Substituents activating

In both media a limit was reached beyond which the introduction of further activating substituents did not increase the rate of nitration this limit was identified as the rate of encounter of the nitronium ions and the aromatic molecules. 

Under these first-order conditions the rates of nitration of a number of compounds with acetyl nitrate in acetic anhydride have been determined. The data show that the rates of nitration of compounds bearing activating substituents reach a limit by analogy with the similar phenomenon shown in nitration in aqueous sulphuric and perchloric acids ( 2.5) and in solutions of nitric acid in sulpholan and nitro-methane ( 3.3), this limit has been taken to be the rate of encounter of the nitrating entity with the aromatic molecule. 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

The tendency towards a-substitution is also seen in the reactions of naphthalene derivatives containing de-activating substituents. Thus,... 

C—H bonds are polarized by attached unsaturated carbon substituents. Such groups "activate" the neighbouring CHj, CHp or CH groups in the following order CR=NR > COR > CN > COOR > CR = NR > Ph > CR=CRj. Two activating substituents reinforce each other. 

Olefin synthesis starts usually from carbonyl compounds and carbanions with relatively electropositive, redox-active substituents mostly containing phosphorus, sulfur, or silicon. The carbanions add to the carbonyl group and the oxy anion attacks the oxidizable atom Y in-tramolecularly. The oxide Y—O" is then eliminated and a new C—C bond is formed. Such reactions take place because the formation of a Y—0 bond is thermodynamically favored and because Y is able to expand its coordination sphere and to raise its oxidation number. 

The presence of activating substituent on the carbocyclic ring can, of course, affect the position of substitution. For example, Entries 4 and 5 in Table 14.1 reflect such orientational effects. Entry 6 involves using the ipso-directing effect of a trimethylsilyl substituent to achieve 4-acetylation. 

All alkyl groups not just methyl are activating substituents and ortho para direc tors This IS because any alkyl group be it methyl ethyl isopropyl tert butyl or any other stabilizes a carbocation site to which it is directly attached When R = alkyl... 

SUBSTITUENT EFFECTS IN ELECTROPHILIC AROMATIC SUBSTITUTION ACTIVATING SUBSTITUENTS... 

Table 12 2 summarizes orientation and rate effects m electrophilic aromatic sub stitution reactions for a variety of frequently encountered substituents It is arranged m order of decreasing activating power the most strongly activating substituents are at the top the most strongly deactivating substituents are at the bottom The mam features of the table can be summarized as follows... 

Some of the most powerful activating substituents are those m which an oxygen atom IS attached directly to the nng These substituents include the hydroxyl group as well as alkoxy and acyloxy groups All are ortho para directors... 

Substituent Effects in Electrophilic Aromatic Substitution Activating Substituents... 

Because we have come to associate activating substituents with ortho para directing effects and deactivating substituents with meta the properties of the halogen substituents appear on initial inspection to be unusual... 

Section 12 15 When two or more substituents are present on a nng the regioselectiv ity of electrophilic aromatic substitution is generally controlled by the directing effect of the more powerful activating substituent... 

A nitro group is a strongly activating substituent in nucleophilic aromatic substitution where it stabilizes the key cyclohexadienyl anion intermediate... 

A hydroxyl group is a very powerful activating substituent and electrophilic aro matic substitution m phenols occurs far faster and under milder conditions than m ben zene The hrst entry m Table 24 4 for example shows the monobrommation of phenol m high yield at low temperature and m the absence of any catalyst In this case the reac tion was carried out m the nonpolar solvent 1 2 dichloroethane In polar solvents such as water it is difficult to limit the brommation of phenols to monosubstitution In the fol lowing example all three positions that are ortho or para to the hydroxyl undergo rapid substitution... 

The hydroxyl group of a phenol is a strongly activating substituent and electrophilic aromatic substitution occurs readily m phenol and its deriv atives Typical examples were presented m Table 24 4... 

Activating substituent (Sections 12 10 and 12 12) A group that when present in place of a hydrogen causes a particular reaction to occur faster Term is most often applied to sub stituents that increase the rate of electrophilic aromatic sub stitution... 

When activating substituents are present in the benzenoid ring, substitution usually becomes more facile and occurs in accordance with predictions based on simple valence bond theory. When activating substituents are present in the heterocyclic ring the situation varies depending upon reaction conditions thus, nitration of 2(177)-quinoxalinone in acetic acid yields 7-nitro-2(177)-quinoxalinone (21) whereas nitration with mixed acid yields the 6-nitro derivative (22). The difference in products probably reflects a difference in the species being nitrated neutral 2(177)-quinoxalinone in acetic acid and the diprotonated species (23) in mixed acids. 

Conflicting reports on the nitration of phenazine have appeared, but the situation was clarified by Albert and Duewell (47MI21400). The early work suggested that 1,3-dinitroph-enazine could be prepared in 66% yield under standard nitration conditions however, this proved to be a mixture of 1-nitrophenazine and 1,9-dinitrophenazine (24). As with pyrazines and quinoxalines, activating substituents in the benzenoid rings confer reactivity which is in accord with valence bond predictions thus, nitration of 2-methoxy- or 2-hydroxy-phenazine results in substitution at the 1-position. 

The preparation of benzo fused pyrido[3,2- i]pyrimidines has furnished the only examples of the classic reaction of this type, the Bischler-Napieralski, involving the cyclization of 5-aryl-4-acylaminopyrimidines to 6-alkylpyrimido[4,5-c]isoquinolines, e.g. (157)->(158) (73YZ330). As often found in this reaction, the presence of activating substituents appears necessary (78CPB245). 

When the preferred substitution position (cf. 110 and 111) is occupied, activating substituents can facilitate substitution in other positions (cf. examples in Sections 4.02.1.4.2 and 4.02.1.4.5) ipso attack can also occur if the substituent is itself easily displaced. 

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