ORGANIC RADICALS

Background & Introduction
A radical is an atomic or molecular species having an unpaired, or odd, electron. Some radicals, such as nitric oxide (NO), are relatively stable, but most are so reactive that their isolation and long-term study is not possible under normal laboratory conditions. The electrons in most stable organic compounds are paired in atomic or molecular orbitals, so the total electron count is an even number. Molecular oxygen (O2) is a rare example of a stable biradical (two unpaired electrons having the same spin), with an even number of electrons.

Early chemists used the term "radical" for nomenclature purposes, much as we now use the term "group". Many doubted that such open-valenced species could exist, although there was circumstantial evidence for their participation in gas phase reactions. Credit for the first isolation and characterization of a "free radical" goes to Moses Gomberg, a young instructor at the University of Michigan. In 1900 Gomberg attempted a synthesis of hexaphenylethane by reacting triphenylmethyl chloride with finely divided metals such as silver and zinc. When air was excluded from the reaction, he obtained a yellow solution, the color of which darkened reversibly on heating and cooling. This solution yielded a colorless, crystalline C38H30 hydrocarbon which Gomberg assumed to be hexaphenylethane.

If the yellow solution was exposed to air (or oxygen) a C38H30O2 peroxide was obtained, and identified by reduction to the known alcohol, triphenylmethanol. In a similar fashion the yellow solution reacted with iodine to produce triphenylmethyl iodide.

Gomberg concluded that the colored solutions contained reactive triphenylmethyl free radicals, formed by thermal dissociation of their dimer (Keq = 2 • 10–4 at 25º C). The exceptional stability of this carbon radical is attributed to odd electron delocalization into the three phenyl rings. Discrete Kekule formulas demonstrate that this benzyl-like decocalization places the electron on ortho and para carbons, but not on meta carbons.

The resonance structures may give the impression that the triphenylmethyl radical is planar (flat). Actually the phenyl groups are turned by about 35º, producing a shape similar to a three bladed propellor. Despite this twist, the p-pi orbital overlap is still over 80%, so the electron delocalization is not seriously diminished.

More than fifty years later, the reactive dimer of triphenylmethyl radical was shown to be the para-coupled compound and not hexaphenylethane. The steric crowding of phenyl groups in the simple ethane dimer is apparently so severe that bonding between two 3º-carbon atoms is prohibited. Since the electron delocalization places radical character at the para carbons of the phenyl groups, bonding to this relatively unhindered location is preferred, although at the cost of one benzene ring's aromaticity. If the para-locations are themselves hindered by large meta substituents, then an unstable hexaarylethane may actually be formed.



Other relatively stable radicals, such as galvinoxyl have been prepared and studied. These species usually owe their stability to a combination of odd electron delocalization and steric hindrance to dimerization, as the ortho tert-butyl groups in galvinoxyl demonstrate. The term "free radical" is now loosely applied to all radical intermediates, stabilized or not.



Detection and Observation of Radicals
Only triphenymethyl and a few other stabilized radicals may be generated in concentrations suitable for examination by traditional laboratory methods. Evidence for the transient existence of more reactive radical species in chemical reactions usually requires special techniques, including low-temperature isolation in solids and high speed spectroscopic probes. However, an interesting chemical detection of the methyl radical was carried out by the Austrian chemist Fritz Paneth not long after Gomberg's preparation of triphenylmethyl radical. The Paneth experiment involved gas phase thermal decomposition of tetramethyllead to methyl radicals and lead atoms in a glass tube.Gaseous tetramethyllead is carried through the glass reactor tube in a stream of nitrogen.

Electron Paramagnetic Resonance

The same unpaired or odd electron that renders most radical intermediates unstable and highly reactive may be induced to leave a characteristic "calling card" by a magnetic resonance phenomenon called "electron spin resonance" (esr) or "electron paramagnetic resonance" (epr). Just as a proton (spin = 1/2) will occupy one of two energy states in a strong external magnetic field, giving rise to nmr spectroscopy; an electron (spin = 1/2) may also assume two energy states in an external field. Because the magnetic moment of an electron is roughly a thousand times larger than that of a proton, the energy difference between the spin states falls in the microwave region of the spectrum (assuming a moderate magnetic field strength). The lifetime of electron spin states is much shorter than nuclear spin states, so esr absorptions are much broader than nmr signals.

One way of improving the signal to noise ratio in esr spectra is to display them as first derivatives rather than absorptions. In practice, esr spectra may be quite complex.This complexity is the result of hyperfine splitting of the resonance signal by protons and other nuclear spins, an interaction similar to spin-spin splitting in nmr spectroscopy. For example, the esr signal from methyl radicals, generated by x-radiation of solid methyl iodide at -200º C, is a 1:3:3:1 quartet (predicted by the n + 1 rule). The magnitude of signal splitting is much larger than nmr coupling constants (MHz rather than Hz), and is usually reported in units of gauss. The complexity of the triphenylmethyl spectrum is due to three different hyperfine splittings: 3 para hydrogens, 6 ortho hydrogens & 6 meta hydrogens. Ideally this should produce 196 lines, but imperfect resolution reduces the number observed.


