AM1 study of the tautomerism of 2- and 4-pyridones and their thio-analogs

Journal of Molecular Structure (Theochem), 184 (1989) 179-192 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands

AM1 STUDY OF THE TAUTOMERISM AND THEIR THIO-ANALOGS

ALAN R. KATRITZKY,

MIROSLAW

179

OF 2- AND 4-PYRIDONES

SZAFRAN*

Department of Chemistry, University of Florida, Gainesville, FL 32 611 (U.S.A.) JOHN STEVENS Corporate Research Laboratories/3M St. Paul, MI 55 144 (U.S.A.) (Received 6 May 1988)

ABSTRACT The geometries, relative stabilities, proton affinities, ionization potentials, and dipole momenta for the different tautomers of 2- and 4-pyridones, for their thio-analogs, and for their methylated and pro&mated derivatives were calculated with full geometry optimization using the AM1 method. In each case the AM1 prediction of the tautomer most stable in the gas phase was experimentally confirmed. Calculated proton affinities are in qualitative agreement with experimental values. The optimal AM1 geometry of 2-pyridone and 2-pyridinethione agree well with available crystallographical data, except that the predicted 2C=S and 4C=S bonds are shorter than the experimental ones.

INTRODUCTION

H

X

0 II

N H

XH

= x=o,s

An understanding of the tautomeric equilibria of heterocycles especially those of lactim-lactam (X = 0 ) and thiol-thione (X = S ) types shown in structures *On leave from Department

of Chemistry,

A. Mickiewicz University,

0166-1280/89/$03.50

0 1989 Elsevier Science Publishers

B.V.

60 780 Poznan, Poland.

H

’

H’

b

d

c 1

x=0

2 x=s

clN’ x

/”

CL QIH ly’

I'

I

x’

H

“!

cly’ x/c’H H

d

c

b 5 X=0

6 X-S

HI\" i\ H H. b

7x=0

r”

I

H.

H.

c

d

8 x-s

XH

b

3 x=0

4 x=s

d 9 x=0

,lO

x=s

11 x=0-

12 X=S

Fig. 1.Tautomers and conformers of free and protonated pyridines investigated in this study.

(la,lb) helps our understanding of many areas of chemistry and biochemistry, e.g., the rationalization of physical and chemical properties the quantitative reactivity of heterocycles [ 1,2], the variation of intrinsic stabilities vs. solvent effects [ 3,4], the concept of, and tests of, aromaticity [ 51, the mechanisms of enzymatic catalysis and receptor interactions [ 61, and possibly even the mechanism of mutation during DNA replication [ 2,7].

181

The tautomeric equilibria of pyridones and thiopyridones (laand lb) in the ground state, in solution in polar solvents, or in the solid state have been well studied and have been shown to lie almost totally in the lactam and thione forms, respectively, by UV [3,4] and X-ray [8], IR [9], ‘H NMR [lo] and basicity measurements [ 5b,ll]. Studies in the vapor phase of 2- and 4-0x0and 2- and 4-thio-pyridines by IR [ 121, by mass spectrometry [ 131, by photoelectron spectroscopy [ 141 and by IR investigations in an argon matrix [ 151, by contrast indicate that the hydroxy- and mercapto-forms predominate in the gas phase. Numerous theoretical studies using almost every available method have attempted to reproduce the tautomerization energies for pyridone/hydroxypyridine equilibria and for those of similar heterocyclic systems [ 16-391. Simulations of hydrogen bonding and solvent interactions reproduce qualitatively the shift in the equilibrium towards the pyridone form in condensed phases [ 28-311. However, quantitative agreement with the tautomerization energies determined experimentally in the vapor have been difficult to obtain. Geometry optimization, basis-set flexibility, correlation energy, and zero-point vibration have all been recognized as making important contributions to these and related [ 331 isomerization reactions. The experimental energies for substituted pyridines can be reproduced well by calculation at either the STO-3G or 3-21G basis set levels over a wide range of substituents, but the minimal basis set gives the better absolute agreement overall [37]. The total energy differences of the various equilibria obtained by the MNDO method are comparable to those derived by the STO-3G method [26]. For the geometries, MIND0/3 gives good bond lengths (comparable with 3-21G) but poor angles, while MNDO and the minimal basis set give poor bond lengths but good and comparable bond angles [ 381. In the present paper, the geometries, ionization potentials, dipole moments, relative energies and proton affinities of each of the tautomers of 2- and 4-0x0and 2- and 4-thio-pyridines, and of their methyl and protonated derivatives (Fig. 1) have been calculated using the AM1 method, and the results compared with recent experimental studies [ 14,40-421. METHOD OF CALCULATION

All calculations were carried out with complete geometry optimization. The AM1 [ 43 1, MNDO [ 441 and MIND0/3 [ 451 calculations were performed with the MOPAC program (version 3.0) [46] on Micro VAX II. The ab initio calculations on pyridine-2-thiol and 2-methylthiopyridine were carried out using the modified HONDO method employed in the ab initio suite of programs from QUIPU [47]. The restricted Hartree-Fock method was used with the basis sets defined in the reports and the search for stable geometry was ended when the component of the gradients reached 0.601.

