Noteworthy Chemistry

June 20, 2011

Here’s a new way to determine fluoride ion quantitatively in organic and aqueous media. P. Sokkalingam and C. H. Lee* at Kangwon National University (Chun-Chon, Korea) used a modified coumarin scaffold to detect fluoride ion in water and MeCN by using chromogenic and fluorogenic “turn-on” signals.

Commercially available coumarin derivative 1 was protected with a silyl group to form target indicator 2. Silyl ether 2 is nonfluorescent, whereas its anionic form 3 is highly fluorescent. The authors determined that the triisopropylsilyl (TIPS) group can be rapidly and quantitatively deprotected with n-Bu4NF to allow F sensing via a fluorescence “turn-on” mechanism. This is a sensitive method for detecting F in solution.

Fluorescence studies showed strong emission at 500 nm from nonfluorescent 2 when it is titrated with F in MeCN, indicating that F removes the TIPS group quantitatively. The authors estimate the detection limit for F to be ≈50 nM, an extremely low value compared with other chemodosimeters.

Adding other anions (e.g., Cl, Br, I, CN, AcO, NO3, PhCO2, SCN, H2PO4, and HSO4) has no effect on absorbance or fluorescence and demonstrates the selective nature of receptor 2 for F. This fluoride-sensing process can be observed by visible color change or bright fluorescence under UV light.

Receptor 2 is less sensitive in water than in MeCN, but it can detect F within ≈10 min. In the aqueous studies, the authors added 0.5% MeCN to improve the poor water solubility of 2. They also showed that the method can detect fluorides with metallic cations as quickly as quaternary ammonium fluorides by simply adding chelating agents such as crown ethers.

The authors prepared paper test strips that were soaked in a solution of 2 in MeCN, then air-dried. The strips were immersed in aqueous F solution and dried again. The color of the test strip immediately changed from colorless to bright yellow and was intensely fluorescent under UV light. This shows that 2 is a good indicator for F in aqueous media.

The authors believe that their study defines a simple, highly selective system that detects F in organic and aqueous media, based on its affinity for silicon. The indicator also produces chromogenic and fluorogenic signals when exposed to F, which could lead to the development of a commercial system for detecting F. (J. Org. Chem. 2011, 76, 3820–3828; W. Jerry Patterson)

UV light initiates intramolecular cycloaddition in different ways. The intermolecular cycloaddition of enynes and 2-pyridones is triggered by UV irradiation and generates as many as six compounds (Kulyk, S., et al. Org. Lett. 2010, 12, 3296−3299). The same researchers at Temple University (Philadelphia) and Villanova University (PA), led by S. M. Sieburth, investigated the y UV light–initiated intramolecular cycloaddition of these moieties in detail.

Compounds 15 were the starting enyne–2-pyridones in the study. The double bonds in compounds 13 react, whereas the triple bonds survive under UV irradiation. Even though 1 and 2 are isomers, they generate different structures.

Both unsaturated bonds in compounds 4 and 5 take part in cycloaddition reactions. The initial products are so unstable that they form multiple dimers. (Org. Lett. 2011, 13, 2180−2183; Sally Peng Li)

This Barbier allylation uses indium granules and aluminum foil. The Barbier allylation is a one-pot C–C bond–forming reaction in which a metal, an allylating agent, and a carbonyl substrate are used to form a secondary or tertiary alcohol. Several metals have been used in this reaction, but indium powder is particularly useful because of its reactivity and its compatibility with organic and aqueous media. This protocol, however, requires stoichiometric amounts of the metal in powdered form.

M. Preite*, H. A. Jorquera-Geroldi, and A. PÉrez-Carvajal at the Pontifical Catholic University of Chile (Santiago) developed a Barbier allylation method that uses catalytic amounts of granular indium, which is less expensive than the powdered metal, and readily available aluminum foil as stoichiometric metal. They added an aldehyde or ketone, allyl bromide, 0.01–0.1 equiv indium, and 0.9–1.0 equiv of small pieces of aluminum foil to DMF and heated the mixture at 40–50 °C for 18–20 h to produce homoallylic alcohols after aqueous workup. In/Al ratios <1:10 required longer reaction times.

The yields were >70% for several substrates, including aliphatic, aromatic, and heteroaromatic aldehydes and ketones. Water can be used as the reaction medium in place of DMF, and aluminum powder can be used instead of foil. The reaction does not take place in the absence of indium.

The mechanism involves a transmetalation from an indium alcoholate to an aluminum alcoholate before the homoallylic alcohol is eliminated. This method uses environmentally benign metals and is amenable to scale-up. (Arkivoc 2011 [vii], 380–388; JosÉ C. Barros)

Gold nanowire–carbon nanotube hybrids have high aspect ratios. W. Yang, L. Dai, and coauthors at the University of Sydney, Deakin University (Victoria, Australia), Soochow University (Jiangsu, China), and Case Western Reserve University (Cleveland) developed a method for making gold nanowire–carbon nanotube hybrids with high aspect ratios. From hexane dispersions of the components, they assembled hydrophobic, oleylamine-functionalized, flexible gold nanowires along the lengths of multiwalled carbon nanotubes (MWCNTs). The assembly is driven by strong van der Waals and hydrophobic interactions of the modified nanowires with untreated MWCNTs.

