M. Esseffar

Structure-musk odour relationship studies of tetralin and indan compounds using neural networks

Models of the relationships between structure and musk odour of tetralin and indan compounds were elaborated with a multilayer neural network using the back-propagation algorithm. The neural network was used to classify the compounds studied into two categories (musk or non-musk). The cross-validation procedure was used to assess the predictive power of the network. Each molecule was described by eight global parameters: five steric and three electronic descriptors. The neural networks results were successfully compared to those given by the k-Nearest Neighbours and the Bayesean methods, both in the classification and prediction tests. The contribution of each descriptor to the structure-odour relationships was evaluated. Three out of the eight descriptors were thus found to be the most relevant in the molecular description for the prediction of musk odour. This research points out that neural networks are likely to become a useful technique for structure-odour relationships.

Basicity of some carbonyl compounds towards iodine monochloride: experimental and theoretical study

Intermolecular charge-transfer (CT) complexes between a wide range of carbonyl compounds and iodine monochloride were spectroscopically studied in the UV–visible region. Equilibrium constants and Gibbs energy changes of 1:1 charge transfer complexes were determined in CCl4 solution. The ICl basicity scale in CCl4 of the set of carbonyl derivatives included in this study is well correlated with the I2 basicity scale in the same solvent. Ab initio calculations at HF/LANL2DZ* and MP2(full)/LANL2DZ* were carried out in order to clarify the structures of these CT complexes. Two different conformations, depending on the characteristics of the substituents, may be found. In one of them the ICl moiety lies in the plane of the carbonyl group, in the other the ICl subunit is perpendicular to the CO group. The perpendicular complexes are favored by bulky substituents for which the HOMO has a clear π-character. Both kinds of complexes can be spectroscopically distinguished since they present the CT absorption at different wavelengths. In both kinds of complexes the carbonyl–ICl interaction is essentially electrostatic. The substituent effects were analyzed through the use of the Taft–Topsom model. Experimental data in solution and theoretical estimates were found to follow a good linear relationship.

AM1 THEORETICAL STUDY ON THE MECHANISM OF 1,3-DIPOLAR CYCLOADDITION REACTION OF 1,2,4-TRIAZEPINE AND FORMONITRILE OXIDE

Abstract The gas phase mechanism of 1,3-dipolar cycloaddition reaction of 1,2,4-triazepine with formonitrile oxide, leading to six regioisomers A, A′, B, B′, C and C′, is studied computationally. The structures of the transition states and the activation energies for all the paths conducting to the formation of the products mentioned above, are calculated by the AM1 semiempirical method. This method is seen to predict correctly the preferred pathway for the title reaction. It is found that, in the gas phase, the mechanism leading to the most stable product is concerted. The periselectivity and regioselectivity predicted are in good agreement with experimental evidence. It is found that the CC dipolarophile is the selective one leading to the formation of the preferred cycloadduct. The formation of the C–C and C–N bonds at the transition states is significantly more advanced than that of the others.

Basicity of lactones and cyclic ketones towards I2 and ICl. An experimental and theoretical study

Intermolecular charge transfer (CT) spectra of several complexes between cyclic ketones and lactones and molecular iodine and iodine monochloride were studied in the UV-visible region. Equilibrium constant and free energy changes of the formed complexes were determined in solution. Ab initio calculations at HF/LANL2DZ* and MP2(full)/LANL2DZ* were carried out to establish the nature of the complexation site in the case of lactones, to determine the complex structures and to examine the ring size effect. Although range of the basicity towards I2 and ICl of compounds studied was small, it was found that cyclic ketones are more basic than lactones. This basicity difference decreases from small to large cycles and practically vanishes for six- and seven-membered rings. A comparative analysis between basicities of lactones and aliphatic esters towards I2 and ICl has also been carried out. Experimental data in solution were found to be linearly correlated with theoretical results in the gas phase. Proton affinities of cyclic ketones and aliphatic carbonyl compounds that do not present any secondary interaction with the Lewis acid correlate very well with their gas-phase basicity towards I2 and ICl.

Nitro derivatives of pyrrole, furan and 1H-tetrazole: ring or nitro bases?

The gas-phase basicity of pyrrole, furan, 1H-tetrazole and their nitro derivatives has been analyzed by means of high level ab initio and DFT calculations. The gas-phase basicity of 2-nitrofuran was also determined by means of FT-ICR mass spectrometry. Our results indicate that although pyrrole and furan behave as carbon bases in the gas phase, their nitro derivatives protonate preferentially on the nitro group. Conversely, both 1H-tetrazole and its 5-nitro derivative protonate preferentially on the ring, because the intrinsic basicity of the nitro group is significantly dampened when the group is attached to a tetrazolic ring. For the 5-nitro-1H-tetrazole the most stable protonated species corresponds to an open structure formed by protonation on N1, which is followed by a N1–N2 bond cleavage. This non-cyclic structure is entropically favored and therefore it should be the one observed in ICR measurements.

APPLICATION OF NEURAL NETWORKS TO STRUCTURE-SANDALWOOD ODOUR RELATIONSHIPS

Neural networks have proved to be particularly successful in their ability to identify non-linear relationships. This paper shows that a three-layer back-propagation neural network is able to learn the relationship between the sandalwood odour and molecular structures of 85 organic compounds belonging to acyclic, cyclohexyl, norbornyl, campholenyl and decalin derivatives. Four steric and three electronic parameters were used to describe each molecular structure. Odour was coded by a binary variable. The neural network was used to classify the compounds into two groups and to predict their odours (sandalwood or non-sandalwood). The results obtained were compared with those given by discriminant analysis, and found to be better. The most important descriptors were revealed on the basis of correlation analysis.

