Pyridine activated, electrophilic aromatic

The empirical data for electrophilic aromatic substitution on benzocycloalkenes over a variety of reactions and conditions show a consistent trend of increased Cp selectivity due primarily to C deactivation, with some indication that Cp activation occurs in benzobicycloalkenes. Acidity work on the benzocycloalkenes and related pyridines demonstrates clearly the extent of deactivation. The rehybridization model of Finnegan and Streitweiser has been postulated to account for the deactivation. Thummel s correlation of C y -H P a provided the necessary link between rehybridization and deactivation. Theories involving bond fixation in the Wheland intmnediate deserve some further consideration but are not essential to an understanding of the present empirical data. 

Electrophilic aromatic substitutions The chemistry of pyrimidine is similar to that of pyridine with the notable exception that the second nitrogen in the aromatic ring makes it less reactive towards electrophilic substitutions. For example, nitration can only be carried out when there are two ring-activating substituents present on the pyrimidine ring (e.g. 2,4-dihydroxypyrimidine or uracil). The most activated position towards electrophilic substitution is C-5. 

The methyl groups are electron-donating and activate aromatic compounds toward electrophilic aromatic substitution (see Secs. 4.10 and 4.11). Therefore, 2,6-dimethylpyridine undergoes nitration under much milder conditions than required by pyridine. Notice that nitration occurs ortho and para to the methyl groups. 

Activated pyridines will do electrophilic aromatic substitution... 

Complex 13 undergoes electrophilic substitution with aromatic substrates. Thus, treatment with benzene in dichloromethane at ambient temperature results in the formation of the diphenyl complex 15 (Scheme V. Reaction of 13 with pyridine (5-6 equivs) in dichloromethane affords a new complex that is the result of pyridine a-CH activation. The NMR data clearly show two chemically equivalent coordinated pyridines and pyridine that has lost one of the a-hydrogens. Structure 16 is proposed from the preliminary data. The formation of 15 and 16 was quantitative by NMR monitoring, but these compounds are reactive and have not been isolated as pure solids. While main group Lewis acids are well known to undergo aromatic substitutions (e.g., mercurations, thallations, etc.) (33), relatively little is known about the ability of transition metal complexes to undergo electrophilic aromatic substitution (34). 

Electrophilic substitution of 3-methoxy-4-methylaniline (655) by the complex 663 leads to the molybdenum complex 664. Oxidative cyclization of complex 664 with concomitant aromatization using activated commercial manganese dioxide provides 2-methoxy-3-methylcarbazole (37) in 53% yield (560). In contrast, cyclization of the corresponding tricarbonyliron complex to 37 was achieved in a maximum yield of 11 % on a small scale using iodine in pyridine as the oxidizing agent (see Scheme 5.49). 

Pyridine is deactivated toward electrophilic attack, but it is activated toward attack by electron-rich nucleophiles that is, it is activated toward nucleophilic aromatic substitution. If there is a good leaving group at either the 2-position or the 4-position, a nucleophile... 

Electrophilic substitution in the azoles is intermediate in facility between pyridine on the one hand and pyrroles, thiophenes and furans on the other the presence of the electron-withdrawing imine unit has an effect on the flve-membered aromatic heterocycles just as it does when incorporated into a six-membered aromatic framework, i.e. the comparison is like that between benzene and pyridine (Chapter 7). The order of reactivity - pyrrole > furan > thiophene - is echoed in the azoles, though the presence of the basic nitrogen complicates such comparisons. The regiochemistry of electrophilic attack can be rationalised nicely by comparing the character of the various ring positions - those that are activated in being flve-membered in character and those that are deactivated by their similarity to a- and y- positions in pyridine. 

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