Cyclopropyl radicals reactivity

Carbon-centered organic radicals are highly reactive trivalent species with only one nonbonding electron. While most known radicals have their unpaired electron in a pure p- or a delocalized Ji-orbital, there are also examples of radicals centered in s/t" hybrid o-orbitals, such as the well known phenyl and cyclopropyl radicals. The first radical reported in the literature is credited to Gomberg s landmark paper in 1900 when he postulated the formation of triphenylmethyl radical 36, also known as tri-fyj 99,100 jj-jjyj j-adical is an example of a persistent radical that exists in equilibrium... 

Aryl radicals are much more reactive than alkyl radicals (k ca. 2 x 106M-1 s 1), and rather more reactive than cyclopropyl radicals (ca. 8 x 107) or vinyl radicals (ca. 3 x 10s). Fluoroalkyl radicals are also about 100 times more reactive than alkyl radicals, because of contributions from structures Rf 6 - H -4+SnR3 to the transition state. Singlet-excited acetone is twice as reactive as triplet-excited acetone, which shows a similar reactivity to that of the /-butoxyl radical (k ca. 2 x 108M-1 s-1). 

With dimethyl disulfide as the electrophile the cis/trans-ratio is 90 10 even in tetrahydrofuran. Competition experiments show that this reaction is much faster than the usual alkylations, which afford mainly frans-compounds68). With the sulfur electrophile a single electron transfer (SET) seems likely generating a cyclopropyl radical as a reactive species, which naturally displays a different selectivity compared to the enolate anion. 

Unlike alkyl halides in SN2 reactions or alkylhthiums in SE2 reactions, radicals have no intrinsic stereochemical preference at the reactive centre, except that trigonal radicals, and even cyclopropyl radicals, provided that there is an a electronegative... 

VI. CYCLOPROPYL-SUBSTITUTED REACTIVE INTERMEDIATES A. Cyclopropylcarbinyl Radicals... 

Rate constants for hydrogen atom abstraction by cyclopropyl radical from tri-n-butylstannane and germane have been measured, and relative reactivities for a series of hydrocarbon radicals are Ph (350), c-Pr (50), Me (7.0), and t-Bu (1.0) A review of the properties of cyclopropyl radicals with particular emphasis on stereochemistry and substituent effects has appeared... 

From the relative reactivity data, shown in Table 2, which describes the thermal decomposition of biscyclopropanoyl peroxide in a series of substituted benzenes, Shono and Nishiguchi have concluded that the cyclopropyl radical more closely resembles the... 

In its relative reactivity toward toluene, ethylbenzene and cumene the more highly substituted 1-methyl-2,2-diphenylcyclopropyl radicaP , derived from the decomposition of the precursor diacyl peroxide, resembles the chlorine radical more than it does the phenyl radical (Table 3). Similarly, comparison of the relative reactivities of primary, secondary and tertiary aliphatic hydrogens toward chlorine atoms (1.0 3.6 4.2) and phenyl radicals (1.0 9.3 44) with the relative reactivities of the C-H bond in the methanol/ethanol/2-propanol series toward the 1-methyl-2,2-diphenylcyclopropyl radical (1.0 2.4 15) further confirms the low selectivity of the cyclopropyl radical. Again, this radical resembles the chlorine atom in its reactivity more than it does the phenyl radical. 

In so far as the rate of formation of radicals reflects their stability or reactivity the findings of Hart and Wyman are instructive. In carbon tetrachloride the rate of decomposition of benzoyl peroxide was twice as fast as that of biscyclopropanoyl peroxide. Ingold and coworkers have found that in the photodecomposition of benzoyl and biscyclopropanoyl peroxides, in carbon tetrachloride at 298 K, the phenyl radicals produced reacted faster (7.8 x 10 M s ) than the cyclopropyl radicals (1.5 X 10 M s ). These results are consistent with C-H bond dissociation energies for benzene (llOkcalmol) and cyclopropane (106kcal mol ) which implies that the cyclopropyl radical should be less reactive than the phenyl radical. In subsequent work they also showed that at ambient temperatures radical reactivities decreased along the series /c = Ph > (Me)2 C=CH > cyclopropyl > Me. Table 4 records the absolute rate constants for the reaction of these radicals with tri-n-butylgermane. 

