Dihydro-2-pyridone

The importance of ring size holds also for tautomerism of -pyrrol-5-ones and. d -dihydro-6-pyridones. While the former compounds behave as cyclic 1-methyl-2-alkyl-2-hydroxy-5-pyrrolidones 179) (76) [or, on distillation, as the dehydrated l-methyl-2-alkyl-J -pyrrolones (77)], the latter compounds exist as acyclic N-methylamides of 8-oxo-acids (78) [as shown by infrared spectroscopy (/80)j. The dehydration of 78 during distillation to form l-methyl-2-alkyl-. -dihydro-6-pyridones (79) is achieved only with difficulty. 

Nuclear magnetic resonance measurements have led to the conclu-sion that 2-pyridones have about 35% of the aromaticity of benzene and that the formally related l,2-dihydro-2-methylenepy-ridine is not aromatic. A substantial contribution by such resonance is indicated by the electronic spectrum of 2-quinolone, which is... 

Asymmetric synthesis and synthetic utility of 2,3-dihydro-4-pyridones 99JHC1491. 

The primary fragmentations of 5-methylsulfonyl-6-phenyl-2-pyridone (41) and its 3,4-dihydro analogue (42) are dominated by the methylsulfonyl substituent and not by the pyridone moiety26. Equation (18) summarizes the most important primary fragmentations and shows that the pyridone ions m/z 186 and 170 yield the pyrrole-type ions m/z 158 and 142 only after the sulfonyl side-chain has been broken off. Since the mass spectrum... 

The fluoboric acid-catalyzed aza-Diels-Alder reaction of aldimine and Danishefsky s diene proceeds smoothly to afford dihydro-4-pyridones in high yields [90] (Equation 4.16). Unstable aldimines generated from aliphatic aldehydes can be prepared in situ and allowed to react under one-pot reaction conditions. This one-pot Bronsted acid-catalyzed three-component aza-Diels-Alder reaction affords the adducts in good to high yields. 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

The oxidation of silyl enol ethers 111 with palladium(n) acetate is a convenient nnethod for the preparation of synthetically useful 2,6-disubstituted 2,3-dihydro-4-pyridones 112 <95TL(36)9449>. 

H)-Pyridone, 6-ethoxy-4,5-dihydro- (8) 2(3H)-Pyridinone, 6-ethoxy-4,5-dihydro- (9) (41879-47-4)... 

The procedure described here for the preparation of succinimide silver salt is a modification of one reported for the formation of the silver derivative of maleimide. The alkylation step is modeled after the procedure of Comstock and Wheeler/ who prepared 2-ethoxypyrrolin-5-one in unspecified 3deld, and is an improvement over a later procedure developed in the laboratories of the submitters/ The general scheme has been successfully applied to the preparation of a variety of 2-ethoxypyrrolin-5-ones (Table 1) as well as 6-ethoxy- and 6-propoxy-4,5-dihydro-2(3H)-pyridone from the corresponding five- and six-membered cyclic imides/... 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

Similar aza-Diels-Alder reactions of Danishefsky s diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate or sodium tetraphenylborate to afford dihydro-4-pyridones in high yields (Eq. 12.49).117 Antibodies have also been found to catalyze hetero-Diels-Alder reactions.118... 

Methylquinoline (2) 3-methyl-2(lH)quinolinone (3) 5,6-dihydro-5,6-dihydroxy-3-me thy 1-2(1 H)quinolinone (4) 6-hydroxy-3 -methyl-2( 1 H)quinolinone (5) 5,6-dihydroxy-3-methyl-2(lH)quinolinone (6) 3-methyl-2,4,6-trihydroxypyridine (1) 4-Methylquinoline (2) 4-methyl-2(lH)quinolinone (3) 7,8-dihydro-7,8-dihydroxy-4-methy 1-2(1 H) quinolinone (4) 8-hydroxy-4-methyl-2(lH)quinolinone (5) 7,8-dihydroxy-4-methyl-2(1 H)quinolinone (6) 6-hydroxy-5-(2-carboxyethenyl)-4-methyl-2( 1 H)pyridone... 

In Scheme 6.230, the multistep synthesis of 2,3-dihydro-4-pyridones is highlighted [411]. The pathway described by Panunzio and coworkers starts from a dioxin-4-one precursor, which is readed with 2 equivalents of benzyl alcohol under solvent-free microwave conditions to furnish the corresponding /1-diketo benzyl esters. Subsequent treatment with 1 equivalent of N,N-dimethylformamide dimethyl acetal (DMFDMA), again under solvent-free conditions, produces an enamine, which is then cyclized with an amine building block (1.1 equivalents) to produce the desired 4-pyridinone produds. All microwave protocols were conducted under open-vessel conditions using power control. 

