeneous catalytic hydrogenation has been discovered.     

Efficient one-pot synthesis of 1-alkoxy-2-arylaminoimidazolines from N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides and arylisothiocyanates

A new synthetic approach towards 1-alkoxy-2-aminoimidazolines that uses N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides as nucleophile reagents for the reaction with isothiocyanates is reported. Hence, the synthesis of 1-alkoxy-2-aminoimidazolines was performed in high yield with a one-pot procedure involving thiourea formation, nosyl group removal and spontaneous cyclization (42-77% overall yield).     

Facile synthesis of C-phosphanylformamidines via a carbene pathway

A direct synthetic approach to C-phosphanyl-N,N-dialkyl-N′-aryl(alkyl)-formamidines was developed. It was shown that phosphorylation of the formamidines proceeds at the nitrogen atom affording N-phosphanylformamidinium salts. Upon deprotonation, these salts gave C-phosphanylformamidines via formation of carbenes followed by a 1,2-phosphorus shift.     

Synthesis of bioactive 1-alkyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-diones and N-aryl-2-aminomethylene-1,3-indanediones using water as the solvent

Through a [2+3] cycloaddition reaction, a new environmentally friendly method was developed to enable the synthesis of bioactive 1-alkyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-diones and N-aryl-2-aminomethylene-1,3-indanediones using water as the solvent with good yields and minimum requirement of purification. This new green synthetic protocol is simple and suitable for scale-up synthesis.     

Rhodium-catalysed synthesis of fused pyrimidine derivatives employing N-sulfonyl-1,2,3-triazoles as a 1-aza-[4C] synthon

A new synthetic application of N-sulfonyl-1,2,3-triazoles acting as a 1-aza-[4C] synthon via the 1,2-shift reaction of an α-imine rhodium carbene was developed for the synthesis of fused pyrimidine derivatives. The high reactivity of the strained three-membered 2H-azirine ring facilitated the unusual cyclization of electron-deficient dienes with electron-deficient dienophiles. The compatibility was good with common functionalities tolerated. Excellent chemoselectivity was observed, and no reactions occurred between the rhodium carbene and 2H-azirine. The products could be converted into seven-membered multi-functionalized 1H-1,4-diazepine derivatives, illustrating the potential application of the protocol in medium-sized N-heterocycle synthesis.     

Multiblock copolymer synthesis via controlled radical polymerization in aqueous dispersions. Part 1: Synthesis of S-tert-alkyl-N,N-alkoxycarbonylalkyldithiocarbamates

In a novel two- or three-step synthetic route, S-(1,4-phenylenebis(propane-2,2-diyl)) bis(N-methyldithiocarbamate) is reacted at low temperature with various alkyl chloroformates to form various S-tert-alkyl-N,N-alkoxycarbonylmethyl-dithiocarbamate RAFT agents. Also an alternative and novel synthetic route towards S-(1,4-phenylenebis(propane-2,2-diyl)) bis(N-methyldithiocarbamate), is proposed.     

Interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines—a pathway to new sterically hindered N,N-disubstituted o-aminophenols

The interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines has been studied. The synthetic procedure was developed in order to synthesize a series of new N,N-disubstituted o-aminophenols. The interaction of 3,5-di-tert-butyl-o-benzoquinone with dimethylamine leads to 2-(N,N-dimethylamino)-4,6-di-tert-butyl-phenol, which is oxidized in the reaction medium by the parent 3,5-di-tert-butyl-o-benzoquinone forming spirocompound 4,5′,6,7′-tetra-tert-butyl-3′-methyl-3′H-spiro[1,3-benzodioxol-2,2′-[1,3]benzoxazole].