The basicity of sulfonamides and carboxamides. Theoretical and experimental analysis and effect of fluorinated substituent

Abstract

The basicity of a series of sulfonamides and carboxamides with respect to protonation and hydrogen-bonded complex formation with phenol was investigated by calculations using the Becke three-parameter hybrid functional combined with Lee-Yang-Parr correlation functional with the 6-311G** and 6-311++G** basis sets and by infrared spectroscopy. The effect of fluorinated substituent was studied for the two series. The proton affinity of nitrogen in sulfonamides is higher than oxygen, in contrast to carboxamides, which are protonated at oxygen. The phenyl group in benzenesulfonamide increases the basicity of both heteroatoms, but more strongly of the nitrogen, whereas in benzamide the effect on the two heteroatoms is about the same. The CF 3 group equally decreases the basicity of nitrogen and oxygen atoms in sulfonamides and carboxamides. The second fluorinated substituent decreases the basicity of oxygen in (CF 3 CO) 2 NH more strongly than of nitrogen. For sulfonamides, the same effect results in the reverse of the center of basicity from nitrogen in (MeSO 2 ) 2 NH to oxygen in (CF 3 SO 2 ) 2 NH. All studied carboxamides give H-complexes via the carbonyl oxygen, whereas for sulfonamides two types of H-complexes, with the OHÁÁÁN and OHÁÁÁO=S, were found theoretically, the latter being more stable. The exception is bisimide (CF 3 SO 2 ) 2 NH, for which only the OHÁÁÁO=S complex is stable. Experimentally, only the oxygen-bound complexes are observed. Analysis of the natural charges revealed an 'abnormal' increase of the electron density on the NH group by electron-acceptor substituents in CF 3 SO 2 NHR, which was explained using the natural bond orbital analysis by loosening of the S-N bond because of orbital interactions with the s* SÀN orbital.

Stereoelectronic structure and self-association of N-trimethylsilylsulfonamides RSO2NHSiMe3 (R = Me, CF3, Ph)

“…The protonation of N-trimethylsilylsulfonamides I-III and their isostructural organic analogs IV-VI at the nitrogen atom is 4-6 kcal/mol more preferable than at the oxygen atom. Similar results were obtained when studying the acid-base properties of a series of sulfonamides [10], whereas in carboxamides the protonation at the oxygen atom is preferable by energety due to the conjugation in the amide moiety, which increases the basicity of the carbonyl oxygen in the amide group. The basicity of the nitrogen and oxygen atoms is decreased in the derivatives of triflamide II, IV and increased in benzenesulfonamides III, VI.…”

“…[1][2][3][4][5][6][7]. Similar to amides of carboxylic acids, sulfonamides are capable of formation of hydrogen bonds [8][9][10][11][12][13], both the oxygen and the nitrogen atoms being able to act as the center of basicity in these compounds. Thus, according to the data of NMR spectroscopy and quantum chemistry, the protonation at the nitrogen atom of the sulfonamide group is somewhat preferable than at the oxygen atom [9][10][11][14][15][16][17].…”

“…Similar to amides of carboxylic acids, sulfonamides are capable of formation of hydrogen bonds [8][9][10][11][12][13], both the oxygen and the nitrogen atoms being able to act as the center of basicity in these compounds. Thus, according to the data of NMR spectroscopy and quantum chemistry, the protonation at the nitrogen atom of the sulfonamide group is somewhat preferable than at the oxygen atom [9][10][11][14][15][16][17]. However, the oxygen atom can also be involved in the formation of a hydrogen bond, and its spectroscopic basicity has been measured by IR spectroscopy by evaluating the constants of complex formation with MeOH and p-FC 6 H 4 OH [18,19].…”

“…Similar to carboxamides, sulfonamides form heteroand self-associates [8,12,13,[20][21][22][23]. Self-association is most pronounced in the derivatives of trifluoromethanesulfonic acid, since the presence of trifluoromethyl substituent at the sulfur atom decreases the basicity of the sulfonyl oxygen and simultaneously substantially increases the acidity of the NH group [10,11,24,25]. The introduction of a silicon atom in the molecule results in substantial changes in its stereoelectronic structure and, consequently, in the physicochemical properties of the compounds.…”

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

“…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.…”