Ketyl

Wliile the earliest TR-CIDNP work focused on radical pairs, biradicals soon became a focus of study. Biradicals are of interest because the exchange interaction between the unpaired electrons is present tliroiighoiit the biradical lifetime and, consequently, the spin physics and chemical reactivity of biradicals are markedly different from radical pairs. Work by Morozova et al [28] on polymethylene biradicals is a fiirther example of how this method can be used to separate net and multiplet effects based on time scale [28]. Figure Bl.16.11 shows how the cyclic precursor, 2,12-dihydroxy-2,12-dimethylcyclododecanone, cleaves upon 308 mn irradiation to fonn an acyl-ketyl biradical, which will be referred to as the primary biradical since it is fonned directly from the cyclic precursor. The acyl-ketyl primary biradical decarbonylates rapidly k Q > 5 x... 

Figure Bl.16.13. Kineties of the CIDNP multiplet effeet (frill eurve) the ealeulated CIDNP kineties for the produet of disproportionation of bis-ketyl biradieal (O) experimental kineties for the CH CHCOH) protons of the produets IV, V and VI of the seeondary biradieal. Reprinted from [28].

Figure Bl.16.19. (a) CIDEP spectrum observed in die photolysis of xanthone (1.0 x 10 M) in cyclohexanol at room temperature. The stick spectra of the ketyl and cyclohexanol radicals with RPM polarization are presented, (b) CIDEP spectrum after the addition of hydrochloric acid (4.1 vol% HCl 0.50 M) to the solution above. The stick spectra of the ketyl and cyclohexanol radicals with absorptive TM polarization are presented. The bold lines of the stick spectra of the cyclohexanol radical show the broadened lines due to ring motion of the radical. Reprinted from [62].

The one-electron reduction of thiazole in aqueous solution has been studied by the technique of pulse radiolysis and kinetic absorption spectrophotometry (514). The acetone ketyl radical (CH ljCOH and the solvated electron e were used as one-electron reducing agents. The reaction rate constant of with thiazole determined at pH 8.0 is fe = 2.1 X 10 mole sec in agreement with 2.5 x 10 mole sec" , the value given by the National Bureau of Standards (513). It is considerably higher than that for thiophene (6.5 x 10" mole" sec" ) (513) and pyrrole (6.0 X10 mole sec ) (513). The reaction rate constant of acetone ketyl radical with thiazolium ion determined at pH 0.8 is lc = 6.2=10 mole sec" . Relatively strong transient absorption spectra are observed from these one-electron reactions they show (nm) and e... 

CgH COO from BPO. The first type involves direct radical displacement on the oxygen—oxygen bond and is the preferred mode for nucleophilic radicals, eg, -CH(R)OR7 The second type involves radical addition to, or abstraction from, the hydrocarbyl group adjacent to the peroxide this is the preferred mode for electrophilic radicals, eg, Cl C (eq. 32). In the last type (eq. 33), there is hydrogen donation from certain hydrogen-donating radicals, eg, ketyls (52,187,188,199). 

Dimethyl carbonate is available from Aldrich Chemical Company, Inc. The checkers dried the tetrahydrofuran Immediately before use by distillation from the sodium ketyl of benzophenone under a nitrogen atmosphere. The submitters purchased sodium hydride (50% oil dispersion) from Alfa Products, Morton/Thiokol, Inc. The checkers used 12.24 g of a 50% dispersion of sodium hydride in mineral oil obtained from the same supplier. The dispersion was washed with three portions of pentane to remove the mineral oil and the remaining sodium hydride was allowed to dry under nitrogen. 

Diethyl ether was dried by the submitters by refluxing over lithium aluminum hydride and was distilled immediately before use. The checkers distilled diethyl ether from the sodium ketyl of benzophenone before use. 

Benzene is distilled over benzophenone ketyl and stored under a nitrogen atmosphere. 

Ethyl ether is freshly distilled from sodium/benzophenone ketyl at atmospheric pressure under nitrogen. 

Ether was distilled from sodium ketyl of benzophenone. The dissolution of n-butyllithium in ether was slightly exothermic. 

Tetrahydrofuran was distilled from sodium ketyl of benzophenone. 

