Electrochemical fluorination of N,N-dimethylperfluoroacylamides

The electrochemical fluorination (ECF) of N,N-dimethylperfluoroacylamides gives the corresponding perfluoro-N,N-dimethylacylamides in low yield. With increase of the number of carbon atoms in the perfluoroacyl radical the yield of the required perfluoro-N,N-dimethylacylamides is slightly increased.     

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.     

Polyfluorinated arylnitrosamines

N-Methyl-, N-n-butyl-, N-t-butylperfluoroarylamines undergo nitrosation with nitrous acid to give the corresponding N-nitroso derivatives. Perfluoroaryl groups were selected from the benzene, indane, biphenyl, naphthalene and pyridine series. According to ¹H and ¹⁹F NMR spectra, N-nitroso-N-methyl derivatives of polyfluoroarenes consist of E and Z isomers with the former prevailing. The more bulky n-butyl group promotes an increase in the formation of Z isomers. Only Z isomers have been obtained from N-t-butyl derivatives of perfluorinated 4-toluidine and 4-aminopyridine. The structure of the Z isomer of N-nitroso-N-methylperfluoro-4-toluidine is confirmed by X-ray data.     

An effective C-C double bond formation via Cu(I)-catalyzed dehydrogenation

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.     

Stereoselective radical cyclizations of N-(2-halobenzoyl)-cyclic ketene-N,X(X=O, S)-acetals

2-Alkyloxazolines and 2-alkylthiazolines react with 2-halobenzoyl chlorides to form N-(2-halobenzoyl)-cyclic ketene-N,O-acetals and N-(2-halobenzoyl)-cyclic ketene-N,S-acetals in excellent yields, respectively. These ketene acetals readily undergo stereocontrolled aryl radical cyclizations to afford the central six-membered rings of substituted-2,3,10,10α-tetrahydrooxazolo[3,2-b]isoquinolin-5-ones and their 2,3,10,10α-tetrahydrothiazolo[3,2-b]isoquinolin-5-one analogs. The tertiary N,O- and N,S-radicals formed upon aryl radical reaction at the ketene-N,X(X=O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from both Bu₃SnH and (Me₃Si)₃SiH was investigated. The N,S-heterocyclic fused ring products may have potential medical value.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

Synthesis of N,N-Ac,Boc laurylthio sialoside and its application to O-sialylation

The combination of the 5-N-tert-butoxycarbonyl (Boc) group of laurylthio sialoside and cyclopentyl methyl ether (CPME) as a solvent enhanced the reactivity and α-selectivity of the sialyl donor during sialylation. Selective deprotection of the N-Boc group of sialoside, including an acid-sensitive isopropylidene function, was successfully achieved by Yb(OTf)₃-SiO₂. Transformation of N,N-Ac,Boc into an N-acetylglycolyl group of sialoglycoside was easily performed via selective N-deacylation of the mixed Ac-N-Boc carbamate, subsequent Boc group removal, and acylation.     

DFT study of the reaction sites of N,N′-substituted p-phenylenediamine antioxidants

The geometry of N,N′-diphenyl-p-phenylenediamine (DPPD), N-phenyl-N′-(1′-methylbenzyl)-p-phenylenediamine (SPPD), N-phenyl-N′-(1,3-dimethyl-butyl)-p-phenylenediamine (6PPD), N-phenyl-N′-isopropyl-p-phenylenediamine (IPPD), and N-(1-methyl-1-phenylethyl)-N′-phenyl-p-phenylenediamine (CPPD) as well as of their dehydrogenation products has been optimized at B3LYP/6-31G^∗ level of theory. Our results support the idea of formation of stable ketimine Ph-NC structures (instead of quinonediimine structures) during consecutive dehydrogenation of SPPD, 6PPD, and IPPD antioxidants despite the formation of tertiary carbon-centered radicals in the first dehydrogenation step is energetically preferred for SPPD only.     

