Vinylogous N,N-dimethylaminomethylenation of 3-[(1-substituted)ethylidene]-oxindoles with N,N-dimethylformamide dimethylacetal

An efficient stereoselective synthesis of various 3-(3-dimethylaminoprop-2-enylidene)oxindoles has been disclosed. The compounds were synthesized via a vinylogous N,N-dimethylaminomethylenation at the γ-position of 3-[(1-substituted)ethylidene]oxindoles with DMF-DMA.     

Synthesis of N,N-dialkylaminobenzonitriles and halo-(N,N-dialkyl)benzamidines by reaction of halobenzonitriles with lithium amides

3- and 4-N,N-Dialkylaminobenzonitriles and 4-chloro-(N,N-dialkyl)benzamidines were isolated by reacting 4-chlorobenzonitrile with hindered lithium amides under thermodynamic (0 °C) and kinetic control conditions (−78 °C), respectively. As previously reported, a benzyne mechanism seems to be confirmed since N,N-dialkylaminobenzonitriles are formed. Only benzamidines were isolated in fair to high yields at both 0 °C and −78 °C with non-hindered lithium amides. Exploitation and mechanistic rationale of the reaction of different halobenzonitriles are also reported.     

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.     

Synthesis and characterization of a tetraruthenium butterfly cluster containing a quadruply-bridging ligand derived from an N,N′-dipyrid-2-ylurea

The tetraruthenium cluster complex [Ru₄(μ₄-κ⁴-dmpu)(CO)₁₀], H₂dmpu = N,N′-bis(6-methylpyrid-2-yl)urea, has been prepared by treating [Ru₃(CO)₁₂] with H₂dmpu in toluene at reflux temperature. An X-ray diffraction study has determined that this cluster has a butterfly metallic skeleton hold up by a doubly-deprotonated N,N′-bis(6-methylpyrid-2-yl)urea ligand (dmpu). This ligand has the pyridine N atoms attached to the wing-tip Ru atoms and the amido N atoms spanning Ru-Ru wing-edges, in such a way that the cluster has C₂ symmetry. The donor atoms of doubly-deprotonated N,N′-dipyrid-2-ylureas seem to be appropriately arranged to hold butterfly tetranuclear clusters.     

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.     

Direct glycan structure determination of intact N-linked glycopeptides by low-energy collision-induced dissociation tandem mass spectrometry and predicted spectral library searching

Intact glycopeptide MS analysis to reveal site-specific protein glycosylation is an important frontier of proteomics. However, computational tools for analyzing MS/MS spectra of intact glycopeptides are still limited and not well-integrated into existing workflows. In this work, a new computational tool which combines the spectral library building/searching tool, SpectraST (Lam et al. Nat. Methods2008, 5, 873–875), and the glycopeptide fragmentation prediction tool, MassAnalyzer (Zhang et al. Anal. Chem.2010, 82, 10194–10202) for intact glycopeptide analysis has been developed. Specifically, this tool enables the determination of the glycan structure directly from low-energy collision-induced dissociation (CID) spectra of intact glycopeptides. Given a list of possible glycopeptide sequences as input, a sample-specific spectral library of MassAnalyzer-predicted spectra is built using SpectraST. Glycan identification from CID spectra is achieved by spectral library searching against this library, in which both m/z and intensity information of the possible fragmentation ions are taken into consideration for improved accuracy. We validated our method using a standard glycoprotein, human transferrin, and evaluated its potential to be used in site-specific glycosylation profiling of glycoprotein datasets from LC-MS/MS. In addition, we further applied our method to reveal, for the first time, the site-specific N-glycosylation profile of recombinant human acetylcholinesterase expressed in HEK293 cells. For maximum usability, SpectraST is developed as part of the Trans-Proteomic Pipeline (TPP), a freely available and open-source software suite for MS data analysis.     

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.     

Synthesis of N,N-diethyldithiocarbamate functionalized 1,4-polyisoprene, from natural rubber and synthetic 1,4-polyisoprene

