Tautomeric Equilibria of Hydroxypyridines in Different Solvents: An ab

J. Phys. Chem. 1996, 100, 16141-16146

16141

Tautomeric Equilibria of Hydroxypyridines in Different Solvents: An ab Initio Study Jiahu Wang and Russell J. Boyd* Department of Chemistry, Dalhousie UniVersity, Halifax, NoVa Scotia, Canada B3H 4J3 ReceiVed: May 7, 1996; In Final Form: July 28, 1996X

The solvent dependence of the tautomeric equilibria of 2-, 3- and 4-hydroxypyridines is investigated by means of self-consistent reaction field (SCRF) theory. The tautomeric equilibrium constants (KT) in cyclohexane, chloroform, and acetonitrile are predicted at both the Hartree-Fock (HF) and the second-order MøllerPlesset perturbation theory (MP2) levels. It is found that log KT is linearly dependent upon the solvent polarity as measured by the Kosower Z parameter, in agreement with earlier experimental findings. Based on this relation, log KT is predicted to be 1.72, 0.86, and 5.65 for 2-, 3-, and 4-hydroxypyridines, respectively, in aqueous solutions.

1. Introduction

SCHEME 1

The solvent dependence of tautomeric equilibria has been the subject of many experimental studies.1-3 The tautomeric equilibria of hydroxypyridines have also been studied theoretically owing to their relevance to the oxoamino h hydroxyamino tautomerism of nucleic acids.4-6 It has been well established that solvents with large dielectric constants favor the more polar tautomers. For the tautomerism of hydroxypyridine/pyridone systems as drawn in Scheme 1, this means that the equilibria will shift toward the right-hand side in more polar solvents because the oxo-form tautomer is usually the more polar species. Most of the previous studies were concerned with tautomerism in specific solvents. Gordon and Katritzky,1 on the basis of systematic experimental investigations, proposed a quantitative relation between the hydroxypyridine/pyridone tautomeric equilibrium constant and the solvent polarity Z.

log(KT1/KT2) ) R(Z1 - Z2)

(1)

where KT1 and KT2 are the equilibrium constants in solvents 1 (with Kosower polarity Z1) and 2 (with Kosower polarity Z2) and R is a constant dependent on the chemical species of the solutes. Kosower7,8 obtained this empirical measure of solvent polarity Z according to the transition energy of the chargetransfer absorption band of 1-alkylpyridinium iodide. Earlier theoretical studies of tautomeric reactions were essentially concerned with those that happen in the gas phase. It is only recently that efforts have been made to simulate tautomeric processes in solvents.9-12 Of the documented theoretical studies involving media, most are for solvation in aqueous solutions.13 Much less attention has been paid to tautomeric equilibria in nonaqueous solutions.6,14,15 The selfconsistent reaction field theory, coupled with ab initio molecular orbital theory, has been found to be quite useful for accounting for solvent effects, especially those with relatively low dielectric constants. In this article, we employ the ab initio self-consistent reaction field theory to investigate the tautomeric equilibria of three different hydroxypyridine/pyridone systems in cyclohexane, chloroform, and acetonitrile solutions. 2. Computational Details The ab initio molecular orbital calculations were carried out with the Gaussian-9416 program. Geometry optimizations for all six species [1a-3b] were performed at the Hartree-Fock (HF) level with the 6-31G** basis set.17 For the gas phase, X

Abstract published in AdVance ACS Abstracts, September 1, 1996.

S0022-3654(96)01295-6 CCC: $12.00

geometries were also predicted at the second-order MøllerPlesset (MP2) level. Energies at the optimized geometries have also been predicted at the HF and MP2 levels with the larger 6-31+G** basis set. The use of diffuse functions on heavy atoms has been found to be important for properly predicting the solvation effect of dipolar species.12 The solvation effect is taken into account via the selfconsistent reaction field (SCRF) method. This method is based on Onsager’s reaction field theory18,19 of electrostatic solvation. In this model, the solvent is considered as a uniform dielectric with a given dielectric constant . The solute is situated in a spherical cavity of radius a0 in the solvent medium. The permanent dipole of the solute then induces a dipole (reaction field) in the surrounding medium, which in turn will interact with the solute’s dipole. This solute-solvent interaction is updated until self-consistency is achieved. This interaction term is treated as a perturbation in the Hamiltonian of the isolated © 1996 American Chemical Society