The action of the valine derivatives 87 on the diene 86 under EtAlCU catalysis resulted in a mixture of cycloadducts 88, which on hydrolysis with aqueous methanolic sodium carbonate furnished a mixture of the dihydro-2-pyridones 89 and 90 and the esters 91 and 92. In the case of imines derived from aliphatic aldehydes, e.g. 87 (R = Pr), all four types of product were isolated, whereas imines from aromatic aldehydes, 87 (R = Ph, 3-CIC6H4 etc.), gave only the esters 91 and 92 (equation 55). All products were formed in yields of 64-84% and in high de49. 

Under the influence of zinc chloride, Danishefsky s diene 4 reacts with simple imines to give dihydro-y-pyridones 100 (e.g. R1 = n-Bu, Ph, Bn R2 = Pr, i-Pr, Ph) in 62-76% yields (equation 58)51. In contrast, the Et2AlCl-catalyzed reaction of the diene 86 with benzylidenemethylamine (101) results in the formation of the dihydro-a-pyridone 102 (equation 59)52. 

The first step in the total synthesis of the alkaloid ( )-ipalbidine 104 was the reaction of the diene 103 with A1-pyrrol ine (equation 60)53. The proportions of threo- and m // TO-dihydro- -pyridones, 106 and 107, respectively, produced in the diethylaluminium chloride-catalyzed reactions of the a-benzyloxyimines 105 (R = n-CsHn, i-Pr or i-Bu) with the diene 86 (equation 61), depend on the nature of R and the amount of imine used54. 

The enantioselective (76-90% ee) formation of the dihydro-y-pyridones 113 from various imines 112 (R = Ph, 3,5-xylyl or 3-pyridyl) and Danishefsky s diene 4 in the presence of 4 A molecular sieves and one equivalent of a catalyst prepared from triphenyl... 

As a general rule, in the case of CSPs featuring hydrophobic pockets, a decrease of mobile phase flow-rate results in an increase of chromatographic resolution (Rs), as a consequence of better stationary phase mass transfer [78]. This change has significant impact mostly in RP mode [17]. In the NP enantioselective separations of two test solutes (4-hexyl-5-cyano-6-methoxy-3,4-dihydro-2-pyridone and... 

It has been claimed that cardiotonic activity is retained upon replacement of the pyridone moiety in the amrinone molecule by a 3(2 /)-pyridazinone system (9) [7]. Moreover, the patent literature covers various cardiotonic 6-(pyridyl)-3(2//)-pyridazinones and 4,5-dihydro congeners as exemplified by (10), which have been developed in the United States [8-11], Also 3-amino-... 

However, 2,3-dihydro-4(lH)-pyridone [248] is also claimed to be N-protonated (Sugiyama et al., 1969) because the absorption maximum of its hydrochloride occurs virtually at the same wavelength (325 nm) as for the base itself (327 nm). According to Table 5, this would be an indication of O-protonation. Monocyclic ketones ([249], R = MeCO) with uninhibited mesomerism show O-proto-... 

Figure 3.31. Scope of Rh/(i )-binap-catalyzed asymmetric 1,4-addition of ArZnCl to 2,3-dihydro-4-pyridones.

Reduction of o /i-unsatin-ated lactams, S,6-dihydro-2-pyridones, with lithium aluminum hydride, lithium alkoxyaluminum hydrides and alane gave the corresponding piperidines. 5-Methyl-5,6-dihydro-2-pyridone (with no substituent on nitrogen) gave on reduction with lithium aluminum hydride in tetrahydrofuran only 9% yield of 2-methylpiperidine, but l,6-dimethyl-5,6-dihydro-2-pyridone and 6-methyl-l-phenyl-5,6-dihydro-2-pyridone afforded 1,2-dimethylpiperidine and 2-methyl-1-phenylpiperidine in respective yields of 47% and 65% with an excess of lithium aluminum hydride, and 91% and 92% with alane generated from lithium aluminum hydride and aluminum chloride in ether. Lithium mono-, di- and triethoxyaluminum hydrides also gave satisfactory yields (45-84%) [7752]. 

The photo-isomerization of certain pyridines to Dewar pyridines is described in Section 3.2.1.2.2, and the formation of bridged ring 6H-1,2-dihydro-3-pyridones in Section 3.2.1.10.4. 

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