Anomeric Effects in Sulfamides

Abstract

Sulfamides, together with their simpler sulfonamide analogs, are common functional groups in a significant number of biologically active compounds. This is partly due to their unique electronic structure and conformational behavior, which mimics the tetrahedral intermediate involved in many proteases, esterases, and related enzymes. Here, the origin of these unique structural elements are analyzed in the context of a coupled, double anomeric effect using DFT calculations, including conformational scans, and NBO analysis. It is shown that these coupled interactions can be implicitly parametrized in MM3* type force fields using the quantum-guided molecular mechanics (Q2MM) method, yielding accurate force field parameters for molecular mechanics studies of sulfamides and sulfonamides.

Crystal Structure and Vibrational Spectra of ClSO2NHC(O)F

“…The S–N bond of 1.642(2) Å is significantly shorter than reported for typical S–N bonds [1.74 Å] . The shortened S–N bond can be explained by negative hyperconjugation, where electron density of the nitrogen lone pair is donated to the σ*(S–N) and σ*(S–O) orbitals . The S–O bonds of 1.408(1) Å and 1.410(1) Å are comparable to the S–O bonds in SO 2 ClF .…”

Tuning the Anomeric Effect in Sulfamide with Superacids

“…I nt he case of an equimolara mounto ft he Lewis acids, salts containing the [H 2 NSO 2 NH 3 ] + cation are formed. By employing an excess of the Lewis acids (BF 3 ,A sF 5 ,o rS bF 5 )w ith respect to sulfamide only in the case of SbF 5 was an N,N'-diprotonation achieved leadingtot he formation of [H 3 The antisymmetric NH 2 stretching modes that occur at 3376 and 3384 cm À1 are blue-shiftedb y4 0cm À1 ,w hereas the symmetric NH 2 stretching modes in the range of 3294 to 3250 cm À1 and are blue-shifted by approximately70cm À1 com-pared to the neutral compound. [8] For the d-isotopomeric species the corresponding ND 2 stretching modes are observed in the range of 2545 to 2476 cm À1 and are in fair agreementw ith the Te ller-Redlich rule for an isotopicH /D shift.…”

“…Wiest and co-workersr eported as imilar value for the barrier of rotation around the SÀNb ond in the neutral compound. [5] This remarkable increase of the rotationalb arrier can be considered as am easure for the reinforcemento ft he anomeric effect.…”

“…[5] The authors reported quantum chemical studies on sulfamide giving ar eason for its unique propertiesa nd rigidity. [5] The latter is explained by an anomeric effect, whereby electron density from the nitrogen lone pairs is donated to the s*(SÀO) and s*(SÀN), providing 37 kJ mol À1 of stabilization energy. [5] This result can also be considered as an explanation for the relatively short SÀN bonds of 1.627(1) observed in the crystals tructure of H 2 NSO 2 NH 2 .…”

“…[5] The latter is explained by an anomeric effect, whereby electron density from the nitrogen lone pairs is donated to the s*(SÀO) and s*(SÀN), providing 37 kJ mol À1 of stabilization energy. [5] This result can also be considered as an explanation for the relatively short SÀN bonds of 1.627(1) observed in the crystals tructure of H 2 NSO 2 NH 2 . [6] Given that the anomeric effect is initiated by the donation of electron density of the nitrogen lone pairs, one could assume that this effect can be abolished by an N-protonation leadingt ot he [H 2 NSO 2 NH 3 ] + cation.…”