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Noteworthy Chemistry

July 27, 2015


Reduce click-reaction energy consumption with visible light. Photochemical ligation reactions are excellent candidates for “click” chemistry, which features atom-efficient reactions, mild conditions, and minimal waste. One drawback of irradiation-mediated transformations, however, is the high energy they usually require. Most use irradiation with UV light that may induce undesired side reactions and can be especially detrimental to biological targets.

Therefore, pushing the energy level of photochemical click reactions into the realm of visible light is a highly sought-after goal. J. P. Blinco, C. Barner-Kowollik, and coauthors at Karlsruhe Institute of Technology (Germany), Evonik Industries AG (Marl, Germany), and Queensland University of Technology (Brisbane, Australia) made the first step in this direction. Their elegant design combines a visible-light–absorbing pyrene unit bonded to a photoreactive azirine group in a stable but readily visible-light–activatable ligator (1 in the figure).

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When irradiated by light at a wavelength of ≈400 nm, compound 1 rapidly ring-opens to give the pyrenyl nitrile ylide, a 1,3-dipolar species that is highly reactive toward electron-deficient double or triple bonds. The cycloaddition reaction between activated 1 and dipolarophiles then forms five-membered nitrogen-containing heterocycles.

The researchers demonstrated the versatility of 1 with a variety of substrates, including maleimides, fumarates, acrylates, acetylenes, and polymers that contain these groups. The reactions proceed under ambient conditions without a catalyst and are complete within 1 min with, in many cases, quantitative conversion.

This strategy gives chemists a promising tool for catalyst-free, residue-free chemical reactions. It is particularly ideal for in situ ligation in biological systems. In addition, the pyrenyl group can be functionalized to incorporate substituents that absorb light of different wavelengths. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201504716; Xin Su)

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Magnesium iodide is a selective deprotecting agent. Protecting groups (PGs) are important in organic synthesis because they allow reactions to be run on functionalized substrates. Several methods are available for protection and subsequent deprotection, but some require harsh conditions.

I. Parrot and coauthors at the University of Montpellier and the University of Maine (Le Mans, both in France) conducted a systematic study of magnesium iodide (MgI2) as a selective deprotecting reagent. Using amino acids and peptides as scaffolds because of their importance in organic and medicinal chemistry and their functional diversity and chirality, the authors explored the use of MgI2 in tetrahydrofuran (THF) under microwave irradiation.

The authors found that MgI2 has distinct selectivity patterns. It can deprotect esters, N-triphenylmethyl (N-trityl) groups, and tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Z), and allyloxycarbonyl (alloc) carbamates; but it does not react with ethers, amides, or fluorenylmethoxycarbonyl (Fmoc) carbamates.

In a “green” context, MgI2 can deprotect Z and alloc groups without the need for palladium-catalyzed hydrogenation. Also, the THF solvent can be replaced by its greener 2-methyl derivative.

Treating the doubly protected dipeptide Boc-Phe-Gly-OEt with MgI2 for 5 min deprotects Boc; after 2 h, the ethoxy group is cleaved as well. MgI2 can also be used to cleave PGs from Merrifield, 2-chlorotrityl, and Wang resins, but not from the Rink amide resin. In summary, this method allows rapid, green, mild, racemization-free cleavage of PGs in good yields. (Chem. Eur. J. DOI: 10.1002/chem.201501799; José C. Barros)

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Compound droplets form four-phase linear junctions. The equilibrium shapes of simple droplets hanging from horizontal fibers are well established, but the situation becomes more complex for compound fluidic systems. Thermodynamic laws suggest that three phases meet along a line, whereas four phases should join at a single point. A recent study of compound droplets demonstrated what may be the first observation of a linear junction of four phases.

Compound droplet systems can be used to understand and develop a variety of microfluidic devices in which water droplets are encased in oil coatings to prevent evaporation and contamination. Such devices include "open digital microfluidic" systems that allow sample transfers, biochemical reactions, and analyte detection on a microliter scale. These systems use programmable sequences of dispensing, moving, splitting, and merging droplets on an open surface. Optofluidics combines microfluidic and nanophotonic technologies to produce lab-on-a-chip and biophotonic devices.

F. Weyer and coauthors at the University of Liège (Belgium), Karlsruhe Institute of Technology (Germany), and the University of Applied Sciences (Karlsruhe) show that compound droplets on horizontal fibers adopt specific geometries. Depending on the surface tensions, the air–oil–fiber triple contact line can remain separate from the oil–water–fiber triple contact line; or the lines can merge to form air–oil–water–fiber quadruple lines.

The authors used droplets of colored water, with and without a soap solution, encased in silicone oil and suspended from nylon fibers. Pure water droplets form spherical caps, with well-defined contact angles, surrounded by oil. Soapy water droplets spread inside the oil droplet, and the inner contact line moves toward the outer contact line. For some volume ratios of soapy water to oil, the contact lines merge to form a quadruple contact. The authors used numerical modeling to replicate this effect.

