Noteworthy Chemistry

July 13, 2015


A dual strategy optimizes an asymmetric fluorination. M. Gray, S. G. Leach, and co-workers at GlaxoSmithKline Medicines Research Center (Stevenage, UK) describe the development and scale-up of a synthesis of a selective spleen tyrosine kinase inhibitor. One of the key steps is the asymmetric fluorination of a 2-oxopiperidine-3-carboxylate ester (1 in the figure)

Asymmetric fluorination of a 2-oxopiperidine-3-carboxylate ester

In the initial conditions (ethyl ester substrate 1a, a BINAP-palladium complex catalyst, and N-fluorobenzenesulfonimide [NFSI] fluorinating agent), the product was made in only 44% enantiomeric excess (ee). [BINAP is 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl.] Ligand screening showed that bulkier chiral ligands such as xylylBINAP or SEGPHOS [5,5’-bis(diphenylphosphino)-4,4’-bi-1,3-benzodioxole] gave improved enantioselectivity, but only at 5 mol% catalyst loading.

Using a bulkier tert-butyl ester (1b) as the substrate helped, but the modifications still gave a product with only 65–80% ee. Finally, (–)-menthyl ester substrate 1c and (R)-BINAP as the ligand solved the problem; the authors made the fluorinated menthyl ester (2c) in 100% diastereomeric excess and 70% isolated yield. (Org. Process Res. Dev. DOI:10.1021/acs.oprd.5b00131; Will Watson)

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Photochemical battery keeps going and going. Anode degradation and dissolution are especially problematic in aqueous rechargeable batteries (ARBs). These difficulties cause safety concerns and capacity fading (a decrease in the amount of charge a battery can deliver).

M. O. Thotiyl and coauthors at the Indian Institute of Science Education and Research (Pune), Acharya Institute of Technology (Bangalore, India), and the National Chemical Laboratory (Pune) developed an ARB (see schematic) that uses light to trigger electrochemical reactions. This battery avoids several problems with anode materials, and it can be recharged in ≈30 s with a chemical charging agent. 

Schematic of photochemical battery

The titanium nitride photoanode has a native oxynitride surface layer that absorbs UV–visible light. The cathode is iron(III) hexacyanoferrate(II) {KFe[Fe(CN)6]} supported on carbon, and the electrolyte solution, which contains the sodium persulfate (Na2SO8) charging agent, is 3 M potassium chloride.

The open-circuit voltage of a single cell is ≈0.74 V in the dark, 1.2 V under artificial visible light, and 1.1 V under ambient light. Light generates electron–hole pairs in the anode material. The electrons reduce the iron(III) in KFe[Fe(CN)6] to iron(II) {K2Fe[Fe(CN)6]} in the cathode.

The holes oxidize water to molecular oxygen, as shown by oxygen bubble formation after the first discharge. After the first cycle, SO4•– hole scavenging replaces water oxidation as the balancing reaction.

The battery’s discharge capacity is negligible in the dark; but it delivers 77.8 mA•h/g under artificial visible light, 55.5 mA•h/g in ambient light, and just over 80 mA•h/g for UV–visible light. After the battery is discharged, the system is left in the open-circuit state for 30 s, during which the Na2S2O8 reoxidizes the K2Fe[Fe(CN)6].

The battery was used to power a light-emitting diode under ambient light; it retained 97.9% of its initial capacity after 100 cycles. The titanium nitride photoanode showed no degradation, producing almost identical X-ray diffraction patterns before and after 100 cycles. Na2S2O8 is consumed irreversibly during battery recharging and must be replaced when it is exhausted; this chemical, however, is inexpensive and readily available. (J. Phys. Chem. C DOI: 10.1021/acs.jpcc.5b02871; Nancy McGuire)

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How basic can neutral organic superbases get? Neutral organic superbases, the most important type of superbases, are increasingly used in organic synthesis and catalysis because of their excellent chemical stability and efficient proton-transfer ability. Developing stronger superbases is one of the major goals in this research area.

