A general and convenient synthesis of N-aryl piperazines

A general and convenient synthesis of N-aryl piperazines from bis(2-chloroethyl)amine hydrochloride and a broad range of anilines in diethylene glycol monomethyl ether is described.     

A new and convenient synthesis of 13,16-diazaestrone analogs

Imidazolidine-2,4-dione was chemoselectively N-alkylated at the imidic NH with several 2-(3,4-dihydro-1-naphthalenyl)ethyl-4-methylphenylsulphonates to give the corresponding imides for the first time which on selective reduction at one of the carbonyl groups followed by cyclization in PPA gave the corresponding title compounds.     

A convenient method for the synthesis of N-hydroxyureas

Treatment of amines with 1-(4-nitrophenol)-N-(O-benzylhydroxy)carbamate yields the O-benzyl protected N-hydroxyureas. Hydrogenation of the O-benzyl protected N-hydroxyureas over 5% Pd/BaSO₄ cleanly gives the N-hydroxyureas in good yield. In addition to primary and secondary aliphatic and aromatic amines, this method converts amino sugars to the corresponding N-hydroxyureas without extensive protecting group chemistry.     

A convenient synthesis of iminosugar-C-glycosides via organometallic addition to N-benzyl-N-glycosylhydroxylamines

N-Benzyl-N-glycosylhydroxylamines were prepared in very good yield via condensation of furanoses and pyranoses with N-benzylhydroxylamine at 110°C for 30 min under solvent-free conditions. These anomeric sugar-hydroxylamines exist in equilibrium with the open-chain nitrone form. In fact upon treatment with various organometallic reagents, the corresponding adducts were obtained with good to high diastereoselectivity. These adducts were converted into iminosugar-C-glycosides by reductive dehydroxylation and intramolecular cyclization.     

A convenient synthesis of the core trisaccharide of the N-glycans

A convenient synthesis of the core trisaccharide of the N-glycans was described. Orthogonal one-pot glycosylation of three monosaccharide building blocks was performed to furnish β-glucosyl chitobiose, which was then transformed to β-mannosyl chitobiose by intramolecular epimerization of the C-2 position of the β-glucoside. The key glucosyl donor 7c with differentiated 2,3-OH was prepared following the 4,6-O-benzylidene-protected 1,2-orthoester strategy.     

Application of directed metalation in synthesis. Part 4: Expedient synthesis of substituted benzo[b]thiophene and naphthothiophene

A short, simple and inexpensive synthesis of several diversely substituted benzo[b]thiophenes and one naphthothiophene is described. The method involves introduction of methylsulfanyl group ortho- to the amide function of readily available N,N-diethylamides of aryl carboxylic acid by directed metalation. Thioindoxyls, obtained in high yields through side-chain deprotonation and cyclisation in one pot, are reduced to benzo[b]thiophene or napthothiophene.     

N-ferrocenoyl benzotriazole: A convenient tool for the synthesis of ferrocenoyl esters

A new synthesis methodology has been presented for the preparation of the ferrocenoyl esters. Ferrocene carboxylic acid was derivatized using direct 1H-benzotriazole/SOCl₂ methodology to prepare N-ferrocenoyl benzotriazole as a convenient tool for the functionalization of ferrocene ring. N-ferrocenoyl benzotriazole was reacted with alcohols in mild conditions to prepare ferrocenoyl esters in high purity and in good yield. The solid state structure of benzyl-1-ferrocenoate, 2f, has also been determined by X-ray crystallography. In the crystal structure, intermolecular C-H···O hydrogen bonds link the molecules into a two-dimensional network. The π···π contacts between the cyclopentadiene rings and cyclopentadiene and phenyl rings, [centroid-centroid distances = 3.296(1) and 3.750(1) Å] may further stabilize the structure. Two weak C-H···π interactions are also found.     

A convenient synthesis of 3,3,3-trifluoroalanine derivatives

A one-pot synthesis of N-substituted 3,3,3-trifluoroalanine esters from alkyl trifluoropyruvates and carboxamides or substituted ureas was developed.     

A convenient and efficient method for the synthesis of mono- and N,N-disubstituted thioureas

A convenient method for the synthesis of mono- and N,N-disubstituted thioureas by the debenzoylation of N-substituted- and N,N-disubstituted-N′-benzoylthioureas with hydrazine hydrate under solvent-free conditions has been developed. N-Substituted-N′-benzoylthioureas and hydrazine hydrate were mixed, and stirred at room temperature without a solvent to give the corresponding N-substituted thioureas in high yields.     

A convenient microwave-assisted synthesis of N-glycosyl amino acids

Optimization of coupling reactions of glycosylamines with Fmoc-protected aspartic acid, by microwave approach, is described. Different reaction conditions, quantities of substrates and solvents were tested to develop simple and reproducible methodologies. The best results were obtained using new triazine-based coupling reagents with a monomode microwave Discover® BenchMate™ instrument (CEM). The N-glycosyl amino acids were then deprotected to achieve final products for SPPS.     

