Matrix-isolation FTIR, theoretical structural analysis and reactivity of amino-saccharins: N-(1,1-dioxo-1,2-benzisothiazol-3-yl)-N-methyl amine and -N,N-dimethyl amine

Abstract

a b s t r a c tIn this work, two novel amino-substituted derivatives of saccharin, N-(1,1-dioxo-1,2-benzisothiazol-3-yl)-N-methyl amine (MBAD) and N-(1,1-dioxo-1,2-benzisothiazol-3-yl)-N,N-dimethyl amine (DMBAD), were synthesized and characterized, and their molecular structure and vibrational properties were investigated by matrix-isolation FTIR spectroscopy and theoretical calculations undertaken using different levels of approximation. The calculations predicted the existence of two conformers of MBAD. The lowest energy form was predicted to be considerably more stable than the second conformer (DE > ca. 20 kJ mol À1) and was the sole form contributing to the infrared spectrum of the compound isolated in solid xenon. Both conformers have planar amine moieties. In the case of DMBAD, only one doubly-degenerated-by-symmetry conformer exists, with the amine nitrogen atom considerably pyramidalized. The effect of the electron-withdrawing saccharyl ring on the C-N bond lengths is discussed. The different structural preferences around the amine nitrogen atom in the two molecules were explained in terms of repulsive interactions involving the additional methyl group of DMBAD. Observed structural features are correlated with the reactivity exhibited by the two compounds towards nucleophiles. The experimentally obtained spectra of the matrix-isolated monomers of MBAD and DMBAD were fully assigned by comparison with the corresponding calculated spectra.

Structure and Photochemistry of a Saccharyl Thiotetrazole

“…Quantum-chemical calculations were performed with density functional theory using either the valence double-ζ polarized 6-31++G(d,p) or extended-valence triple-ζ polarized 6-311++G(3df,3pd) basis set − and the B3LYP or O3LYP functional. , Inclusion of both diffuse and polarization functions in the basis sets was required for a more accurate approximation of the calculated infrared spectra, since vibrational modes involving hypervalent S atoms (in particular the >SO 2 stretching and bending modes) are known not to be correctly predicted at a lower level of approximation. , The use of the B3LYP or O3LYP functional with the 6-311++G(3df,3dp) basis set was found to be appropriate to attain reliable results with moderate computational effort. ,,, Geometries were optimized using the direct inversion in the iterative subspace (DIIS) method . The transition state was located using the synchronous-transit quasi-Newton method (QST3 implementation). , The optimization of geometries was followed by harmonic vibrational calculations undertaken at the same level of theory.…”

“…44,45 Inclusion of both diffuse and polarization functions in the basis sets was required for a more accurate approximation of the calculated infrared spectra, since vibrational modes involving hypervalent S atoms (in particular the >SO 2 stretching and bending modes) are known not to be correctly predicted at a lower level of approximation. 46,47 The use of the B3LYP or O3LYP functional with the 6-311++G(3df,3dp) basis set was found to be appropriate to attain reliable results with moderate computational effort. 12,13,46,47 Geometries were optimized using the direct inversion in the iterative subspace (DIIS) method.…”

“…46,47 The use of the B3LYP or O3LYP functional with the 6-311++G(3df,3dp) basis set was found to be appropriate to attain reliable results with moderate computational effort. 12,13,46,47 Geometries were optimized using the direct inversion in the iterative subspace (DIIS) method. 48 The transition state was located using the synchronous-transit quasi-Newton method (QST3 implementation).…”

Conformational Landscape, Photochemistry, and Infrared Spectra of Sulfanilamide

“…With the general aim of contributing to the better understanding of the structural and spectroscopic properties of the compound and of its chemical reactivity, in the present study, we intend to achieve the following main objectives: ( i ) to obtain a more detailed structural and vibrational characterization of SA using a higher level of theory than those used in the previous studies. Specifically, it has been shown , that the theoretical description of molecules containing the SO 2 fragment requires the use of highly polarized basis functions, so that a detailed investigation of the potential energy surface of SA was carried out in this study using the 6-311++G­(3df,3pd) basis set. These calculations also provided fundamental data about the barriers for conformational isomerization, which proved to be of critical importance for the interpretation of the experimental results, in particular for the rationalization of the sole presence in these experimental conditions of the most stable conformer in the studied cryogenic matrices; ( ii ) to register and interpret the IR spectra of monomeric SA isolated in noble gas (Ar, Xe) cryogenic matrices and investigate its unimolecular photochemistry under these experimental conditions; ( iii ) to investigate the nature of the neat solid phases produced by fast deposition of the vapor of the compound onto a cooled (∼10 K) substrate and after annealing of the initially formed solid phase to higher temperatures (within the 10–290 K temperature range).…”

Saccharin Aza Bioisosteres—Synthesis and Preclinical Property Comparisons

“… a Conditions: (i) fresh Ph 3 PCl 2 (1.15 equiv), TEA (2 equiv), DCM/CHCl 3 , 35 °C, 5 h; (ii) various amines (3 equiv), 1.5–6 h, rt (reference numbers of known compounds are in parentheses). − …”