Ernani A. Basso

Triterpenic acids from Eugenia moraviana

A novel triterpene, characterized as 6a-hydroxybetulinic acid, was isolated from the leaves and stems of Eugenia moraviana (Myrtaceae), known in Brazil as Cambui, together with three known compounds, platanic acid, betulinic acid and b-sitosterol. Unequivocal 1H and 13C assignments of 6a-hydroxybetulinic acid (3b,6a-dihydroxy-20(29)-lupen-28-oic acid) and platanic acid were undertaken by spectral analysis including NOE and 2 D NMR experiments.

Semiempirical and ab initio calculations versus dynamic NMR on conformational analysis of cyclohexyl-N,N-dimethylcarbamate

Axial-equatorial conformational proportions for cyclohexyl-N,N-dimethyl carbamate have been measured, for the first time, by the Eliel method, 1H and 13C dynamic nuclear magnetic resonance (DNMR). The results were compared against those determined by theoretical calculations. By the Eliel method at least five experimentally independent measureables were used in CCl4, CDCl3 and CD3CN. The 1H and 13C low temperature experiments were performed in CF2Br2/CD2Cl2 . Semiempirical methods MNDO, AM1 and PM3 and ab initio molecular orbital calculations at the HF/STO-3G and HF/6-31G(d,p) levels have been performed on the axial and equatorial conformers populations. All applied methods correctly predict the equatorial conformer preference over the axial one. The resulting equatorial preferences determined by NMR data and theoretical calculations are in good agreement.

Structural characterization of two novel potential anticholinesterasic agents

Abstract Two novel compounds with possible anticholinesterase activity have been synthesized containing a carbamate and a dimethylamine group in 1,2-positions of a cyclohexane ring ( cis and trans isomers). Conformer populations were established by a combination of NMR 1 H coupling constant analysis and DFT (B3LYP/6-311+G(d,p)) calculations. 13 C chemical shifts were calculated in order to confirm signal attributions. The cis isomer adopts a conformation in which the carbamate group lies at the axial position (>99%), whereas the trans isomer adopts a diequatorial arrangement (98%). These preferences have been explained in terms of syn -1,3-diaxial interactions of the individual groups.

SUBSTITUENT-INDUCED 1H CHEMICAL SHIFTS OF 3-SUBSTITUTED CAMPHORS

The high‐field 1H NMR analysis of 3‐substituted camphors with OH, OMe, SMe, NHMe, NMe2 and Me substituents at endo and exo positions, and also with an oxo substituent, is reported. The substituent‐induced chemical shifts (SCS) obtained for these difunctional systems, including those from previous work on 3‐halocamphors, were examined in view of multilinear correlations with steric and electronic parameters. The resultant data show a strong contribution from the electric field mechanism, principally for the protons closer to the substituent. Carbonyl group interference on the expected SCS for the α‐proton is also observed, with less deshielding than those of substituted bornanes and norbornanes.

Effect of Sulfur Oxidation on the Transmission Mechanism of 4JHH NMR Coupling Constants in 1,3-Dithiane

Long-range 4J(HH) couplings in 1,3-dithiane derivatives are rationalized in terms of the effects of hyperconjugative interactions involving the S=O group. Theoretical and experimental studies of 4J(HH) couplings were carried out in 1,3-dithiane-1-oxide (2), cis-1,3-dithiane-1,3-dioxide (3), 1,3-dithiane-1,1,3-trioxide (4), and 1,3-dithiane-1,1,3,3-tetraoxide (5) compounds. Hyperconjugative interactions were studied with the natural bond orbital, NBO, method. Hyperconjugative interactions involving the LP(O), oxygen lone pair and sigma*(C2-S1) and sigma*(S1-C6) antibonding orbitals yield an increase of 4J(H(eq)-H(eq)) couplings. Long-range 4J(H(ax)-H(ax)) couplings were also observed between hydrogen atoms in axial orientation, which are rationalized as originating in hyperconjugative interactions involving the bonding sigma(C6-H(ax)) and antibonding sigma*(S=O) orbitals. The symmetry for orbital interactions is possible only when the S=O group is in the axial orientation.

