Radical reactions, mechanistic studies

There is a discussion of some of the sources of radicals for mechanistic studies in Section 11.1.4 of Part A. Some of the reactions discussed there, particularly the use of azo compounds and peroxides as initiators, are also important in synthetic chemistry. One of the most useful sources of free radicals in preparative chemistry is the reaction of halides with stannyl radicals. Stannanes undergo hydrogen abstraction reactions and the stannyl radical can then abstract halogen from the alkyl group. For example, net addition of an alkyl group to a reactive double bond can follow halogen abstraction by a stannyl radical. 

Rate constants for Reaction (3.14) were measured directly by LFP techniques and are collected in Table 3.4 [23-27]. These values reflect the overall (ormolecu-lar) reactivity of the substrates regardless of the site or mechanism of the reaction. Mechanistic studies have shown that the attack of the t-BuO radical on EtsSiH occurs in about 80 % of the cases at the SiH moiety and in 20 % at the ethyl groups at 27 °C [23], whereas the attack on (Mc3 Si)3 SiH occurs in about 95 % of the cases at the SiH moiety and in 5 % at the trimethylsilyl groups at 27 °C [26]. 

The reactions of copper salts with diacyl peroxides have been investigated quite thoroughly, and the mechanistic studies indicate that both radicals and carbocations are involved as intermediates. The radicals are oxidized to carbocations by Cu(II), and the final products can be recognized as having arisen from carbocations because characteristic patterns of substitution, elimination, and rearrangement can be discerned " ... 

The first three chapters discuss fundamental bonding theory, stereochemistry, and conformation, respectively. Chapter 4 discusses the means of study and description of reaction mechanisms. Chapter 9 focuses on aromaticity and aromatic stabilization and can be used at an earlier stage of a course if an instructor desires to do so. The other chapters discuss specific mechanistic types, including nucleophilic substitution, polar additions and eliminations, carbon acids and enolates, carbonyl chemistry, aromatic substitution, concerted reactions, free-radical reactions, and photochemistry. 

In contrast to the abundant examples of radical cleavage, only a few proposals of ionic cleavage of carbon-carbon a bonds have been put forward in the long saga of mechanistic studies on heterolytic cleavage reactions. 

Wangberg 1,1 Barnes, KH Becker (1997) Product and mechanistic study of the reaction of NO3 radicals with a-pinene. Environ Sci Technol 31 2130-2135. 

This reaction has been the subject of a great deal of theoretical and mechanistic study, largely because of the commercial importance of the polymers to which it can give rise. Like the other radical reactions we have discussed, it can be said to involve three stages—(a) initiation, (i>) propagation, and (c) termination ... 

Numerous autoxidation reactions of aliphatic and araliphatic hydrocarbons, ketones, and esters have been found to be accompanied by chemiluminescence (for reviews see D, p. 19 14>) generally of low intensity and quantum yield. This weak chemiluminescence can be measured by means of modern equipment, especially when fluorescers are used to transform the electronic excitation energy of the triplet carbonyl compounds formed as primary reaction products. It is therefore possible to use it for analytical purposes 35>, e.g. to measure the efficiency of inhibitors as well as initiators in autoxidation of polymer hydrocarbons 14), and in mechanistic studies of radical chain reactions. 

The intensive mechanistic studies of phenoxyl self-reactions proved a great variety of mechanisms and rate constants of these reactions [2,3,6], The substituents can dramatically influence the mechanism and kinetics of self-reactions. Due to free valence delocalization the phenoxyl radical possesses an excess of the electron density in the ortho- and para-positions. Mono- and disubstituted phenoxyls recombine with the formation of labile dimers that after enolization form bisphenols [3,6],... 

Although pathway 2 in the oxidation process (Scheme 2) may be considered analogous to mechanisms proposed for carbon hydroxylations catalyzed by cytochrome P-450, abstraction of an electron from the lone pair on nitrogen (pathway 1) would be a more likely first step in these types of reactions. It is reasonable to assume that the nature of substituents R, R2, and R3 would greatly influence the rate and path of reaction. The mechanistic possibilities in Scheme 2 are undoubtedly simplistic in their representation of the active oxygen species of cytochrome P-450 and are by no means comprehensive. However, these pathways do serve to illustrate.the role of radical substrate intermediates in cytochrome P-450-catalyzed reactions. More detailed analyses of mechanistic studies on these and other cytochrome P-450-mediated reactions can be found in recent reviews on the subject 49, 50, 60). 

Mechanistic studies of homogenous chemical reactions involving formation of (P)Rh(R) from (P)Rh and RX demonstrate a radical pathway(9). These studies were carried out under different experimental conditions from those in the electrosynthesis. Thus, the difference between the proposed mechanism using chemical and electrochemical synthetic methods may be due to differences related to the particular investigated alkyl halides in the two different studies or alternatively to the different reaction conditions between the two sets of experiments. However, it should be noted that the electrochemical method for generating the reactive species is under conditions which allow for a greater selectivity and control of the reaction products. 

Numerous synthetic and mechanistic studies were done to investigate this reaction further, and a variety of enediynes have been thermalized in the presence of radical traps such as 1,4-cyclohexadiene. Even though large excesses of radical traps were employed, the yields of the substituted benzenes were often moderate at best. Most important of all, Tour et al.50 demonstrated that 1,4-naphthalene diradicals generated in solution couple to eventually form a polymer [Eq. (9)]. 

Cyclohexyl xanthate has been used as a model compound for mechanistic studies [43]. From laser flash photolysis experiments the absolute rate constant of the reaction with (TMS)3Si has been measured (see Table 4.3). From a competition experiment between cyclohexyl xanthate and -octyl bromide, xanthate was ca 2 times more reactive than the primary alkyl bromide instead of ca 50 as expected from the rate constants reported in Tables 4.1 and 4.3. This result suggests that the addition of silyl radical to thiocarbonyl moiety is reversible. The mechanism of xanthate reduction is depicted in Scheme 4.3 (TMS)3Si radicals, initially generated by small amounts of AIBN, attack the thiocarbonyl moiety to form in a reversible manner a radical intermediate that undergoes (3-scission to form alkyl radicals. Hydrogen abstraction from the silane gives the alkane and (TMS)3Si radical, thus completing the cycle of this chain reaction. 

The photochemical reduction of 1-methylquinolinium ions by (TMS)3SiH proceeds regioselectively to afford the corresponding 1,4-dihydroquinones in a water-acetonitrile solvent system (Reaction 4.47) [83]. Mechanistic studies demonstrated that the reactions are initiated by photoinduced electron transfer from the silane to the singlet excited states of 1-methylquinolinium ions to give the silane radical cation-quinolinyl radical pairs, followed by hydrogen transfer in the cage to yield 1,4-dihydroquinones and silicenium ion. Silyl cations are quenched by water. 

Arnaud, R., Barone, V., Olivella, S., and Sole, A., Ab initio mechanistic studies of radical reactions, addition of methyl radical to acetylene and ethylene, Chem. Phys. Lett. 118, 573 (1985). 

In a mixture of liquid ammonia with alcohol, ketoenols and pinacols are still formed along with secondary alcohols. Process selectivity was enhanced on the basis of mechanistic studies (Rautenstrauch et al. 1981). The initial stages of the reaction include the formation of ketone anion-radicals and their dimerization with a metal cation participation. This dimerization results in pina-col formation as shown in Scheme 7.6. 

---