Noteworthy Chemistry
May 5, 2008
Functionalize carbon nanotubes with minimal electronic perturbation
Palladium(II) can catalyze olefin dioxygenation
1,2-Diamines and 1,2-amino alcohols from common chiral intermediates
Avoid sulfur contamination from sodium thiosulfate reaction workups
Use “frozen” ionic liquids to create micro- and nanoparticles
Self-assembled organic nanoparticles have dual-color emission capability
A three-component Ugi reaction leads to α-amino amides
Functionalize carbon nanotubes with minimal perturbation to their electronic structures. Carbon nanotubes (CNTs) have many exotic properties but are notoriously insoluble and difficult to process. Much effort has focused on solubilizing CNTs in common solvents through noncovalent and covalent routes. Noncovalent routes, such as polymer “wrapping”, can greatly enhance CNT solubility, but this makes CNT surfaces less accessible. Covalent routes can disrupt the electronic structure of CNTs and compromise their beneficial properties.
A. Suri, A. K. Chakraborty, and K. S. Coleman* at Durham University (U.K.) have developed a new noncovalent route for CNT functionalization that can ensure macroscopic processibility and avoid appreciable structural perturbation. The researchers modified single-wall CNTs with tertiary phosphines by using a simple procedure that presumably relies on charge transfer between the electron-donating phosphorus atom and the electron-deficient CNTs.
The phosphine modification causes the CNTs to “debundle”, allowing them to be dispersed in common solvents. The CNTs’ electronic properties are not significantly disturbed, and their surfaces are still accessible because the degree of functionalization is as low as ~1 atom%. (Chem. Mater. 2008, 20, 1705–1709; Ben Zhong Tang)
Palladium(II) can catalyze olefin dioxygenation. Osmium-catalyzed olefin dioxygenation is well known, but the analogous reaction catalyzed by much less toxic palladium has eluded chemists until now, as reported by Y. Li, D. Song*, and V. M. Dong* at the University of Toronto. For the vicinal oxidation of trans-stilbene using hypervalent iodine as the oxidant, catalysts such as palladium acetate showed no activity over 16 h. However, cationic complexes such as [Pd(dppp)(H2O)2](OTf)2 catalyzed the stilbene oxidation in 72% yield within 2 h, with a 6:1 syn/anti oxidation selectivity; dppp is diphenyl-1-pyrenylphosphine and TfO is trifluoromethanesulfonate.
The complex contains an electron-rich phosphine ligand and the noncoordinating counterions that are suitable for generating sites of coordinative unsaturation. On the basis, in part, of isotope-labeling experiments, the authors propose that olefins first π-coordinate, then insert to produce the Pd(II) alkyl. They further posit that an SN2-like attack by acetate in the reaction mixture produces the observed products. Linear and cyclic olefin substrates could be oxidized, with product yields in the range 60–95%. Reactions with 4-hydroxy-substituted olefins produced substituted THF rings. (J. Am. Chem. Soc. 2008, 130, 2962–2964; David A. Schiraldi)
Construct 1,2-diamines and 1,2-amino alcohols from common chiral intermediates. The bioactive compounds (+)-CP-99,994 (2) and (+)-L-733,060 (3) are potent and selective human neurokinin-1 substance P receptor antagonists. These antagonists have excellent potential for treating major depression; they are comparable with selective serotonin reuptake inhibitors (SSRIs).
B. Wang, M.-H. Xu, G.-Q. Lin, and coauthors at Fudan University and the Chinese Academy of Sciences (both in Shanghai) synthesized compound 2, a syn-1,2-diamine, and compound 3, a homochiral syn-1,2-amino alcohol, from a common chiral sulfonylamino alcohol (1). The initial synthesis of 1 was carried out by the reductive coupling of 4-pivaloxybutanal with (R)-phenyl-N-tert-butanesulfinylimine.
Several subsequent steps led to cyclizing 1 to the key piperidine ring, which formed target compound 2 that features the syn-1,2-diamine functionality. Similarly, the formation (in several steps) of a piperidine intermediate was a key route to syn-1,2-amino alcohol 3.
Both synthetic routes are efficient and lead to high overall yields from the common chiral intermediate 1. Products 2 and 3 provide easy access to a full spectrum of vicinal diamines and amino alcohols with well-defined stereochemistry. (J. Org. Chem. 2008, 73, 3307–3310; W. Jerry Patterson)
Avoid sulfur contamination from sodium thiosulfate reaction workups. Many halogenation reactions are quenched or washed with Na2S2O3 solution. R. Vaidyanathan and co-workers at Pfizer (Groton, CT) investigated this process and show that it can lead to contamination of the organic halide with as much as 4% sulfur. They describe the conditions that exacerbate contamination and provide solutions to the problem.