Methods of Generating Free Radicals

The homolytic cleavage of covalent bonds produces radicals, and since this is an endothermic process, it requires the introduction of energy from the surroundings. Heat serves this purpose by collisional interconversion of kinetic energy into vibrational energy, and the temperature required for bond homolysis will be proportional to the bond dissociation energy. Absorption of light may also lead to radical species by intra- or intermolecular conversion of the increased electronic energy into vibrational energy. As expected, weaker covalent bonds dissociate into radicals more readily than stronger covalent bonds.

A. Thermal Cracking
At temperatures greater than 500º C, and in the absence of oxygen, mixtures of high molecular weight alkanes break down into smaller alkane and alkene fragments. This cracking process is important in the refining of crude petroleum because of the demand for lower boiling gasoline fractions. Free radicals, produced by homolysis of C–C bonds, are known to be intermediates in these transformations. Studies of model alkanes have shown that highly substituted C–C bonds undergo homolysis more readily than do unbranched alkanes. In practice, catalysts are used to lower effective cracking temperatures.

B. Homolysis of Peroxides and Azo Compounds
In contrast to stronger C–C and C–H bonds, the very weak O–O bonds of peroxides are cleaved at relatively low temperatures ( 80 to 150 ºC ). The resulting oxy radicals may then initiate other reactions, or may decompose to carbon radicals.
Organic azo compounds (R–N=N–R) are also heat sensitive, decomposing to alkyl radicals and nitrogen. Azobisisobutyronitrile (AIBN) is the most widely used radical initiator of this kind, decomposing slightly faster than benzoyl peroxide at 70 to 80 ºC. The thermodynamic stability of nitrogen provides an overall driving force for this decomposition, but its favorable rate undoubtedly reflects weaker than normal C-N bonds.

C. Photolytic Bond Homolysis
Compounds having absorption bands in the visible or near ultraviolet spectrum may be electronically excited to such a degree that weak covalent bonds undergo homolysis. Examples include the halogens Cl2, Br2 & I2 (bond dissociation energies are 58, 46 & 36 kcal/mole respectively), alkyl hypochlorites, nitrite esters and ketones. . Ketones undergo n to π* electronic excitation near 300 nm. The resulting excited state is a diradical in which one of the odd electrons is localized on the oxygen atom. Cleavage of an alkyl group may then take place.

D. Electron Transfer
The action of inorganic oxidizing and reducing agents on organic compounds may involve electron transfers that produce radical or radical ionic species. Ferrous ion, for example, catalyzes the decomposition of hydrogen peroxide ( Fenton's reagent ) and organic peroxides. In some cases the radical intermediates formed in this manner are sufficiently stable to be studied in the absence of oxygen.

The alkali metals lithium, sodium and potassium reduce the carbonyl group of ketones to a deep blue radical anion called a "ketyl. A similar reduction of benzene and its derivatives also proceeds by way of radical anion intermediates.

E. Hydrogen and Halogen Atom Abstraction
If free radical reactions are to be useful to organic chemists, methods for transfering the reactivity of the simple radicals generated by the previously described homolysis reactions to specific sites in substrate molecules must be devised. The most direct way of doing this is by an atom abstraction, as shown here.

R–H + X• –––> R• + H–X

Indeed, when X is Cl or Br, this is a key step in the alkane halogenation chain reaction. Hydrogen abstraction reactions of this kind are sensitive to the nature of both the attacking radical ( X•) and the R–H bond. . Thus the rate of reaction of 1º C–H with Cl• is a thousand times faster than with Br•. However, the less reactive bromine atom shows much greater selectivity in discriminating between 1º, 2º and 3º C–H groups.
Certain C–H bonds are so susceptible to radical attack that they react with atmospheric oxygen (a diradical) to form peroxides. Typical groups that exhibit this trait are 3º-alkyl, 2º & 3º-benzyl and alkoxy groups in ethers.


R–H + O2 –––> R• + •O2H –––> R–O–O–H

The exceptional facility with which S–H and Sn–H react with alkyl radicals makes thiophenol and trialkyltin hydrides excellent radical quenching agents, when present in excess. At equimolar or lower concentration they function well as radical transfer agents..

Carbon halogen bonds, especially C–Br and C–I, are weaker than C–H bonds and react with alkyl and stannyl radicals to generate new alkyl radicals. This reaction has been put to practical use in a mild procedure for reducing alkyl halides to alkanes.