Electrophilic reactive intermediates

Alcohol attack generates an unstable intermediate that undergoes nucleophilic attack by CL at carbon. Compare electrostatic potential maps of methanol, thionyl chloride intermediate, and phosphorus trichloride intermediate. What features of these maps are consistent with an electrophilic reactive intermediate ... 

It should be noted that acetylhydrazine can also be further metabolized to an electrophilic reactive intermediate by cytochrome P-450. This will be discussed in detail in chapter 7. 

Resorcinol is water-soluble and readily conjugated and eliminated. The chemical has no known potential for formation of electrophilic reactive intermediates comparable to those derived from the other dihydroxybenzenes. Resorcinol was tested in various genetic toxicology assays, including in-vitro bacterial and mammalian assays and in-vivo mammalian assays. It gave negative results in all studies, with the exception of a positive response in the two in-vitro studies that assessed chromosomal aberrations in human lymphocytes from whole blood cultures however, resorcinol did not induce chromosomal aberrations in human fibroblasts. 

Glutathione contains a nucleophilic -SB group which In many cases detoxifies electrophilic reactive Intermediates through formation of stable glutathione conjugates, as In the case of paracetamol. 

The reduction in the yield of 2 at lower temperatures is not due to retardation of the rate of capture of diethyl amine by the electrophilic reactive intermediate. DeGraff et al. [26] found that there was no appreciable temperature dependence to the amine trapping reaction. Leyva et al. [69] confirmed this result (Table 3) but found that the yield of the 1/f-azirine intermediate is dramatically reduced upon laser flash photolysis of solutions of phenyl azide 1 and diethylamine in 2-MTHF. 

Potential to form electrophilic reactive intermediate(s) through chemical, photochemical, or metabolic activation ... 

Fig. 10.32. Some examples of activated double bonds as electrophilic reactive intermediates.

Fig. 9 Formation and detoxification on an electrophilic reactive intermediate (modified from Wells 2007)...

The presence of a leaving group on the C3-methyl inereases the likelihood of formation of electrophilic reactive intermediates. 

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