16142 J. Phys. Chem., Vol. 100, No. 40, 1996

Wang and Boyd

TABLE 1: Optimized Geometries of 2-Hydroxypyridine and 2-Pyridone in the Gas Phase and Solutionsb solutionsa

gas phase  ) 2.0

 ) 4.8

 ) 35.9

-0.002 -0.001 0.001 -0.002 0.000 0.003 0.000 0.000 0.000 0.000 -0.001 0.01 0.01 0.02 -0.04 0.02 0.10 0.06 0.04 0.02 0.00

-0.004 -0.003 0.003 -0.003 0.000 0.005 0.000 0.000 0.000 0.000 -0.001 0.01 0.01 0.04 -0.08 0.03 0.21 0.13 0.07 0.06 -0.01

-0.005 -0.005 0.004 -0.004 0.001 0.008 0.000 0.000 0.000 0.000 -0.001 0.03 0.02 0.05 -0.10 0.00 0.37 0.18 0.10 0.07 0.00

2-Hydroxypyridine 1.332 0.000 1.401 0.000 1.387 0.001 1.399 0.000 1.389 0.000 1.360 0.001 0.970 0.000 1.080 0.000 1.082 0.000 1.081 0.000 1.084 0.000 124.36 0.06 117.53 -0.02 119.32 -0.01 118.32 0.02 117.34 -0.12 105.09 -0.19 119.87 0.05 120.08 0.02 121.30 -0.01 121.02 -0.01

0.000 -0.001 0.001 -0.001 0.000 0.002 0.000 0.000 0.000 -0.001 0.000 0.10 -0.04 -0.01 0.03 -0.19 -0.35 0.08 0.04 -0.03 -0.01

-0.001 -0.001 0.001 0.000 0.000 0.003 0.000 0.000 0.000 -0.001 0.000 0.12 -0.04 -0.02 0.04 -0.28 -0.49 0.09 0.05 -0.04 -0.03

variable

HF

MP2

r(N-C1) r(C1-C2) r(C2-C3) r(C3-C4) r(C4-C5) r(C1-O) r(N-H1) r(C2-H2) r(C3-H3) r(C4-H4) r(C5-H5) ∠(NC1C2) ∠(C1C2C3) ∠(C2C3C4) ∠(C3C4C5) ∠(OC1N) ∠(H1NC1) ∠(H2C2C1) ∠(H3C3C2) ∠(H4C4C3) ∠(H5C5C4)

1.382 1.457 1.342 1.438 1.339 1.203 0.996 1.073 1.076 1.072 1.074 113.70 121.12 121.50 117.59 120.51 114.76 116.32 119.62 121.46 123.26

1.405 1.450 1.368 1.424 1.365 1.235 1.012 1.081 1.083 1.079 1.081 112.59 122.03 121.21 118.16 120.37 113.78 116.21 119.41 121.72 123.84

r(N-C1) r(C1-C2) r(C2-C3) r(C3-C4) r(C4-C5) r(C1-O) r(O-H1) r(C2-H2) r(C3-H3) r(C4-H4) r(C5-H5) ∠(NC1C2) ∠(C1C2C3) ∠(C2C3C4) ∠(C3C4C5) ∠(OC1N) ∠(H1OC1) ∠(H2C2C1) ∠(H3C3C2) ∠(H4C4C3) ∠(H5C5C4)

1.308 1.396 1.372 1.395 1.374 1.335 0.946 1.073 1.076 1.074 1.076 123.97 117.24 119.71 117.53 117.77 108.14 119.92 119.96 121.61 120.66

2-Pyridone

a

Change from the gas phase to solution (HF/6-31G**). b Bond lengths are given in angstroms and bond angles in degrees.

