Noteworthy Chemistry

June 9, 2014

Evaluate your options for making a phenyl ether. M. Sera and co-workers at Takeda Pharmaceutical (Osaka, Japan) scaled up the synthesis of a dipeptidyl peptidase-4 inhibitor under development as an antidiabetes drug. The original route to this 6-alkoxyisoquinolone compound began with 4-hydroxyphthalic acid, which contains an oxygen substituent at what would become the 6-position. The high cost of 4-hydroxyphthalic acid, however, led the authors to study another route.

An alternative route that used an ortho-lithiation step with 4-methoxybenzoic acid as the starting material was abandoned when an alkylation step later in the synthesis failed. The authors eventually adopted a strategy that starts from 4-bromophthalic anhydride. In this route, the required 1,2-substitution pattern is in place for isoquinolone formation; a Buchwald–Hartwig coupling was used to introduce the alkoxy substituent. The route was scaled up to provide kilogram quantities of product in seven steps and 22% overall yield, much better than the original route (16 steps and 5% overall yield. (Org. Process Res. Dev. DOI: 10.1021/op5000072; Will Watson)

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Terahertz spectroscopy substantiates the AIE mechanism. Aggregation-induced emission (AIE) is a seemingly contradictory phenomenon in which a fluorophore’s emission is enhanced upon aggregation instead of being quenched. AIE has been widely studied and used in applications such as biosensors, organic light-emitting diodes, and display devices. The underlying mechanism for AIE, however, is still being debated.

Among the postulates that attempt to explain this phenomenon, the restriction of intramolecular rotation (RIR) mechanism has been supported by experimental and computational evidence. But it was not until J. A. Zeitler, B. Z. Tang, E. Pickwell-MacPherson, and colleagues at the Chinese University of Hong Kong, the University of Cambridge (UK), and the Hong Kong University of Science and Technology used terahertz time-domain spectroscopy (THz-TDS) to study molecular motions of AIE molecules that the RIR mechanism was directly validated.

Rotation of TPE phenyl groups

The authors chose tetraphenylethylene (TPE, 1 in the figure), a typical AIE-active molecule, for their study because the rotation and rocking motion frequencies of the phenyl groups in crystalline 1 lie in the terahertz range. The terahertz spectra of TPE do not change when it is irradiated with ultraviolet light at 80 K; this observation excludes the possibility of an E/Z isomerization mechanism. As the temperature increases, TPE’s rotational motions become increasingly active and its emission intensity decreases. Rotation allows excited-state TPE to dissipate energy in a nonemissive pathway.

The authors combined the THz-TDS data with computational modeling results to present solid evidence that the change in TPE emission directly correlates with the rotational changes of its phenyl groups. This work not only demonstrates the utility of THz-TDS for studying photophysical properties, but it also provides a theoretical basis for designing and applying new AIE materials. (Mater. Horiz. DOI: 10.1039/C3MH00078H; Xin Su)

[Coauthor Ben Zhong Tang is a leading AIE researcher and one of our regular contributors. See the next article.—Ed.]

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Modified polycarbazoles detect explosives. Polycarbazole (PCz) is an electron-rich conjugated polymer. Electron-deficient nitroaromatic compounds such as 2,4,6-trinitrotoluene (TNT) are well-known explosives. PCz thus has the potential to detect these explosives because it can undergo donor–acceptor interactions with them.

Tetraphenylethylene (TPE) is a luminogen that emits efficiently in the solid state (see previous article). U. Scherf and coauthors at the University of Wuppertal (Germany) and Jilin University (China) incorporated TPE substituents onto PCz chains and demonstrated the usefulness of the resulting PCz-TPE polymers (1 in the figure) as explosive detectors with robust responses.

PCz-TPE explosives detector

One PCz-TPE polymer the authors studied is a random copolymer with a 50% TPE content (1; x = y = 0.5). Its solution is almost nonemissive, with a fluorescence quantum yield (FF) as low as 0.8%. Its solid films, however, are highly fluorescent (FF = 21%).

