Noteworthy Chemistry

July 4, 2011

Detect multiple analytes with a single indicator. Specific ribosides such as S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are biomarkers for methylation status and oxidative stress. 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside is a model for succinylpurine metabolites associated with a rare autism spectrum disorder. The R. M. Strongin research group at Portland State University (OR) showed that these ribose-containing molecules are selectively detected by a single rhodamine-based bis(boronic acid) indicator in the presence of other carbohydrate-based compounds such as fructose.

By monitoring wavelength- and time-dependent spectral information, Strongin and co-workers optimized a rigorous data collection method for multiple analyte detection with a single rhodaminebis(boronic acid) fluorophore (1). This technique makes it possible to selectively identify various analytes by using spectra extracted from multidimensional data sets at specific times or by monitoring the intensity at a specific wavelength as a function of time.

In the presence of ribose-containing molecules, dye 1 was monitored over time at wavelengths in the excitation range (470–620 nm) for an emission range between 520 and 690 nm. The collected data sets were displayed as contour plots of excitation–emission matrices (EEMs). The data provided specific analyte signatures, and the EEMs showed distinguishable patterns for each structurally related analyte.

The method also allowed selective detection within mixtures in which the signatures of individual analytes were present, but the features of the major analyte dominated. (Chem. Commun. 2011, 47, Advance Article DOI: 10.1039/c1cc11343g; Gary A. Baker)

Use acetone cyanohydrin for tertiary amine α-cyanation. α-Amino nitriles (2) are versatile intermediates for synthesizing alkaloids and α-amino acids. Current routes to α-amino nitriles require excess NaCN in acidic solution to generate toxic HCN in situ. The high concentration of NaCN in the reaction mixture, however, can deactivate the ruthenium catalyst.

S. Verma, S. L. Jain*, and B. Sain at the Indian Institute of Petroleum (Dehradun) used acetone cyanohydrin (1) as a substitute for NaCN to prepare α-amino nitriles, with RuCl3 as the catalyst and H2O2 in MeOH as the oxidant. Because 1 is a liquid reagent, it allows the slow, controlled addition of the cyanide to the reaction mixture, making the HCN source safe to handle and avoiding catalyst deactivation by excess cyanide ion.

The authors used several substituted N,N-dimethylanilines, piperidines, pyrrolidines, and tetrahydroquinolines as substrates and achieved yields in the 70–90% range. Tributylamines, however, do not react under these conditions. The reaction can also be run without solvent.

The authors propose a mechanism similar to that of NaCN cyanation (Murahashi, S-I.; Komiya, N.; Terai, H. Angew. Chem., Int. Ed. 2005, 44, 6931–6933): Ruthenium is oxidized by H2O2; the ruthenium oxide undergoes nucleophilic attack by the trisubstituted amine; and the quaternary ammonium species is cyanated by HCN released by 1 to regenerate Ru(III) and liberate the desired product. (Cat. Lett. 2011, 141, 882–885; JosÉ C. Barros)

Which vacuum dryer should you use: tray, rotary, or conical screw? P. Kontcho Kom, W. Cook, and E. Kougoulos* at Pfizer Pharmatherapeutics (Sandwich, UK) conducted laboratory drying experiments (30-g scale) on three water-wet materials—Lactose FastFlo 316, Avicel PH200, and an active pharmaceutical ingredient (API)—in tray, rotary, and conical screw vacuum dryers. They investigated the effect of vacuum, temperature, rotary speed, and input particle size on drying time and final particle size.

Particles of Lactose FastFlo 316 and the API agglomerated in the tray and rotary dryers and disintegrated in the conical screw dryer. There was little change in the physical properties of Avicel PH200 in any of the dryers. Overall, tray drying had the poorest heat-transfer performance and greatest degree of agglomeration. (Org. Process Res. Dev. 2011, 15, 360–366; Will Watson)

Haloazapentacenes optimize semiconductor properties. Organic ambipolar materials are valuable in device applications such as light-emitting transistors and metal oxide semiconductors. In ambipolar materials, both electron and hole transport can take place; this allows manufacturing techniques to be simplified.

H.-L. Zhang and coauthors at Lanzhou University (China) and the University of Akron (OH) studied the azapentacene scaffold for this use (Liu, Y.-Y., et al. J. Am. Chem. Soc. 2010, 132, 16349–16351). They now report the synthesis of tetrachloro-substituted azapentacenes to tune the performance characteristics of these structures as ambipolar organic field-effect transistors (OFETs).

The authors describe synthetic procedures for brominated and chlorinated (1) azapentacenes. Their characterization data concentrate on the chlorinated derivative.

Brominated pyridine derivative 2 and diethynyltetrachloroanthraquinone 3 react under cyclization conditions to form azapentacene quinone 4. This reaction is followed by a modified ethynylation–deoxygenation sequence to produce target triisopropylsilylethynyl-substituted azapentacene 1. Structure 1 is deep blue in color and is stable in solution and the solid state—even in air and ambient light.

The absorption λmax for 1 occurs at 647 nm with an absorption onset of ≈690 nm in solution. Thin films of 1 exhibit a significant red shift, pointing to strong intermolecular electronic interaction within the film. The lowest unoccupied molecular orbital energy is much lower than that of unsubstituted pentacene, a characteristic of higher affinities and a potential indication of n-channel semiconduction.

