Oxygen nucleophiles aromatic nucleophilic substitution

All the mechanisms so far discussed take place at a saturated carbon atom. Nucleophilic substitution is also important at trigonal carbons, especially when the carbon is double bonded to an oxygen, a sulfur, or a nitrogen. Nucleophilic substitution at vinylic carbons is considered in the next section at aromatic carbons in Chapter 13. 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

Irradiation of a-bromoacetophenones in methanol yields only ionic products (i.e. nucleophilic substitution and Favorskii-type rearrangement products) if there is an ortho-methoxy substituent in the aromatic ring152. This is due to stabilization of the intermediate cation as a result of interaction between the lone pair on the oxygen of the ortho-methoxy group and the vacant p-orbital of the cation. With an ortho-acetoxy substituent in the ring... 

Treatment with base (NaH can be used) now converts the OH group into an alkoxide and it does the next aromatic nucleophilic substitution. In this reaction we are attacking the position metato the ketone so we cannot put the negative charge on the oxygen atom. The remaining three fluorines must stabilize it by the inductive effect we described earlier. 

Pyridones are easy to prepare (see Chapter 44) and can be alkylated on oxygen as predicted by their structure. A more important reaction is the direct conversion to chloropyridines with POCI3. The reaction starts by attack of the oxygen atom at phosphorus to create a leaving group, followed by aromatic nucleophilic substitution. The overall effect is very similar to acyl chloride formation from a carboxylic acid. 

Oddly enough, oxygen causes activation in nucleophilic substitution here in precisely the same way it activates aromatic ethers toward electrophilic substitution (Sec. 17.8) the common feature is, of course, development of a positive charge in the transition state of the rate-determining step.)... 

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