solute, and the solvation energy calculated through this scheme corresponds to the electrostatic contribution to the free energy of solvation. For a solvent with a low dielectric constant, this contribution is the major factor. In this solvation model, the solvation energy is very sensitive to the chosen cavity radius. Several different methods for determining the cavity size have been proposed. Here, we follow the quantum mechanical approach proposed by Wong et al.,12 which involves determining the 0.001 au electron density envelope and scaling this envelope by a factor of 1.33 to obtain the solute volume. An extra 0.5 Å is added to the resultant a0 to account for the nearest approach of solvent molecules. For all six species, this method leads to a cavity radius a0 ) 3.8 Å. This value is the same as that reported by Wong et al.12 for the 2-hydroxypyridine/pyridone system and is also very close to the one based on a simple van der Waals surface.6 3. Geometrical Structures The optimized geometrical parameters are summarized in Tables 1-3 for 2-, 3-, and 4-hydroxypyridine/pyridone, respectively. All six species are found to have planar minima

in the gas phase and in cyclohexane ( ) 2.0), chloroform ( ) 4.8), and acetonitrile ( ) 35.9) solutions through the vibrational analysis at the corresponding HF/6-31G** optimized geometries. Pyridones have also been found to be planar by X-ray diffraction and microwave spectroscopy.20 The present tabulated geometrical parameters of 2-pyridone and 2-hydroxypyridine at both the HF and MP2 levels are the same as those given by Wong et al.12 The solvent effects on the geometrical parameters can be clearly seen through the changes of bond lengths and bond angles in different solvents, as shown in Tables 1-3. In general, the changes are more significant in the oxo-form tautomers than in the hydroxy-form ones. The C-O bond is affected the most by the solvation. Except in 3- and 4-hydroxypyridine, the C-O bond becomes longer in solution than in the gas phase. In 3-pyridone, the C-O bond length increases by almost 0.02 Å when it is transferred from the gas phase to acetonitrile solution. The bonds in the pyridine ring lengthen and shorten alternately, which can be explained through the contribution of the dipolar resonance structures. The same pattern of altenation is observed for the bond angles within the ring as well. ∠(COH) increases

Hydroxypyridines in Solvents

J. Phys. Chem., Vol. 100, No. 40, 1996 16143

TABLE 2: Optimized Geometries of 3-Hydroxypyridine and 3-Pyridone in the Gas Phase and Solutionsb solutionsa

gas phase  ) 2.0

 ) 4.8

 ) 35.9

0.002 -0.003 -0.003 0.001 -0.001 0.006 0.001 0.000 0.000 0.000 0.000 0.03 -0.03 0.16 -0.19 0.25 0.15 -0.17 0.03 0.19 -0.09

0.004 -0.007 -0.004 0.002 -0.001 0.011 0.002 0.000 0.000 -0.001 0.000 0.04 -0.05 0.32 -0.36 0.50 0.30 -0.36 0.03 0.37 -0.18

0.007 -0.011 -0.006 0.002 -0.001 0.017 0.002 0.000 0.001 -0.001 0.001 0.07 -0.06 0.44 -0.49 0.73 0.43 -0.52 0.03 0.53 -0.25

3-Hydroxypyridine 1.342 0.000 1.399 0.000 1.396 0.000 1.391 0.000 1.396 0.000 1.368 -0.001 0.966 0.000 1.087 0.000 1.082 0.000 1.082 0.000 1.083 0.000 123.45 0.03 118.86 -0.02 117.96 0.01 119.26 0.00 123.11 0.06 108.61 0.10 116.45 0.00 119.62 -0.03 120.52 -0.02 120.75 0.01

0.000 0.000 0.000 0.000 0.000 -0.001 0.000 0.000 0.000 0.000 0.000 0.03 -0.02 0.01 0.00 0.09 0.19 0.01 -0.04 -0.03 0.00

0.000 0.000 0.000 0.000 0.000 -0.001 0.000 0.000 0.000 0.000 0.000 0.04 -0.01 -0.01 0.01 0.11 0.27 0.01 -0.02 -0.05 -0.02

variable

HF

MP2

r(N-C1) r(C1-C2) r(C2-C3) r(C3-C4) r(C4-C5) r(C2-O) r(N-H1) r(C1-H2) r(C3-H3) r(C4-H4) r(C5-H5) ∠(NC1C2) ∠(C1C2C3) ∠(C2C3C4) ∠(C3C4C5) ∠(OC2C1) ∠(H1NC1) ∠(H2C1N) ∠(H3C3C2) ∠(H4C4C3) ∠(H5C5C4)

1.325 1.438 1.441 1.370 1.386 1.222 0.998 1.072 1.075 1.075 1.070 121.88 112.43 122.51 120.96 122.29 117.05 117.32 117.03 120.40 125.32

