Noteworthy Chemistry

October 3, 2011

Make poly(ionic liquid)s by cobalt-mediated radical polymerization. Poly(ionic liquid)s (PILs) combine the unique properties of ionic liquids (e.g., chemical and thermal stability, high electrical conductivity, and controllable solubility and viscosity) with the desirable aspects of polymers (e.g., film formation and processibility). Eventually they may have more applications than molecular ILs. C. Detrembleur, D. Taton, and coauthors at the University of Liège (Belgium), the National Center for Scientific Research (Pessac, France), and the University of Bordeaux (Pessac) investigated the cobalt-mediated radical polymerization of IL monomers and determined the impact of solvents on the reaction.

Imidazolium salts are typical ILs. The authors chose 1-vinyl-3-ethylimidazolium bromide (1) as the monomer for the polymerization reaction. They treated Co(acac)2 with 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) to form Co(III) complex 2, which generates reactive radicals at ambient temperature; acac is acetylacetonate. Complex 2 dissociates to become the initiator and controlling agent for the polymerization. A reversible deactivation process helps control the reaction.

The authors discovered that the solvent has a profound effect on reaction rate and chain growth. The reaction proceeds moderately rapidly in MeOH, but DMF coordinates with cobalt and accelerates radical-forming C–Co bond cleavage. Adding MeOH to the DMF reaction medium suppresses chain growth and helps to control the reaction. The authors, however, found that the reaction is easiest to control when MeOH is the only solvent, and they used it in their subsequent investigation of IL radical copolymerization. (Macromolecules 2011, 44, 6397−6404; Sally Peng Li)

Back to Top

Run a hydroformylation reaction in tert-butyl alcohol. T. Storz and co-workers at Pfizer (Pearl River, NY, and Groton, CT) developed a practical procedure for hydroformylating norbornene and a subsequent oxidation reaction to produce the sodium salt of (±)-2-exo-norbornanecarboxylic acid. A solvent screen identified toluene, i-PrOAc, MeCN, and CH2Cl2 as suitable solvents for the hydroformylation reaction.

The authors chose t-BuOH for the solvent because it allows the hydroformylation and oxidation reactions to be telescoped. The oxidation is run with TEMPO [(2,2,6,6-tetramethylpiperidin-1-yl)oxyl] and NaClO2. The carboxylic acid sodium salt is produced in 80% isolated yield on an 11-kg scale. (Org. Process Res. Dev. 2011, 15, 942–945; Will Watson)

Back to Top

Prepare thiazolidinones from three components in one pot. 2-Thioxo-1,3-thiazolidin-4-ones (rhodanines) are medicinally useful sulfur–nitrogen heterocycles. Some derivatives in this class have a wide range of antimalarial, antibacterial, antiviral, antitumor, anti-inflammatory, or herbicidal activity.

Although 5-arylidenerhodanines are cited frequently in the literature, the corresponding 5-alkylidene analogues are not as well known. A. M. Jacobine and G. H. Posner* at Johns Hopkins University (Baltimore) describe a convergent synthesis of N-alkyl-5-(Z)-alkylidenerhodanines exemplified by structure 1 in the figure.

The authors’ synthetic strategy is based on a three-component, sequential 1 + 2 + 2–atom formation of the five-membered heterocyclic ring that starts with amine addition to CS2 to give dithiocarbamate anion 2 in situ. Anion 2 displaces chloride from α-chloro-β,γ-alkenoate ester 3 to give uncyclized intermediate 4. Alkene isomerization of 4 produces 5, another intermediate, in which the alkene is conjugated with the ester group. Ring-forming cyclization of 5 produces target rhodanine scaffold 1 functionalized with an alkylidene group.

The authors prepared 1 on a 250-mg scale. They demonstrated the potential of this method by preparing a close analogue of the drug epalrestat, a rhodanine with aldose reductase inhibitory properties. Their procedure produced this potential drug structure in chromatographically pure form in 48% yield. (J. Org. Chem. 2011, 76, 8121–8125; W. Jerry Patterson)

Back to Top

Self-assembly of large graphene oxide sheets leads to the spontaneous formation of a lyotropic liquid crystalline phase. Rod-shaped, disklike molecules are mesogenic units for assembling liquid crystals (LCs). Lyotropic LC phases have been observed in solutions of rod-shaped carbon nanotubes and sheetlike graphenes at high colloidal concentrations—up to ≈90 mg/mL). Using graphene oxide (GO) as mesogen, a research team led by J.-K. Kim at the Hong Kong University of Science & Technology (Kowloon) generated lyotropic LCs at concentrations as low as 1 mg/mL or 0.1 wt %.

