Preparation and reactions of pyridones: steric and electronic effects on cycloadditions with 2(1H)-pyridones

Abstract

The reactions of a series of substituted 2(1 H)-pyridones with dimethyl butynedioate have been studied. Cycloadditions across the 3,6-positions can be observed in certain instances and are particularly favoured where steric buttressing occurs between the substituent groups of the starting pyridones. The pyridone could not be induced to react with simple olefins, either by intermolecular or, via incorporation of alkenyl substituents, by intramolecular processes. From the results it is shown that 2-pyridones can be encouraged to behave as reactive classical dienes in cycloaddition reactions.2( ~H)-PYRIL)oNEs have long attracted chemical attention for their hetero-aromatic character.l Studies, on their ability to sustain an induced ring current, led to estimates that they should possess only ca. 35% of the aromaticity of benzene, implying that the conjugated system should act as a diene in Diels-Alder type cycloaddition reactions2 An X-ray crystallographic study on 1-methyl-2-pyridone (1) supports this view, in that it is shown to contain carbon-carbon bonds which are alternately long and short.3 However, early attempts to illustrate such reactivity failed, partly owing to competing nucleophilic addition of the amide group to the dien~phile.~. Thus, ethoxyacetylene produces a mix-

Pyridone Functionalization: Regioselective Deprotonation of 6‐Methylpyridin‐2(1H)‐ and ‐4(1H)‐one Derivatives

“…Use of 1.0 equiv. of base and addition of electrophile at –10 °C was required to form the desired product 5d cleanly with isolation in a low yield of 20 %, as found by Sammes, who obtained 6.6 % yield by operating at –23 °C. In comparison, 5a and 5b were obtained in significantly lower yields of 37 % and 38 %, respectively when n BuLi was employed as base.…”

“…While the addition of electrophiles to lithiated methyl pyridines continues to be studied in depth, there is a lack of information on reactions of metalated 6‐methyl‐2‐ and 2‐methyl‐4‐pyridones. Only limited examples of alkylation of 2‐pyridone methyl substituents are reported in the literature, along with early pioneering work on ring and N ‐substituent lithiation . A heterocyclic methyl group represents a source of diversity for ring functionalization, although conditions to selectively effect lithiation of a pyridine ring while leaving a methyl substituent intact have also been developed .…”

Six pyrimidonium salts: determination of their crystal structures and studies of their prototropic behaviour in solution

“…Crystal structures of the 2-pyritnidone hydrochlorides [5][6][7][8][9][10] The results are shown in Tables 1-6. Each of the structures consists of 2-pyrimidonium cations and chloride anions, the packing being dominated by N-H .…”

“…The chains in 7 contain two crystallographically independent C1-anions, each of which resides on a crystallographic twofold axis perpendicular to the direction of propagation; thus adjacent cations are related by a twofold rotation about an axis containing the symmetrically bridging chloride anion. The structures of [8][9][10], N-methylated derivatives of 5-7, respectively, consist of strongly N-H . .…”

Alkoxy(alkyl)silylalkyl derivatives of nitrogen-containing heterocycles

“….SiMe n (OMe) 37n , where n = 0 or 1, were synthesised in 65% ± 86% yields by the reaction of S-sodium derivatives of 8-mercaptoquinoline, 2-mercaptobenzooxazole, 2-mercaptobenzothiazole and 2-mercaptobenzoimidazole with trimethoxy-(chloromethyl)and dimethoxymethyl(chloromethyl)silanes (1) in a polar aprotic solvent (DMF, DMSO) for 2 ± 3 h at 80 ± 90 8C. 40 ± 42 SNa N + ClCH2SiMen(OMe)37n The synthesis of trimethylsilylalkyl-substituted pyrrole, 43, 44 piperidine, 45 pyridine, 46 ± 49 2-pyridone, 50 pyrrolidine, 51,52 pyrazole, imidazole, benzoimidazole, 53 quinoline, 54 ± 56 3,4-dimethylisoxazole, 57,58 2-mercaptobenzothiazole, 59,60 benzothiazole, 61 indole, 62 tetrazole, 63 pyrimidine 64 and carbazole 65 makes wide use of C-, N-or S-lithium derivatives of these heterocycles. The latter are obtained by the reaction of the corresponding heterocyclic compounds with RLi (R = Me, Bu n , Bu t , Ph, NPr i…”