Pyridone anions, alkylation

Reaction of pyridones with diazoalkanes involves deprotonation as the first step, forming an alkyldiazonium cation which then rapidly alkylates the pyridone anion 2-pyridone gives mainly 0-methyl derivatives, but 4-pyridone gives mixed 0- and A-methyl derivatives. 

Pyridone anion undergoes N-alkylation in dimethylformamide (DMF) when the counterion is Na . O-Alkylation is favored in a heterogeneous reaction using the Ag salt in nonpolar solvents (59). 

Another ambident anion species which shows cation and solvent dependent alkylation behavior is pyridone. Although N-alkylation is preferred thermodynamically, and benzylation of the sodium salt yields predominantly the N-alkylated product, 0-alkylation of the anion is favored by dipolar aprotic solvents and soft cations [58]. In pentane or benzene, the silver salt of pyridone anion is 0-benzylated. Likewise, under phase transfer conditions, where the anion is presumably paired with a quater-... 

M-substituted 2-pyridones can be prepared by N-alkylation, under basic conditions (pfCa of the amide proton is 11). The resulting anion can then react on either nitrogen or oxygen depending on the conditions employed [24-27]. Also, several direct methods for the construction of N-substituted 2-pyridones have been reported. Two such examples can be seen in Scheme 3 where the first example (a) is an intramolecular Dieckmann-type condensation [28] and the second (b) is a metal-mediated [2 -I- 2 + 2] reaction between alkynes with isocyanates [29,30]. 

It is thus possible to A -alkylate a pyridone by exploiting its acidity. As with enolate anions (see Section 10.2), there is the possibility for 0-alkylation and A-alkylation. Although it depends upon the... 

A convenient one-step conversion of moderately activated nitroarenes to phenols was achieved in DMSO via nucleophilic nitrite displacement by the anion of an aldoxime.153 TTie resulting O-arylaldox-ime is rapidly cleaved to the phenol derivative under the reaction conditions. The reaction is also applicable to activated fluorides and even to 2-chloropyridine which, at 110 °C, is converted to 2-pyridone in 72% yield.153 A somewhat related process concerns the synthesis, in 82-92% yield, of 4-alkoxybenzoni-triles (45 R = Me, CH2-oxirane, CHrfh, CHMeCTfcMe from O-alkyl-4-nitrobenzaldoximes (44) via hydride-induced elimination of the alkoxide followed by alkoxy denitration (Scheme 17).154... 

The carbonyl tautomers deprotonate at N-H, generating ambident anions that can react at either oxygen or nitrogen, depending on the exact conditions for example 0-alkylation can be achieved with silver carbonate. They are converted, as with the pyridones, into halo-quinolines and halo-isoquinolines by reaction with phosphorus halides. 

Diazinones, like pyridones, react with phosphorus halides with overall conversion into halides. Anions produced by A-deprotonation of diazinones are ambident, with phenolate-like resonance contributors, but they generally react with electrophilic alkylating agents at nitrogen, rather than oxygen, giving A-alkyl diazinones. 

Like pyridones, oxy-diazines are readily deprotonated under mild conditions, to give ambident anions which can be alkylated conveniently by phase-transfer methods, alkylation usually occurring at nitrogen. " M-Arylations of uracils also proceed in this way with, for example, l-fluoro-4-nitrobenzene."" 3-Pyridazinones alkylate cleanly on N-2 under phase-transfer conditions," but the regiochemistry of uracil alkylation is sometimes difficult to control (see also below). Uracils are sufficiently acidic to take part in Mitsunobu reactions." ... 

Nitro derivatives of a variety of heteroaromatic compounds enter the VNS reactions with alkyl hydroperoxide anions to produce the expected hydroxylation products [41, 137-139]. For instance, the VNS hydroxylation of 2-chloro-5-nitropyridine with ferf-butylhydroperoxide was shown to give 2-chloro-5-nitro-6-hydroxypytidine that exists in its tautomeric form of pyridone [41] (Scheme 44). It should be stressed that the SNAr of chlorine located in the highly activated position 2 was not competing with the VNS. 

Inter- and intramolecular HWE reactions of 5-(diethoxyphosphoryl)-l-acyl-2-alkyl(aryl)-2,3-dihydro-4-pyridones showed very interesting results by Comins and Ollinger. Treating phosphomate 38 with f-BuOK forms anion, followed by addition of the aldehyde, and raising the reaction temperature to 35 °C gave good yields of the desired enones 39. An... 

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