The authors used 1 to prepare gate transistors that can be incorporated into ambipolar OFET devices with excellent properties. Very high hole and electron mobilities—as high as 0.12 and 0.14 cm2/(V·s), respectively—were measured with gold electrodes. These results confirm the efficient performance of ambipolar OFET devices based on an azapentacene scaffold. The authors also observed that silver electrode–based OFETs prepared from 1 have high, balanced charge carrier mobilities, a desirable feature for reducing cost without sacrificing performance. (Org. Lett. 2011, 13, 2880–2883; W. Jerry Patterson)

“See” mercuric ion with gold nanoparticles. Mercuric ion (Hg2+) is an environmental pollutant and health hazard. Conventional methods for analyzing Hg2+ are costly, complex, and unsuited for quick detection. A simple colorimetric detection method would be ideal for point-of-use applications. Colorimetric systems based on oligopeptide-functionalized gold nanoparticles (AuNPs) have been reported, but the nonspecific assays respond to several metal ions.

X. Chen and coauthors at Nanyang Technological University (Singapore) and Jilin University (Changchun, China) developed a Hg2+-specific colorimetric assay that uses AuNPs and oligopeptides without prior chemical modification of the nanoparticles. The citrate-capped AuNPs are stable and red-colored in aqueous solution. When linear oligopeptides with cysteine termini are added to the solution, the AuNPs aggregate, and their color changes from red to blue. When Hg2+ is present, however, the oligopeptide probes bind to the ions and lose their ability to induce AuNP aggregation. The nanoparticle solution therefore remains red.

This assay is easy to use (simple mixing of AuNPs and oligopeptide) and has a flexible working range (10 nm–>100 μm) and high Hg2+ selectivity (tolerance of multiple metal ions). The portable assay is particularly attractive for detecting Hg2+ in complex mixtures such as industrial waste and river water. (Small 2011, 7, 1407–1411; Ben Zhong Tang)

Polyimide nanofibers prevent fires on nylon surfaces. Some polymers are highly flammable. They decompose when heated and produce chemicals that burn easily. Flame-retardant fillers that are added to generate noncombustible compounds or to prevent the flammable components from burning may alter polymer properties.

B. Schartel and coauthors at the BAM Federal Institute for Materials Research and Testing (Berlin) and the Phillips University of Marburg (Germany) propose temperature-resistant coatings for protecting the integrity of polymer substrates. They designed a polyimide membrane that prevents nylon from burning.

The polyimide is derived from the step polymerization of dianhydrides and diamines. Polycondensation of pyromellitic dianhydride (1) and 4,4-oxydianiline (2) generates an intermediate polymer, 3. Removing the water produced in the reaction facilitates propagating the polymerization and growth of long chains. Additional water removal induces the formation of polyimide 4.

Free-standing polymer 4 does not ignite or flame, but decomposes thermally. It absorbs heat at high temperatures, so when it is coated onto a flammable polymer, it delays polymer ignition. For example, coated nylon dissociates and the combustible products accumulate under the polymer 4 “skin”. (Polym. Adv. Technol. 2011, 22, Early View DOI: 10.1002/pat.1994; Sally Peng Li)

Expand the scope of propargylic alcohol synthesis. The original method for preparing propargylic alcohols produces key building blocks for numerous natural products and bioactive materials. Many of the earlier synthetic techniques require strong-metal bases, heavy-metal catalysts, or bulky ligands. In some cases, enolizable aldehyde or ketone substrates cannot be used.

To overcome many of these limitations, V. R. Chintarreddy, K. Wadhwa, and J. G. Verkade* at Iowa State University (Ames) developed a mild route to secondary and tertiary propargylic alcohols. The use of tetrabutylammonium fluoride (n-Bu4NF) as the catalyst in the reaction of trialkylsilylalkynes with aldehydes or ketones is key to their process.

The reaction typically proceeds in a one-pot process with aromatic or aliphatic aldehyde substrates and produces the corresponding secondary propargylic alcohols in high yields. The figure illustrates the scope of this reaction with the formation of products 1 and 2.

The unique contribution of n-Bu4NF to this reaction is its bulky n-butyl groups, which make it highly soluble in polar organic solvents. This property provides a nucleophilic fluoride source and a possible source of electrophilic quaternary ammonium cations for activating carbonyl groups.

When aryl trifluoromethyl ketone substrates are used in place of aldehydes, the corresponding tertiary CF3-functionalized propargylic alcohols (3) are also produced in high yields. In this case, no acid workup is required because hydrolysis occurs during chromatographic workup. The literature contains many examples of trifluoromethyl-containing variants of bioactive molecules that feature an alkyne substituent. One notable example of this structural motif is the anti-HIV drug efavirenz.

The authors stress that their study extends and broadens this synthetically important reaction with a mild, efficient protocol. No strong bases are required, and there is no need for organometallic reagents or metal–ligand combinations. All substrates in this study were converted to the desired products at room temperature with a low loading of relatively inexpensive, commercially available n-Bu4NF. (J. Org. Chem. 2011, 76, 4482–4488; W. Jerry Patterson)

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