Ring-deactivating substituents

Aluminum chloride is a stronger Lewis acid than iron(lll) bromide and has been used as a catalyst in electrophilic bromination when as in the example shown the aromatic ring bears a strongly deactivating substituent... 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

Mercury(II) acetate tends to mercurate all the free nuclear positions in pyrrole, furan and thiophene to give derivatives of type (74). The acetoxymercuration of thiophene has been estimated to proceed ca. 10 times faster than that of benzene. Mercuration of rings with deactivating substituents such as ethoxycarbonyl and nitro is still possible with this reagent, as shown by the formation of compounds (75) and (76). Mercury(II) chloride is a milder mercurating agent, as illustrated by the chloromercuration of thiophene to give either the 2- or 2,5-disubstituted product (Scheme 25). 

R Substituents affect the reactivity of the aromatic ring. Some substituents activate the ring, making it more reactive than benzene, and some deactivate the ring, making it less reactive than benzene. In aromatic nitration, for instance, an -OH substituent makes the ring 1000 times more reactive than benzene, while an —N02 substituent makes the ring more than 10 million times less reactive. 

In extension of the alkylation reactions to polychlorobenzenes, polychlorinated benzenes such as 1,2,4-trichlorobenzene and 1,2,., 4-tetrachlorobenzene were alkylated with (l,2-dichloroethyl)trichlorosilanes in the presence of aluminum chloride catalyst. Although the electron-withdrawing chlorine substituents on the ring deactivated the electrophilic substitution reaction, the alkylation... 

A wide variety of aromatic compounds can be brominated. Highly reactive ones, such as anilines and phenols, may undergo bromination at all activated positions. More selective reagents such as pyridinium bromide perbromide or tetraalkylammonium tribromides can be used in such cases.18 Moderately reactive compounds such as anilides, haloaromatics, and hydrocarbons can be readily brominated and the usual directing effects control the regiochemistry. Use of Lewis acid catalysts permits bromination of rings with deactivating substituents, such as nitro and cyano. 

All these rings undergo easy electrophilic substitution at the 2-position. Particularly for pyrrole and furan the high reactivity often leads to low yields and sometimes it is useful to incorporate deactivating substituents such as C02H which can later be removed. 

Case 1. If X is an electron-donating group it becomes the C-6 substituent in the indole ring. The substituent deactivates C-3 of the quinone to nucleophilic attack. Attack at C-5 is preferred to C-6 because of the more electrophilic character of the C-l carbonyl. Examples X = OMe, OH. 

Rearrangement was observed in the reaction of benzyl alcohol with xenon difluoride106, while deactivating substituents on the phenyl ring even improved the selectivity of the transformation and the yields of fluoromethoxy derivatives formed rose to 75-85% (Scheme 39). 

The reagents and the mechanism for the nitration of an aromatic ring have already been discussed. The reaction is very general and works with almost any substituent on the ring, even strongly deactivating substituents. 

Friedel-Crafts acylation, does not work when ring has strong deactivating substituents... 

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