The level of sulfur contamination depends on the organic solvent used. Toluene gives very low contamination—0.07% in the test reaction, the conversion of 4-aminobenzonitrile to 4-iodobenzonitrile via the diazonium salt. The amount of sulfur contamination correlates with the solubility of water in the solvent.
The pH of the reaction mixture before the wash or quench also is a factor. Very low levels of sulfur (0.02%) are detected in alkaline systems, but much higher levels are associated with neutral (2.2%) or acidic systems (4.4%). The best way to avoid the problem is to use NaHSO3 or ascorbic acid solution as the wash or quench reagent; no sulfur is detected in either case. (Org. Process Res. Dev. 2008, 12, 116–119; Will Watson)
Use “frozen” ionic liquids to create micro- and nanoparticles. Ionic liquids (ILs), salts that have melting points <100 °C, consist of bulky organic cations paired with a wide range of organic and inorganic anions. ILs have many desirable properties, such as high thermal stability, nonflammability, no measurable vapor pressure under ordinary conditions, and inherent “designability”. All of these properties contribute to broad applications as “green” solvents for organic and inorganic synthesis; electrolytes in batteries, fuel cells, and solar cells; stationary phases in chromatography; and media for nanomaterials synthesis.
I. M. Warner and coauthors at Louisiana State University (Baton Rouge) and Oak Ridge National Laboratory (TN) have advanced the IL field by developing a procedure to generate uniform and stable micrometer-sized to nanoscale particles composed of solidified 1-butyl-2,3-dimethylimidazolium hexafluorophosphate ([bm2im][PF6]), an IL with a melting point slightly higher than body temperature. They synthesized the IL by using a novel oil-in-water (o/w) melt–emulsion–quench templating method that yields near-spherical particles with mean diameters that depend on the droplet size of the internal phase of the o/w emulsion. This method makes control possible in the nanometer–micrometer regime (45 nm–3 μm).
The authors report that the geometry, dimensions, and composition can be further controlled by varying several other experimental parameters, including temperature, emulsion type, surfactant choice, and the identity of the IL building block. The ease, rapidity, and simplicity of this preparation, coupled with the designer nature of ILs, suggest great potential for solid-state IL particles in many disciplines within the biomedical, materials, energy, and analytical communities. (Nano Lett. 2008, 8, 897–901; George Xiu Song Zhao)
Self-assembled organic nanoparticles have dual-color emission capability. Light-emitting materials are being explored as fluorescent bioprobes. Inorganic quantum dots have been studied as potential tags in immunofluorescence labeling, but their cytotoxicity critically hampers their applications in living systems. An alternative choice is organic dye-loaded nanoparticles, but they tend to quench themselves. So the development of biocompatible, emissive solid-state materials is still being sought.
J. Kim and coauthors at the University of Michigan (Ann Arbor) and Chungnam National University (Daejeon, Korea) synthesized a new benzoxazole molecule that self-assembles with functionalized diacetylene molecules to form nanoparticles with an average 80 nm diam. Whereas the benzoxazole molecule emits weak green light in solution with a quantum yield (ΦF) of 3% in THF, its nanoparticles exhibit aggregation-induced fluorescence enhancement with a >10-fold higher ΦF value (38%).
The authors polymerized the diacetylene passivation layer in the self-assembled nanoparticles, and the resultant polydiacetylene emitted red light upon excitation by visible light. They then achieved selective targeting and dual-color visualization of patterned arrays of avidin (an egg white protein) by using highly luminescent biotinylated nanoparticles to realize the promise of the organic nanoparticles for immunofluorescence labeling. (Adv. Mater. 2008, 20, 1117–1121; Ben Zhong Tang)
A three-component Ugi reaction leads to α-amino amides. This multicomponent process is a classic example of a one-pot reaction that combines three or more substrates simultaneously. S. C. Pan and B. List* at the Max-Planck Institute for Coal Research (Mülheim an der Ruhr, Germany) describe a three-component catalytic version of the Ugi reaction that transforms an aldehyde, a primary amine, and an isocyanide into an α-amino amide. Their method uses water as the internal nucleophile and benzenephosphinic acid as the optimum catalyst, leading to a perfectly atom-economic reaction.
The scope of the reaction was expanded by varying the substituent groups on all three reactants. Yields were as high as 91% and generally good for all combinations except aliphatic amine reactants.
To illustrate how easily the reaction is carried out, the authors combined the three reactants and the catalyst in a dry flask with dry toluene and stirred the mixture for 12–36 h at 80 °C. The mixture was then poured onto a silica gel column to give pure product. The authors point out that this procedure features a broad scope, operational simplicity, practicality, and mild reaction conditions; and it leads to a wide range of α-amino amide products. (Angew. Chem., Int. Ed. 2008, 47, 3622–3525; W. Jerry Patterson)
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