Estael Ochoa

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.

Alkylation of Benzoyl and Furoylthioureas as Polydentate Systems

Abstract A study of the behaviour towards alkylation of a series of benzoyl and furoylthioureas with 3,3-disubstitution has been carried out using NMR determinations. X-Ray data and semiempirical theoretical calculations demonstrated that the most stable conformation for these molecules is the so-called quasi-S. Also an explanation of the high selectivity towards the S-alkylation of these systems, based on the high contribution of the sulphur atom to the HOMO in acylthioureas is given for the title compounds. Steric factors are responsible for the difference between the percentages obtained for the S-alkylated product in 1-(4-methylbenzoyl)-3,3-diethylthiourea and 1-benzoyl-3,3-dibenzylthiourea.

A joint theoretical and experimental structural study of 5-carboxyethyl-3-(2 '-furfurylmethyl) tetrahydro-2H-1,3,5-thiadiazine-2-thione

Abstract X-Ray analysis and semiempirical AM1 and ab initio HF/3-21G ∗ and HF/6-31G ∗ calculations reveal a favourable envelop conformation (A) for 3,5-disubstituted tetrahydro-2 H -1,3,5-thiadiazines in which the N5 atom lies out of the main plane. NOE experiments show that this conformer (A) is also found in solution.

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.