Using high-resolution microscopy techniques, the authors discovered that the assembly procedure aligns uniform gold nanowires into nanostripes over large sections of MWCNTs. The process occurs for nanowire aspect ratios (length/diam) between 80:1 and 2000:1. The self-assembly of gold nanowires along MWCNTs can be mitigated by modifying the polarity of the nanotube surfaces by functionalizing them with sodium dodecyl sulfate.

Molecular dynamic simulations demonstrated the roles that the surface forces and the proximity of the nanowires to the MWCNTs (which is controlled by evaporation rate) play in driving the assembly process. Microcontact printing was also used to form patterned arrays of nanowire–MWCNT hybrids. When the hybrids are used to form devices for electron-transport studies, they feature a good balance of electron conductivity and low resistance. (Chem. Mater. 2011, 23, 2760–2765; LaShanda Korley)

Consider all stages when developing a safe oxidation process. In the course of developing orally active non-nucleoside reverse transcriptase inhibitors against HIV reverse-transcriptase mutation, M. Alam and co-workers at Merck Sharp & Dohme (Hoddesdon, UK, and Rahway, NJ) oxidized a pyrazolopyridine to its N-oxide with m-chloroperbenzoic acid (mCPBA) in HOAc. Because of the inherent instability of mCPBA, they undertook a thorough hazard analysis that encompassed not only the reaction stage but also the preparation of the mCPBA solution and the reaction quench.

Dissolving mCPBA in HOAc acid is endothermic and requires heating to complete the dissolution. Overheating must be avoided, however, so the peroxy acid was dissolved at 25 °C. The reaction temperature was maintained at 55 °C, and excess oxidizing agent was quenched with NaHSO3. Additional dilution with water precipitated the pyrazolopyridine N-oxide product. (Org. Process Res. Dev. 2011, 15, 443–448; Will Watson)

A fluorescent hybrid polymer is a sensitive probe for explosives. Fluorescent materials have attracted much attention as probes for explosives because of their great sensitivity and convenience. They are often laborious and inefficient to synthesize, however, and this hampers manufacturing scale-up and limits the scope of practical applications.

J. Cao, Y.-J. He, B.-H. Han, and coauthors at the National Center for Nanoscience and Technology (Beijing), the Graduate University of the Chinese Academy of Sciences (Beijing), and Beijing Institute of Technology developed a polymeric organic–inorganic hybrid (1) that can be prepared by a one-pot procedure and used as a fluorescence sensor for explosives.

The authors synthesized the hybrid by heating a solution of organic (2) and inorganic (3) monomers to reflux. The aqueous suspension and solid powder of 1 are highly fluorescent because of the unique aggregation-induced emission of its tetraphenylethylene units.

The fluorescence is quenched by adding the explosives 2,4,6-trinitrotoluene (TNT) or picric acid (PA) to 1 in suspension or by exposing the powder to the explosive compounds. Quenching is caused by efficient electron transfer from electron donor 1 to electron acceptor TNT or PA. Polymer 1 detects PA more sensitively (as low as 0.1 ppm) because of the additional energy transfer from the excited state of 1 to the ground state of PA. (Polym. Chem. 2011, 2, 1124–1128; Ben Zhong Tang)

Here’s a unique catalytic oxidation of alkenes to α-diketones. The synthesis of α-diketones is an important chemical transformation, and various methods are reported in the literature. Most methods are limited in selectivity, scope, yield, practicality, or functional group tolerance.

X. Wan and coauthors at Soochow University (Suzhou, China) and Lanzhou University (China) describe a method for introducing two oxygen atoms across an alkene—conceptually the most direct route to α-diketones. Using (E)-1,2-diphenylethylene as the test substrate, the authors developed optimized conditions for catalytic oxidation to benzil. They found that a ruthenium catalyst complex with Bu4NI as cocatalyst and t-BuOOH as the preferred oxidant promotes this transformation efficiently under mild conditions.

The authors used 25 substrates to test the scope of the reaction and found that trans– and cis–alkyl or aryl alkenes can be converted equally efficiently. They demonstrated the procedure’s functional group tolerance by converting substrates with ester (as in the figure), fluoro, chloro, bromo, ether, nitrile, ketone, trifluoromethyl, amide, or alkyne substituents on the aryl rings. They also showed that sterically demanding alkenes can be converted to the desired diketones in satisfactory yields. (Org. Lett. 2011, 13, 2274–2277; W. Jerry Patterson)

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