1.349 1.450 1.459 1.380 1.398 1.246 1.013 1.080 1.083 1.082 1.077 121.41 112.71 122.64 121.16 122.25 117.14 117.12 116.78 120.50 125.81

r(N-C1) r(C1-C2) r(C2-C3) r(C3-C4) r(C4-C5) r(C2-O) r(O-H1) r(C1-H2) r(C3-H3) r(C4-H4) r(C5-H5) ∠(NC1C2) ∠(C1C2C3) ∠(C2C3C4) ∠(C3C4C5) ∠(OC2C1) ∠(H1OC2) ∠(H2C1N) ∠(H3C3C2) ∠(H4C4C3) ∠(H5C5C4)

1.320 1.385 1.385 1.379 1.387 1.350 0.943 1.079 1.075 1.075 1.076 123.11 118.46 118.20 119.00 122.93 111.15 116.71 119.67 120.73 120.67

3-Pyridone

a

Change from the gas phase to solution (HF/6-31G**). b Bond lengths are given in angstroms and bond angles in degrees.

as the solvent dielectric constant  gets larger. In fact, all the structural changes become more prominent in more polar solvents. 4. Tautomeric Energies The calculated total and relative energies in the cyclohexane, chloroform, and acetonitrile solutions are given in Tables 4-6. The dipole moments of the species are also tabulated. The oxoform tautomers all have larger dipole moments than their hydroxy-form counterparts. In cyclohexane, the differences are 3.07, 6.47, and 4.38 D for the 2-, 3-, and 4-hydroxypyridine/ pyridone pairs. These differences become even larger when the systems are put into higher dielectric constant solvents such as chloroform and acetonitrile. The solvation effects on the tautomeric equilibria can be assessed through examination of the relative stabilities (∆G) of the two tautomers in different solvents. From Table 4, we notice that at the HF level, 2-hydroxypyridine is favored over 2-pyridone in cyclohexane and this trend is inverted in chloroform. In the more polar acetonitrile solvent, the tautomeric equilibrium [1a h 1b] shifts even further to the right. The change in free energy can be broken down into the

electronic energy part (∆E), the zero-point energy part (∆ZPE), and the thermal correction to the enthalpy (∆(H - H0)) and the entropy (-T∆S) part. All contributions play important roles in this case. Including electron correlation at the MP2 level causes the equilibrium to shift to the left but it appears this change in ∆G is almost constant in the three different solvents. Wong et al.12 have found that inclusion of electron correlation at the QCISD level leads to further systematic changes of ∆G and results in a better agreement with experimental results. The extra stabilization of the oxo-form tautomer is also seen in the 3- and 4-hydroxypyridine/pyridone systems. Because the differences in the dipole moments of the oxo- and hydroxyform tautomers are bigger in these two systems than in the 2-hydroxypyridine/pyridone case, they demonstrate more significant solvent effects. Including electron correlation has been found to lower quite dramatically the energy of 3-pyridone, a zwitterion as represented by 2b. This leads to a large drop of ∆G and an increase of the equilibrium constant KT (∆G ) -RT ln KT of the tautomeric reaction. The predicted tautomeric equilibrium constants (log KT) in cyclohexane (Z ) 52), chloroform (Z ) 63.2), and acetonitrile

16144 J. Phys. Chem., Vol. 100, No. 40, 1996

Wang and Boyd

TABLE 3: Optimized Geometries of 4-Hydroxypyridine and 4-Pyridone in the Gas Phase and Solutionsb solutionsa

gas phase  ) 2.0

 ) 4.8

 ) 35.9

-0.003 0.002 -0.003 0.004 0.001 0.000 0.000 -0.05 0.05 -0.04 0.02 -0.02 0.00 -0.17

-0.005 0.004 -0.006 0.008 0.002 0.000 0.000 -0.11 0.11 -0.08 0.05 -0.05 0.02 -0.34

-0.008 0.006 -0.009 0.012 0.003 0.000 0.001 -0.21 0.17 -0.12 0.07 -0.10 0.05 -0.49

4-Hydroxypyridine 1.343 0.000 1.394 0.000 1.395 0.000 1.396 0.001 1.391 -0.001 1.365 -0.002 0.966 0.001 1.084 0.000 1.084 0.000 1.081 0.000 1.084 0.000 124.30 0.05 118.32 0.02 118.56 -0.06 118.30 0.03 123.72 0.15 108.74 0.25 116.09 0.02 120.42 -0.01 120.00 -0.06 119.73 -0.05

