Noteworthy Chemistry

May 26, 2014

A mixed metal oxide forms a "greener" yellow pigment. Mineral-based pigments are preferable to organic dyes in applications that require long-term stability and heat resistance. Common commercial yellow pigments include PbCrO4, Pb2Sb2O7, and CdS, all of which are toxic and face increasing regulatory restrictions.

S. P. Radhika, K. J. Sreeram*, and B. U. Nair at the Council of Scientific and Industrial Research (Chennai, India) prepared an environmentally benign molybdenum-doped gadolinium/cerium oxide yellow pigment. Their procedure consisted of a low-temperature citrate sol–gel process followed by heat treatment (calcination). The resulting pigment particles sizes ranged from nanometers to micrometers (see figure; scale bar is 5 μm). 

Gadolinium/cerium oxide yellow pigment particles

The authors’ process provides good size and shape control for the pigment particles. Introducing Mo6+ changes the material from white to dark yellow. The maximum yellow character (less green, more red) was observed at 0.35 mol% molybdenum doping, although the color was yellow at all doping levels between 0.05 and 0.35%. The color did not lighten or darken with doping.

The addition of mineralizers (NaF and NH4H2PO4) improved the pigment's ability to cover an underlying color at a lower covering thickness. Mineralizers such as CaF2, Na2CO3, and H3BO3 shifted the hue toward orange-yellow.

Near-infrared (NIR) reflectance, an important factor for keeping house and car interiors cool, is ≈70–87% for paints and coatings that contain conventional yellow pigments. The 0.35 mol% Mo-doped pigment showed an NIR reflectance of 91%, possibly because of its particle size and phase structure.

The authors tested the pigment's ability to retain its color when it was dispersed into an alkyd paint medium and when it was incorporated into a poly(methyl methacrylate) solid. The pigment was resistant to acids and alkalis, resisted bleeding into a variety of solvents, and had good light-fastness.

Its stability and the absence of toxic metal ions make the pigment a good candidate for coloring children's toys, home interior finishes, and other applications that involve human contact. (ACS Sustainable Chem. Eng. 2014, 2, 1251–1256; Nancy McGuire)

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Use flow NMR to measure hydrogen in solution. Pressurized hydrogen gas and synthesis gas (syngas, a mixture of hydrogen and carbon monoxide) are widely used in catalytic reduction reactions, especially in large-scale chemical manufacturing. Accurately measuring the concentration of hydrogen dissolved in liquids is important for monitoring reaction progress, understanding reaction mechanisms, and optimizing reaction conditions.

The ideal technique for measuring hydrogen concentrations under high pressure should avoid anything that interferes with the reaction in progress, including pressure relief, exposure to air, and loss of volatiles. J. Y. Buser* and A. D. McFarland at Eli Lilly (Indianapolis) developed a method for monitoring dissolved hydrogen under high pressure in real time, using nuclear magnetic resonance (NMR) spectroscopy in line in the gas stream.

The authors’ basic experimental setup consists of a Parr reactor connected to a pressurized hydrogen cylinder and an NMR spectrometer. A high-pressure liquid chromatography pump circulates reaction solutions between the reactor and the spectrometer.

After they calibrated and optimized the system, the authors could accurately measure dissolved hydrogen concentrations in a 50–1000 psi pressure range at room temperature in five common solvents. They used p-toluic acid as the internal standard. The same instrument configuration was used to establish reaction kinetics, including the direct measurement of kLa, the gas–liquid volumetric mass transfer coefficient, in hydroformylation reactions.

This method can also be used to monitor other reactants, intermediates, and products simultaneously. The authors believe that their technique can be expanded to other NMR-responsive nuclei and that it can be diversified by coupling it with additional analytical techniques. (Chem. Commun. 2014, 50, 4234–4237; Xin Su)

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Magnesium ion switches phosphorescence on; fluoride turns it off. Materials that produce light when their particles form aggregates (aggregation-induced emission, or AIE) have been combined with metal-ion ligands to develop light-emitting materials. Phosphorescent AIE systems can be used for time-gated assays that eliminate unwanted fluorescence by the substance being analyzed, and phosphorescent materials can, in theory, achieve 100% electroluminescent efficiency.  Until now, however, switching on the phosphorescence of organic color-producing entities required that these entities be directly involved in the metal-ion coordination processes.

M. Gingras, P. Ceroni, and coauthors at the University of Bologna (Italy) and Aix-Marseille University (Marseille, France) synthesized terpyridine (tpy) ligand 1 (see figure) and showed that its complexation with metal ions causes an AIE effect.

Formation of a phosphorescent polymer by metal-ion complexation

Ligand 1 consists of a hexakis(phenylthio)benzene (hpb) core and six tpy peripheral groups. Its solution is nonemissive, but treating it with Mg2+ ions leads to strong phosphorescence because of the formation of a metal-coordination polymer (2) in which intramolecular rotation is restricted. The images below structures 1 and 2 illustrate the AIE phosphorescence

The polymeric structure of 2 serves as a light-harvesting antenna. Excitation of the [Mg(tpy)2]2+ units sensitizes the phosphorescence of the hpb core with almost 100% efficiency. The phosphorescence of 2 can be easily switched off by disassembling its supramolecular structure by adding F ions, which sequester the Mg2+ ions. (J. Am. Chem. Soc. 2014, 136, 6395–6400; Ben Zhong Tang)

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Turn inexpensive biomass into valuable pharmacophores. Synthetic chemists continue to develop simple, efficient ways to synthesize pharmacophores, the biologically active subunits in drug molecules. Ideal routes produce pharmacophores in as few steps as possible from inexpensive raw materials and reagents.

