Electrophilic aromatic trifluoromethylation

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

Turning now to electrophilic aromatic substitution in (trifluoromethyl)benzene we con sider the electronic properties of a trifluoromethyl group Because of their high elec tronegativity the three fluorine atoms polarize the electron distribution m their ct bonds to carbon so that carbon bears a partial positive charge... 

Because the carbon atom attached to the ring is positively polarized a carbonyl group behaves m much the same way as a trifluoromethyl group and destabilizes all the cyclo hexadienyl cation intermediates m electrophilic aromatic substitution reactions Attack at any nng position m benzaldehyde is slower than attack m benzene The intermediates for ortho and para substitution are particularly unstable because each has a resonance structure m which there is a positive charge on the carbon that bears the electron withdrawing substituent The intermediate for meta substitution avoids this unfavorable juxtaposition of positive charges is not as unstable and gives rise to most of the product... 

Just as there is a mar-ked difference in how methyl and trifluoromethyl substituents affect the rate of electrophilic aromatic substitution, so too there is a marked difference in how they affect its regioselectivity. 

The pKa of p-(tiifluoromethyl)benzoic acid is 3.6. Is the trifluoromethyl substituent an activating or deactivating group in electrophilic aromatic substitution ... 

Trifluoromethyl)benzene (benzotrifluoride, 15) was the first organic fluoride to incorporate a trifluoromethyl group. By a standard nitration process, it formed l-nitro-3-(trifluoromethyl)-benzene (16) which was reduced to the 1-amino derivative, 17. This we a-directive influence on electrophilic aromatic substitution contrasted with that for fluorobenzene, which gave 4-and 2-nitro products. 

B-l. Consider the following statements concerning the effect of a trifluoromethyl group, —CF3, on an electrophilic aromatic substitution. 

By far the most common methods for the preparation of dibenzoselenophenes and 2-benzoselenophenes, like the synthesis of 1-benzoselenophenes, rely upon the annulation of the heterocyclic ring system onto a preformed benzene ring and mostly involve the formation of one or two Se-C bonds as their key steps, with only a few exceptions [1, 119, 120], Intramolecular electrophilic aromatic substitution of biphenyl-2-yl trifluoromethylselenide to 5-(trifluoromethyl)dibenzoselenopheni um triflate (62) [99, 143] and synthesis of tetramethoxydibenzoselenophene (95) (Scheme 26) [144, 145] are examples. 

Toluene undergoes nitration some 20-25 times faster than benzene. Because toluene is more reactive than benzene, we say that a methyl group activates the ring toward electrophilic aromatic substitution. (Trifluoromethyl)benzene, on the other hand, undergoes nitration about 40,000 times more slowly than benzene. We say that a triflu-oromethyl group deactivates the ring toward electrophilic aromatic substitution. 

The preceding explanation would seem to explain most of the data in Table 8.21, but there is one apparent discrepancy. We might have expected the methoxy substituent to be electron-donating, but it gives the same product orientation as does trifluoromethyl. This intuitive expectation of the substituent effect of methoxy is based primarily on its influence on electrophilic aromatic substitution (SeAr) and on nucleophilic aromatic substitution (SwAr) reactions, both of which involve attachment of a species to an aromatic ring to form a cr complex. In contrast, the carbanionic intermediates presumed to be formed in the benzyne reaction have the nonbonded pair of electrons in... 

We can understand how the trifluoromethyl group affects orientation in electrophilic aromatic substitution if we examine the resonance structures for the arenium ion that would be formed when an electrophile attacks the ortho, meta, and para positions of trifluoromethylbenzene. 

PROBLEM 14.45 Eixplain why the trifluoromethyl group is meta-directing in electrophilic aromatic substimtion. Would you expect CF3 to be activating or deactivating Why ... 

Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene 474 Substituent Effects in Electrophilic Aromatic Substitution Activating Substituents 476 Substituent Effects in Electrophilic Aromatic Substitution Strongly Deactivating Substituents 480 Substituent Effects in Electrophilic Aromatic Substitution Halogens 482 Multiple Substituent Effects 484 Retrosynthetic Analysis and the Synthesis of Substituted Benzenes 486 Substitution in Naphthalene 488 Substitution in Heterocyclic Aromatic Compounds 489... 

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