*Solvent effect on the tautomerism of 4-aminopyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides*

A detailed study of the tautomerism of 4-amino-1H-pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide has been carried out using different theoretical methods. Semiempirical, molecular orbital and density functional theory based ab initio methods have been used to study all the possible tautomers of this compound in the gas phase. Several continuum solvation models have been used to estimate the relative stability of the tautomers in water. Complexes with one and two molecules of water have been considered to take into account the specific solute–solvent interactions. Finally, these results have been compared with UV spectrophotometry data, giving good agreement between theoretical and experimental results in aqueous solution.

DOI:10.1002/(SICI)1097-461X(1997)62:5<477::AID-QUA4>3.0.CO;2-T

*Atomic charges derived from different methods. A comparative study applied to SO2 heterocycles.*

Atomic charges were calculated at ab initio level using different methods of charge determination to compare them and estimate their utility in the electronic description of heterocycles containing the SO_{2} moiety. Those procedures implemented on the Gaussian92 program were included [Mulliken population analysis, Weinhold-Reed natural population analysis (NPA) and CHELPG]. The first two are based on the molecular orbitals while in the third one the charges are derived by fitting the electrostatic potential. Two sets of compounds were chosen to represent the different characteristics of the SO_{2} heterocycles studied: simpler five-member heterocycles and SO_{2} small derivatives. These molecules were optimized at the HF/6-31G^{*} level and their energy evaluated by a punctual calculation MP2/6-31G^{*}//HF/6-31G^{*}. The dipole moments for these molecules were obtained by using all the methods previously mentioned and compared with the SCF, MP2, and experimental dipole moments. The influence on the charges of some atoms by changing the electronegativity of neighboring atoms has also been investigated for these compounds. The results obtained show that the best methods to describe the electronic distribution of the oxathiole studied are Mulliken and CHELPG at the MP2 level of calculation. The charge distributions obtained with these two methods for these particular heterocycles are discussed.

*Ab initio calculations of the methylsulfonate and phenylsulfonate anions*

Owing to the importance of the sulfonate group in organic and pharmaceutical chemistry a theoretical study at an ab initio level has been carried out for this ionic group. The geometric, electronic and energy properties of the methyl- and phenyl-sulfonate anions have been calculated by optimizing with the Hartree–Fock (HF) 6-31G* and 6-31 + G* basis sets and including correlation effects at the second-order Moller–Plesset (MP2) level. In addition, the harmonic vibrational frequencies and the zero-point vibrational energy of the different conformers of these compounds have been evaluated.

*Synthesis, hydrolysis reactions and conformational study of 2-substituted 3,5-diamino-4-nitroso-2H-1,2,6-thiadiazine 1,1-dioxides*

The 2-substituted 3,5-diamino-4-nitroso-2H-1,2,6-thiadiazine 1,1-dioxides are present in solution as a mixture of two rotational conformers of the nitroso group that are stabilized by hydrogen bonds with the amino groups in positions 3 and 5. The stability of these conformations has been studied using ^{1}H, ^{13}C and ^{15}N NMR spectroscopy, as well as molecular orbital ab initio calculations. In addition, hydrolysis reactions of these compounds have been carried out affording 5-amino-4-hydroxyimino-3-oxo-3,4-dihydro-2H-1,2,6-thiadiazine 1,1-dioxides and 4-amino-3-oxo-2,3-dihydro-1,2,5-thiadiazole 1,1-dioxides.

DOI: 10.1002/(SICI)1099-1395(199604)9:4<203::AID-POC771>3.0.CO;2-K

*Theoretical and experimental analysis of properties in heterocycles containing the aminosulfonylamino moeity*

A the theoretical and experimental analysis of the geometric and electronic properties of compounds containing the aminosulphonylamino moiety was carried out. The theorethical properties were calculated using molecular orbital ab initio methods at the Hartree-Fock (HF) and second order Moller-Plesset (MP2) levels of theory, local density functional (LDF) ab initio methods and the semi-empirical method, SAM1, on sulphamide and seven heterocyclic compounds containing the aminosulphonylamino group. The experimental analysis has been performed using X-ray structures of related compounds gathered in the Cambridge Structural Database together with experimental analysis with the theoretical results indicates that none of the methods studied is the most adequate to describe the geometry and the electronic distribution of these molecules. The use of the 6-31G* basis set to compate the geometry of these molecules and methods which include electronic correlations (MP2/6-31G*//RHF/6-31G*, MP2/6-31G* and LDF) to quantify their electronic distribution are proposed.

