Cycloaddition/Electrocyclic Ring Opening Sequence between Alkynyl Sulfides and Azodicarboxylates To Provide N,N-Dicarbamoyl 2-Iminothioimidates.

The α-oxidized thioimidates are useful bidentate ligands and are important motifs in pharmaceuticals, pesticides, and fungicides. Despite their broad utility, a direct route for their synthesis has been elusive. Herein, we describe a one-step synthesis of N,N-dicarbamoyl 2-iminothioimidates from easily accessible thioacetylenes and commercially available azodicarboxylates (20 examples, ≤99% yield). Additionally, the mechanism of the transformation was extensively explored by variable-temperature NMR, in situ IR, and quantum mechanical simulations. These experiments suggest that the reaction commences with a highly asynchronous [2 + 2] cycloaddition, which leads to a four-membered diazacyclobutene intermediate with a barrier consistent with the observed reaction rate. This intermediate was then isolated for subsequent kinetic measurements, which yielded an experimental barrier within 1 kcal/mol of the calculated barrier for a subsequent 4π electrocyclic ring opening leading to the observed iminothioimidate products. This method represents the first direct route to α-oxidized thioimidates from readily accessible starting materials.

Accessing the Rare Diazacyclobutene Motif.

A formal [2 + 2] cycloaddition of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) with electron-rich alkynyl sulfides and selenides is described. These investigations provide a convenient method to access diazacyclobutenes in good yield while tolerating a relatively broad substrate scope of thio-acetylenes. This method provides ready access to a unique and hitherto rarely accessible class of heterocycles. A combination of dynamic NMR, X-ray crystallography, and computation sheds light on the potential aromaticity of the scaffold.

Novel O-glycosidic gossypol isomers and their bioactivities.

Novel glycosidic gossypol analogs, 7,7'-gossypol diglucoside tetraacetate GS1, 6,7'-gossypol diglucoside tetraacetate GS2, 7,7'-gossypol diglycoside GS1', 6,7'-gossypol diglycoside GS2' were obtained by the ultrasound-assisted reaction of the potassium salt of gossypol with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide under PTC conditions and were fully characterized by 1D NMR ((1)H NMR, (13)C NMR, DEPT, 1D NOE), 2D NMR (HMBC, HMQC), FTIR, HRMS and HPLC. The anticancer activities, cytotoxic effects as well as anti-trypanosomal activities of these novel glycosidic gossypols were explored and suggest that gossypol glycosides could be used to develop new candidates for anticancer drugs and anti-trypanosomal agents.

Effect of perfluoroalkyl chain length on proton conduction in fluoroalkylated phosphonic, phosphinic, and sulfonic acids.

The effects of increasing perfluoroalkyl chain length on the molecular properties of viscosity, diffusivity, and ionic conductivity of a series of acid model compounds analogous to comb-branch perfluorinated ionomers functionalized with phosphonic, phosphinic, and sulfonic protogenic groups are reported. Anhydrous proton transport by a Grotthuss-like hopping mechanism was observed to occur efficiently in phosphorus-based fluoroalkylated model acids but only when there is a relatively low perfluoroalkyl content. The decrease in degree of dissociation of the protogenic groups follows the order phosphonic > phosphinic > sulfonic, and the degree of dissociation and the magnitude of ion-ion correlations are approximately independent of chain length.

Perfluoroalkyl phosphonic and phosphinic acids as proton conductors for anhydrous proton-exchange membranes.

A study of proton-transport rates and mechanisms under anhydrous conditions using a series of acid model compounds, analogous to comb-branch perfluorinated ionomers functionalized with phosphonic, phosphinic, sulfonic, and carboxylic acid protogenic groups, is reported. Model compounds are characterized with respect to proton conductivity, viscosity, proton, and anion (conjugate base) self-diffusion coefficients, and Hammett acidity. The highest conductivities, and also the highest viscosities, are observed for the phosphonic and phosphinic acid model compounds. Arrhenius analysis of conductivity and viscosity for these two acids reveals much lower activation energies for ion transport than for viscous flow. Additionally, the proton self-diffusion coefficients are much higher than the conjugate-base self-diffusion coefficients for these two acids. Taken together, these data suggest that anhydrous proton transport in the phosphonic and phosphinic acid model compounds occurs primarily by a structure-diffusion, hopping-based mechanism rather than a vehicle mechanism. Further analysis of ionic conductivity and ion self-diffusion rates by using the Nernst-Einstein equation reveals that the phosphonic and phosphinic acid model compounds are relatively highly dissociated even under anhydrous conditions. In contrast, sulfonic and carboxylic acid-based systems exhibit relatively low degrees of dissociation under anhydrous conditions. These findings suggest that fluoroalkyl phosphonic and phosphinic acids are good candidates for further development as anhydrous, high-temperature proton conductors.

