Solvent effect on preferred protonation sites in nicotinate and isonicotinate anions

Abstract

Potentiometric determinations of the two successive acidities of nicotinic and isonicotinic acids (AH,') have been carried out in aqueous dimethyl sulfoxide mixtures containing up to 95% Me2S0 by volume. In both systems, the results reveal that the addition of Me,SO induces a proton transfer from the pyridinium ring to the carboxylate group, the tautomeric equilibrium between the neutral forms of the two acids being displaced toward the zwitterionic form (AH') in aqueous solution, but toward the molecular form (AH0) in Me,SO. An analysis of the data by means of Hammett relationships previously established for benzoi'c acids over the whole range of H,O/Me,SO mixtures allowed the four microscopic acidity constants as well as the tautomeric equilibrium constant KT pertaining to the complete ionization scheme of the two acids to be determined. At 20°C, there are equal populations of the tautomeric AH0 and AH' species in the mixtures containing 38 and 47% Me,SO for the nicotinic and isonicotinic systems, respectively. Hammett relationships describing the ionization behaviour of a number of substituted pyridinium cations in H,O/Me,SO mixtures are also discussed. Possible reasons accounting for the peculiar effects exerted by the NH,, CONH,, and COOH substituents on the process are suggested.Key words: nicotinic and isonicotinic acids, substituted pyridines, acidities, tautomeric equilibrium, protonation sites, water -dimethyl sulfoxide mixtures.Resume : Les deux aciditts successives des acides nicotinique et isonicotinique (AH,' ) ont Cte determinees par potentiometrie dans des milieux eau-dimCthylsulfoxyde contenant jusqu'a 95% de Me,SO en volume. L'addition de Me,SO provoque le transfert protonique du cycle pyridinium vers le groupement carboxylate, de sorte que la forme zwitterionique AH*, trks majoritaire dans I'eau, ckde progressivement la place B la forme molCculaire AH0 qui devient unique dans le dimethylsulfoxyde. Le traitement des resultats, h I'aide des relations de Hammett d'energie libre prealablement Ctablies pour les acides benzo'iques dans les mtlanges H,O/Me,SO, permet les determinations des quatre constantes microscopiques et de la constante de tautomtrie KT decrivant le schema des ionisations successives de ces deux diacides. A 20°C, on a CgalitC entre les populations des formes zwitterionique (AH') et molCculaire (AH0) dans 1es milieux contenant respectivement 38% (acide nicotinique) et 47% (acide isonicotinique) de MezSO en masse. Les relations de Hammett d'Cnergie libre, dtcrivant l'ionisation d'un grand nombre de pyridines substituCes dans IesmClanges H20/Me,S0, sont discuttes. Les effets particuliers observes pour les substituants NH,, CONH, et COOH sont analysts.

Ionization constants of all seven positional isomers of quinolinesulfonamides and quinoline-N,N-dimethylsulfonamides

“…All quinolinesulfonamides studied are less basic then the parent quinoline (pK a (water) = 4.94 [53][54][55]) by one up to five order. This may be due to strong electron-withdrawing nature of the sulfamoyl substituent which decreases the electron density of the whole quinoline moiety, also including nitrogen ring-atom.…”

Thermochemistry of aqueous pyridine-3-carboxylic acid (nicotinic acid)

“…The latter was calculated from the differences between the D dil H m values given by equation (8) and their experimental counterparts [24] and represents the corresponding standard deviation multiplied by Student's factor for 95% confidence level (t = 2.132 for 16 independent measurements). Aqueous nicotinic acid is an amphiprotic system composed of three species in equilibrium (scheme 1): one positively charged (H N þ C 5 H 4 COOH), another neutral and largely of zwitterionic type (H N þ C 5 H 4 COO À ) [25][26][27][28][29], and a third one negatively charged (NC 5 H 4 COO À ). Their mole fractions at a given pH and temperature can be predicted from the acidity constants (normally expressed as pK a s) for the equilibria in scheme 1 [30].…”

Mass spectrometric decompositions of copper complexes with esters and amides of nicotinic acid

“…Structural studies of copper(II) complexes with pyridine‐3(and 4)‐carboxamide and N,N ‐diethylpyridine‐3‐carboxamide suggest that the Cu(II) is principally coordinated by the nitrogen of the pyridine ring. It is well known that the pyridine nitrogen is more basic than the nitrogen of the amide group (p K a values of 3.28–3.5, 3.42, and 0.48 for pyridine‐3‐carboxamide, N,N ‐diethylpyridine‐3‐carboxamide and acetamide, respectively) 8, 14, 15…”