Helicity of N,N′-diaryl-trans-1,2-diaminocyclohexane derivatives. Implications for molecular helicity manipulations

Derivatives of trans-1,2-diaminocyclohexane (DACH), useful as chiral ligands, scaffolds and building blocks, differ in their conformation. The conformation of N,N′-diaryl-DACH derivatives was studied by the semiempirical and DFT computational methods and by exciton-coupled circular dichroism. It was found that, contrary to M-helical N,N′-diimine, N,N′-diimide and N,N′-diamide derivatives, the aromatic residues in N,N′-diphenyl derivatives are oriented to form a P-helix for the (R,R)-DACH absolute configuration. The helicity of the bis-aryl system is modified in the case of 1-naphthyl or 2-naphthyl derivatives. Further switching of helicity has been demonstrated by either protonation or mono-N-acetylation of N,N′-diaryl DACH derivatives.     

Selective N-debenzylation of amides with p-TsOH

N-Benzylamides were debenzylated efficiently with 4 equiv. of p-TsOH in refluxing toluene. Good to quantitative yields of the desired primary amides were obtained within 2-4 h from a wide variety of N-2,4-dimethoxybenzylamides. N-4-Methoxylbenzyl amides and N-benzylamides were also debenzylated cleanly. In the case of N-2,4-dimethoxylbenzylamides, selective N-debenzylation was possible in the presence of N-Fmoc, N-t-BOC or N-trityl-protection. Protected amino acid amides survived these conditions without any detectable epimerization.     

Ruthenium trichloride catalyzed synthesis of 2,3-unsaturated-N-glycosides via Ferrier azaglycosylation

An efficient, economical and mild protocol for the synthesis of 2,3-unsaturated-N-glycosides has been developed using ruthenium(III) chloride. The Ferrier azaglycosylation of glycals with various N-nucleophiles such as sulfonamides, benzamides, carbamates and N-substituted sulfonamides proceeded smoothly to afford the corresponding 2,3-unsaturated-N-glycosides or ‘N-pseudoglycals’ in good yields (64–98%). High α-anomeric selectivity was observed with N-substituted sulfonamides such as N-benzyl or N-phenyl sulfonamides under similar conditions.     

Synthesis and network structure of ionic poly(N,N-dimethylacrylamide-co-acrylamide) hydrogels: Comparison of swelling degree with theory

At four different charge densities, ionic hydrogels based on N,N-dimethylacrylamide (DMAAm), acrylamide (AAm), and itaconic acid (IA) were synthesized by free-radical cross-linking copolymerization in water with N,N-methylenebis(acrylamide) (BAAm) as the cross-linker, ammonium persulfate (APS) as the initiator, and N,N,N′,N′-tetramethylenediamine (TEMED) as the activator. The swelling behaviors of these hydrogels were analyzed in buffer solutions at various pH. It was observed that the swelling behavior of cross-linked ionic poly(N,N-dimethylacrylamide-co-acrylamide) [P(DMAAm-co-AAm)] hydrogels at different pHs agreed with the modified Flory-Rehner equation based both on the phantom network and affine network models and the ideal Donnan theory. In addition, the kinetics of swelling of the hydrogels was studied in pH 2, 5 and 9 buffer solutions. The swelling curves exhibited the characteristic features of transport process, apparently the Fickian diffusion of fast rates.     

Rapid and efficient microwave-assisted synthesis of 5-amino-3-aralkoxy(methoxy)amino-1,2,4-oxadiazoles

The microwave-assisted synthesis of 5-amino-3-aralkoxy(methoxy)amino-1,2,4-oxadiazoles starting from N¹-aralkoxy-(methoxy)-N³-cyano-O-phenylisoureas and hydroxylamine is described. N¹-Aralkoxy(methoxy)-N³-cyano-O-phenylisoureas are readily accessible by treatment of diphenyl N-cyanimidocarbonate with O-substituted hydroxylamines.     

PTSA catalyzed straightforward protocol for the synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles in PEG

An efficient PTSA catalyzed synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles has been described using S-ethylated-N-acylthioureas as substrates and polyethylene glycol as solvent.     

Selective O-acylation of unprotected N-benzylserine methyl ester and O,N-acyl transfer in the formation of cyclo[Asp-Ser] diketopiperazines

The synthesis of two diastereomeric cyclo[Asp-N-Bn-Ser] diketopiperazines (2a and 2b) was investigated. Initial formation of the Boc-aspartyl-N-benzyl serine isopeptide methyl esters (4a and 4b) was observed, which derive from the selective O-acylation of unprotected (S)- or (R)-N-benzylserine. This unexpected O-acylation is preferred over the formation of the tertiary amide and the resulting ester bond is stable in solution to O,N-acyl transfer. The O,N-acyl migration is then triggered by cleavage of the Boc protecting group and treatment with base, which also promotes immediate cyclization to the diketopiperazines.     

