THEREVERSIBLE HYDRATION OF 2- AND 4-PYRIDINECARBOXALDEHYDES
4509
The Reversible Hydration of 2- and 4-Pyridinecarboxaldehydes.
I.
Equilibrium Studies'
by Y. Packer,* J. E. Meany, and B. J. Nist Department of Chemistry, University of Washington, Seattle, Washington 98105
(Received June 933, 1967)
Quantitative measurements have been carried out on the fractions of hydration of 2- and 4pyridinecarboxaldehyde as a function of both pH and temperature. Parallel determinations of the position of equilibrium in D20 by ultraviolet spectrophotometry (270, 305, and 320 mp) and by nmr show that the results afforded by these two methods are in complete accord. The thermodynamic parameters for these two reactions have been determined. For the hydration of 2-pyridinecarboxaldehyde and of 4-pyridinecarboxaldehyde in DzO, standard free energies, AG", heats, AH", and entropies of hydration, AS", were deduced as -0.35 and -0.08 kcal mole-', -3.8 and -4.2 kcal mole-', and -13.8 and - 13.9 eu, respectively. These quantities are compared to those obtained from the hydration of several aliphatic carbonyl compounds.
Introduction We have recently reported that the pyridinealdehydes, especially 2- and 4-pyridinecarboxaldehyde, provide valuable substrates for the study of the mode of hydration of the zinc metalloenzyme, carbonic anh y d r a ~ e . ~I?n ~addition, we have shown that the hydration of 2-pyridinecarboxaldehyde is very susceptible to metal ion catalysi~.~Because these reactions are reversible CSHJ'J*C:HO
+ HzO
C&H4NCH(OH)z (1)
a detailed knowledge of the equilibrium constant as a function of both temperature and pH is a prerequisite for the quantitative analysis of the kinetic data. Although earlier workers have determined the ultraviolet spectra of these aldehydes in HzO-dioxane mixtures, the equilibrium constants which can be deduced from their publications have not been in good agreement.5j6 A fundamental difficulty in deducing the fraction of hydration of aldehydes is that it is necessary to assume that the absorption of the corresponding hydrate is negligible in the region of the n-r* absorption band associated with the carbonyl group. While this assumption is essentially correct for aliphatic aldehydes, due care should be applied in studying heteroaromatic aldehydes because here the rl band generally conceals the weaker n-n* band. Another difficulty is asso-
ciated with the determination of the ultraviolet spectra in water of the completely unhydrated aldehydes, i.e., the ultraviolet spectra at zero reaction. I n this connection it is often found that the carbonyl absorption of carbonyl compounds which are not appreciably hydrated is stronger in water than in hydrocarbon solv e n t ~ . ~Consequently, it seems likely that values of ERCHO based on measurements in nonaqueous media may be too low. In this paper, we report the results of a study pertaining to the hydration of 2- and 4-pyridinecarboxaldehyde using both the spectrophotometric and the nmr techniques. The hydration equilibria as deduced by these two methods are shown to be in complete accord. The extent of hydration has been accurately determined as a function of both pH and temperature, and the thermodynamic parameters associated with the hydration processes are determined. (1) This work was supported by U. S. Public Health Service grants from the National Institutes of Health. (2) Author to whom correspondence should be addressed. (3) Y. Pocker and J. E. Meany, Biochemistry. 6, 239 (1967). (4) Y. Pocker and J. E. Meany, J . Am. Chem. Soc., 89, 631 (1967). (5) K. Nakamoto and A. E. Martell, ibid., 81, 5857 (1959). (6) S. Cabani and P. Cecchi, Ann. Chim. (Rome), 49, 205 (1959). (7) M. Dertooz and J. Nasielski, Bull. SOC.Chim. Belgees, 70, 794 (1961).
Volume 7 1 , Number 13 December 1967
Y. POCKER, J. E. MEANY,AND B. J. NIST
45 10
Experimental Section 2- and 4pyridinecarboxaldehydes (Aldrich Chemical Co., Inc.) were twice distilled under reduced pressure in a nitrogen atmosphere: bp (2-pyridinecarboxaldehyde) 60-61" (12 mm) ; bp (4-pyridinecarboxaldehyde) 76-77" (12 mm). Heavy water (Liquid Carbonic Division of General Dynamics Corp.) contained at least 99.7% DzO. With the exception of diethylmalonic acid, the chemical components of the buffers used were commercially available compounds, analytical or reagent grade or of comparable purity. Our method of preparing diethylmalonic acid has been reported p r e v i ~ u s l y . ~ ~For ~ ~ *all - ~ spectrotometric determinations, the following buffer components were employed: HCl (pH