Left, oil–pure water droplet; right, oil–soapy water droplet

For pure water encased in oil, the oil droplet hangs from the water droplet, which adheres to the fiber (left in the figure). Detachment depends only on the diameter of the water droplet. For soapy water, the oil and water move together along the fiber (right); the detachment process is controlled by the diameter of the fiber. (Langmuir DOI: 10.1021/acs.langmuir.5b01391; Nancy McGuire)

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“Green herders” can corral oil spills. Chemicals used to collect spilled oils into thickened slicks are known as chemical herders. Following an oil spill, booms and chemical herders are used to corral the oil into slicks ≈3 mm thick so that it can be burned off. Chemical herding is the only method that can be used in remote ice-covered water and loose drift-ice conditions where booms cannot be deployed. The in situ burning minimizes the long-term risks of persistent toxicity in a marine ecosystem.

Amphiphilic chemical herders are sprayed on the water surrounding an oil spill and form a monomolecular layer on the surface of the water. When it reaches the oil, the herder lowers the air–sea surface tension “so that the spreading coefficient becomes negative, and the slick retracts as the air–oil and oil–water tensions pull back at the contact line”. The best known herders currently in use are silicone polyethers (Silsurf A108 and Silsurf A004-D; Siltech Corp., Toronto), which are not biodegradable and persist in the marine environment; their toxicological and environmental effects have not been documented.

G. John and coauthors at the City College of the City University of New York (NYC) and Tulane University (New Orleans) set out to find a green herder that performs as well as the silicone products. Their objective was to “design and develop sacrificial and effective green herding amphiphiles” based on phytol. Phytol is abundant, inexpensive, and readily obtainable from marine algae; it is a major component of the sea surface monolayer; and it is readily biodegradable.

The authors prepared and studied two phytol-based cationic amphiphiles, PIm and PPy*. To qualify as green herder, the molecule must

  • be liquid at temperatures between 5 and 35 °C,
  • spread spontaneously into a thin film on the surface water,
  • have a low evaporation rate, and
  • lower the surface tension of the water to ≈25 mN/m.

The authors tested PIm and PPy in fresh and saline water at ≈5, ≈20, and ≈35 °C to mimic natural conditions. Macondo crude oil was used to simulate a spill. The performance of the herders is measured according to the size and thickness of the “slick”; their efficiency is based on herding dynamics, that is, the speed of herding. The herders thickened the oil slicks by ≈5-, ≈7-, and ≈25-fold at ≈5, ≈20, and ≈35 °C, respectively, during the first 10 min of the experiments.

The herding dynamics of both green herders are similar to the Silsurfs. The authors were also interested in the sacrificial (degradation) tendencies of the phytol-based herders. When their phytol “tails” rearrange, the green herders release small molecules and other degradation products that are not harmful to the marine ecosystem. The fragments are based on a plant-derived molecule that is hydrolyzed within 1 month. In contrast, the Silsurfs’ stability guarantees their longevity in the ecosystem.

The researchers are confident that the new herders are valid replacements for the silicone ethers. (Sci. Adv. DOI: 10.1126/sciadv.1400265; Beth Ashby Mitchell)

*PIm is 1-methyl-3-[2-oxo-2-(phytyloxy)ethyl]-1H-imidazol-3-ium bromide; PPy is 1-[2-oxo-2-(phytyloxy)ethyl]pyridinium bromide.

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Prepare a “rotor” molecule quickly and cheaply. The bicyclic structure of bicyclo[2.2.2]octane-1,4-dicarboxylic acid (4 in the figure) has several applications in organic chemistry such as in molecular rotors and metal–organic frameworks. Synthesizing this compound, however, requires several steps and long reaction times; and it uses bad-smelling thiol compounds and potentially explosive Raney nickel.

Improved synthesis of bicyclo[2.2.2]octane-1,4-dicarboxylic acid

N. Le Marquer, M. Y. Laurent, and A. Martel* at the University of Maine (Le Mans, France) developed an easy, rapid way to synthesize the target molecule. Starting from diethyl succinate (1), they prepared the bicyclic core (2) under microwave (MW) irradiation for 12 h. The presence of ester groups prevented them from using the traditional Wolff–Kishner reaction to reduce the ketone groups, so they converted the ketones to semicarbazones (3) and reduced it in the solid phase to give target molecule 4 in 49% overall yield.

This simple, rapid method is much less expensive than the traditional one. Bicyclic diacid 4 cost ≈5€/g to prepare versus ≈26€/g in the Raney nickel method. (Synthesis DOI: 10.1055/s-0034-1380432; José C. Barros).

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Pyrenylarizine structure