The researchers used a modified chemical process to prepare stable dispersions of GO sheets from exfoliated graphite. Their goal was to minimize possible breakage of the GO sheets. By eliminating sonication, they obtained gram quantities of monolayer GO sheets with ultralarge sizes (areas as high as 10,000 μm2) and high yields (>80%). The extremely high aspect ratio (>30,000:1) of the GO sheets allowed them to self-align to form of a lyotropic nematic LC phase in aqueous colloidal suspensions at extraordinarily low GO concentrations. (Adv. Funct. Mater. 2011, 21, 2978–2988; Ben Zhong Tang)

Back to Top

Here’s a simple way to trifluoromethylate aromatic heterocycles. The trifluoromethyl (CF3) group is present in several drugs, agrochemicals, dyes, and polymers; but adding CF3 to arenes requires harsh conditions or toxic reagents. P. S. Baran and co-workers at the Scripps Research Institute (La Jolla, CA) devised an easier, milder method for trifluoromethylating heterocyclic aromatic rings.

The authors’ protocol makes use of innately reactive C–H bonds in heterocycles. The group screened several reagents in the transformation and found that solid, bench-stable CF3SO2Na (the Langlois reagent) is a reliable trifluoromethylation agent. Optimization of the reaction with 4-acetylpyridine (1) as the substrate (see figure) showed that a two-phase solvent system (CH2Cl2–H2O), with t-BuOOH and a metal catalyst (Fe, Cu, or Co), generates the CF3SO2· radical, which releases SO2 and CF3· to react with the heteroarene.

Using this method, which is functional-group tolerant, broad in scope, and scalable, the authors trifluoromethylated several heterocycles. Even compounds that are insoluble in CH2Cl2 can be used as substrates if they are soluble in water. The method, however, has selectivity problems with arenes that have more than one reactive C–H bond, and some substrates give low yields. (Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 14411–14415; José C. Barros).

Back to Top

Go with the flow: Shear forces induce a cubic lipid phase. A. M. Seddon, A. M. Squires, and coauthors at the University of Bristol (UK), the University of Reading (UK), and Lund University (Sweden) used flow alignment and dilution to the generate a stable inverse bicontinuous cubic (QIID) phase of the lipid 1-monoolein (MO) from the sponge phase (L3, 40 wt% MO in the solvent). The solvent was 40 vol% 1,4-butanediol in water.

Diluting the solvent with more water to lower the 1,4-butanediol content to 15 vol% enhances the interfacial curvature under shear flow and leads to an aligned cubic QIID phase. The self-assembled bicontinuous lipids are stable for ≥10 min when the flow field is removed. The authors obtained similar effects in a Couette cell, although with different orientations. This work has potential applications in nanomaterial templating, with an emphasis on protein structure and crystallization. (J. Am. Chem. Soc. 2011, 133, 13860–13863; LaShanda Korley)

Back to Top

Create telechelic polymers with regioregular morphologies. Recent studies show that glassy–rubbery semicrystalline multiblock copolymers can be made by hydrogenating copolymers that contain poly‍(1,4-butadiene) segments. These materials exhibit unusual mechanical strength and elasticity because of the nature of the in-chain crystalline blocks. Hydrogenation, however, typically fails to form highly crystalline, defect-free polymer segments because of 1,2-regiodefects in the resulting linear low-density poly‍(ethylene-co-butylene) with undesirably low backbone carbon atom chain lengths.

Other ways to incorporate highly crystalline polyethylene segments into block copolymers involve ring-opening metathesis polymerization (ROMP) techniques that use symmetric acyclic olefin chain-transfer agents. Initiating agents such as 1, with terminal alkoxyamine functionalities, allow the formation of α,ω-telechelic copolymers with chain-end functional groups that mediate chain extension block copolymerization.

M. Mahanthappa and co-workers at the University of Wisconsin–Madison optimized this method by synthesizing 1 (Figure 1) and using it in ROMP in the presence of cycloalkene 2 to form perfectly regioregular α,ω-telechelic poly‍(1,4-butadiene) 3 with alkoxyamine termini (Figure 2).

The authors show that 3 is a macroinitiator for nitroxide-mediated polymerizations of styrene and isoprene monomers. It yields unimodal multiblock copolymers illustrated by structure 4 in Figure 2. (TIPNO is 2,2,5-trimethyl-4-phenyl-3-azahexane nitroxide.) Subsequent diimide hydrogenation of the multiblock copolymers forms previously unknown glassy–rubbery semicrystalline multiblock copolymers (5). NMR analysis showed that the in-chain isoprene segments are substantially hydrogenated, with ≈65% saturation.

The center block is completely saturated and provides the desired high-density linear polyethylene segments with high crystallinities and melting points. These segments are regiodefect-free. The authors note that these complex multiblock copolymers with polydisperse high-density polyethylene segments are inaccessible by other polymerization techniques. (Macromolecules 2011, 44, 7141–7148; W. Jerry Patterson)

Back to Top

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