All moleculeswereassumedplanar (exceptfor the protonsof methylgroups) . One proton of any methyl group was placed in the plane of the pyridine ring. The geometriesof 2- and 4-aminopyridineswere taken as the starting point for the geometriesof the correspondinglactim and thiol tautomers [481. The crystal geometrieswere used as initial input for 2-pyridone and 2-pyridinethione [ 8b 1. Starting geometriesof other tautomerswere based on crystallographic interatomic distances [49]: the C-H, N-H, O-H and S-H distances were taken as 1.08,1.01,0.96 and 1.3, respectively.Results are listed in Tables 1-9. In the ease where more than one planar arrangementof an OH or an SH groupis possible (i.e. the 2-isomers), referenceis made only to the more stable configuration. RESULTS AND DfSCUSSION

The optimizedbond lengthsand anglesfor the 16 moleculesstudiedare given in Tables l-4. For 2- and 4-oxopyridinesthe averagedifferencesbetweenbond lengthsand bond angles found using AM1 and the 3-21G basis set are 0.02 A and 1.5O,respectively,The comparison of the AM1 geometryof 2- and 4-0x0and 2- and 4-thio-p~i~nes with MNDU and MI~O~3 data has shown that the bond length obtained by the AM1 method is, in many cases, intermediate between the bond lengths determinedby MNDO and MIND0/3, For 2-pyridone and 2-pyridinethione,our AMl*optimizedgas-phasestructureyieldsbond lengthswhich differ by up to 0.039 A from those found in previouslyreported solid-statecrystallo~aphic studies [ 8 1, whereconsiderablein~rmole~lar hydrogen bonding occurs. The calculated 2C=S and 4C=S bond lengths are shorter than the experimental valuesby 0.12 A. It is interestingto compare the geometryof the oxopyri~nes with the pyridinethiones.The replacementof 2C=O and 4C=O with 2C=S and 4C=S causes only small changes of bond length in the ring geometry: the bonds between atom 2C or 4C and neighbouringring atoms am shortened by about 0.02 A. The replacement of Z-oor 4C-Q- with 2C-S- or 4C-S- causes similar shorteningby about 0.01 A.

The relativestabilities (RS) of the oxo- and thio-pyridinesare summarized in Table 5. The collected RS seem to be less sensitiveto the geometrythan to the methodof calculation.Roth the MINDOf and the ab initio methods (STO3G, 3-216) favor 2-pyridone too strongly. MNDU and AM1 predict correct

3-21Gb

exp’

expd

116.6 120.9 119.9 119.7 121.4 121.4 120.1 125.3 122.3 118.6 120.5 116.4

1.412 1.465 1.359 1.429 1.372 1.374 1.000 1.246 1.098 1.101 1.097 1.105

111.5 122.1 121.3 118.1 128.3 118.8 113.7 129.3 120.3 118.3 120.7 108.7

1.398 1.464 1.371 1.437 1.374 1.366 1.032 1.218 1.104 1.107 1.109 1.112 114.9 121.5 120.5 120.1 120.0 124.4 119.4 128.0 121.2 118.6 120.6 114.9

1.429 1.475 1.366 1.444 1.372 1.390 1.003 1.229 1.090 1.091 1.089 1.094 112.7 122.3 122.2 116.0 121.8 125.1 126.0

125.8

1.236

1.401 1.444 1.334 1.421 1.371 1.335

113.5 122.1 120.9 117.9 120.9 124.6

1.390 1.449 1.339 1.437 1.340 1.368 0.999 1.220 1.066 1.075 1.068 1.072

126

115 121 121 118 120 124

1.373 1.405 1.347 1.392 1.352 1.387 0.92 1.262 0.90 0.93 1.04 1.04

1.342 1.424 1.400 1.411 1.402 1.335 1.321 1.103 1.108 1.103 1.115 0.951 122.8 116.3 121.0 117.3 123.2 119.7 116.9 120.6 119.6 121.4 115.6 116.6

1.359 1.419 1.392 1.399 1.403 1.345 1.375 1.097 1.100 1.098 1.105 0.971 123.9 117.6 119.0 119.0 123.1 117.0 116.1 123.9 120.7 120.1 115.4 109.4