Biomass is a promising feedstock for pharmacophores because it is widely available and contains well-understood chiral centers that are intrinsically bioactive. Z. Zuo and D. W. C. MacMillan* at Princeton University (NJ) used α-amino acids, which are abundant in biomass, to develop a one-step catalytic method for generating benzylic amines, a class of valuable pharmacophores.

The authors anticipated that tert-butoxycarbonyl (Boc)–protected α-amino acids could be decarboxylated in the presence of a photoredox catalyst and then undergo radical–radical coupling with radical anions derived from an arene. They proposed that single-electron transfer (SET) processes mediated by iridium(III)-based catalyst 1 would generate cyanoaryl radical 3 from arene 2 and α-carbamoyl radical 5 from α-amino acid 4 (see figure). Subsequent C−C bond formation between 3 and 5 would yield benzylic amine product 6.

A benzylic amine formed by radical–radical coupling

The authors screened catalysts and reaction conditions for the decarboxylative arylation between Boc-protected proline and 1,4-dicyanobenzene. They obtained the highest yield (83%) of the racemic benzylic amine with 2 mol% catalyst 1, CsF as the base, dimethyl sulfoxide as the solvent, and irradiation with a 26-W fluorescent light bulb at room temperature.

The protocol is compatible with a wide range of amino acid substrates and can be applied to α-oxygen–containing carboxylic acids. Several cyanoarenes can be used as coupling partners. This is a convenient way to form Csp3Csp2 bonds, and it can overcome synthesis problems that would otherwise be difficult to solve. (J. Am. Chem. Soc. 2014, 136, 5257–5260; Xin Su)

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A specific vinyl reagent gives the desired regioisomer in a Heck reaction. Pharmaceutical manufacturing processes rely on reactions that reliably produce large quantities of the desired compounds, with the organic functional groups located in the desired positions on the backbone structure (regioisomers). In the course of developing a scalable synthesis of a hepatitis C drug candidate, Z. J. Song and co-workers at Merck Research Laboratory (Rahway, NJ) used a Heck reaction to couple an iodobenzoate with N-vinylphthalimide. When they used palladium acetate as the catalyst and triethylamine as the base in 2-methyltetrahydrofuran (2-MeTHF) solvent, the reaction was regioselective toward the terminal carbon atom of the vinyl group. The terminal/internal coupling ratio was 9:1.

Other vinylamides (e.g., N-vinylpyrrolidinone and N-vinylacetamide), vinyl ethers, and vinyl acetate react mainly at the internal carbon of the vinyl group. The major isomer of the N-vinylphthalimide product was isolated in 76% yield with high purity after recrystallization from 2-MeTHF. (Org. Process Res. Dev. 2014, 18, 423–430; Will Watson)

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Crystal chirality directs an asymmetric photoreaction. Chiral molecules, those with mirror-image left- and right-handed versions, are common in biological processes. Often, producing pharmaceutical compounds requires separating the biologically active isomer from the non-active one. This usually requires using external chiral sources such as chiral catalysts, but sometimes you can achieve the same result when achiral substrates form chiral crystals.

Statistically, only 8% of achiral molecules spontaneously form crystals with chiral structures. It is not yet possible to predict chiral crystallization, but chiral derivatives of compounds that crystallize chirally can be made by using rational design.

H. Koshima and colleagues at Ehime University (Japan), the Tokyo Institute of Technology, and Rigaku Corp. (Tokyo) report an example of this phenomenon in which an achiral triisopropylbenzophenone derivative undergoes stereoselective photocyclization induced by its chiral crystal environment.

The authors synthesized and crystalized three 2,4,6-triisopropylbenzophenones substituted with p-, m-, and o-benzylamides. Of the three achiral compounds, only para-substituted derivative 1 (see figure) formed chiral crystals, as determined by solid-state circular dichroism spectroscopy. Analysis of compound 1 crystals showed that they exist as counterclockwise (M) and clockwise (P) helices. 

Stereoselective photocyclization of compound 1

The authors subjected ground M-form crystals of 1 to ultraviolet irradiation under an argon atmosphere at 15 ºC for 24 h. The resulting enantioselective cyclization reaction gave chiral cyclobutenol product (R)-2 in 100% yield and 94% enantiomeric excess (ee). Similarly, (S)-2 was obtained from P-crystals in 100% yield and 95% ee.

The photocyclization also caused cracks along the direction perpendicular to the crystals’ long axis, likely caused by breaking hydrogen bond networks. In contrast to the solid-phase reaction, the solution-phase photolysis of 1 gave only a 65% yield and produced a racemic mixture of 2. (J. Org. Chem. 2014, 79, 3088–3093; Xin Su)

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