Predictions aromatic substitution reaction

Electronic effects in conjugated systems may be computed with the Hiickel HMO method. Electron densities are used to predict aromatic substitution reactions, and it is possible to refer to radical, nucleophilic, and electrophilic localization energies.For the latter, the term ELENERGY is used in a transform, for example IF ELENERGY ON ATOM 1 BETTER THAN ATOM 2 THEN ADD 20. 

Predicting the Product of an Electrophilic Aromatic Substitution Reaction... 

Aromatic substitution reactions are often complicated and multistep processes. A correlation, however, in many cases can be found between the charged attacking species and the electron density distribution in the molecule attacked during electrophilic and nucleoph c substitution. No such correlation is expected in radical substitution where the attacking particles are neutral, rather a correlation between the reactivities of separate bonds and a free valency index of the bond order. This allows the prediction of the most reactive bonds. Such an approach has been used by researchers who applied quantum calculations to estimate the reactivities of the isomeric thienothiophenes and to compare them with thiophene or naphthalene. " Until recently quantum methods for studying reactivities of aromatics and heteroaromatics were developed mainly in the r-electron approximation (see, for example, Streitwieser and Zahradnik ). The M orbitals of a sulfur atom were shown not to contribute substantially to calculations of dipole moments, polarographic reduction potentials, spin-density distribution, ... 

Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

Predict the product of electrophilic aromatic substitution reactions of pyridine and quinoline. 

Predict the product expected from electrophilic aromatic substitution reactions of pyrrole, furan, and thiophene. 

Predict the effect of these substituents on the rate and regiochemistry of electrophilic aromatic substitution reactions ... 

The situation is more complicated if there is more than one substituent on the benzene ring. However, it is usually possible to predict the major products that are formed in an electrophilic aromatic substitution reaction. When the substituents direct to the same position, the prediction is straightforward. For example, consider the case of 2-nitrotoluene. The methyl group directs to the positions ortho and para to itself—that is, to positions 4 and 6. The nitro group directs to positions meta to itself—that is, also to positions 4 and 6. When the reaction is run, the products are found to be almost entirely 2,4-dinitrotoluene and 2,6-dinitrotoluene, as expected ... 

We talked a lot about regioselectivity two chapters ago, when you learned how to predict and explain which product(s) you get from electrophilic aromatic substitution reactions. The functional group is the aromatic ring where it reacts is the reaction s regioselectivity. Going back further, one of the first examples of regioselectivity you came across was nucleophilic addition to an unsaturated ketone. Addition can take place in a 1,2- or a 1,4-fashion—the question of which happens (where the unsaturated ketone reacts) is a question of regioselectivity, which we discussed in Chapters 10 and 23. We shall leave all discussion of stereoselectivity until Chapters 31-34. 

Sample Problem 18.4 shows how this information can be used to predict the products of electrophilic aromatic substitution reactions. 

Just by knowing the effects summarized in these short lists, we can now predict fairly accurately the course of hundreds of aromatic substitution reactions. We now know, for example, that bromination of nitro enzene will yield chiefly the /M-isomer and that the reaction will go more slowly than the bromination of benzene itself indeed, it will probably require severe conditions to go at ail. We now know that nitration of CeHsNHCOCH, acetanilide) will yield chiefly the o-and / -isomers and will take place more rapidly than nitration of benzene. 

Considerable advances have been made in recent years in the understanding of the aromatic substitution reactions of oxazoles. Molecular orbital calculations (Section III, B) predict that electrophilic attack should occur preferentially at position 5, and indeed this is observed. The relative order of reactivity calculated theoretically is not in complete accord with the experimentally observed order (5 > 4 > 2) therefore it is evident that the electrophilic substitution reactions are rather more complex than the present theoretical calculations would predict. 

When a disubstituted benzene undergoes an electrophilic aromatic substitution reaction, the directing effect of both substituents has to be considered. If both substituents direct the incoming substituent to the same position, the product of the reaction is easily predicted. 

Predict the effect of a substituent on the rate and the regiochemistry of an electrophilic aromatic substitution reaction. 

Complete the following electrophilic aromatic substitution reactions. Where you predict meta substitution, show only the meta product. Where you predict ortho-para substitution, show both products ... 

Two of these positions are already occupied. Only one position remains. We therefore predict that this position is most likely to undergo an electrophilic aromatic substitution reaction. 

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