A novel strategy for the solid-phase synthesis of cyclic lipodepsipeptides

A rapid and efficient Fmoc solid-phase synthesis of cyclic lipodepsipeptide analogue 1 to antibiotic fusaricidin A is described. Our synthetic approach includes resin attachment of the first amino acid via side chain, successful use of combination of four quasi-orthogonal removable protecting groups, stepwise solid-phase synthesis of linear peptide analogue, lipid tail attachment followed by depsipeptide bond formation and on-resin head-to-tail cyclization. Undesired O→N acyl shift, which may occur during Fmoc removal, was successfully avoided by the incorporation of the lipid tail into the linear peptide precursor prior to on-resin depsipeptide bond formation and the ring closure.     

A practical synthesis of 2-(N-substituted)-aminobenzimidazoles utilizing CuCl-promoted intramolecular cyclization of N-(2-aminoaryl)thioureas

A practical protocol for synthesis of 2-(N-substituted)-aminobenzimidazoles was developed. N-(2-Aminoaryl)thioureas undergo a CuCl-promoted intramolecular cyclization to give the corresponding 2-(N-substituted amino)benzimidazoles in good to excellent isolated yields.     

3-Halomethylated cyclic nitronates: synthesis and nucleophilic substitution

A method for the introduction of a halogen atom into the methyl group attached to the C-3 atom of five- and six-membered cyclic nitronates (isoxazoline N-oxides and oxazine N-oxides, respectively) has been studied. The process involves silylation of starting 3-methyl-substituted cyclic nitronates followed by halogenation of the resulting N-(silyloxy)enamines. While five- and six-membered cyclic enamines behave similarly toward elemental bromine and iodine, their reactions with NBS give different products, that were rationalized by stereoelectronic effects. The obtained halogenated nitronates were coupled with various nucleophiles affording new nitronates functionalized at the C-3 position.     

A convenient synthesis of 5-arylamino-4H-pyran-4-ones using palladium-catalyzed amination

A concise approach to 5-arylamino-4H-pyran-4-ones is described via palladium-catalyzed amination reaction. The methodology involved in this Letter is based on protection/deprotection protocols and on manipulation of the 5-hydroxy group of readily available kojic acid. It would provide a new entry to a range of 5-arylamino-4H-pyran-4-ones via Buchwald-Hartwig-type amination reaction on 4H-pyran-4-one unit.     

Mild, convenient and versatile Cu-mediated synthesis of N-aryl-2-imidazolidinones

A mild, general, convenient and practical methodology for the selective copper-mediated mono N-arylation of unprotected 2-imidazolidinone was developed. Strong electron-donating groups and free hydroxy and amino groups on the aryl iodide substrates were well tolerated. The use of n-butanol as the solvent for the copper-catalysed mono-arylation of 2-imidazolidinone is unprecedented.     

A mild high yielding synthesis of oxazole-4-carboxylate derivatives

Several 2,5-disubstituted oxazole-4-carboxylates were prepared in high yields from the methyl esters of N-acyl-β-halodehydroaminobutyric acid derivatives by treatment with a 2% solution of DBU in acetonitrile. The scope of this reaction was investigated and it was found that dehydrodipeptides having a β-bromodehydroaminobutyric acid residue gave the corresponding oxazoles in good yields. The photophysical properties of some of the oxazoles prepared were studied in four solvents of different polarity. All compounds have reasonable high fluorescence quantum yields and a moderate solvent sensitivity, which makes them good candidates to be used as fluorescent probes. One of the fluorescent oxazoles prepared was inserted after cleavage of the methyl ester into two model peptides using a conventional solution phase strategy. The photophysical properties of the labelled peptides were studied in ethanol and water and compared with those of the oxazole. The results obtained showed that the oxazole maintains a good fluorescence level and the same solvent sensitivity when linked to a peptide chain.     

An efficient synthesis of highly substituted pyrroles from β-oxodithiocarboxylates

α-Oxoketene-N,S-acetals, prepared by the reaction of alkyl glycinate hydrochlorides with β-oxodithiocarboxylates followed by alkylation, underwent cyclization in presence of chloromethyleneiminium salt derived from POCl₃/DMF to afford alkyl-3-aryl-4-formyl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates in excellent yields. Alkyl-3-aryl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates were formed in moderate yields when the same N,S-acetals were treated with DBU.     

A one-pot synthesis of substituted salicylnitriles

Phenols were converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and subsequent treatment with aqueous ammonia gave the corresponding imines which were oxidized with IBX to the desired salicylnitriles. The sequence of reactions was conveniently carried out as a one-pot procedure under mild conditions.     

A convenient transformation of α-alkylserines into α-halogenomethyl-α-alkylglycines

An efficient and facile synthesis of N-Boc-α-chloromethyl- and α-bromomethyl-α-alkylglycines is reported that involves cyclization of N-Boc-α-alkylserines to the corresponding β-lactones under Mitsunobu reaction conditions, followed by ring opening with anhydrous MgCl₂ or MgBr₂.     

N-(Diethoxyphosphoryl)-O-benzylhydroxylamine—a convenient substrate for the synthesis of N-substituted O-benzylhydroxylamines

Easily available N-(diethoxyphosphoryl)-O-benzylhydroxylamine was shown to be convenient, orthogonally protected substrate for regioselective N-alkylation by means of diverse halides under basic conditions (sodium hydride/tetrabutylammonium bromide). An efficient procedure for dephosphorylation of N-substituted N-(diethoxyphosphoryl)-O-benzylhydroxylamine to provide N-substituted O-benzylhydroxylamines was also established.