Theoretical and experimental investigation of the polyeletrophilic β-enamino diketone: straightforward and highly regioselective synthesis of 1,4,5-trisubstituted pyrazoles and pyrazolo[3,4-d]pyridazinones

Obtaining a new precursor enamino diketone with five electrophilic centers is reported, along with theoretical and experimental studies of its reactivity against mono- or dinucleophiles. The Fukui function showed that the β-carbon is the most electrophilic center, followed by the carbonyl ketone and the carbonyl ester, respectively. The reaction of enamino diketone with aniline and hydrazines allowed for the synthesis of a new enamino diketone and 1,4-disubstituted pyrazoles-5-carboxylates, respectively. The regiochemistry and mechanism of syntheses of 1,4-disubstituted pyrazoles-5-carboxylates were determined from reaction monitoring by ESI-MS, NMR analysis and crystallographic data, and fully agreed with the theoretical results. The versatility and efficiency of the enamino diketone was demonstrated by the reaction with hydrazines furnishing multi-functionalized pyrazoles and pyrazolo[3,4-d]pyridazinone derivatives with high regioselectivity.

The conformational analysis of 2-halocyclooctanones.

The establishment of the most stable structures of eight membered rings is a challenging task to the field of conformational analysis. In this work, a series of 2-halocyclooctanones were synthesized (including fluorine, chlorine, bromine and iodine derivatives) and submitted to conformational studies using a combination of theoretical calculation and infrared spectroscopy. For each compound, four conformations were identified as the most important ones. These conformations are derived from the chair-boat conformation of cyclooctanone. The pseudo-equatorial (with respect to the halogen) conformer is preferred in vacuum and in low polarity solvents for chlorine, bromine and iodine derivatives. For 2-fluorocyclooctanone, the preferred conformation in vacuum is pseudo-axial. In acetonitrile, the pseudo-axial conformer becomes the most stable for the chlorine derivative. According to NBO calculations, the conformational preference is not dictated by electron delocalization, but by classical electrostatic repulsions.

Infrared and theoretical calculations in 2-halocycloheptanones conformational analysis

2-Halocycloheptanones (Halo=F, Cl, Br and I) were synthesized and their conformational analysis was performed through infrared spectroscopy data. The corresponding conformers geometries and energies were obtained by theoretical calculations at B3LYP/aug-cc-pVDZ level of theory in the isolated state and in solution. It was observed, by both approaches, that the conformational preferences were very sensitive to the solvent polarity, since its increase led to an increase in the population of the more polar conformer. An analysis of these conformational equilibria showed they suffer also the influence of stereoelectronic effects, like hyperconjugation and steric effects. These results were interpreted using natural bond orbital (NBO) analysis, which indicated that the electronic delocalization to the orbital π*(C=O) is directly involved in the stability increase of conformers I and II. The relative effect of the period of the halogen can also be noted, with changes in the conformational preferences and in the energies involved in the interactions of NBO.

Theoretical aspects of the unexpected regiospecific synthesis of pyrazole-5-carboxylates from unsymmetrical enaminodiketones

Pyrazoles are heterocycles with economic importance because of the wide applications of such compounds in the pharmaceutical and agrochemical industries. Pyrazoles can be prepared from the cyclocondensation of unsymmetrical enaminodiketones with hydrazines. However, this method often suffers from the formation of a regioisomeric mixture of pyrazoles with generally poor selectivity. Only in few cases, the regiospecific synthesis was possible. Nevertheless, up to now, the factors behind the regiospecificity of this reaction were unknown. Thus, in this work, we use density functional theory (M06-2X/6-31++G(d,p)) to analyze the reaction mechanism. Our results show that the activation-free energy leading to the possible products are similar, but the products present very different stabilities which explain the formation of a single regioisomer experimentally observed. In this way, the regiospecificity is governed by thermodynamical factors.

Theoretical and experimental investigation on the rotational isomerism in alpha-fluoroacetophenones.

The geometries involved in the conformational equilibria of alpha-fluoroacetophenone, p-nitro-alpha-fluoroacetophenone, and p-methoxy-alpha-fluoroacetophenone were investigated. Theoretical calculations showed that cis and gauche forms (F-C-C=O) are their most stable conformers and that in the vapor phase the gauche conformer is predominant. The three compounds were synthesized, and the conformational behavior in solution was estimated from infrared (IR) and nuclear magnetic resonance (NMR) spectra obtained in solvents of different polarity. Their IR spectra showed one carbonyl absorption for the cis and one for the gauche conformer, and that the cis conformer was preferred in the more polar solvents. (1)J(CF), (2)J(C(O)F), and (2)J(HF) coupling constants were obtained from their NMR spectra, and they also showed a preference for the cis conformer when more polar solvents were used. The vapor phase calculations showed a conformational preference for the gauche form. However, when the solvent effects were included in the calculations, the results were in complete agreement with the experimental data (NMR and IR), the cis conformer being the most stable one.