0.001 0.000 0.001 0.001 -0.001 -0.004 0.001 0.000 0.000 0.000 0.000 0.11 0.03 -0.14 0.07 0.30 0.49 0.01 -0.02 -0.14 -0.10

0.001 0.000 0.001 0.002 -0.002 -0.005 0.001 0.000 0.000 0.000 0.000 0.15 0.03 -0.16 0.08 0.41 0.66 0.02 -0.01 -0.17 -0.13

variable

HF

MP2

r(N-C1) r(C1-C2) r(C2-C3) r(C3-O) r(N-H1) r(C1-H2) r(C2-H3) ∠(NC1C2) ∠(C1C2C3) ∠(C2C3C4) ∠(OC3C2) ∠(H1NC1) ∠(H2C1N) ∠(H3C2C1)

1.365 1.337 1.467 1.206 0.992 1.074 1.073 121.93 121.12 113.81 123.09 119.96 115.53 120.60

1.371 1.361 1.462 1.243 1.006 1.081 1.081 120.96 121.93 113.53 123.24 119.66 115.76 119.78

r(N-C1) r(C1-C2) r(C2-C3) r(C3-C4) r(C4-C5) r(C3-O) r(O-H1) r(C1-H2) r(C2-H3) r(C4-H4) r(C5-H5) ∠(NC1C2) ∠(C1C2C3) ∠(C2C3C4) ∠(C3C4C5) ∠(OC3C2) ∠(H1OC3) ∠(H2C1N) ∠(H3C3C2) ∠(H4C4C3) ∠(H5C5C4)

1.319 1.384 1.386 1.388 1.379 1.340 0.943 1.077 1.076 1.073 1.077 124.31 117.97 118.58 117.90 123.15 111.29 116.28 120.56 120.32 119.52

4-Pyridone

a

Change from the gas phase to solution (HF/6-31G**). b Bond lengths are given in angstroms and bond angles in degrees.

TABLE 4: Calculated Energiesa,b and Dipole Moments (µ)c of 2-Hydroxypyridine and 2-Pyridone in the Gas Phase and Solutions 2-pyridone

E(HF/6-31G**) E(HF/6-31+G**) E(MP2/6-31+G**) ZPE H-H0 S µ ∆E(HF/6-31G**) ∆E(HF/6-31+G**) ∆E(MP2/6-31+G**) ∆ZPE ∆(H-H0) ∆(-TS) ∆Gd ∆Ge ∆Gf

)2

 ) 4.8

-321.580 30 -321.590 73 -322.589 06 63.33 3.68 72.78 4.68

-321.582 12 -321.592 35 -322.590 99 63.33 3.68 72.73 5.15

0.45 0.31 1.87 0.22 0.03 -0.12 0.59 2.01 -0.33

-0.58 -0.60 0.81 0.23 0.02 -0.10 -0.42 0.97 -1.06

2-hydroxypyridine  ) 35.9 Absolute Values -321.583 73 -321.593 86 -322.592 74 63.33 3.67 72.68 5.57

)2

 ) 4.8

 ) 35.9

-321.581 03 -321.591 22 -322.592 05 63.11 3.65 72.39 1.61

-321.581 20 -321.591 40 -322.592 28 63.10 3.66 72.40 1.76

-321.581 36 -321.591 57 -322.592 48 63.08 3.66 72.42 1.89

Relative Values -1.49 -1.43 -0.16 0.25 0.01 -0.08 -1.30 0.02 -2.96

a Based on HF/6-31G** optimized geometries at room temperature (298 K). b E in hartrees; ZPE, H-H , and all the relative values in kcal/mol; 0 S in cal/(mol K). c MP2/6-31+G** values in debye. d HF/6-31G** values. e MP2/6-31+G** values. f Experimental values from ref 2.

(Z ) 71.3) are plotted against the solvent polarity Z in Figure 1 with values from the HF/6-31G** method and in Figure 2 with values from the MP2/6-31+G** method. It is clear that for both cases, log KT behaves almost linearly with respect to the empirical solvent polarity Z. This is consistent with those

reported by Katritzky et al.1,2 These authors have measured the tautomeric equilibrium constants of the above three systems by UV absorption spectra in a wide range of solvents and obtained linear correlations between log KT and the Kosower Z solvent parameters.

