December 5, 2011
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- Couple CO2 and an epoxide to make poly(indenecarbonate)
- Amphoteric polymers respond to physiological changes
- Modified polydopamine coatings carry a one–two punch
- Some of Alfred Werner’s crystal samples show chirality
- Change a precursor, use cross-coupling to shorten a synthesis
- Use fluorinated aziridines to make asymmetric 1,3-oxazolidines
- These compounds fluoresce efficiently in the crystalline state
Couple carbon dioxide and an epoxide to make poly(indenecarbonate). Polycarbonates are among the more useful commercial thermoplastics. Most of these materials are made from bisphenol-A or other bisphenols by condensation polymerization. A viable alternative is the catalytic coupling of oxiranes (epoxides) and CO2. However, most polymers in this class, such as poly(propylenecarbonate), have a low glass-transition temperature (Tg) that limits their industrial applications.
One solution to this problem is using a bulky epoxide monomer with phenyl rings that hinder the molecular rotation of the polymer backbone and increase the Tg. D. J. Darensbourg* and S. J. Wilson at Texas A&M University (College Station) prepared the bulky epoxide structure rac-indene oxide (1) in a simple two-step process.
The authors then used monomer 1 in a CO2 coupling reaction mediated by a Co(III) 2,4-dinitriphenoxide catalyst with a salen derivative ligand in the presence of an onium salt. The reaction is carried out under pressure at low temperature to favor copolymer 2 over the undesired cyclic carbonate 3. Polymer 2 had molecular weights (Mn) of up to 7.1 and a Tg as high as 134 °C. The Tg is the highest yet reported for a polycarbonate produced from epoxide–CO2 coupling, according to the authors.
The Tg of 2 is lower than that of bisphenol A–based polycarbonates, but the authors’ method provides various opportunities to optimize the structure of 2. Appropriate substituents on the phenyl ring and optimization of polymerization conditions may increase molecular weights and result in improved properties. (J. Am. Chem. Soc. 2011, 133, 18610–18613; W. Jerry Patterson)
Amphoteric polymers respond to physiological changes. X. Jia, D. Liang, and co-workers at Peking University (Beijing) designed a copolymer—a protein mimic—that responds to minor changes in physiological environments. Branched polymer 1 has a backbone consisting of the alternating copolymer poly(styrene-alt-maleic anhydride). A functionalized amine graft is used to open the maleic anhydride rings. Graft density can be modified by varying the reaction kinetics.
Because the polymer contains amine and carboxylic acid groups, it forms stable dispersions in water and responds to pH changes. At ambient temperature, the polymer particles are positively charged at low pH and negatively charged at high pH. The isoelectric pH value is 5.1.
Because the side-chain groups are pH- and temperature-sensitive, even minor changes, such as those found under physiological conditions, alter the polymer significantly. For example, at pH 6.2, the carboxylate groups are completely ionized, tertiary amine group ionization is limited, and the particles aggregate at ≈34 °C. If the pH value increases by 0.1 unit, the transition temperature increases by 10 °C. At pH <5.0, carboxylate ionization is replaced by amine ionization. At pH 3.0, the particles do not respond to temperature changes. (Macromol. Chem. Phys. 2011, 212, 2268−2274; Sally Peng Li)
Modified polydopamine coatings carry a one–two punch. P. B. Messersmith and colleagues at Northwestern University (Evanston, IL) incorporated an active antimicrobial (silver) and a passive antifoulant (polyethylene glycol, PEG) into polydopamine (PDA) coatings. A thin (≈4-nm) layer of PDA coated onto a polycarbonate substrate was used to reduce silver from AgNO3 and to bind thiol-terminated PEG covalently to quinone groups in the coating. Directly deposited silver coatings also were prepared for comparison.
The authors’ protocol yielded a bimodal distribution of silver nanoparticles (≈26 and ≈38 nm diam). The size and number of silver particles were controlled by varying incubation time in the AgNO3 solution. Silver was released from the coating at a relatively constant rate over 6 days. PEG grafted onto the silver coating formed a diffusion barrier that extended the release time to 10 days.
As expected, PEG chains hindered the attachment of cells from Gram-positive and Gram-negative bacteria, and cell death was observed within a 24-h incubation time for all silver-loaded substrates. The authors stress that PDA facilitates antifouling and antibacterial characteristics because of its inherent functionality. (ACS Appl. Mater. Interfaces 2011, 3, Article ASAP DOI: 10.1021/am200978h; LaShanda Korley)
Some of Alfred Werner’s crystal samples show chirality. Werner is recognized as the founder of coordination chemistry because he introduced the concept of coordination number—the number of replaceable ligands around a central metal atom. An implication of this concept is that coordination compounds can show chirality (see figure). It took Werner and his group another 10 years to prove the concept by crystallizing single enantiomers; Werner received the Nobel Prize in chemistry in 1913 for this achievement.
