Noteworthy Chemistry

July 25, 2011

Polymerization-induced peracrylate destabilization benefits frontal polymerization. Frontal polymerization is a newly discovered technique in which polymerization begins at the surface of the reaction mixture, and a polymerization “front” advances through the mixture. Heat or photochemical irradiation can be used to initiate and maintain the process. Localized chain growth is triggered by energy generated near the growth site.

In a tube reactor, for example, the polymerization can begin at the top and proceed until all of the monomer is consumed and the reaction terminates at the bottom. This process is useful for curing thick materials.

R. Liska and coauthors at the Vienna University of Technology and Ivoclar Vivadent AG (Schaan, Liechtenstein) noted that with current peroxide initiators temperatures at the polymerization front can reach >200 °C, too high for processing heat-sensitive materials such as those used in dentistry. The initiation temperature can be lowered, but this also lowers the prepolymerization thermal stability of the formulation.

To overcome these problems, the authors developed a technique in which acrylate- or methacrylate-based peroxides are included in the monomer mix. When frontal copolymerization is triggered by heat or irradiation, the peroxides are destabilized, and the polymerization front temperature is significantly reduced.

Compound 1, tert-butyl peracrylate, is the authors’ preferred peroxide monomer. Its dissociation temperature is 103 °C, but it decreases when the monomer copolymerizes with other acrylate monomers.

The authors’ proposed mechanism for the process is shown in the figure. UV irradiation is used to generate free radicals, which attack the double bond of the peroxide monomer to form intermediate radical 2. Subsequent insertion into acrylate units leads to branching. As the polymerization proceeds, the side chains spread. When the peroxide is fully incorporated (3), it dissociates at ≈80 °C. (Macromol. Rapid Commun. 2011, 32, 1096–1100; Sally Peng Li)

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What a difference a neutron makes! Vibrational reporters show promise as sensitive, site-specific probes of the local environment in proteins and nucleic acids. However, the utility of two potential probes, the cyanate and azide groups in phenyl cyanate (PhOCN) and 3-azidopyridine (PyrNNN), respectively, is hindered by accidental Fermi resonance. Specifically, anharmonic coupling between the fundamental cyanate or azide asymmetric stretch vibration with a near-resonant combination band results in an extremely broad, complex absorption profile for both probes, as shown in the blue spectra in the figure.

E. E. Fenlon, S. H. Brewer, and co-workers at Franklin & Marshall College (Lancaster, PA) examined the ability of isotopic “editing” to modulate the accidental Fermi resonance present in PhOCN and PyrNNN effectively. They synthesized and studied eight PhOCN and six PyrNNN isotopomers. Isotopic editing curbed the accidental Fermi resonance, as demonstrated by a modulation of the absorption profiles in the cyanate and azide asymmetric stretch regions. The absorption profiles of several of the isotopomers were greatly simplified, although others remained complex.

Surprisingly, adding a single neutron to the middle atom of the cyanate or azide oscillator converts the respective absorption profiles to essentially a single band resulting from the cyanate or azide asymmetric stretch vibration. This is illustrated by the red spectra in the figure. This method of using isotopic editing to enhance the utility of linear IR probes may be applicable to other vibrational probes that are impeded by accidental Fermi resonance. (J. Phys. Chem. Lett. 2011, 2, 1672–1676; Gary A. Baker)

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A polymer actuator “walks” in response to changing humidity. Living organisms can be considered supramolecular machines that consist of biopolymers that perform their biological functions in response to external stimuli. It is attractive to use synthetic polymers to build molecular actuators that transform microscopic structural change into macroscopic mechanical work. This type of actuator has been built by a team led by J. Sun at Jilin University (Changchun, China).

The actuator contains two synthetic polymer layers: one layer of a thermally cross-linked poly(acrylic acid)–poly(allylamine hydrochloride) (PAA-PAH) assembly and another of UV-cured Norland Optical Adhesives 63 (NOA 63) film. The NOA 63 layer is inert to humidity changes, but the PAA-PAH layer adsorbs and desorbs water as the environmental humidity increases or decreases. Adsorption and desorption result in hydrogel swelling and shrinking, respectively. The mismatch in the humidity response leads to rapid, reproducible bending and unbending movements of the bilayer actuator.

By connecting two “claws” to the ends of the actuator, the researchers made a humidity-driven “walking” device. The device crawls like a worm on a ratchet substrate as the humidity changes. The bilayer actuator can drive a walking device that carries a load 120 times heavier than the actuator to move steadily when the relative humidity oscillates between 11 and 40%. (Angew. Chem., Int. Ed. 2011, 50, 6254–6257; Ben Zhong Tang)

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Cocatalyst “switches” control which diastereomer is produced. W. Hu and co-workers at East China Normal University (Shanghai) developed a one-pot rhodium-catalyzed Mannich condensation of an aryldiazoacetate, a primary alcohol, and a β,γ-unsaturated α-keto ester to produce a tertiary alcohol–tertiary ester whose conformation is determined by a cocatalyst “diastereoselectivity switch”. The key to their technique is the use of AgBF4 or InBr3 as the cocatalyst. The silver cocatalyst favors erythro diastereomer 1 (erythro/threo dr > 94:6), whereas the indium salt leads to threo isomer 2 with equally high efficiency (erythro/threo dr < 4:96).