Photoacid generators (PAGs) based on N-acyl-N-phenylhydroxylamines for carboxylic and sulfonic acids

Simple and efficient photoacid generators (PAGs) for carboxylic and sulfonic acids based on N-acyl-N-phenylhydroxylamines have been demonstrated. Irradiation of o-carboxylates and thermally rearranged o-arenesulfonates of N-acyl-N-phenylhydroxylamines using UV light (≥254 nm) in aqueous methanolic solution resulted in efficient generation of carboxylic and sulfonic acids, respectively. The carboxylic acid generation ability of N-acyl-N-phenylhydroxylamines was found to be dependent on their N-acyl substituents. Further, polymer bearing o-arenesulfonates of N-acyl-N-phenylhydroxylamine was synthesized and demonstrated as PAG for sulfonic acids.     

N,N′,N″-Tri-Boc-guanidine (TBG): a common starting material for both N-alkyl guanidines and amidinoureas

In this Letter, we describe the unexpected reaction pattern of N,N′N″-tri-Boc-guanidine (TBG) with amines at room temperature and under reflux conditions affording N-substituted guanidines and amidinoureas, potentially important compounds with extensive applications in medicinal chemistry. This investigation shows that TBG is an excellent, readily available common starting material for the synthesis of various N-alkyl guanidines as well as N-alkyl-N′-substituted amidinoureas by simply manipulating the reaction conditions.     

Catalytic photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine and carbon dioxide

Photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine (TMB) in MeCN under bubbling of CO₂ proceeded with high catalytic efficiency, giving 3,3-diphenylacrylic acid (DPA) and 3-hydroxy-3,3-diphenylpropionic acid (20). The turnover number (TON=(DPA+20)/TMB) reached 17. Similarly, 1-phenyl-1-cyclohexene yielded cis-2-acetamido-2-phenylcyclohexanecarboxylic acid with TON 5.9. As compared with related N,N-dimethylaniline derivatives, TMB is more resistant to photodecomposition, has the much larger absorbance in the S₀→S₁ transition, and has the lower quenching efficiency by CO₂. Probably these factors are partly responsible for the high TON observed for TMB.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

Antibacterial activity of N-quaternary chitosan derivatives: Synthesis, characterization and structure activity relationship (SAR) investigations

Quaternary N-(2-(N,N,N-tri-alkyl ammoniumyl and 2-pyridiniumyl) acetyl) derivatives of chitosan polymer, chitooligomer, and glucosamine (monomer) were synthesized for the purpose of investigating the structure activity relationship (SAR) for the antibacterial effect. Novel methods were used in the synthesis. The final chitosan and chitooligomer derivatives could thus be obtained in two steps without prior protection of the hydroxyl groups. However, in order to obtain chitosan derivatives with the bulky N,N-dimethyl-N-dodecyl- and N,N-dimethyl-N-butyl side chains three steps were needed, starting from 3,6-O-di-tert-butyldimethylsilyl chitosan (3,6-O-di-TBDMS chitosan) as the key intermediate. The quaternary ammoniumyl acetyl derivatives of glucosamine were synthesized from glucosamine or tetra-O-acetylglucosamine. N,N,N-trimethyl chitosan (TMC) was used as reference compound for investigation of antibacterial activity. Clinical Laboratory Standard Institute (CLSI) protocols were used to determine MIC and MLC for activity against clinically important Gram-positive strains Staphylococcus aureus (ATCC 25923), and S. aureus (MRSA) (ATCC 43300), and Gram-negative strains of Escherichia coli (ATCC 25922), P. aeriginosa (ATCC 27853) and Enterococcus facialis (ATCC 29212). The MIC values for the compounds ranged from 8 to ?8192 mg/L. In general the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitooligomer and glucosamine monomer were more active against bacteria than derivatives with shorter alkyl chains. In contrast the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitosan were less active than derivatives with N-(2-N,N,N-trimetylammoniumyl) acetyl or N-(2-(N-pyridiniumyl) acetyl) quaternary moiety. N,N,N-trimethyl chitosan (TMC) was the most active compound in this study.