N,N-Diethyldithiocarbamate functionnalized 1,4-polyisoprenes were prepared from 1,4-polyisoprenes (natural or synthetic). The syntheses were performed by nucleophilic addition of N,N-diethyldithiocarbamate salts upon oxirane rings of epoxidized units according to a SN2 mechanism with ring opening. Studies on model molecules of epoxidized 1,4-polyisoprene units (1,2-epoxy-1-methylcyclohexane and 4,5-epoxy-4-methyloctane) were previously achieved to develop the procedure. The best yields were obtained at low temperature in polar medium, and more especially in water with sodium N,N-diethyldithiocarbamate (DEDT-Na) as reagent. A diastereospecific addition was noted when reaction was performed in water with DEDT-Na. Afterwards, the developed procedure was successfully generalized to epoxidized synthetic polyisoprenes and epoxidized natural rubber (in THF, then in latex medium). Excellent results were obtained in latex medium with epoxidized natural rubber (ENR) latices. As with the models, a diastereospecific addition of sodium N,N-diethyldithiocarbamate trihydrate onto epoxidized 1,4-polyisoprene units of ENR was observed at the condition to bring the latex medium to pH 8 before introduction of DEDT-Na. Influence of temperature, drc, and DEDT-Na concentration were successively examined to determine the best conditions of the addition on ENR latices.     

Synthesis of an N-glycan decasaccharide of the hybrid type

A hybrid-type N-glycan decasaccharide GlcNAcMan₇GlcNAc₂ was synthesized from the pentasaccharide GlcNAcMan₂GlcNAc₂ as an advanced intermediate and an acyl-protected pentamannosyl donor. Benzyl mannoside was regioselectively benzoylated and glycosylated at OH-3 and OH-6 with a dimannoside to give the 3,6-branched pentamannoside. Coupling of the two pentasaccharides furnished the target decasaccharide in 60% yield. Deprotection of the base labile functions furnished a hybrid-type N-glycan decasaccharide functionalized for the conjugation with peptides or proteins.     

N,N′-Diisopropyl- and N,N′-dicyclohexylthiourea cadmium(II) complexes as precursors for the synthesis of CdS nanoparticles

Crystals of the cadmium(II) complexes of N,N-diisopropylthiourea and N,N-dicyclohexylthiourea were obtained and their X-ray single crystal structures determined. These complexes are air-stable, easy to prepare and inexpensive and decompose cleanly to give good quality crystalline CdS. The nanoparticles of CdS thus obtained showed quantum confinement effects in their optical spectra, with close to band-edge emission in luminescence experiments. The broad diffraction patterns observed are typical of nanodimensional particles. The variation of concentration of precursor-to-HDA ratio change the isolated materials from spheres to rod-shaped. TEM images showed agglomerates of needle-like plate of particles.     

Structure of N,C,N-chelated organotin(IV) fluorides

The set of starting tri-, di- and monoorganotin(IV) halides containing N,C,N-chelating ligand (L^NCN = {1,3-[(CH₃)₂NCH₂]₂C₆H₃}⁻) has been prepared (1-5) and two compounds structurally characterized ([L^NCNPh₂Sn]⁺I₃⁻ (1c), L^NCNSnBr₃ (5)) in the solid state. These compounds were reacted with KF with 18-crown-6, NH₄F or L^CNnBu₂SnF to give derivatives containing fluorine atom(s). Triorganotin(IV) fluorides L^NCNMe₂SnF (2a) and L^NCNnBu₂SnF (3a) revealed monomeric structural arrangement with covalent Sn-F bond both in the coordinating and non-coordinating solvents, except the behaviour of 3a that was ionized in the methanol solution at low temperature. The products of fluorination of L^NCNSnPhCl₂ (4) and 5 were described by NMR in solution as the ionic hypervalent fluorostannates or the oligomeric species reacting with chloroform, methanol or moisture to zwitterionic monomeric stannate L^NCN(H)⁺SnF₄⁻ (5c), which was confirmed by XRD analysis in the solid state.     

Complexes derived from the copper(II)/succinamic acid/N,N′,N″-chelate tertiary reaction systems: Synthesis,structural and spectroscopic studies

The use of succinamic acid (H₂sucm) in Cu^II/N,N′,N″-donor [2,2′:6′,2″-terpyridine (terpy), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (dmbppy)] reaction mixtures yielded compounds [Cu(Hsucm)(terpy)]_n(ClO₄)_n (1), [Cu(Hsucm)(terpy)(MeOH)](ClO₄) (2), [Cu₂(Hsucm)₂(terpy)₂](ClO₄)₂ (3), [Cu(ClO₄)₂(terpy)(MeOH)] (4), [Cu(Hsucm)(dmbppy)]_n(NO₃)_n·3nH₂O (5^.3nH₂O), and [CuCl₂(dmbppy)]·H₂O (6·H₂O). The succinamate(−1) ligand exists in four different coordination modes in the structures of 1–3 and 5, i.e., the μ₂-κO:κO′:κO″ in 1 and 5 which involves asymmetric chelating coordination of the carboxylato group and ligation of the amide O-atom leading to 1D coordination polymers, the μ₂-κ²O:κO′ in 3 which involves asymmetric chelating and bridging coordination of the carboxylato group, and the asymmetric chelating mode in 2. The primary amide group, either coordinated in 1 and 5, or uncoordinated in 2 and 3, participate in hydrogen bonding interactions, leading to interesting crystal structures. Characteristic IR bands of the complexes are discussed in terms of the known structures and the coordination modes of the Hsucm⁻ ligands. The thermal decomposition of complex 5·3nH₂O was monitored by TG/DTG and DTA measurements.     