MINDO/3’

AM1

MNDO

AM1

MIND0/3”

2-OH-pyridine (lc)

2-pyridone(la)

“Ref.27.bBef.34.“Ref.8b. dBef.8a.

l-2 2-3 3-4 4-5 5-6 6-l 1-H 2-o 3-H 4-H 5-H 6-H 0(2)-H l-2-3 2-3-4 3-4-5 4-5-6 5-6-l 6-l-2 2-l-H 3-2-O(2) 4-3-H 5-4-H 6-5-H l-6-H 2-0(2)-H

Parameter

Optimizedbond lengths (A) and bond angles (deg) of 2-oxo-pyridinesfrom differentcalculations

TABLE 1

119.9 120.3 120.3 120.8 116.4 114.1

1.349 1.089 1.097 1.090 1.094 0.950 123.6 117.0 119.4 120.1 121.2 118.7

1.358 1.428 1.397 1.408 1.406 1.357

MNDO

120.1

1.359 1.069 1.071 1.968 1.069 0.969 122.9 117.3 120.1 117.9 122.3 119.5

1.312 1.392 1.375 1.393 1.374 1.334

3-21Gb

119

123 118 120 117 126 116

0.86

1.330 0.95 1.07 0.93

1.338 1.377 1.376 1.382 1.337 1.336

expd

c

121.9 121.2 114.4 121.4 121.7 119.4 120.2 122.6 117.6 122.8 121.0 122.6

1.333 1.362 1.464 1.464 1.361 1.383 0.992 1.105 1.098 1.243 1.098 1.105

119.6 122.4 122.6 122.4 119.6 123.3 118.4 124.7 120.4 123.7 117.2 115.7

1.366 1.364 1.482 1.482 1.364 1.366 1.023 1.113 1.105 1.216 1.105 1.113 120.5 120.8 115.6 120.4 120.5 121.7 118.8 123.9 118.4 122.2 121.0 123.8 121.7 121.9 113.2 121.9 121.7 119.5

1.372 1.334 1.460 1.460 1.334 1.372 0.996 1.070 1.067 1.225 1.067 1.070

1.400 1.363 1.486 1.484 1.364 1.401 0.998 1.094 l&89 1.232 1.089 1.089 121.6 121,1 115.2 121.5 121.2 119.4 120.3 122.5 118.6 122.3 120.1 122.8

1.380 1.370 l&2 1.444 1.369 1.381 0.993 1.105 l*lOO 1.561 1.100 1.105

AM1

3-21Gb

MNDO

AM1

MIND0,‘3”

Pa

4-pyridone 13a)

1.334 1.405 1.420 1.422 1.403 1.337 1.115 1.105 1.322 1.103 1.115 0.951 123.1 117.6 119.5 116.6 124.1 119.0 1203 121.8 115.6 120.8 116.1 114.5

1.105 1.096 1.367 1.098 1.103 0.968 123.6 117.6 119.1 118.9 121.8 119.0 119.7 120.9 116.9 121.5 121.8 108‘0

MINL10/38

(3b)

1.341 1.408 1.399 1.414 1.402 1.353

AM1

4-OH-pace

bond Iengths (A> and bond angles (de& of 4-cmpyridines from ~~~~~~c~~i~~

“Ref. 27. bRef. 34.

l-2 2-3 3-4 4-5 5-6 6-J. 1-H 2-H 3-H 4-x 5-R 6-H X(4u-I l-2-3 2-3-4 3-4-5 4-5-6 5-6-l 6-l-2 2-l-H 3-2-H 4-3-H 5-4-x 6-5-H 5-6-H 4-X(4)-H

@thkd

TrnLE 2

120.8 122.X 117-8 119.8 121.4 113.1

1,089 1.354 1.089 1.094 0.948 123.3 118.1 118.4 119.1 122.2 118.9

1.095

1.351 1.409 I.419 1.421 1.409 1.366

MNDO

1.105 1.998 1.684 1.098 1.105 1.330 123.6 118.0 119.4 118.0 123.6 117.4

1.071 1.070 1.369 1.067 1.071 0.967 123.0 118.9 118.4 118.7 123.2 117.9

120.6 120.0 118.0 120.7 120.4 99.9

1.347 1.407 1.398 1.398 1.407 1.347

AM1

1.327 1.382 1.383 1.386 1.378 1.336

3-21Gb

41,

ii

“Ref. 8b.

z!I(C) l-2-3 2-3-4 3-4-5 4-5-6 5-6-l 6-l-2 6-1-H(C) 1-2-S(H) 2-3-H 5-4-H(X) 6-5-H 5-6-H 2-S-H 3-2-H 4-x-c

