Noteworthy Chemistry

June 22, 2009

Convert aldehydes to α,β-unsaturated aldehydes or enals
Titania–graphene composites for lithium ion battery electrodes
Internal indicator is unsuitable for large-scale synthesis
Biomimetically mineralize hydroxyapatite
Simple, general synthesis of unsymmetrically substituted alkynes
What’s cooking? Molecular gastronomy

This simple one-pot reaction converts aldehydes to α,β-unsaturated aldehydes or enals. Enals are an important class of synthetic intermediates that are essential for many organocatalytic transformations. P. J. Walsh and co-workers at the University of Pennsylvania (Philadelphia) recognized the need for simple and inexpensive routes to these structures.

They developed a one-pot tandem method that begins with the hydroboration of ethoxyacetylene by BH₃∙SMe₂ to form tris(ethoxyvinyl)borane (1), a reagent that is stable for months under nitrogen. Transmetalation from boron to zinc forms an alkene intermediate that adds to aldehydes or ketones to produce intermediate zinc alkoxy enol ethers. Acid-promoted elimination of this intermediate generates the desired enal 2 with two-carbon homologation.

The authors converted an array of substrates to the corresponding enals in good to high yields (72–96%). The figure illustrates the diversity of products (3–6) that can be obtained by using this method. Ketone substrates, however, were less reactive and led to varying results.

The procedure tolerates chiral substrates, as illustrated by the reaction of benzyl-protected 2-hydroxypropanal 7 to give enal 8 with >98% ee following isolation and purification. The authors extended their method to form derivatized enals; one example is trapping the intermediate with dithioglycol to form the unsaturated 1,3-dithiolane 9 in 98% yield. (Org. Lett. 2009, 11, 2117–2119; W. Jerry Patterson)

Use titania–graphene composites for lithium ion battery electrodes. Slow Li⁺ diffusion, poor electron transport, and high resistance are the key problems with Li-ion battery electrode materials that must be solved before the technology can be used extensively. I. A. Aksay and coauthors at Pacific Northwest National Laboratory (Richland, WA) and Princeton University (NJ) attacked the problem by using a thermal expansion method to prepare TiO₂–graphene nanocomposites.

Functionalized graphene sheets (FGS) stabilized by sodium dodecyl sulfate (SDS) surfactant were treated with TiO₂ nanoparticles via a complexation process to form the composites with interspersed SDS molecules. Controlling the conditions produced rutile or anatase TiO₂–graphene phases. Electron microscopy showed that the graphene sheet surfaces were covered with highly dispersed TiO₂ particles because of the presence of the surfactant. Charge–discharge profiles showed that the specific capacity of TiO₂–graphene is greater than that of pure TiO₂. Electrochemical impedance results indicated that the resistivity of the cells decreases with the addition of graphene, which improves the charge rate. (ACS Nano 2009, 3, 907–914; George Xiu Song Zhao)

Contamination problems make an internal indicator unsuitable for large-scale synthesis. While developing a synthesis of a phthalazine-based p38 MAP kinase inhibitor, O. R. Thiel and co-workers at Amgen (Thousand Oaks, CA) found that measuring the endpoint during the formation of the lithium alkoxide of (R)-1,1,1-trifluoropropanol is critical to avoid the formation of impurities during the subsequent S_NAr reaction with 1,6-dichlorophthalazine. On the lab scale, the endpoint was measured by adding 1,10-phenanthroline indicator to the reaction mixture. The indicator turns yellow during the formation of the alkoxide and brown at the equivalence point. Additional trifluoropropanol is added to ensure that no n-BuLi is present during the next reaction.

The authors, however, decided that contamination with 1,10-phenanthroline, and particularly its decomposition products, precluded its use in the scaled up synthesis. They adopted an alternative on-line in situ Raman spectroscopy monitoring method. C–O stretching or deformation bands at ~780 cm^-1 for the alkoxide and ~792 cm^-1 for the alcohol can be used as strong markers to allow on-line monitoring of alkoxide formation. (Org. Process Res. Dev. 2009, 13, 230–241; Will Watson)

Use functionalized polystyrene to biomimetically mineralize hydroxyapatite. A. Ethirajan, U. Ziener, and K. Landfester* at the University of Ulm (Germany) and Max Planck Institute for Polymer Research (Mainz, Germany) developed biomineralization templates using carboxyl-functionalized polystyrene particles (1). They synthesized the particles by miniemulsion copolymerization of styrene with acrylic acid (AA) in the presence of ionic and nonionic surfactants. Stable polystyrene particles were obtained only with low AA comonomer content and the ionic surfactant.