Synthesis of N,N-di(arylmethylidene)arylmethanediamines by flash vacuum pyrolysis of arylmethylazides

Flash vacuum pyrolysis of arylmethylazides 7a-d gave 2,4-diazapentadienes 5a-d in high yield (76-92%). The thermal cyclization of 5a-d gave cis-imidazolines 1a-d, further heating or Swern oxidation of 1a-d gave dehydrogenated products, imidazoles 2a-d.     

Influence of N,N,N′,N′-tetraalkyl terephthalamide on isothermal crystallization kinetics and morphology evolution of polypropylene

The influence of N,N,N′,N′-tetraalkyl terephthalamide (TATA) on the isothermal crystallization kinetics of polypropylene (PP) was studied using differential scanning calorimetry (DSC). It was found that TATA shows a heterogeneous nucleation effect and leads to the formation of β-PP. TATA can not only shorten the crystallization time but also heighten the crystallization temperature of PP. The crystallization rate constant of PP containing TATA is larger than that of pure PP. The evolution of crystalline morphology of PP was investigated on a polarized optical microscopy (POM) equipped with a hot stage and the results showed that the introduction of TATA into PP can quicken the crystallization of PP, which is consistent with DSC results. TATA also leads to a substantial decrease in the spherulite size of PP and the boundaries of spherulites are hardly distinguished.     

A facile procedure for synthesis of 3-[2-(N,N-dialkylamino)ethyl]-3-fluorooxindoles by direct fluorination of N,N-dialkyltryptamines

A practical procedure for the synthesis of 3-fluorooxindole derivatives having basic amine moieties was developed, which involves Selectfluor™-mediated oxidative fluorination of N,N-dialkyltryptamines in the presence of Lewis acid. This procedure was applied to an antimigraine drug, rizatriptan, to afford the corresponding 3-fluorooxindole, which is a potential fluorine-containing drug candidate.     

N,N,N,N-Tetramethyl-1,3-propanediamine as the catalyst of choice for the Baylis-Hillman reaction of cycloalkenone: rate acceleration by stabilizing the zwitterionic intermediate via the ion-dipole interaction

N,N,N^′,N^′-Tetramethyl-1,3-propanediamine (TMPDA) can be used as an efficient catalyst for the Baylis-Hillman reaction of cycloalkenones. The increased reaction rate was thought be derived from the stabilizing effect of the zwitterionic intermediate via the ion-dipole interaction.     

Synthesis, characterization and Schlenk equilibrium studies of methylmagnesium compounds with O- and N-donor ligands - the unexpected behavior of [MgMeBr(pmdta)] (pmdta = N,N,N′,N″,N″-pentamethyldiethylenetriamine)