1-2 2-3 3-4 4-5 5-6 6-1 l-H/l-C 2-S/4-X 3-H 4-H/2-H 5-H

116.8 121.2 119.7 119.3 121.1 121.9 119.9 121.1 116.5 118.9 120.7 122.5

1.390 1.449 1.366 1.425 1.375 1.375 0.999 1.579 1.100 1.101 1.098 1.105

111.8 122.8 120.2 117.9 118.3 121.9 115.1 117.2 116.6 118.6 120.6 123.5

1.358 1.443 1.379 1.432 1.378 1.367 1.031 1.644 1.104 1.107 1.102 1.111

115.0 121.8 120.0 119.3 119.9 123.9 118.0 118.7 116.9 118.7 121.0 123.7

1.401 1.458 1.372 1.440 1.375 1.393 0.956 1.581 1.091 1.091 1.089 1.094

120.3 121.6 120.4 120.6 122.2 110.5

1.696 1.098 1.100 1.098 1.105 1.332 123.8 118.0 119.0 118.7 123.5 116.9 119.6 120.6 120.7 120.2 121.1 100.9

1.68

119

115 123 123 111 127 122

1.739 1.104 1.106 1.106 1.113 1.346 122.8 117.4 119.2 119.3 121.0 120.3

1.353 1.410 1.396 1.396 1.406 1.346

1.330 1.414 1.400 1.407 1.401 1.344

MINDO/S

1.39 1.44 1.29 1.52 1.37 1.33

exp”

AM1

MNDO

AM1

MIND0/3

2c

!&a

1.829 1.072 1.073 1.070 1.069 1.352 122.2 117.9 119.9 118.0 122.2 119.9 116.3 121.9 119.5 120.1 122.4 93.6

119.9 121.6 120.6 120.0 122.4 101.2

1.319 1.388 1.383 1.387 1.378 1.331

4-21G

1.668 1.088 1.091 l.OSO 1.093 1.307 121.9 117.3 119.5 119.7 121.3 120.3

1.332 1.458 1.402 1.401 1.409 1.358

MNDO

122.1 121.4 114.3 121.4 122.0 118.7 119.8 115.6 120.7 122.9 120.9 122.6 122.3

122.2

115.8 120.2 115.4 122.0 120.3 120.2 116.1

120.4 105.5

1.376 1.096 1.105 1.096 1.105 1.424 124.0 117.6 119.7 117.4 124.1 117.2

1.686 1.097 1.105 1.098 1.105 1.728 123.9 118.1 119.0 119.0 123.7 117.1 115.8 119.8 116.5 120.5 120.7

1.345 1.407 1.401 1.410 1.401 1.350

AM1

11

1.346 1.407 1.398 1.400 1.405 1.348

AM1

AM1 1.386 1.362 1.462 1.461 1.362 1.389 1.437 1.243 1.098 1.105 1.098 1.105

12

9

121.8 121.1 115.4 121.3 121.6 118.8 119.9 116.0 120.2 122.3 120.1 122.6

1.384 1.368 1.441 1.442 1.396 1.386 1.439 1.562 1.100 1.105 1.100 1.105

AM1

10 -~--

Optimized bond lengths (A) and bond angles (deg) for 2-thiopyridone derivatives for different calculations

TABLE 3

i;;