Ab initio and density functional theory studies of peri- and regioselectivity in 1,3-dipolar cycloaddition reaction of 1,2-diazepine with nitrile oxide

Abstract The first systematic study of all dipolarophile sites of 1,2-diazepine towards nitrile oxide as dipole via 1,3-dipolar cycloaddition reactions has been carried out. To this end, the structural and energetic aspects of seventy-two isomers were determined by means of ab initio and density functional theory methods at different levels of accuracy were performed on all peri- and regio-isomeric forms. The agreement between the calculated and the experimental geometries, regio- and periselectivity of the studied reaction is good in all instances. The dipole condensation with the norcaradiene dipolarophile has been considered seemingly for the first time. The bis-cycloadduct 3a,3b,7,10a-tetrahydro-10 H-[1,2] oxazolo [4,5-d] [1,2,4] oxadiazolo [4,5-b] [1,2] diazepine is the most stable one as predicted by all methods used in this work. However, the tautomerization study of all forms of 1,2-diazepine seems to rule out the existence of the tautomeric form that provides the above mentioned cycloadduct. Consequently, the bis-cycloadduct 5,10-dioxa-1,2,4,11-tetrazatricyclo[7,3,1,02,6]trideca-3,7,11-triene is the favored product of this reaction.

A topological analysis of bond activations in alcohols and fluoroalkanes by protonation in the gas phase

Abstract The structures of a set of alcohols (R-OH) and fluoroalkanes (R-F) (R=Me, Et, Pr, i -Pr, But or t -But) and their protonated forms were compared by carrying out ab initio molecular orbital studies at the 3-21G, 6-31G ∗ and, in some cases 6-31 + G (d), levels of theory. A topological analysis of the charge density offers quantitative information on the bond activation upon protonation, confirming some preliminary results. For both homologous series of compounds, bond activation follows the sequence Me t -But, with the result that protonation of tert -butylfluoride breaks the C-F bond. We also show that there is a direct relationship between bond activation and intrinsic basicity. We conclude that the intrinsic basicity of these systems depends on their ability to withdraw electronic charge from the C-O or C-F bonding regions, respectively. A preliminary study, at the semiempirical level of the potential surface corresponding to the C-O bond-breaking reaction ofisopropyi and tert -butyl alcohols is presented.

Combined Experimental and Theoretical Study on Hydrogen-Bonded Complexes between Cyclic Ketones, Lactones, and Lactams with 3,4-Dinitrophenol †

The interaction of 3,4 dinitrophenol (DNP) with cyclic ketones, lactones, and lactams was investigated by UV-visible spectroscopy and density functional theory (DFT) methods. Equilibrium constants K(HB) for 1:1 hydrogen bonded complexes were determined in solution in CCl(4) and C(6)H(12). For the entire range of studied bases, the pK(HB) scale, varying between 2.92 for beta-propiolactone to 5.53 for 1-methyl-epsilon-caprolactam, indicates that the basicity increases with the ring size. Geometries, energies, and vibrational characteristics of complexes were obtained by means of DFT calculations. For lactones and lactams, the energy difference between the two most stable conformers, cis and trans, with respect to the ring oxygen (nitrogen) atom, is relatively small, suggesting that the complex observed in solution is probably an equilibrium mixture of both forms. The good correlation between Gibbs free energies in solution and in the gas phase, computed at the B3LYP/6-311++G(3df,2p) level of theory, confirms the reliability of our results. The electron density of the complexes has been analyzed by means of the atoms in molecules (AIM) theory and the natural bond orbital (NBO) method have been used to characterize the orbital interactions. Our theoretical survey shows that the 1:1 complexes are stabilized by a network of conventional and/or nonconventional intermolecular hydrogen bonds.

Prototropic tautomerism of 3,5-(oxo/thioxo) derivatives of 2,7-dimethyl-1,2,4-triazepines

The relative stability of the different tautomers of the 3-thio-5-oxo, 5-thio-3-oxo, 3,5-dioxo and 3,5-dithio derivatives of 2,7-dimethyl-1,2,4-triazepine has been studied through the use of density functional theory (DFT) methods. The structure and vibrational frequencies of all the stable tautomers and all the transition states connecting them have been calculated at the B3LYP/6-31G* level of theory. Final energies have been obtained in single-point B3LYP/6-311+G(3df,2p) calculations. In all the cases the most stable conformer is the oxo-thione, the dioxo or the dithione form, while the mercapto- oxo tautomers are the second more stable structures. This behavior resembles closely that reported in the literature for uracil and its thio derivatives. As for uracil and thio-uracil derivatives, the tautomerism activation barriers are high enough as to conclude that only the oxo-thione structures should be found in the gas phase. The relative stabilities should change, however, in aqueous solution because the corresponding prototropic tautomerisms are accompanied by significant changes in the dipole moment of the system. The ionization of 1,2,4-triazepines involves bonding changes that are consistent with the unimolecular fragmentations observed in their mass spectra. The bonding characteristics of the carbonyl and thiocarbonyl groups depend on their relative positions. When these groups are attached to the carbon between two N atoms, the linkage is weaker than when they are attached to the carbon between C and N atoms. This is clearly reflected in the molecular force field and should be easily detected in the corresponding infrared spectrum, as well as in the reactivitiy of these systems in the gas phase.