MgMe₂ (1) was found to react with 1,4-diazabicyclo[2.2.2]octane (dabco) in tetrahydrofuran (thf) yielding a binuclear complex [{MgMe₂(thf)}₂(μ-dabco)] (2). Furthermore, from reactions of MgMeBr with diglyme (diethylene glycol dimethyl ether), NEt₃, and tmeda (N,N,N′,N′-tetramethylethylenediamine) in etheral solvents compounds MgMeBr(L), (L = diglyme (5); NEt₃ (6); tmeda (7)) were obtained as highly air- and moisture-sensitive white powders. From a thf solution of 7 crystals of [MgMeBr(thf)(tmeda)] (8) were obtained. Reactions of MgMeBr with pmdta (N,N,N′,N″,N″-pentamethyldiethylenetriamine) in thf resulted in formation of [MgMeBr(pmdta)] (9) in nearly quantitative yield. On the other hand, the same reaction in diethyl ether gave MgMeBr(pmdta) · MgBr₂(pmdta) (10) and [{MgMe₂(pmdta)}₇{MgMeBr(pmdta)}] (11) in 24% and 2% yield, respectively, as well as [MgMe₂(pmdta)] (12) as colorless needle-like crystals in about 26% yield. The synthesized methylmagnesium compounds were characterized by microanalysis and ¹H and ¹³C NMR spectroscopy. The coordination-induced shifts of the ¹H and ¹³C nuclei of the ligands are small; the largest ones were found in the tmeda and pmdta complexes. Single-crystal X-ray diffraction analyses revealed in 2 a tetrahedral environment of the Mg atoms with a bridging dabco ligand and in 8 a trigonal-bipyramidal coordination of the Mg atom. The single-crystal X-ray diffraction analyses of [MgMe₂(pmdta)] (12) and [MgBr₂(pmdta)] (13) showed them to be monomeric with five-coordinate Mg atoms. The square-pyramidal coordination polyhedra are built up of three N and two C atoms in 12 and three N and two Br atoms in 13. The apical positions are occupied by methyl and bromo ligands, respectively. Temperature-dependent ¹H NMR spectroscopic measurements (from 27 to −80 °C) of methylmagnesium bromide complexes MgMeBr(L) (L = thf (4); diglyme (5); NEt₃ (6); tmeda (7)) in thf-d₈ solutions indicated that the deeper the temperature the more the Schlenk equilibria are shifted to the dimethylmagnesium/dibromomagnesium species. Furthermore, at −80 °C the dimethylmagnesium compounds are predominant in the solutions of Grignard compounds 4-6 whereas in the case of the tmeda complex7 the equilibrium constant was roughly estimated to be 0.25. In contrast, [MgMeBr(pmdta)] (9) in thf-d₈ revealed no dismutation into [MgMe₂(pmdta)] (12) and [MgBr₂(pmdta)] (13) even up to −100 °C. In accordance with this unexpected behavior, 1:1 mixtures of 12 and 13 were found to react in thf at room temperature yielding quantitatively the corresponding Grignard compound 9. Moreover, the structures of [MgMeBr(pmdta)] (9c), [MgMe₂(pmdta)] (12c), and [MgBr₂(pmdta)] (13c) were calculated on the DFT level of theory. The calculated structures 12c and 13c are in a good agreement with the experimentally observed structures 12 and 13. The equilibrium constant of the Schlenk equilibrium (2 9c ? 12c + 13c) was calculated to be K_gas = 2.0 × 10⁻³ (298 K) in the gas phase. Considering the solvent effects of both thf and diethyl ether using a polarized continuum model (PCM) the corresponding equilibrium constants were calculated to be K_thf = 1.2 × 10⁻³ and K_ether = 3.2 × 10⁻³ (298 K), respectively.     

Synthesis of N,N′-bis and N,N,N′,N′-tetra-[(3,5-di-substituted-1-pyrazolyl)methyl]para-phenylenediamines: new candidate ligands for metal complex wires

A series of tridentate ligands N,N-bis-[(di-substituted-1-pyrazolyl)methyl]arylamines 2-3a,b and benzylamine 4a,b, tetradentate N,N′-bis-[(di-substituted-1-pyrazolyl)methyl]para-phenylenediamines 7a,b and hexadentate N,N,N′,N′-tetra-[(di-substituted-1-pyrazolyl)methyl]para-phenylenediamines 8a,b has been prepared in good yield by condensation of arylamines, benzylamine or para-phenylenediamine with N-hydroxymethyl disubstituted pyrazoles 1a,b. The synthesis and characterisation of these various polydentate ligands are described.     

Michael addition of chiral formaldehyde N,N-dialkylhydrazones to activated cyclic alkenes

The nucleophilic conjugate addition of chiral formaldehyde N,N-dialkylhydrazones 1 to doubly activated cyclic alkenes 2-8 proceeds smoothly to afford the corresponding Michael adducts 14, 16, 18, 20, 22, 24, and 25 in variable yields and selectivities. The reactions take place either spontaneously or in the presence of MgI₂ as a mild Lewis acid depending on the type of substrate. Release of the chiral auxiliary was achieved by transformation of the hydrazone moiety into acetals, dithioacetals or nitriles.     

Synthesis of N-acyl-N,O-acetals from N-aryl amides and acetals in the presence of TMSOTf

Secondary amides undergo in situ silyl imidate formation mediated by TMSOTf and an amine base, followed by addition to acetal acceptors to provide N-acyl-N,O-acetals in good yields. An analogous, high-yielding reaction is observed with 2-mercaptothiazoline as the silyl imidate precursor. Competing reduction of the acetal to the corresponding methyl ether via transfer hydrogenation can be circumvented by the replacement of CY₂NMe with 2,6-lutidine under otherwise identical reaction conditions.