Decades later, researchers (e.g., Bernal, I.; Kauffman, G. B. J. Chem. Educ. 1987, 64, 604–610) reported that Werner overlooked the possibility of crystallizing coordinate compound enantiomers (“spontaneous crystallization”), picking out single crystals, and testing their optical rotation. This would have proven the presence of enantiomers and avoided tediously separating enantiomers by crystallizing them with other chiral compounds.
K.-H. Ernst, H. Berke, and coauthors at the Swiss Federal Laboratories for Materials Science and Technology (DÜbendorf) and the University of Zurich re-examined some of Werner’s original samples with X-ray crystallography. Their results indicate that the larger crystals are racemic and do not exhibit enantiomorphism, but there are few small (<1 mm) enantiomorphic crystals. They conclude that spontaneous crystallization occurred, and the enantiomeric enrichment decreased with crystal size. Why Werner did not test single crystals for optical activity remains a mystery. (Angew. Chem., Int. Ed. 2011, 50, 10780–10787; JosÉ C. Barros)
Change a precursor and use cross-coupling to shorten a synthesis. D. Mitchell and coauthors at Eli Lilly (Indianapolis, IN, and Kinsale, Ireland) and University College Cork (Ireland) originally synthesized 2-(4-bromophenyl)-3-aminothiophene, a drug intermediate, in six steps from ethyl 4-bromphenylacetate in 34–43% yield. The ready availability of methyl 3-aminothiophene-2-carboxylate raised the possibility of a decarboxylative cross-coupling reaction that would produce the same compound in two steps.
Under optimized conditions, the authors converted the methyl thiophene ester to its potassium salt. They then coupled the carboxylate salt with 1-bromo-4-chlorobenzene in DMF–N-methyl-2-pyrrolidone (9:1) at 80 °C with a PdCl2dppf catalyst and n-Bu4NF additive to produce 2-(4-chlorophenyl)-3-aminothiophene HCl in 77% isolated yield; dppf is 1,1’-bis(diphenylphosphino)ferrocene. (Org. Process Res. Dev. 2011, 15, 981–985; Will Watson)
Use fluorinated aziridines to make asymmetric 1,3-oxazolidines. The value of fluorine-substituted pharmaceutical products is well established. The trifluoromethyl group in particular imparts unique stereoelectronic properties. One useful source of trifluoromethyl groups is fluorinated aziridines, which function as masked 1,3-dipoles to form adducts with several nucleophiles. In this regard, T. Hanamoto and co-workers (Org. Lett. 2010, 12, 2548–2550) recently reported a convenient one-step synthesis of 2-trifluoromethyl-N-tosylaziridine (1). (Tosyl [Ts] is p-toluenesulfonyl.)
Hanamoto and coauthors at Sage University (Japan) and Kyushu University (Fukuoka, Japan) now report a silver-promoted 1,3-dipolar cycloaddition of 1 with aldehydes that forms the corresponding 2-substituted cis-4-trifluoromethyl-N-tosyl-1,3-oxazolidines (e.g., 2) with high regio- and stereoselectivity. All of the reactions investigated in this study provide the desired products as single isomers with yields as high as 91%.
Yields, however, varied widely and were sensitive to steric and electronic effects derived from the aldehyde structures. Strangely, the reaction fails when ketones are used in place of aldehydes.
The authors used X-ray crystallographic analysis of the products to provide unambiguous proof of their regio- and stereochemistries. The crystal structures revealed the cis relationship between the CF3 group at the 4-position and the substituent group at the 2-position on the five-membered ring. They point out that this conformation avoids the severe steric repulsion between the bulky tosyl group on the nitrogen atom and the substituents on adjacent carbon atoms in the heterocyclic ring. (Org. Lett. 2011, 13, 6240–6243; W. Jerry Patterson)
These compounds fluoresce efficiently in the crystalline state but not in solution or the amorphous state. Emission of light from an organic fluorophore in the solution state is often quenched in the solid state; the extent of quenching is more severe in the crystalline phase than in the amorphous phase. E. Cariati, C. Botta, and coauthors at the University of Milan, the Institute for the Study of Macromolecules (Milan), and the University of Pavia (all in Italy) observed the opposite phenomenon: The fluorescence of 4-dialkylamino-2-benzylidenemalonic acid dialkyl esters (e.g., 1) is greatly enhanced by crystallization.
The fluorescence of the “simple” fluorogen 1 is barely discernible in solution or in the amorphous solid, with fluorescence quantum yields (ΦF) as low as <0.1%. The crystalline powder, however, is highly fluorescent (ΦF 38%), showing the novel effect of crystallization-induced emission (CIE). The emission of 1 increases with increasing solvent viscosity or lower solution temperature.
Studies of the temperature effects on the emission and NMR spectra of 1 show that rotation around the aryl–olefin axis is the origin of the nonradiative relaxation in solution at room temperature (upper structure in the figure). The peculiar CIE behavior of 1 is therefore related to its crystal structure that restricts intramolecular rotation in the crystalline state (lower structure). (Phys. Chem. Chem. Phys. 2011, 13, 18005–18014; Ben Zhong Tang)