Physical chemistry

“Calmer” Organic Radicals

by Xin Su

November 28, 2016

Free radicals are chemical entities (atoms, molecules, and ions) that have unpaired valence electrons. Because of their unfilled valence shells, radicals are generally highly reactive and difficult to harness and study. Most organic radicals—free radicals derived from organic molecules—have these characteristics, but some are surprisingly stable (see “Stable Organic Radicals, Then and Now”). Stable organic radicals not only increase our understanding of organic bonding and reactivity, but they also are useful in synthesis and materials science.

Diradical–quinoid equilibrium

This past May, Masayoshi Nakano, Henrik Ottosson, Juan Casado, Michael M. Haley, and colleagues at the University of Oregon (Eugene), the University of Malaga (Spain), Uppsala University (Sweden), Osaka University (Japan), and the University of Valencia (Spain) reported a new diradical compound (2 in Figure 1) based on the diindeno[b,i]anthracene framework. Starting from dibromoanthracene precursor 1, they

  1. extended the carbon skeleton by replacing the bromine atoms with 2-formylphenyl groups;
  2. performed two regioselective intramolecular Friedel–Crafts alkylations; and
  3. dehydrogenated the resulting molecule to 2.

In the reaction sequence, SPhos is 2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl; Mes is mesityl (2,4,6-trimethylphenyl); THF is tetrahydrofuran; and DDQ is 2,3-dichloro-5,6-dicyanobenzoquinone. The synthesis of compound 2 is multigram scalable.

Stable Organic Radicals, Then and Now

The first reported stable organic radical was the triphenylmethyl, or trityl, radical (A in the figure). It was discovered and characterized in 1900 by Moses Gomberg, a Russian–American chemist working at the University of Michigan (Ann Arbor). He intended to synthesize hexaphenylethane by heating triphenylmethyl chloride with metallic silver; but, after additional experimentation, he discovered that he had made a stable free radical instead.

The trityl radical combines with itself to form a dimer, but the product is quinoid structure B rather than hexaphenylethane. When a solution of A and B in equilibrium is heated, the concentration of the radical increases.

Sixty years after Gomberg’s discovery, Russian chemists O. L. Lebedev and S. N. Kazarnovskii discovered (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (C), usually called by its acronym TEMPO. This stable radical is widely used to probe complex systems with the use of electron spin resonance spectroscopy and to mediate radical polymerization; it is also used as a reagent in organic synthesis.

Figure 1

Compound 2 consists of a quinoid structure in equilibrium with an aromatic diradical. Deep-violet solid 2 has similar electronic absorption properties as other quinoidal polycyclic hydrocarbons. Varied-temperature NMR measurements of 2 in solution shows more pronounced signal broadening as the temperature increases, indicating that the equilibrium shifts toward the diradical paramagnetic triplet state.

Characterizations of magnetic properties, along with computational simulations, showed that 2 is a stable compound with moderate diradical character, even in the presence of oxygen and at elevated temperatures. Its small singlet–triplet gap allows its magnetic properties to be thermally switched on and off. The researchers also prepared an ambipolar organic field-effect transistor based on 2 that has balanced electron and hole mobilities, demonstrating the potential of this class of compounds as useful organic electronic materials. (Nat. Chem. DOI: 10.1038/nchem.2518)

A twisted diradial

More recently, Curt Wentrup and coauthors at the University of Queensland (Brisbane, Australia) and the University of Heidelberg (Germany) discovered another example of an organic diradical in an almost century-old molecule. In 1925, Russian chemist O. Magidson reported 13,13’-bis(dibenzo[a,i]fluorenylidene) (3 in Figure 2), which is an overcrowded nonplanar polyolefin that has an unusually long C=C bond with a significantly reduced singlet–triplet gap caused by steric hindrance.

Figure 2

Wentworth’s team used spectroscopic measurements to show the presence of a small population of a 90º-twisted diradical triplet even at room temperature. The thermally generated triplet form is stable up to 500 K, beyond which it decomposes to a persistent doublet monoradical. The authors note that delocalization over the large dibenzofluorene system contributes to the stabilization of the excited triplet state. The synthesis of hindered olefins is possibly a new route to stable diradicals. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201607415)

Stabilizing radical anions

Supramolecular chemistry offers alternative strategies to stabilize organic radicals, among which radical-encapsulating synthetic host receptors can effectively protect radicals from oxygen and other reactive substances. Amar H. Flood and colleagues at Indiana University (Bloomington) and the University of Illinois at Urbana–Champaign used the so-called cyanostar macrocyclic receptor with a large cavity and 10 C–H hydrogen-bond donors to stabilize tetrazine-based radical anions (see Figure 3). 

Figure 3

When reduced by bis(cyclopentadienyl)cobalt(II), 1,2,4,5-tetrazines convert to the corresponding radical anions that have solution lifetimes of several hours. The researchers found that these radical anions could be encapsulated into a pair of π-stacked cyanostar receptors. The [2]pseudorotaxanes formed in this way, in which one tetrazine radical anion is threaded through two macrocycles, do not change the electronic properties of the radicals. The lifetimes of the encapsulated radical anions also increased significantly from hours to tens of days. It is likely that both encapsulation and hydrogen bonds contributed to this remarkable noncovalent stabilization of tetrazine radical anions. (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b09459)

More useful radicals ahead

All of these studies have enriched the toolbox for preparing stable organic radicals, and they should lead to more insight into the fundamentals of chemical bonding in organic compounds. With these results, chemists will be able to make progress in using stable organic radicals for controlled synthetic transformations and emerging applications in materials science.