Electrophilic substitution probable intermediate

Now that we have determined that the intermediate in electrophilic aromatic substitution is usually a a complex (see, however, p. 394), let us return to a consideration of Reaction 7.76. Two factors probably combine to cause the observed isotope effect and base catalysis. First, the strong electron-donating groups stabilize the intermediate 76 (Equation 7.77) and make departure of the proton more difficult than proton loss in many other electrophilic substitutions. [Remember, however, that k1 < k2 (see p. 386).] Second, steric interactions between the large diazonium group and the nearby substituents increase the rate... 

Anisole acetylation, which was one of the main reactions investigated, was first shown to be catalysed by zeolite ten years ago by Bayer (13), which was confirmed by Harvey et al. (14), then by Rhodia (15). Large pore zeolites and especially those with a tridimensional pore structure such as HBEA and HFAU were found to be the most active at 80°C, in a batch reactor with an anisole/acetic anhydride molar ratio of 5 and after 6 hours reaction, the yield in methoxyacetophenone (MAP) was close to 70% with HBEA and HFAU zeolites, to 30% with HMOR and 12% with HMFI. With all the zeolites and also with clays and heteropolyacids, the selectivity to the para-isomer was greater than 98%, which indicates that this high selectivity is not due to shape selective effects but rather to the reaction mechanism (electrophilic substitution). The lower conversion observed with HMOR can be related to the monodimensional pore system of this zeolite which is very sensitive to blockage by heavy secondary products. Furthermore, limitations in the desorption of methoxyacetophenone from the narrow pores of HMFI are probably responsible for the low activity of this intermediate pore size zeolite. 

Other (less acidic) ot-substituted isocyano acetates (1, R = H, Me, /Bu, /Pr) [159]. Silver(l) salts (AgOAc) were found to accelerate the reaction, probably by coordination of the terminal NC carbon atom to Ag which increases the a-acidity and NC electrophilicity (Fig. 22). Remarkably, unlike most other reactions reported with a-acidic isonitriles, no additional base or acid is required for the three-component coupling to 2//-2-imidazolines 65. Most likely, the intermediate imine is basic enough to deprotonate the isocyanide. 

Among dichloro bis-electrophiles, malonyl chloride with enamine 183b affords pyridone 189, probably resulting from C-alkylation and cyclocondensation followed by aromatization (02T2821). Finally, o-chloro-benzoylchloride leads to C-benzoylation and subsequent intramolecular substitution of the isolable intermediate to yield quinoline 190 (03ARK (is.2)146). 

A more satisfactory solution to the mechanism of these substitutions now seems experimentally feasible. It is likely that the trisamino chelate (XXXIII) could be completely resolved by salt formation with a suitable optically active acid. The optically pure amine could then be converted by electrophilic cleavage into optically active bromo-, chloro-, and thiocyanate-substituted chelates. It would thus be a simple matter to determine whether these substitutions proceed with complete retention of asymmetry. Further, the question of a symmetrical five-coordinate intermediate in racemization of such compounds could probably be elucidated by a study of solvent polarity or salt effects on the kinetics of the racemization of these chelates. 

Substituted 2-aminonaphthalenes have been prepared on Wang resin by cyclocondensation of resin-bound 2-trifluoromethylphenyl acetate with arylacetonitriles (Figure 10.7). This reaction probably proceeds via an electrophilic o-quinone methide intermediate, formed by base-induced elimination of HF from the resin-bound ester [229]. 

The FO explanation is very simple. An electrophile will attack the propene at the site of the highest HOMO coefficient, i.e. the nonsubstituted carbon atom (Exercise 1, p. 32). This is a simple application of rule 3. This rule implies that the transition state FOs are not very different from the FOs of the starting materials, and it probably works best for reactions with early transition states. The main advantage of the FO approach over that based on the stability of the intermediate cations is its generality it applies not only to Markovnikov s rule but also C-substitution of enolates. 

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