This method adds to the growing list of multicomponent reactions (MCRs) in which simple substrates combine in one operation to form complex molecules with multiple stereogenic centers. The authors note that their reaction features efficient control of product diastereoselectivity under mild conditions. They believe that similar strategies should be applicable to other MCRs for precise stereoselectivity control. (J. Org. Chem. 2011, 76, 5821–5824; W. Jerry Patterson)

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Molecular interactions cause a copolymer to twist and turn. T. Emrick, R. C. Hayward, and colleagues at the University of Massachusetts (Amherst) explored the solution assembly of a series of regioregular poly(3-hexylthiophene)-b-poly(3-triethylene glycol thiophene) [P3HT-b-P3(TEG)T] copolymers of ≈18 kDa Mn. The polymers contained polar ethylene glycol units and nonpolar hexyl side chains to provide solubility contrast and potential metal complexation to control morphology. The P3HT/P3(TEG)T weight ratios were 1:1; 2:1, and 4:1.

The polymers exist as isolated chains in CHCl3, a good solvent for both blocks. Adding MeOH, which is selective for P3(TEG)T, forms fibrillar aggregates that coexist with the solvated chains and, in the 2:1 copolymer, increase in diameter with increasing in MeOH concentration. At a 4:1 CHCl3/MeOH ratio, helical nanofibers with a periodicity of 100 nm appear. Complexation of the TEG segments with potassium ion also induces helical nanostructures with an equal distribution of the left- and right-handed conformations.

Aging these samples produces multistranded helices. A helix with n strands has n times the pitch of a single strand. The authors show that crystallization mediated by solvent quality and metal complexation work in concert to promote aggregation and superstructure formation. Packing differences from steric effects between the P3HT and P3(TEG)T blocks also play a role in coiling the crystalline nanowires. The P3HT/P3(TEG)T ratio also influences fibrillar dimensions, aggregate size, and the propensity for forming helical aggregates. (J. Am. Chem. Soc. 2011, 133, 10390–10393; LaShanda Korley)

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Create multiple stereocenters in a cyclopentanone synthesis. The conventional Nazarov reaction involves treating dienones with Lewis acids to form cyclopentenones. Y.-K. Wu, R. McDonald, and F. G. West* at the University of Alberta (Edmonton) report a variant of this methodology in which conventional dienone substrate 1 reacts with a Lewis acid to form a cyclopentenyl cation intermediate that is efficiently trapped by an electron-rich reagent such as silyl ketene acetal 2. (TBS is tert-butyldimethylsilyl.) The product is densely substituted cyclopentanone 3 with rigidly controlled stereochemistry.

The authors visualize this reaction as an asymmetric domino process that converts 1 to the intermediate cation by the Lewis acid via 4π electrocyclization. The cation is trapped by 2 and subsequently protonated to yield 3. A unique feature of the process is the formation of adducts such as structure 3 as single diastereomers with four new stereocenters in good yield.

The authors demonstrated additional enhancement of the stereochemistry of this process by using unsymmetrical dienone substrate 4, which is trapped with ketene acetal 5 with complete regio- and diastereoselectivity. This sequence forms a single diastereomer (6) with five new stereocenters. Rigorous assignment of all five stereocenters of 6 was made indirectly by oxidizing the product to the corresponding lactone 7, a crystalline solid amenable to X-ray diffraction analysis.

The scope of the domino reaction sequence includes other olefinic trapping agents such as silyl enol ethers and mixed ketene S,O-acetals. The dienone substrate can be populated with as many as four different substituents to form densely substituted products. Isomeric mixtures predominate in some products, but in general excellent diastereofacial selectivity and regioselectivity are obtained. (Org. Lett. 2011, 13, 3584–3587; W. Jerry Patterson)

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What’s the best way to simulate NMR coupling constants by DFT? NMR spectroscopy is recognized as the most widespread and powerful analytical method in organic chemistry. Although several nuclei can be studied by NMR, ordinary 1H NMR remains the most used technique. One type of data derived from NMR is the proton–proton coupling constant (JH–H). Empirical knowledge of these constants allows chemists to elucidate complex structures in organic chemistry.

NMR spectra have been simulated by quantum chemical methods, especially density functional theory (DFT). T. Bally at the University of Freiburg (Germany) and P. R. Rablen at Swarthmore College (PA) compared several DFT methods to determine the best one for simulating coupling constants.

Four terms determine the nuclear spin–spin coupling constant (J): diamagnetic spin–orbit coupling, paramagnetic spin–orbit coupling, the spin–dipole operator, and the Fermi contact (FC) term. The authors wanted to determine which terms are most significant for predicting proton–proton coupling constants.

From a test set of 66 relatively small organic molecules, the authors used several density functionals, basis sets, and methods to simulate 165 JH–H values; they then compared them with experimental values reported in the literature. The results indicated that using only FC terms in the computations gives more accurate results than when all four terms are used. A combination of the popular B3LYP functional and the 6-31G(d,p)u+1s basis set is one of the best and most economical simulation methods. This combination, however, is not the best choice for simulating chemical shifts (δ) by DFT. Even though most NMR measurements are made in the presence of a solvent such as CDCl3, including solvent effects does not produce more accurate calculated J values than gas-phase calculations.

The authors then applied the best B3LYP/6-31G(d,p)u+1s method to an experimental problem: identifying which of four possible 1-azabicyclo[3.2.0]heptane stereoisomers (1-4) are obtained from the reaction shown in the figure. Two products are formed in the reaction, and calculations of the coupling patterns predicted that the isomers were 1 and 2. As seen in the figure, the experimental spectra match well with the predictions.

The authors provide instructions for calculating 1H chemical shifts and JH–H values most economically. They also present scripts for extracting relevant information from the calculations with the Gaussian program in clearly arranged form so that they can be fed into programs for simulating entire 1H NMR spectra. (J. Org. Chem. 2011, 76, 4818–4830, José C. Barros)

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