Dry benzene was obtained by doubly distilling high purity benzene from a soln containing the blue ketyl formed by the reaction of sodium-potassium alloy with a small amount of benzophenone. 

Rapid purification Check for peroxides (see Chapter 1 and Chapter 2 for test under ethers). Pre-dry with CaCl2 or better over Na wire. Then reflux the pre-dried solvent over Na (1 % w/v) and benzophenone (0.2% w/v) under an inert atmosphere until the blue colour of the benzophenone ketyl radical anion persists. Distil, and store over 4A molecular sieves in the dark. 

Two classes of charged radicals derived from ketones have been well studied. Ketyls are radical anions formed by one-electron reduction of carbonyl compounds. The formation of the benzophenone radical anion by reduction with sodium metal is an example. This radical anion is deep blue in color and is veiy reactive toward both oxygen and protons. Many detailed studies on the structure and spectral properties of this and related radical anions have been carried out. A common chemical reaction of the ketyl radicals is coupling to form a diamagnetic dianion. This occurs reversibly for simple aromatic ketyls. The dimerization is promoted by protonation of one or both of the ketyls because the electrostatic repulsion is then removed. The coupling process leads to reductive dimerization of carbonyl compounds, a reaction that will be discussed in detail in Section 5.5.3 of Part B. 

When saturated steroidal ketones are reduced in ammonia, an alcohol is usually present to act as a proton donor and high yields of steroidal alcohols are obtained. Under these conditions, reduction probably proceeds by protonation of the radical-anion (or ketyl) (61), which results from a one electron addition to the carbonyl group, followed by addition of a second electron and proton. Barton has proposed that reduction proceeds via protonation of the dianion (62) arising from addition of two electrons to the carbonyl group. This proposal implies that the ketyl (61) undergoes addition of a second electron in preference to undergoing protonation by the... 

Huffman found that treatment of cholan-12-one (65b) with lithium and ammonia for 2 hours followed by addition of propanol gives 40 % of a pinacol together with 48.5 % of 12-ols in which the ratio of 12j5 12a is 19 1. This predominance of the 12 -ol was interpreted in terms of slow formation of a dianion of type (62) followed by its equilibration to the thermodynamically most stable configuration, i.e. one which affords the 12j5-ol upon protonation. An alternative explanation is that reduction in the presence of methanol involves protonation of a ketyl such as (61) by methanol, whereas in the absence of methanol reduction proceeds via the dianion (62) which is protonated on... 

The initial step of the coupling reaction is the binding of the carbonyl substrate to the titanium surface, and the transfer of an electron to the carbonyl group. The carbonyl group is reduced to a radical species 3, and the titanium is oxidized. Two such ketyl radicals can dimerize to form a pinacolate-like intermediate 4, that is coordinated to titanium. Cleavage of the C—O bonds leads to formation of an alkene 2 and a titanium oxide 5 ... 

The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

Photoredox systems involving carbonyl compounds and amines are used in many applications. Carbonyl compounds employed include benzophenone and derivatives, a-diketones [e.g. benzil, cainphoroquinone (85),2W 291 9,10-phenanthrene quinone], and xanthone and coumarin derivatives. The amines are tertiary and must have a-hydrogens [e.g. N,A7-dimethylani 1 ine, Michler s ketone (86)]. The radicals formed are an a-aminoalkyl radical and a ketyl radical. 

Toluene (99.9%) is purchased from Fisher and dried by distillation under argon from sodium benzophenone ketyl. 

The submitters used THF that was freshly distilled over Na/K alloy NMP was distilled over CaH2. The checkers used commercially available anhydrous THF and NMP obtained from Aldrich Chemical Co. There appears to be a slight increase in yield when THF distilled from sodium/benzophenone ketyl is used instead of the commercial THF. All other solvents used were of reagent grade quality and were used without further purification. 

Tetramethydisiloxane was purchased from Lancaster Synthesis Inc. and used as received. THF was obtained from Mallinckrodt Inc. and freshly distilled from sodium/benzophenone ketyl. 

Tetrahydrofuran (THF) was distilled from sodium/benzophenone ketyl under a nitrogen atmosphere. 

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