Hydroxypyridines in Solvents

J. Phys. Chem., Vol. 100, No. 40, 1996 16145

TABLE 5: Calculated Energiesa,b and Dipole Moments (µ)c of 3-Hydroxypyridine and 3-Pyridone in the Gas Phase and Solutions 3-pyridone )2 E(HF/6-31G**) E(HF/6-31+G**) E(MP2/6-31+G**) ZPE H-H0 S µ ∆E(HF/6-31G**) ∆E(HF/6-31+G**) ∆E(MP2/6-31+G**) ∆ZPE ∆(H-H0) ∆(-TS) ∆Gd ∆Ge

-321.527 81 -321.540 15 -322.560 16 63.12 3.64 72.53 7.87 21.61 20.13 10.59 0.50 -0.17 0.25 22.19 11.18

3-hydroxypyridine

 ) 4.8

 ) 35.9

Absolute Values -321.532 71 -321.537 10 -321.544 76 -321.549 09 -322.565 09 -322.569 64 63.15 63.17 3.63 3.62 72.43 72.35 8.72 9.51 18.60 17.33 7.58 0.55 -0.18 0.29 19.26 8.24

)2

 ) 4.8

 ) 35.9

-321.562 25 -321.572 23 -322.577 04 62.62 3.81 73.36 1.40

-321.562 35 -321.572 37 -322.577 17 62.60 3.81 73.41 1.51

-321.562 44 -321.572 50 -322.577 30 62.58 3.82 73.44 1.61

Relative Values 15.90 14.69 4.81 0.59 -0.20 0.32 16.61 5.52

a Based on HF/6-31G** optimized geometries at room temperature (298 K). b E in hartrees; ZPE, H-H , and all the relative values in kcal/mol; 0 S in cal/(mol K). c MP2/6-31+G** values in debyes. d HF/6-31G** values. e MP2/6-31+G** values.

TABLE 6: Calculated Energiesa,b and Dipole Moments (µ)c of 4-Hydroxypyridine and 4-Pyridone in the Gas Phase and Solutions 4-pyridone )2 E(HF/6-31G**) E(HF/6-31+G**) E(MP2/6-31+G**) ZPE H-H0 S µ ∆E(HF/6-31G**) ∆E(HF/6-31+G**) ∆E(MP2/6-31+G**) ∆ZPE ∆(H-H0) ∆(-TS) ∆Gd ∆Ge ∆Gf

-321.566 12 -321.577 19 -322.576 19 63.24 3.76 73.22 7.53 1.84 1.35 2.62 0.33 0.03 -0.10 2.10 2.88

4-hydroxypyridine

 ) 4.8

 ) 35.9

Absolute Values -321.570 51 -321.574 46 -321.581 40 -321.585 30 -322.581 02 -322.585 46 63.30 63.35 3.72 3.70 73.02 72.87 8.33 9.07 -0.53 -0.84 0.02 0.40 -0.01 -0.05 -0.18 0.37 -0.15

)2

 ) 4.8

 ) 35.9

-321.569 06 -321.579 34 -322.580 37 62.91 3.73 72.87 3.15

-321.569 67 -321.580 06 -322.581 05 62.90 3.73 72.85 3.43

-321.570 19 -321.580 72 -322.581 68 62.89 3.72 72.83 3.67

Relative Values -2.68 -2.87 -2.37 0.46 -0.02 -0.01 -2.26 -1.95 -0.90

a Based on HF/6-31G** optimized geometries at room temperature (298 K). b E in hartrees; ZPE, H-H , and all the relative values in kcal/mol; 0 S in cal/(mol K). c MP2/6-31+G** values in debyes. d HF/6-31G** values. e MP2/6-31+G** values. f Experimental values from ref 2.