One common strategy is to expand conjugated molecular frameworks to delocalize the positive charge upon protonation (e.g., in the phosphazene series P1–P7 [1 and 2 in the figure]). One question naturally arises: Will this process reach a limit, that is, what is the highest achievable superbasicity?

Phosphazenes P1 and P7

I. Leito, I. A. Koppel, and co-workers at the University of Tartu (Estonia) used computational methods to discover the answer. They conducted density functional theory calculations to predict the upper limits of basicity for five families of potentially extremely strong superbases.

The researchers propose a theoretical model that correlates basicity increase with the expansion of the molecular framework. This relationship can then be extrapolated numerically to predict the upper boundary. They applied their model to dimethylaminophosphazenes, dimethylamino phosphorus ylides, 2,5-dimethylimidazolidinophosphazenes, guanidine phosphorus ylides, and guanidino phosphorus carbenes. They varied the number of phosphorus atoms (an indicator of the degree of framework extension) from 0 to 7, which correlated with basicity increase.

The computational results for the family of guanidino phosphorus carbenes suggest that the gas-phase basicity could reach ≈370 kcal/mol, which is stronger than the strongest inorganic alkali metal oxides, rubidium oxide and cesium oxide. The results also showed that simple alkylphosphazenes could reach pKa values of >50.

This work bridges experimental and computational research in organic superbases and provides useful insights into the structure–basicity relationship for common superbases. Although large bases are predicted to be highly basic, they are impractical to synthesize and use. The authors suggest that new designs should focus on smaller structural units that are more efficient in increasing basicity instead of pursuing larger molecular frameworks. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201503345; Xin Su)

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Selectively remove the solder from electronic components. It is estimated that 20–25 million tons of electronic waste is produced each year. Printed circuit boards (PCBs), a major constituent of e-waste, consist of high-purity metals that are desirable to recycle for environmental and economic reasons.

To recycle PCBs, the tin-lead solder that holds them together must be removed to access the electronic components (ECs). Currently, solder is removed by heating PCBs, which can damage the components. Z. Guo and coauthors at Shanghai Second Polytechnic University and the University of Tennessee (Knoxville) developed a chemical removal method based on dissolving the Sn–Pb solder.

The authors used a commercially available aqueous fluoroboric acid (HBF4) solution and an oxidant to remove the solder. They screened several oxidants and found that the best one was hydrogen peroxide (H2O2). Additional experimentation determined the best combination of time, temperature, and reagent concentration to dissolve tin and lead, but not copper.

The researchers used their method to disassemble the PCB from a liquid crystal display (LCD). After 35 min, all of the electronic components were freed from the board and appeared to be unchanged. The method should be an important addition to the EC recycling process. (ACS Sustainable Chem. Eng. DOI: 10.1021/acssuschemeng.5b00136; José C. Barros)

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Make several changes to control a reactive crystallization. The reaction of a 2-acylbenzoic acid (1a in the figure) with 5 equiv hydrazine hydrate (H2NNH2•H2O) in refluxing ethanol forms a phthalazin-1(2H)-one (2); but the isolated yield is only 66%, and the product is entrained with hydrazine. The underlying problems are that the product starts to crystallize uncontrollably at the beginning of the H2NNH2•H2O addition and that a large excess of H2NNH2•H2O is used. 

Original and improved syntheses of phthalazin-1(2H)-one 2

S. M. Mennen and co-workers at Amgen (Cambridge, MA) made several changes to solve these problems:

  • They reduced the H2NNH2•H2O excess to 1.1 equiv.
  • They produced a more reactive substrate, the acylimidazole (1b), in situ by treating the acid with carbonyldiimidazole (CDI).
  • They changed the solvent to dimethylformamide (DMF).
  • They controlled the addition of water at the end of the reaction to reduce the solubility of the product.

These modifications led to an 80% isolated yield. (Org. Process Res. Dev. DOI:10.1021/acs.oprd.5b00135; Will Watson

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