Carbonyl addition-radical fragmentation

Table II. Relative Rate Constants and Reaction Exothermicities of Carbonyl Addition-Radical Fragmentation of Carbonyl-Containing Molecules with C6H5N ...

In addition to fragmentation by the McLafferty rearrangement, aldehydes and ketones also undergo cleavage of the bond between the carbonyl group and the a carbon, a so-called a cleavage. Alpha cleavage yields a neutral radical and a resonance-stabilized acyl cation. 

We examined the reactions of C6H5 N with the series of carbonyl-containing molecules listed in Table II (10). Because H+ transfer is a competing reaction channel in some of these reactions, we factored out of the total rate constants that part due to carbonyl addition and radical fragmentation, and these rate constants were made relative to that for acetone these kreic=0 values are given in the middle column of Table II. 

Figure 6.36. Proposed mechanism for the C17-C20 lyase reaction catalyzed by CYPI7A. The key steps involve addition of a P450 ferric peroxide species to the C20 carbonyl and subsequent free radical fragmentation of the peroxyhemiacetal,...

This comparison suggests that of these two similar reactions, only alkene additions are likely to be a part of an efficient radical chain sequence. Radical additions to carbon-carbon double bonds can be further enhanced by radical stabilizing groups. Addition to a carbonyl group, in contrast, is endothermic. In fact, the reverse fragmentation reaction is commonly observed (see Section 10.3.6) A comparison can also be made between abstraction of hydrogen from carbon as opposed to oxygen. 

The fragmentation of alkoxyl radicals is especially favorable because the formation of a carbonyl bond makes such reactions exothermic. Rearrangements of radicals frequently occur by a series of addition-fragmentation steps. The following two reactions involve radical rearrangements that proceed through addition-elimination sequences. 

The alkoxy radical of Scheme 18.3 (upper reaction) could scission to produce the same carboxyl radical as seen in the Norrish type 1 path (Scheme 18.1, path A) discussed above. As such, it is an additional source of CO2 but not taken into account in the report by Day and Wiles [25], Not reported but still obvious, the other fragment of this scission is an aliphatic aldehyde that could also have been one of the aldehyde carbonyl IR signals reported [11, 25], Hydrolysis of this chain end would yield the reported glyoxal [21],... 

The gaseous dichlorocarbene radical cation reacted with alkyl halides via a fast electrophilic addition to form a covalently bonded intermediate (CI2C—X—R)+ in a Fourier transform ion cyclotron resonance mass spectrometer. This intermediate fragments either homolytically or heterolytically to produce net halogen atom or halogen ion transfer product. Addition of carbonyls to the carbene ion is followed by homolytic cleavage of the C-O bond to yield a new carbene radical cation. 

Addition reactions of carbon radicals to C—O and C—N multiple bonds are much less-favored than additions to C—C bonds because of the higher ir-bond strengths of the carbon-heteroatom multiple bonds. This reduction in exothermicity (additions to carbonyls can even be endothermic) often reduces the rate below the useful level for bimolecular additions. Thus, acetonitrile and acetone are useful solvents because they are not subject to rapid radical additions. However, entropically favored cyclizations to C—N and C—O bonds are very useful, as are fragmentations (see Chapter 4.2, this volume). 

Another fundamental reaction of >C=0 involves its reactivity as a base. In the Brpnsted sense, >C=0 - may react with a proton donor to produce a neutral ketyl radical (>C(.)OH, Figure 2, reaction 2). This is an important process when the reduction of a carbonyl compound is carried out under acidic conditions or in a protic media (e.g. elec-trochemically, with less reactive reducing reagents such as Mg or Zn, or when >C=0"-is produced via PIET and R3N"+ has available a-protons). The follow-up chemistry of >C(.)OH is that of a neutral free radical (dimerization to form pinacols, addition to unsaturated compounds, fragmentations/ring-openings, etc.), and thus beyond the scope of this chapter. 

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