The slopes at the HF level (Figure 1) have been predicted to be 0.072, 0.213, and 0.166 for 2-, 3-, and 4-hydroxypyridine/ pyridone, respectively, compared to 0.08, 0.15, and 0.10 based on the fitting of the experimental data.1,2 The agreement for the 2-hydroxypyridine/pyridone system is very good and for the other two, the trends are also right. Since the electron correlation contribution is essentially constant, the slopes at the MP2 level are just slightly larger at 0.076, 0.215, and 0.184. The intercepts, however, are affected, and for the 3-hydroxypyridine/pyridone system, it is shifted upward by a few units. The Kosower Z parameter, which is scaled to the transition energies of 1-alkylpyridium iodide in different solvents, is a better empirical measure of solvent polarity in this case, since the systems discussed are quite similar to the reference one. It includes both the specific and nonspecific interactions between the solvent and solute and leads to a good linear correlation between log KT and Z. Based on the linear relationship between log KT and Z, we can extrapolate to obtain the equilibrium constants of the three tautomeric processes in more polar solvents such as aqueous

solution, for which the present solvation model does not work well because of the strong effects of the first few solvation shells. Using the linear relations obtained above, however, would allow us to predict KT through extrapolation. For example, with the slopes and intercepts at the HF level, the log KT for the 2-pyridone tautomerism is found to be 2.26, close to the experimental value of 2.96. Similarly, the extrapolated and experimental log KT for the 4-hydroxypyridine/pyridone system are 5.46 and 3.29, respectively. The latter example shows a large discrepancy, but this seems to be common to other theoretical predictions6,15 as well. Szafran et al.6 studied the solvation effects on the tautomeric equilibrium of 4-pyridone by employing a semiempirical quantum chemical method and observed improved results for log KT in aqueous solution (from -1.2 to 9.5 by AM1 and from -2.1 to 5.9 by PM3) upon inclusion of one specific water molecule. By use of the linear relation at the MP2 level, the extrapolated log KT are 1.72 and 5.65 for the 2- and 4-hydroxypyridine/pyridone, respectively. For the tautomeric equilibrium between 3-pyridone and 3-hydroxypyridine, the extrapolated log KT is -7.29 based on the

16146 J. Phys. Chem., Vol. 100, No. 40, 1996

Figure 1. Plot of calculated log KT at the HF/6-31G** level vs Z for 2-pyridone/2-hydroxypyridine (s), 3-pyridone/3-hydroxypyridine (‚‚‚), and 4-pyridone/4-hydroxypyridine (- - -) in cyclohexane, chloroform, and acetonitrile solutions.

Wang and Boyd tautomeric equilibria. The bond lengths lengthen and shorten alternately in the pyridine ring. The equilibria shift in the direction of the more polar tautomer (oxo form) when the dielectric constant of the solvent increases. The present results show a roughly linear relation between log KT and the solvent polarity parameter Z, in agreement with the early experimental observations. Electron correlation included at the MP2 level affects mainly the intercept of the linear relation between log KT and Z. On the basis of the linear relations between log KT and Z, tautomeric equilibrium constants in aqueous solutions are predicted. The extrapolated log KT is 2.62 and 5.46 compared with the experimental values of 2.96 and 3.29 for the 2- and 4-hydroxypyridine/pyridone systems with the relations obtained at the HF level theory. By use of the relations at the MP2 level, the log KT is predicted to be 1.72 and 5.65, respectively. For the 3-hydroxypyridine/pyridone system, electron correlation plays a big role and at the MP2 correlated level of theory, the equilibrium constant (log KT) is predicted to be 0.86, indicating an almost equal amount of the oxo- and hydroxy-form tautomers in water. Acknowledgment. This work has been supported by grants from the Natural Sciences and Engineering Research Council of Canada, NSERC (to R.J.B.). J.W. thanks the Killam Trust for a Killam postdoctoral fellowship. References and Notes

Figure 2. Plot of calculated log KT at the MP2/6-31+G** level vs Z for 2-pyridone/2-hydroxypyridine (s), 3-pyridone/3-hydroxypyridine (‚‚‚), and 4-pyridone/4-hydroxypyridine (- - -) in cyclohexane, chloroform, and acetonitrile solutions.

relation at the HF level. But once electron correlation is included, the value increases to 0.83 at the MP2 level. From the early experiments, 3-hydroxypyridine (2a) has indeed been found to be the predominant component in the gas phase. In aqueous solution, 2a and 2b appear in an approximate 1:1 mixture,20,21 which would give a very small log KT, in agreement with the MP2 extrapolated value. 5. Conclusions This paper presents a self-consistent reaction field study of tautomeric equilibria of 2-, 3-, and 4-hydroxypyridine/pyridone in cyclohexane, chloroform, and acetonitrile solutions. The method predicts the structural changes as well as the shift of

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