In the presence of 200 mg of ionic surfactant, functionalized polystyrene particles were produced with diameters that increased from 162 to 254 nm with an increase in AA concentration from 1 to 3wt%. In contrast, greater incorporation of AA (up to 10%) and higher yields (~90–100%) of smaller functional PS particles were obtained with a nonionic surfactant, but extensive dialysis and exchange procedures were needed before they could be templated.

The authors discuss several trends pertaining to surface charge as a function of surfactant type and AA concentration. Higher carboxylate surface charge was obtained with the nonionic surfactant at a given AA content, and surface charge density increased with increasing AA content for both types of surfactants.

Calcium and phosphate ions (5:3 mol ratio) were added sequentially at pH 10 to form hydroxyapatite on the functionalized polystyrene particles (2). Carboxylate functionalization and optimal surfactant concentration are necessary for hydroxyapatite growth, and the degree of hydroxyapatite formation directly correlates with surface charge density. For a given AA comonomer content, the hydroxyapatite nanocrystals (19–22 nm) form more uniformly across the functionalized polystyrene particles derived from the nonionic surfactant. Although hydroxyapatite surface coverage was incomplete and minimal amounts of precipitated bulk hydroxyapatite crystals were also formed, the authors found that the hydroxyapatite crystals were bound to the surface of the polystyrene particles. (Chem. Mater. 2009, 21, 2218–2225; LaShanda Korley)

Here’s a simple, general synthesis of unsymmetrically substituted alkynes. K. A. Davies, R. C. Abel, and J. E. Wulff* at the University of Victoria (BC) noted the important function of this type of structure in biological receptors. Their strategy was to use the reaction of benzyl bromides or chlorides with terminal alkynes with copper catalysis in a mild, operationally simple process. This method leads to a range of functionalized benzyl-substituted propiolates with the use of commercially available benzyl halides. The reaction conditions were optimized by adding K₂CO₃ as the required base and Bu₄NI as a phase-transfer catalyst.

This method makes it possible to “decorate” substituted alkyne products such as 1 with a wide range of functional groups from the benzyl halide and alkyne reactants. The scope of the reaction includes ester, amide, keto, trimethylsilyl, sulfone, and alkyl groups on the alkyne reactant. This is the first report of a successful coupling reaction of electron-poor acetylenes such as methyl propiolate. Aryl substituents on the benzyl halide include benzyloxy, methoxy, alkyl, hydroxyl, and chloride groups. Product yields varied widely, but several reactant combinations produced near-quantitative yields of 1.

The authors point out that many of the reactants they used are commercially available, and that the reaction does not require strong bases, expensive catalyst systems, or high temperature. The reaction is relatively insensitive to small quantities of moisture or air. (J. Org. Chem. 2009, 74, 3997–4000; W. Jerry Patterson)

What’s cooking? Molecular gastronomy. Until ~20 years ago, no one studied the chemical changes that occur during food preparation. However, almost all aspects of cooking, from slicing vegetables to induce enzymatic reactions to the thermal reactions of meat, involve some form of molecular transformation.

H. This at INRA/AgroParis Tech presents an account of molecular gastronomy, a discipline established in 1988. The original objectives of the discipline were to “model ‘culinary definitions’, collect and test ‘culinary precisions’, explore (scientifically) the art component of cooking, and explore the ‘social link’ of cooking”.

The author discusses the formalism of “complex disperse systems” (CDS) and the “nonperiodical organization of space” (NPOS). CDS describe foods in terms of equations that capture the physical nature of its component materials (gas, oil, water, and solid). This tool can be used to develop new dishes, such as “Chantilly chocolate”, a mousse without eggs. The NPOS formalism describes components as dimensional objects. The two definitions are combined to describe gels that are related to plant or animal tissues.

Chemical modifications of raw materials (culinary reactants) are also studied in molecular gastronomy. For example, a study of the relationship between cooking temperature and protein denaturation in eggs revealed two distinct coagulation temperatures: 65 °C (top photo) and 71 °C (bottom).

Molecular gastronomy was inspired by the drug-design process; but predicting physical, biological, chemical, and organoleptical properties of prepared dishes from their CDS–NPOS formulas has yet to be successful. (Acc. Chem. Res. 2009, 42, 575–583; José C. Barros)