Yamila Verdecia

X-Ray and theoretical structural study of novel 5,6,7,8-tetrahydrobenzo-4H-pyrans

Abstract The X-ray crystal structure of three substituted tetrahydrobenzo-4H-pyrans ( 6a–c ) is presented and the experimental findings compared with the theoretical values calculated at the semiempirical (AM1, PM3) and ab initio (HF/6-31G∗) levels. A good agreement between both experimental and theoretical data is found showing a flattened boat conformation for the 4H-pyran ring and a pseudo-axial orientation of the aryl ring on the C4 position. The geometrical features of these systems ( 6a–c ) reveal that they present the structural requirements to act as calcium antagonists.

Structural study of 3,4-dihydropyridones and furo[3,4-b]-2(1H)-pyridones as potential calcium channel modulators

Abstract A structural study of 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones (4a-d) and hexahydrofuro-[3,4-b]-2-(1H)-pyridones (5a-d) has been carried out using X-ray analyses, semiempirical (AM1) calculations, NOE experiments and coupling constants. From the two favoured conformers (A and B), conformation A bearing the phenyl ring in a pseudoaxial position turned out to be the most stable both in the solid state and in solution. Compounds 4a-d fulfil, from the structural point of view, all the requirements needed for exhibiting an antagonist calcium effect and an agonist effect should be expected for compounds 5a-d.

Pyridazine Derivatives. Part 21: Synthesis and Structural Study of Novel 4-Aryl-2,5-dioxo-8-phenylpyrido[2,3-d]pyridazines

Abstract New substituted 4-aryl-2,5-dioxo-8-phenylpyrido[2,3-d]pyridazines 4a–f have been prepared in one step from the corresponding arylidene substituted Meldrums acid (1) and 5-amino-6-phenyl-3(2H)-pyridazinone (2) in good yields. Semiempirical theoretical calculations (AM1) reveal two favoured conformations (A and B) for compounds 4a–f, with a screw boat conformation in the pyridone system and a planar pyridazinone ring. X-Ray crystallographic analysis shows that in the solid state, conformation A bearing the phenyl ring in a pseudoaxial position is the most stable. Compounds 4a–f fulfil, from the structural point of view, all the requirements needed for exhibiting cardiotonic effects.

Synthesis of methyl 4-aryl-6-methyl-4,7-dihydro-1H-pyrazolo-[3,4-b]pyridine-5-carboxylates from methyl 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydropyridine-5-carboxylates

Novel methyl 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylates 3a–e have been prepared in a two step procedure from the readily available 2-oxo-1,2,3,4-tetrahydropyridine-5-carboxylates 1a–e by treatment with the Vilsmeier–Haack reagent. Further treatment of the novel o-chloroformyl substituted methyl 1,4-dihydropyridine-5-carboxylates 2a–e with hydrazine affords the corresponding methyl pyrazolo[3,4-b]pyridine-5-carboxylates in good yields. Semiempirical calculations reveal a favoured geometry with a boat conformation in the dihydropyridine system and a planar pyrazole ring.

Solid-phase synthesis of 4-aryl substituted 5-carboxy-6-methyl-3,4-dihydropyridones

Substituted 3,4-dihydro-2-pyridones have been efficiently prepared by solid-phase synthesis using Wang resin from the immobilised β-ketoester and further Hantzsch-type heterocyclisation.

An overview of the retro‐Diels‐Alder reaction in semiunsaturated heterocyclic rings: mass spectra of new substituted 1,4,5,6,7,8‐hexahydroquinolines and their oxo‐analogues 5,6,7,8‐tetrahydro‐4H‐chromenes

Electron impact ionization (EI), chemical ionization (CI), electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to investigate a number of relatively large and structurally related new heterocycles such as substituted 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes. In the EI spectra the hexahydroquinolines undergo the loss of the substituent attached at the C4 position, while the 4H-chromenes undergo a retro-Diels-Alder reaction (RDA) after elimination of the C4 substituent. Under chemical ionization conditions the RDA reaction is observed only for the 4H-chromenes. The ESI-MS/MS spectra reveal results similar to the EI and CI spectra, since the 4H-chromenes undergo RDA reactions while the hexahydroquinolines form a very stable even-electron pyridium ion derived from the loss of the C4 substituent.

1H and 13C spectral assignment of 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes

1H and 13C NMR spectroscopic data for 1,4,5,6,7,8‐hexahydroquinolines and their oxa‐analogues, 5,6,7,8‐tetrahydro‐4H‐chromenes, were fully assigned by combination of one‐and two‐dimensional experiments (DEPT, HMBC, HMQC). Both heterocyclic systems show similar spectroscopic properties with some remarkable differences. Copyright

Synthesis, crystal structure and molecular modeling (AM1) of two 5-arylidene derivatives of Meldrum's acid

The synthesis and structural characterization of two 5-Arylidene derivatives of Meldrums acid (2,2-dimethyl-1,3-dioxane-4,6-dione) are described: 5-(4-Nitrobenciliden)-2,2-dimethyl-1,3-dioxane-4,6-dione (3a), and 5-(4-Methoxybenciliden)-2,2-dimethyl-1,3-dioxane-4,6-dione (3b). The structure of 3a was refined to R1 = 0.0421 for 2148 reflections (with I > 2σ (I)). Crystal data for 3a: C13H11NO6, orthorhombic, space group Pbca, a = 16.008(3), b = 6.137(1), c = 25.281(5) Å, V = 2483.6(8) Å3, Z = 8. The structure of 3b was refined to R1 = 0.0496 for 4681 reflections (with I > 2σ(I)). Crystal data for 3b: C14H14O5, triclinic, space group P1, a = 9.131(2), b = 9.922(2), c = 14.490(3)Å, α = 85.076(6), β = 84.80(3), γ = 89.37(2)°,V = 1302.4(5) Å3, Z = 4. The results of crystallographic and molecular modeling (AM1) were compared. The molecules in the crystal are held together, in both compounds, by van der Waals forces and C—H···O hydrogen bond interactions.

Synthesis, crystal structure, and molecular modeling (AM1) of Methyl 6-chloro-4-(2-chlorophenyl)-5-formyl-2-methyl-1, 4-dihydropyridine-3-carboxylate

The synthesis and structural characterization of Methyl 6-chloro-4-(2-chlorophenyl)-5-formyl-2-methyl-1,4-dihydropyridine-3-carboxylate is described. The structure was refined to R1 = 0.0470 for 2665 reflections (with I > 2σ(I)). Crystal data: C15H13C12NO3, monoclinic,space group P21/c, a = 11.163(9), b = 14.484(8), c = 9.422(7) Å, V = 1512.9(19) Å3, Z = 4. The results of crystallographic and molecular modeling (AM1) were compared. The Cl atom attached to the phenyl group has two possible orientations, having 75% (sp) and 25% (ap) occupancy, respectively. The molecules in the crystal are held together by means of intermolecular hydrogen bonds of the type N=H...O and by C=H...O interactions.

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

The electron impact mass spectra of new 5-acetyl-4-aryl-6-methyl-2(1H)pyridones have been studied. A dominant peak in all the spectra is due to cleavage of the CO-NH bond of the amido group with charge retention on the carbonyl group. This fragmentation is followed by a hydrogen rearrangement to the nitrogen atom forming ketene intermediates; this pathway leads to a highly stabilized ion which constitutes the base peak in the spectra in most of the compounds studied. Copyright 1999 John Wiley & Sons, Ltd.