*Comparison of methods to estimate geometric and electronic properties on sulfur containing compounds*

A theoretical and experimental analysis of the geometric and electronic properties of compounds containing the aminosulphonylamino moiety was carried out. The theoretical properties were calculated using molecular orbital ab initio methods at the Hartree-Fock (HF) and second order Möller-Plesset (MP2) levels of theory, local density functional (LDF) ab initio methods and the semi-ab initio method, SAM1, on sulphamide and seven heterocyclic compounds containing the aminosulphonylamino group. The experimental analysis has been performed using x-ray structures of related compounds gathered in the Cambridge Structural Database together with experimental dipole moments and ^{13}CNMR shifts of some of the compounds studied. Comparison of the experimental analysis with the theoretical results indicates that none of the methods studied is the most adequate to describe the geometry and electronic distribution of these molecules. The use of the 6-31G* basis set to compute the geometry of these molecules and methods which include electronic correlation (MP2/61G*//RHF/6-31G*, MP2/6-31G* and LDF) to quantify their electronic distribution are proposed.

*Comparative aromaticity study on heterocycles containing S, SO, and SO2*

Owing to the importance of the concept of aromaticity, different indices have been developed to try to quantify this property. The possible π delocalization through an XSO_{n}X group (X = C, N; n = 0, 1 or 2) could explain heteroaromaticity in rings containing the moiety. For that reason, the aromaticity of five-membered sulphurcontaining rings with different oxidation numbers (S, SO and SO_{2}) and including no (thiophene), one (isothiazole) or two (1,2,5-thiadiazole) adjacent atoms was investigated. Ab initio calculations were carried out to determine geometrical parameters (planarity of the ring, bond length and bond order), electronic structure (charge distribution and dipolar moment) and the participation of d-orbitals of sulphur. According to these calculations, only compounds with S(II) can be considered to be aromatic, whereas compounds bearing S(IV) or S(VI) are better described as ylides.

*A theoretical study of the structure and tautomerism on 1,2,4,6-thiatriazine 1,1-dioxide*

"Ab initio" theoretical Calculations have been used to study the structure and annular tautomerism of 2(4)H-1,2,4,6-thiatriazine 1,1-dioxide. The 4H-tautomer has been found to be the most stable in agreement with ^{1}H-, ^{13}C- and ^{15}N-nmr data.

*Structure of 1,2,6-thiadiazine 1,1-dioxides*

Ab initio theoretical calculations were carried out on the three tautomers, NH, OH and CH, of 1,2,6-thiadiazine 1,1-dioxides. Different basis sets were employed in order to obtain an adequate description of these cyclic sulphamide derivatives. A coherent picture is obtained which includes relative stability of tautomers (NH > CH > OH), non-planarity of NH and CH tautomers and electronic distribution (Boys' localized orbitals).

*A molecular study of the conformation (inversion and rotation barriers) and electronic properties of sulphamide*

Abinitio calculations have been used to study the conformational potential surface of sulfamide, by considering the S—N bond rotations and the nitrogen inversion processes. The lowest energy conformation (b) is found for a cis–trans arrangement of the amino groups, although conformations with cis–cis (a), trans–trans (c), and near staggered (c′) arrangements lie close in energy. Nitrogen inversion barriers are very low, and consequently one may expect forms b andc′ to be the only ones present in the gas phase. Conformer a is very polar, its dipole moment being twice that of b, so it may be favored in condensed media or in polar-solvent solutions. The relative stability of the different isomers is governed by interactions between the amino protons and between the nitrogen lone pairs. Our results show that d–π backbonding, involving the dorbitals on sulfur, is responsible for the multiple bond character of the S—O linkage, but is very small in the S—N interactions. The role of the sulfur d-orbital exponent, when a 6-31G* basis is used, is analyzed on a series of model compounds containing S^{II}, S^{IV}, and S^{VI}. Although the inclusion of d functions on sulfur is crucial to describing correctly the bonding in sulfamide, the results obtained do not change appreciably if a second set of d functions is centered on sulfur. Nevertheless, only when polarization functions are also included for first-row atoms is the description of the system reliable. Keywords: sulfamide, inversion and rotational barriers, sulfurd-functions.