Novel hexahydrofuro[3,4‐b]‐2(1H)‐pyridones from 4‐aryl substituted 5‐alkoxycarbonyl‐6‐methyl‐3,4‐dihydropyridones

Abstract

The title compounds 6 have been prepared in a one‐step procedure from the corresponding 4‐aryl substituted 5‐alkoxycarbonyl‐6‐methyl‐3,4‐dihydropyridones 4 in good yields. Quantum chemical calculations reveal a non‐planar molecule with a distorted dihydropyridone ring and two favoured conformations. The 13C nmr data and theoretical calculations support a strong push‐pull effect on the olefinic moiety.

1H and 13C spectral assignment of 2(1H)‐pyridone derivatives

“…It is worth mentioning that in their 13 C NMR spectra these compounds show the signal for C-6 at a higher υ value (¾149.5 ppm) than those expected for typical olefinic carbons atoms, whereas C-5 appears (¾105 ppm) at lower υ values. These findings have been accounted for by the strong push-pull effect of the groups linked to the olefinic double bonds, similarly to that observed previously in other related molecules.…”

“…These findings have been accounted for by the strong push-pull effect of the groups linked to the olefinic double bonds, similarly to that observed previously in other related molecules. 19,20 Since we have achieved unambiguous assignments for all the 1 H NMR resonances, 13 C NMR resonances were assigned in a straightforward manner by analysis of the HMQC spectra 705 Spectral Assignments and Reference Data for the protonated carbon atoms on the basis of chemical shift theory, substituent effects and DEPT data. Quaternary carbons were assigned by analysis of the HMBC spectra.…”

“…11 In general, these dihydropyridones can be easily prepared from Meldrum's acid by a heterocyclization reaction of aˇ-keto ester or acetylacetone and an aromatic aldehyde in the presence of ammonium acetate. 12,13 In connection with our studies of novel calcium channel modulators, we have previously described the synthesis and conformational study of 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridines 14 and 5-acetyl-4-aryl-3,4-dihydro-6-methyl-2(1H)-pyridones. 15 Recently we also reported a solid-phase synthesis method 16 and a solventfree synthesis under microwave irradiation of 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones.…”

Solid‐Phase Synthesis and Structural Study of Substituted 1,4,5,6‐Tetrahydro‐6‐oxopyridine‐3‐carboxylic Acids

“…In connection with our studies on novel calcium channel modulators, we previously described the synthesis in solution and the conformational study of 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridines [18,19] and 5-acetyl-4-aryl-3,4-dihydro-6-methyl-2(1H)pyridones [20]. This strategy involves a multi-component reaction of Meldrums acid, alkyl acetoacetate or acetylacetone and substituted aro-matic aldehydes in the presence of ammonium acetate and acetic acid as solvent.…”

Mass spectral fragmentation patterns of new 5-acetyl-4-aryl-6-methyl-2(1H)pyridones

“…4 In general these dihydropyridones can be easily prepared from Meldrum's acid by heterocyclization reaction with a bketo ester and an aromatic aldehyde in the presence of ammonium acetate in acetic acid as solvent. 5 Retro-Diels-Alder cleavage 6 is reported in the literature as the main mass spectrometric fragmentation reaction of pyridones, together with the loss of the substituents attached to the heterocyclic ring. 7 It is surprising that, in spite of the interest in these heterocyclic systems, the mass spectrometric behaviour study has not been fully investigated.…”