Aqueous Compatible Fullerene-Doxorubicin Conjugates.

Covalent conjugates of fullerene C(60) and the highly effective anticancer drug doxorubicin (DOX) were prepared and studied. The conjugation was through the amide linkage to preserve the intrinsic properties of DOX and fullerene cage. As designed, the conjugates with hydrophilic ethylene glycol spacers exhibited much improved aqueous compatibility, with significant solubility in water-DMSO mixtures. The anti-neoplastic activities of DOX were apparently unaffected in the conjugates according to evaluations in vitro with a human breast cancer cell line.

Oxidation of 2-propanol and cyclohexane by the reagent "hydrogen peroxide-vanadate anion-pyrazine-2-carboxylic acid": kinetics and mechanism.

The vanadate anion in the presence of pyrazine-2-carboxylic acid (PCA [identical with] pcaH) efficiently catalyzes the oxidation of 2-propanol by hydrogen peroxide to give acetone. UV-vis spectroscopic monitoring of the reaction as well as the kinetics lead to the conclusion that the crucial step of the process is the monomolecular decomposition of a diperoxovanadium(V) complex containing the pca ligand to afford the peroxyl radical, HOO(.-) and a V(IV) derivative. The rate-limiting step in the overall process may not be this (rapid) decomposition itself but (prior to this step) the slow hydrogen transfer from a coordinated H2O2 molecule to the oxygen atom of a pca ligand at the vanadium center: "(pca)(O=)V...O2H2" --> "(pca)(HO-)V-OOH". The V(IV) derivative reacts with a new hydrogen peroxide molecule to generate the hydroxyl radical ("V(IV)" + H2O2 --> "V(V)" + HO(-) + HO(.-)), active in the activation of isopropanol: HO(.-) + Me2CH(OH) --> H2O + Me2C(.-)(OH). The reaction with an alkane, RH, in acetonitrile proceeds analogously, and in this case the hydroxyl radical abstracts a hydrogen atom from the alkane: HO(.-) + RH --> H2O + R(.-). These conclusions are in a good agreement with the results obtained by Bell and co-workers (Khaliullin, R. Z.; Bell, A. T.; Head-Gordon, M. J. Phys. Chem. B 2005, 109, 17984-17992) who recently carried out a density functional theory study of the mechanism of radical generation in the reagent under discussion in acetonitrile.

1H NMR spectroscopic studies of the conformational isomers of pyrrolidinofullerenes.

Mixed bis-adduct derivatives of C60 containing a pyrrolidine and a malonate methano group were synthesized. Three regioisomers, the e', the trans-2, and the trans-3, were isolated and characterized. In-depth NMR studies of these methano-pyrrolidinofullerenes showed that the nitrogen inversion on the pyrrolidine moiety is not a fast event in the 1H NMR time scale as previously regarded. Solvent effects, variable temperature experiments, and protonation of the pyrrolidine nitrogen are addressed.

Alternatively modified bingel reaction for efficient syntheses of C60 hexakis-adducts.

It was found that the C60 hexakis-adduct (Th) bearing 12 electron-donating N,N-dimethylaniline moieties could not be synthesized by the Bingel-Hirsch method with either classical or deviated experimental parameters in a one-pot reaction. A different modification to the original Bingel reaction without the use of any templating agent was necessary for high-yield synthesis of the compound. The generalization of this alternatively modified Bingel method to the preparation of other C60 hexakis-adducts is demonstrated. [structure: see text].

Trimetallic nitride endohedral metallofullerenes: reactivity dictated by the encapsulated metal cluster.

