Double a-cleavage

Cyclohexanone has been examined by deuterium-labeling to reveal the mechanism of propyl loss, [M-43], m/z 55, from its molecular ion, M = 98 [35,36]. The corresponding signal is the base peak of the spectrum (Fig. 6.11). Clearly, one deuterium is incorporated in the fragment that is shifted to m/z 56 in case of the [2,2,6,6-D4]isotopolog, which is consistent with the above three-step mechanism. 

Of course, a-cleavage can also occur in alicyclic ketones and other heteroatom-substituted alicyclic compounds. However, a single bond cleavage cannot release a neutral fragment, because this is still adhering to another valence of the functional group  

Following the logic of the deuterium labeling, regioisomers of cyclohexanones, cyclohexylamines, cyclohexylalcohols and others can be identified by strict application of the above mechanism. Regardless of some limitations of the method, e.g., that it is impossible to distinguish a 2,3-dimethyl from a 2-ethyl or 3-ethyl derivative, the method provides a valuable aid in structure elucidation. 

Example Propyl and pentyl loss from 2-ethyl-cyclohexylamine molecular ion, = 127 (odd m/z) are competitive (Fig. 6.12). Pentyl loss, m/z 56 (even m/z), is favored over propyl loss, m/z 84 (even m/z), in accordance with Stevenson s Rule. The peak at m/z 98 may be rationalized in terms of ethyl loss due to a minor contribution of 1,4-H shift, i.e., from position 3 instead of the predominant 1,5-H shift from position 2. The [M-CHs] peak, m/z 112, is accompanied by a [M-NHs] signal, m/z 110, which is typical of primary - and to a lower extend also secondary - amines. 

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Fig. 6.12. El mass spectram of 2-ethyl-cyclohexylamine. Double a-cleavage allows to identify the -substitution on one side of the ring. Spectrum used by permission of NIST. NIST 2002.

Hydroxyoxaziridines like (117) undergo double ring cleavage to form, for example, a nine-membered keto lactam (81AG(E)670). 

Ketones in which the double bond is located in the p,y position are likely candidates for a-cleavage because of the stability of the allyl radical that is formed. This is an important process on direct irradiation. Products then arise by recombination of the radicals or by recombination after decarbonylation. 

This two-step sequence is a valuable alternative to the direct double bond cleavage by ozonolysis. 

The keto group must come from double bond cleavage so we may add anything we please as R in (17), The obvious choice is hydrogen as (17) can then be made by a Wittig reaction on available aldehyde (18). 

Wyss, A., Carotene oxygenases a new family of double bond cleavage enzymes, J. Nutr. 134, 246S, 2004. 

A surprising exception has been reported with evidence for a cleavage reaction in the case of divinyl sulphone. In non-aqueous and slightly acidic media, the behaviour of a., ji-unsaturated aromatic sulphones is also complex (see Table 7) since the cleavage and the saturation may compete. Strongly electrophilic double bonds undergo Michael additions in aprotic solvents by slowly protonated anions. Transfer of labile hydrogen may also lead to unactivated bases. It is noteworthy that in numerous cases (Table 6) the saturation is the preferred route. 

The ozonolysis of carotenoids was employed in order to obtain oxygenated cleavage products for biological tests, for example, for lycopene. In this case, among a series of products, one product formed by a double oxidative cleavage was purified and characterized as ( , ,/ )- 4 - methyl - 8 -oxo-2,4,6-nonatrienal, and it was shown to be active in the induction of apoptosis in HL-60 cells (Zhang et al. 2003). 

This compound chemiluminesces when exposed to air or oxygen. Its CL was first demonstrated by Fletcher and Heller [47, 48] and suggested to occur via formation of a dioxetane by addition of oxygen across the ethylenic double bond. Cleavage of the dioxetane to form excited tetramethylurea results in excitation of the tetrakis (dimethylamino) ethylene, whose CL is in good agreement with the fluorescence spectrum of the parent compound. The reaction has been used for the analysis of oxygen [49, 50],... 

The allyl 2-nitrophenyl sulphoxide is apparently not an intermediate in this reaction as the MS of the latter compound is dominated by a cleavage reaction giving rise to C3H5+, whereas the ions corresponding to a loss of the HSC>2 radical apparently are of low intensity86. Thus, it was concluded that the double oxygen transfer to sulphur most probably should be formulated as a concerted reaction86. 

Example The oxidative addition of dimethyl disulfide (DMDS) transforms the double bond to its 1,2-bis-thiomethyl derivative (a). Induced by charge localization at either sulfur atom, the molecular ions of DMDS adducts are prone to a-cleavage at the former double bond position (b). This gives rise to sulfonium ions that are readily identified from the mass spectrum (Chap. 6.2.5). The method can be extended to dienes, trienes, and alkynes. [70,71] (For the mass spectral fragmentation of thioethers cf. Chap. 6.12.4). 

There is some information concerning the reaction of ozone with chemicals under aqueous conditions. The information available suggests that double-bond cleavage takes place, just as it does under nonaqueous conditions, except that ozonides are not formed. Instead, the zwitterionk intermediate reacts with water, producing an aldehyde and hydrogen peroxide. In addition to double-bond cleavage, a number of other oxidations are possible. Mudd et showed that the susceptibility of amino acids is in the order cysteine, tryptophan, methionine. 

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