Acidites and partition coefficients of fluoromethanesulfonamides

Abstract

The half-neutralization potentials (HNP) of a series of biologically active fluoromethanesulfonamides were determined in 67% N, N-dimethylformamide-water. A plot of aqueous pKa vs. HNP for nine methanesulfonamides and fluoromethanesulfonamides in the series was used to calculate the pKa's of the remaining water-insoluble sulfonamides. The pKa's of eight aryl-substituted 1,1,1 -trifluoro-lV-phenylmethanesulfonamides correlated better with the Hammett substituent constant than with ~or <rphenoi• The Hammett reaction constant p was 2.15. The stepwise addition of fluorine atoms to the (methanesulfonyl)amino moiety in three related series of aryl-substituted fluoro-fV-phenylalkanesulfonamides gave a linear acidity increase of 1.47 pKa units per fluorine. Partition coefficients were measured in 1-octanol-water for 28 1,1,1-trifluoro-JV-phenylmethanesulfonamides. The results demonstrated that this type of compound is considerably more lipophilic (log P = 3.05 for 1,1,1-trifluoro-N-phenylmethanesulfonamide) than the corresponding carboxylic acids or phenols. The effect of the stepwise increase of -fluorine content upon partition coefficient was not linear, but a second-order equation provided an excellent correlation.

Energy of Formation of an Acyclic N-Methyltrifluoromethanesulfonamide Dimer

“…N-Methyltrifluoromethanesulfonamide (I) was synthesized by the procedure reported in [13]; its physical constants and spectral parameters coincided with those reported previously [2].…”

“…We anticipated that the energy of selfassociation of trifluoromethanesulfonamides per hydrogen bond should be considerably greater. Sulfonamides containing perfluoroalkyl groups exhibit a high acidity (pK a 6.39 [12] and 7.56 [13] for trifluoromethanesulfonamide and N-methyltrifluoromethanesulfonamide, respectively), and their cyclic dimers in the gas phase are stable up to 400 K. These data suggest formation of a fairly strong hydrogen bonds despite relatively weak electron-donor power of the S=O group in substituted methanesulfonamides [6,14]. In order to elucidate this problem, it is necessary to estimate the energy of hydrogen bond formation in different self-associates of trifluoromethanesulfonamides.…”

Easy Synthesis of New Chiral Tetradentate N4 Schiff Bases and Their Use as Ligands for Metal Complexes

“…[13] We are focussing on new chiral Schiff base ligands containing sulfonamido functionalities in place of the phenolic groups on salen ligands. As the pK a values of C 6 H 5 NHSO 2 CF 3 , [14] C 6 H 5 NH-tosyl [15] and phenol [16] are 4.45, 8.46 and 9.89, respectively, the acidity of these sulfonamides is higher than that of phenol. Deprotonation of the sulfonamide ligand should therefore be easy and should facilitate its complexation to transition metals to form chiral complexes.…”

An Efficient Strategy for the Synthesis of 1-(Trifluoromethylsulfonamido)propan-2-yl Esters and the Evaluation of Their Cytotoxic Activity

“…Two main methods of synthesis of triflamides and other perfluoroalkanesulfonamides have been described: The reaction of the corresponding fluoroalkylsulfonyl fluorides RFSO 2 F with ammonia or amines, [1][2][3][4][5][6] and the raction of trifluoromethanesulfonyl chloride CF 3 SO 2 Cl or triflic anhydride (CF 3 SO 2 ) 2 O normally, in the presence of triethylamine to bind the eliminated triflic acid. [7][8][9] Different approaches based on the Mitsunobu reaction 10) and the intermolecular bromoesterification of allylic sulfonamides have also been reported.…”

“…36) It is noteworthy that the addition of fluorine atoms conferred them with high acidity and lipophilicity. 4,5,37) In the present study, we carried out the synthesis of a new series of 1-(trifluoromethylsulfonamido) propan-2-yl benzoate derivatives. The strategy employed the ring opening of the oxazoline precursor in the presence of trifluoromethanesulfonic anhydride to give compounds 3a-g in good overall yields.…”