The first derivatives of Y(3)N@C(80) have been synthesized and fully characterized. 1,3-Dipolar cycloaddition of N-ethylazomethine ylide yielded mainly the pyrrolidine monoadduct of the icosahedral (I(h)()) symmetry cage exclusively at a [6,6] double bond. The same regioselectivity on a [6,6] double bond was observed when the endohedral compound was cyclopropanated with diethyl bromomalonate. These results are in pronounced contrast to those observed for icosahedral symmetry Sc(3)N@C(80), for which all reported derivatives add completely regioselectively to [5,6] double bonds. (1)H NMR, (13)C NMR, and HMQC spectroscopy revealed that the addition pattern on Y(3)N@C(80) resulted in a pyrrolidinofullerene derivative with unsymmetric pyrrolidine carbons and symmetric geminal protons. The cyclopropanated monoadduct exhibited symmetric ethyl groups on the malonate, consistent with regioselective addition at a [6,6] double bond. Attempts to perform the same cyclopropanation reaction on (I(h)()) Sc(3)N@C(80) failed to yield any identifiable products. These observations clearly indicate that the reactivity of trimetallic nitride endohedral metallofullerenes toward exohedral chemical functionalization is profoundly affected and effectively controlled by the nature of the endohedral metal cluster.

The first fulleropyrrolidine derivative of Sc3N@C80: pronounced chemical shift differences of the geminal protons on the pyrrolidine ring.

The first pyrrolidine adduct on Sc(3)N@C(80) was synthesized and fully characterized. Addition of the N-ethylazomethine ylide occurs regioselectively on a [5,6] double bond on the surface of the icosahedral symmetry Sc(3)N@C(80), exactly in the same position as that described previously for a Diels-Alder adduct of the same compound.(11a,b) This addition pattern results in symmetric pyrrolidine carbons and unsymmetric geminal hydrogens on the pyrrolidine ring, as confirmed by (1)H and (13)C NMR spectroscopy, especially by HMQC. The shielding environment experienced by these geminal hydrogens differs by 1.26 ppm, indicative of pronounced ring current effects on the surface of this endohedral fullerene. This represents the first fully characterized pyrrolidine adduct on an endohedral metallofullerene.

NMR detection of single-walled carbon nanotubes in solution.

The detection of nanotube carbons in solution by (13)C NMR is reported. The highly soluble sample was from the functionalization of (13)C-enriched single-walled carbon nanotubes (SWNTs) with diamine-terminated oligomeric poly(ethylene glycol) (PEG(1500N)). The ferromagnetic impurities due to the residual metal catalysts were removed from the sample via repeated magnetic separation. The nanotube carbon signals are broad but partially resolved into two overlapping peaks, which are tentatively assigned to nanotube carbons on semiconducting (upfield) and metallic (downfield) SWNTs. The solid-state NMR signals of the same sample are similarly resolved. Mechanistic and practical implications of the results are discussed.

Simple modification in hexakis-addition for efficient synthesis of c(60)-centered dendritic molecules bearing multiple aromatic chromophores.

In the templated hexakis-addition reaction of malonic esters with C(60) to prepare dendritic macromolecules that are terminated symmetrically with 12 derivatized pyrenes, a simple modification to use a much larger excess of the bromination agent resulted in dramatic increases in the product yields. [structure: see text]

Deuterium attachment to carbon nanotubes in deuterated water.

A systematic investigation on the unusual attachment of labile deuterium to carbon nanotubes in deuterated water and alcohols is reported. The carbon nanotubes were solubilized through the established functionalization of the nanotube-bound carboxylic acids to allow solution-phase reaction and characterization. The deuterium attachment was found under several experimental conditions, including the use of deuterated ethanol as a co-reactant in the nanotube functionalization reaction and the refluxing of functionalized or simply purified carbon nanotubes in deuterated water and alcohols. The solubility of the functionalized carbon nanotube samples in common organic solvents and water allowed unambiguous (2)H NMR characterization. The reproducible broad (2)H NMR signal at approximately 6.5 ppm is assigned to carbon nanotube-attached deuterium species. The assignment is supported by the results from FT-IR measurements. The carbon-deuterium interaction is so strong that the corresponding vibration resembles the typical C-D stretching mode in the characteristic frequency region. The FT-IR peak intensities also correlate well with the (2)H NMR signal integrations in a series of samples. Mechanistic implications of the results are discussed.