The researchers explored the polymer’s potential for detecting explosives by using 1,3,5-trinitrobenzene (TNB), a TNT analogue, as a model nitroaromatic explosive. TNB strongly quenches the emission of PCz-TPE aggregates in aqueous media with a quenching constant as high as 1.26 ´ 106/M.

The authors demonstrated a potential practical application of their method: When they coated filter paper strips with the polymer and exposed the strips to liquid- or vapor-phase TNB, the nitroaromatic rapidly quenched the PCz-TPE’s emission. (Polym. Chem. DOI: 10.1039/C4PY00251B; Ben Zhong Tang)

Should we medicate our toddlers for ADHD? On May 16, 2014, the Centers for Disease Control and Prevention released a report stating that more than 10,000 American toddlers are medicated for attention deficit hyperactivity disorder (ADHD). There are no standard practice guidelines from the American Academy of Pediatrics (AAP) for diagnosing ADHD in children younger than 3 years old. Treating toddlers with stimulant medications such as Adderall (an amphetamine) or Ritalin (methylphenidate) is outside established pediatric guidelines.

S. N. Visser compiled the report from Medicaid and private insurance claims of families in Georgia. She found that one in ≈225 toddlers on Medicaid is being treated for ADHD with drugs. Extrapolation of this figure leads to the number of at least 10,000 medicated 2- and 3-year olds nationwide.

Aside from concerns that the safety and efficacy of these medications have not been adequately explored in such a young age group, this trend is an example of our drug-dependent society. Behavioral problems such as impulsivity and hyperactivity are developmentally appropriate for toddlers, according to experts; and, although ADHD drugs can calm these behaviors, possible side-effects such as growth suppression are especially risky for young developing minds.

There may be certain extreme situations in which such medication should be used for toddlers, for example, if they are at risk for harming themselves or others. But in most cases, nonpharmacological measures, such as nutritional and environmental modifications, should be effective treatments until a child is a bit older, and experts can determine whether an ADHD diagnosis is appropriate. (Schwartz, A. The New York Times, May 16, 2014; Abigail Druck Shudofsky)

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A single emitter makes robust white-light OLEDs. Light-emitting diodes (LEDs), especially those composed of organic materials (OLEDs), have advantages such as higher energy efficiency, longer lifetimes, and smaller profiles over traditional incandescent light sources. High-performance monochromic red, green, and blue OLEDs based on iridium and platinum phosphorescent complexes have been developed; but white OLEDs are still not practical for general use.

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One of the most promising strategies for achieving white-light emission involves doped blue emitters, which form excimers that produce white light. G. Li, T. Fleetham, and J. Li* at Arizona State University (Tempe) sought to improve the efficiency of current blue light–emitting dopants by developing a platinum complex they call Pt7O7 (1 in the figure) that greatly enhances the efficiency and stability of blue and white emission when it is integrated into OLEDs.

The symmetric tetradentate cyclometalated complex Pt7O7 is prepared by using a solvothermal reaction between a bisimidazolium ligand and Pt(COD)Cl2. (COD is 1,5-cyclooctadiene.) The quasi-reversible reduction property of Pt7O7 is ideal for stable phosphorescence emission.

OLED devices prepared with low Pt7O7 concentrations (2 wt%) exhibit blue monomer electroluminescence with CIE (Commission Internationale de l'Éclairage) coordinates of 0.12, 0.24. The peak external quantum efficiency (EQE) and the peak power efficiency of these devices reached 26.3% and 32.4 Lm/W, respectively, surpassing most other platinum- and iridium-based blue-light emitters.

When the authors increased the Pt7O7content to 14 wt%, the CIE coordinates of the device shifted to the white region (0.37, 0.43) as the result of excimer emission. The device also showed a high color rendering index of 70 and a peak EQE of 25.7%. Its enhanced stability was evidenced by a 36-h lifetime at 50% initial luminance. (Adv. Mater. DOI: 10.1002/adma.201305507; Xin Su

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Pt7O7 complex that forms white light–emitting OLEDs