Synthesis of anticonvulsant sulfamides. Theoretical study of the related mechanism

Abstract

A theoretical study of the mechanisms associated with the synthesis of anticonvulsant symmetric N,N¢-substituted sulfamides is presented. Two possible synthetic routes are compared, which mainly differ in the use of pyridine as a nucleophilic agent in the reaction mechanism. Geometry optimization techniques and transition-state detection at the B3LYP/6-31G** level, modeling the solvent by means of an isodensity polarizable continuum approach, allow the most suitable method for the experimental process to be discerned.

3D-QSAR design of novel antiepileptic sulfamides

“…The substituted sulfamides have been synthesized according to previously reported procedures 24,[40][41][42][43][44] (Scheme 1 compounds 2a-e), by condensation of an excess of amine with sulfuryl chloride (Scheme 1). We have found a non-favorable effect of pyridine in the reaction, 45,46 and it was not used as a reactant.…”

Sulfamic Acid and Its N- and O-Substituted Derivatives

“…Geometry optimization techniques and transition state (TS) detection at the B3LYP/6-31G** level indicate that for synthesis of symmetric N,N′-substituted sulfamides the "direct route" rather than a pyridine-assisted route is favorable. 889 Seventeen sulfamides made up of mono-, di-, tri-, and tetrasubstituted compounds have been synthesized and assessed as possible anticonvulsant agents. Sulfamides (nPrNH) 2 SO 2 and nBuNHSO 2 NH 2 performed well in the two standard tests, namely, the MES and the PTZ tests.…”

“…The α-anomeric form is more stable than the β form with solvent effects included, and calculated NMR shift data support findings regarding configuration and conformation assignments of this sulfamide Theoretical methods have been used to examine some other sulfamides also. Geometry optimization techniques and transition state (TS) detection at the B3LYP/6-31G** level indicate that for synthesis of symmetric N,N′-substituted sulfamides the “direct route” rather than a pyridine-assisted route is favorable . Seventeen sulfamides made up of mono-, di-, tri-, and tetrasubstituted compounds have been synthesized and assessed as possible anticonvulsant agents.…”