It has also been shown in radical substitution at the 2-position of a series of 4-substituted (CN, MeO, Me) protonated pyridines, that the cyclopropyl radical is the least nucleophilic of the cycloalkyl radicals This low nucleophilicity is consistent with the observed difficulty in oxidizing the cyclopropyl radical by Cu ". The lack of reactivity of the 2-phenylcyclopropyl radical, generated by the thermal decomposition of the 2-phenyl-cyclopropanepercarboxylic acid, towards the 0-0 peracid bond to yield 2-phenylcyclo-propanol is also in line with the radical s weak nucleophilicity However from a study of relative rates of hydrogen abstraction to olefin addition of the cyclopropyl radical to a variety of olefins (Table 7) Stefani and coworkers concluded that the cyclopropyl radical was decidedly nucleophilic. 

In summary, the cyclopropyl radical behaves as a highly reactive and poorly selective rapidly inverting a radical with a degree of nucleophilicity that has not been firmly established. 

As we have previously discussed the cyclopropyl radical is a very reactive radical. When in addition we consider the appreciable activation energy 22 kcal mol" ) " necessary for the cyclopropyl radical to rearrange to the allyl radical we are not surprised that rearrangements are not always observed. The cyclopropyl radical prefers to react with solvent by abstracting hydrogen, the activation energy for which is reported " to be only 7kcalmol ... 

The ratio of dimeric product to cyclopropane product is a measure of the reactivity of the solvent toward the cyclopropyl radical. Table 14 shows the results of such a study. 

Cyclopropyl radicals, anion radicals and anions 727 TABLE 14. Relative reactivity of various solvents toward the l-methyl-2,2-diphenylcyclopropyl radical ... 

Another interesting feature related to the a nature of the cyclopropyl and vinyl radicals is their reactivity. In general, a radicals are more reactive and less selective than n radicals. Phenyl, vinyl, and cyclopropyl a radicals will abstract hydrogen atoms from saturated hydrocarbons at 77 K, conditions under which k radicals are unreactive [23]. In Ruchardt s [24] radical reactivity classification, based on the reaction of a series of o and n radicals with BrCClj and CCl, the cyclopropyl radical, an inverting a radical in an sp -hybridized orbital, closely resembled the noninverting phenyl radical. Further support for this finding... 

Absolute rates for hydrogen abstraction form the stannane, the second propagation step, have also being measured.17 These are indeed exceedingly efficient processes. These rates are on the higher end of the scale with relatively little spread (Figure 4.2). Aromatic, vinylic and cyclopropyl radicals react fastest, at close to the diffusion limit, whereas aliphatic radicals are some 100 times slower, with not much difference between primary, secondary and tertiary systems. Benzylic radicals, on the other hand, are the least reactive. 

A large number of 1,1-dihalocyclopropanes have been converted to monohalocyclopropanes by a wide range of reducing agents. Most reductions occur via a cyclopropyl radical or a cyclopropyl anion. Such intermediates are in general configurationally unstable, and the monohalides are therefore in most cases obtained as mixtures of stereoisomers. The reactivity diminishes in the order C-I > C-Br > C-Cl > C-F. In a number of cases selective cleavage of... 

Alkyl radicals are conveniently generated by photodecomposition of azoalkanes. A kinetic study of the rearrangement of cyclopropyl radicals (1), obtained by photolysis of the azoalkanes (2), has been described. Particularly high radical concentrations leading to a dramatic change in the product ratio of tetrakis(pentafluoro-ethyl)hydrazine and perfluorobutane have been achieved in the pulsed laser excitation of perfluoroazoethane. On photolysis, azosulphonates also function as radical traps, with the formation of hydrazyl radicals as reactive intermediates. ... 

Unlike alkyl halides in SN2 reactions or alkyllithiums in SE2 reactions, radicals have no intrinsic stereochemical preference at the reactive centre, except that trigonal radicals, and even cyclopropyl radicals, provided that there is an a electronegative substituent, can retain the configuration of their halide precursors.1030 Otherwise, radicals, being somewhere in between cations and anions, show some of the same stereochemical preferences discussed in Chapter 5, such as attack on the exo face of bicyclic systems, and on the less hindered face of open-chain double bonds, which is useful when the less hindered face can be... 

Reaction of cyclopropyl bromides are especially significant here, since cyclopropyl radicals are much more reactive in H-atom transfer reactions than typical alkyl radicals, so that extensive trapping by DCPH(D) would be expected but is not found 166. Bven so. this evidence is weak for a number of reasons. 

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