Noteworthy Chemistry

April 8, 2013

Produce hydrogen from methanol at low temperature. Methanol (MeOH) is a promising hydrogen carrier because it is a liquid and contains 12.6% hydrogen. Hydrogen production from MeOH (MeOH reforming), however, requires high temperatures (>200 °C) and pressures (25–50 bar).

M. Beller and coauthors at the University Rostock (Germany), the Institute of Biomolecular Chemistry (Sassari, Italy), and the University of Sassari developed a method to reform MeOH that uses ruthenium catalysts under mild conditions. In the presence of either of two pincer-type ruthenium complexes (1 or 2) as homogeneous catalysts, the transformation proceeds at <100 °C and ambient pressure.

Based on NMR data, the researchers believe that the reaction proceeds in three dehydrogenation steps:

  1. MeOH breaks down to hydrogen and formaldehyde (HCHO) molecules.
  2. HCHO reacts with water to liberate a second hydrogen molecule and formic acid (HCO2H).
  3. HCO2H decomposes to release a third hydrogen molecule and CO2.

The catalysts’ turnover frequencies (4700/h) and turnover numbers (>350,000) are excellent. The hydrogen product is contaminated with only small amounts (<10 ppm) of methane and CO.

Under alkaline conditions, the system is stable up to 3 weeks. The hydrogen yield from the reforming reaction is 27%. The system operates in H2O–MeOH mixtures, but excessive amounts of water lower the yield. This study may lead to hydrogen production onboard vehicles. (Nature 2013, 495, 85–89; José C. Barros)

Here’s a way to set process mass intensity targets. D. P. Kjell and colleagues at Eli Lilly (Indianapolis) describe a method for setting process mass intensity (PMI) targets for commercial drug manufacturing. The targets are based on molecular complexity and projected market demand. PMI is a key metric for evaluating the sustainability of a process; setting a target is a motivator for generating efficient synthetic routes and minimizing waste.

The authors’ model takes account of the number of chiral centers in a molecule, the number of heteroatoms, and the aromatic fraction of the molecule. The target value calculated from the model is lowered for higher predicted production volumes and raised for lower ones. This ensures that effort is directed toward the highest tonnage products, which generate the greatest amounts of waste. (Org. Process Res. Dev. 2013, 17, 169–174; Will Watson)

This platinum nanocatalyst works better naked. Heterogeneous catalysts are usually attached to solid supports. It is generally believed that the supporting substances enhance catalytic activity. A study by A. D. Chowdhury, S. Bhaduri*, and G. K. Lahiri* at the Indian Institute of Technology Bombay (Mumbai), however, shows that a “naked” platinum nanocatalyst is more efficient than its supported counterparts.

The authors first prepared naked platinum nanoparticles (PtNPs, 1) from (tert-Bu4N)2[Pt15(CO)30] in DMF at 100 °C without any additives. The chainlike nanoparticles are in the 2–3-nm size range. Catalysts supported on zeolite MCM-41 (2) and water-soluble poly(diallyldimethylammonium chloride) (PDADMAC, 3) were used as references for evaluating catalytic performance.

In a hydrogenation test, catalyst 1 reduced substrates such as styrene, cyclohexanone, and methyl pyruvate with turnover frequencies several times greater than 2 and 3 in almost all cases. In addition, 1 modified with cinchonidine, a chiral alkaloid, exhibits a better-balanced combination of turnover number and enantioselectivity than 2 in the asymmetric hydrogenation of methyl pyruvate to methyl lactate. Catalyst 3 shows no enantioselectivity in this reaction.

Cinchonidine-modified 1 also catalyzes the oxidation of racemic methyl lactate to methyl pyruvate with kinetic resolution (≤50% ee) to leave (R)-methyl lactate as the major unreacted enantiomer. The authors believe that the better-regulated and more easily accessible 111 crystal faces of the PtNPs are responsible for the excellent catalytic performance of 1. (RSC Adv. 2013, 3, 5341–5344; Xin Su)

Make biomimetic honeycomb structures with biological functions. Preparing molecular honeycomb structures often involves complicated procedures. As a result, biological applications of these biomimetic structures have not been explored. J. Qin and co-workers at the Dalian Institute of Chemical Physics (China) and the Hong Kong University of Science and Technology (Kowloon) report a straightforward procedure for synthesizing delicate honeycomb structures that have biological functions.

The authors’ procedure depends on the synergistic effect of rapid precipitation of poly(lactic acid-co-glycolic acid), a double emulsion template, and internal effervescent salt decomposition. The process makes it possible to create unique honeycomb structures that are inaccessible by other methods.

The size of the honeycomb structures and its internal cavities can be tuned by varying the concentration of the effervescent agent. The biomimetic structures can serve as microcarriers for cell culture and drug release and show promise for use in tissue engineering and drug delivery. (Small 2013, 9, 497–503; Ben Zhong Tang)

Use a cyano group to direct aryl ortho-halogenation. Aryl halides are valuable as precursors to complex structures when used in various homo- and cross-coupling reactions. The electron-withdrawing cyano group usually deactivates electrophilic halogenation and directs substitution at the meta positions.

B. Du, X. Jiang, and P. Sun at Nanjing Normal University (China) used cyclometalation-based ortho C–H bond activation to develop an efficient, scalable method for palladium-catalyzed ortho-halogenation of aryl nitriles with N-halosuccinimides (NXS; X = Cl, Br, I).

The authors used the ortho-iodination of benzonitrile (1) as a model reaction to identify the best catalyst and optimum conditions. They found that Pd(OAc)2 is a better palladium source than Pd(TFA)2, Pd(acac)2, Pd(PPh3)4 and PdCl2. (TFA is trifluoroacetate; acac is acetoacetonato.) With 5 mol% Pd(OAc)2, 1.1 equiv NIS, and 0.5 equiv p-toluenesulfonic acid (PTSA) in 1,2-dichloroethane (DCE), 2-iodobenzonitrile (2) is obtained in 84% yield.

This protocol can be applied to a broad range of benzonitrile derivatives. For 3-substituted benzonitriles, halogenation occurs only at the 6-position, probably because of steric hindrance. Similarly, ortho bromination and chlorination of benzonitrile derivatives proceed with good yields under the same conditions when NBS and NCS, respectively, are used.

The researchers believe that intermediate 4, formed by cyclopalladated intermediate 3, undergoes oxidative addition with NXS to yield intermediate 5, which gives 2 after reductive elimination. The protocol is readily scalable with slight yield decreases on the gram scale. The authors demonstrated the practicality of their method in the synthesis of anticancer natural products paucifloral F and isopaucifloral F. (J. Org. Chem. 2013, 78, 2786–2791; Xin Su)

What do you think of Noteworthy Chemistry? Let us know.