POI'I

860’1 101’1 001’1 Z89’T LPP’I 888’1 ELB’I GZP’T P96’T 09p’I 96E’l

Wl’I 860’1 1Ol’T 001’1 f.53Yl 9w1 98E’l ZLE’I 9Zp’I Z9E’1 19P’T P6&‘1

O’ZZT YLIT ZTZI 8’OZT O’OZI L-611 8’021 L-LIT

9’911

O’BZl P’OZI 9’881

901’1 L6OT TOT’1 660’1 LPZ’T OPP’I 8LE’l ZLE’I LZP’T 89&T WP’T 6lP’l

S’TZT P’OZl 6’811 8’911 L-811 O’TZT B’OZl Z’ZZl L-611 KG11 6’lZl 6’911

POl’l 860’1 101’1 080’1 8Pz’l lvvl a38&‘1 IL8’1 9Zp’I 991’1 E9P’I 8lP’l

L’ZZI 8’611 8’811 6’911 z’611 8’811 6’OZl O’lZl P’OZl 8’611 O’lZl 6’911

-0LLs

3E

P9

ZPE’I 888’1 EOE’T 061’1 96E’1 ZSE’T

WIV

39

L-811 LTZI 9’611 Z’611 L’LIT. Z’EZI EBL’I EOT’T 660’1 OOT’T 8607 OIL7

L’811 LIZI 8’611 L’811 2’811 6’ZZl 8ZL’l &Ol’l 660’1 660’1 9607 OTL’I

P’LU Z’VZT tiLlI 9’611 6’811 O’ZZl Z6L’l 980-l 080’1 pso’l 080’1 89L’1

P9

6’801 L’ZZl 9’OZl L’OZI 9’IZI Ij’911

8’PO1 B’ZZl 8’611 O’lZl O’TZT 8711

z’9OT

WOZT T’OZT L’611 8’lZI 9’801

3E -0LTdS

q9

SW-1 9Op’l 86E’l 968’7 ElP’l TSE’T

Z9E’l Z8E’l 06E’l 088’1 66E’l Z9B’l q9

Z’LII E’EZT 1’611 9’811 E’811 9’BZl 19L’1 POT’1 860’1 680’1 660-l 9BL.l

LXOT Z’TZT Z’OZl 6’OZl B’OZl 8’OZl

p’s11 B’PZI 7811 6’811 1’6TT G’ZZT 96L’T L80’1 180’T PSO’I ZSO’T OLL’T

0’66 P’OZl E’OZl VIZ1 9’611 G’LTT

1wv

89

LP&‘l sop’1 969’1 868’1 8lP’l 8PB’l

S’LTT 6’ZZl 8’811 1’611 0’811 9’EZl PELT POT’1 860’1 001’1 860’1 869’1

6’801 9’lZl 9’OZl 9’OZT 9’OZl 9’lZl

P9

8PE’l Pop’1 96E’l E6E’l LlP’l Z9E’l

0’911 l’PZ1 0’611 8’811 0’811 Z’PZl 9ZP’T 901’1 L60’1 001’1 L60’1 88ET

O’lZl I’OZl 6’OZl L’OZI 6x11

39

8P8’1 POP’1 961’1 E6ff-1 LTP’T 091’1

0’911 T’PZl 0’611 v-911 O’IZl 9’PZl SZP’T z;Ol’l L6OT 001’1 9Pl’l 888’1

l’OZ1 tioz1 9’liZT 6’611

O’TZl

99

6PI’l GOP’1 86E’l 06E’l PZp’l 89E’l

8’911 O’EZl 0’611 6’811 9’Lll l’PZ1 LZP’T PO17 860’1 001’1 L60’1 188’1

L’lZl 6’611 9’OZl 6’611 9’lZl

UVV

89

lPE’1 ZOvl LGE.1 68E’l PZp’l LBE’l

B’BZT p’611 1’611 P’Lll 6’PZl LZp’l POT’1 860’1 660’1 960’1 6LE’l

9’911

9’121 8’671 l’OZ1 p’611 S’ZZl H-9-9 H-9-9 H-P-9 H-B-Z x-z-1 3-l-9 z-1-9 l-9-9 9-9-P 9-P-C P-E-Z ‘E-z-l 3-X H-9 H-9 H-P H-E x-z 3-l l-9 9-9 9-P P-E 8-Z Z-l

3-x-z

187 TABLE 5 The relative stability (RS”, kcal mol-‘) Geometry optimization method

Energy calculation method

AMI

AM1

MINDO/B

MINDO/S

MNDO MNDO MNDO STO-3G STO-3G 3-21G 3-21G 3-21G Exp. (vapor phase)

MNDO A31 H31 STO-3G 3-21G 3-21G 6-21G 6-31G**

G[NH/XHl

of 2-, 2-thio-, 4-, and 4-thio-pyridone tautomersb

2-pyridone

0.4 -3.8’ -4.3d 9.7 -1.7 -0.5 15.4 -2.0 -1.7 -2.1 1.0 0.3 + 2.4 0.4-0.5

2-thiopyridone

I-pyridone

3.81

7.8

8.8

4.0

5.5

14.9

0.1

18.6 0.4 0.7 -0.1 3.6 6.9f 1.9 0.1

4-thiopyridone

Ref.

9.2

this 27

9.8

0.1 0.04

32 33 33 33 33 33 33 33 39 3 40

*RS=E(la~tam)-E(lactim)orRS=~~(lactam)-dH~(lactim).bTheminussignindicatesthat the lactam form is more stable. ‘Tautomer lc.dTautomer Id. TABLE 6 Calculated heat of formation (kcal mol-I), some bond lengths (A) from the AM1 method Parameter

2-OH-pyridine

2-pyridine

2-SH-pyridine

2-pyridinethione

Monomer AH, r(C-X/C=X) r(X-H/N-H)

-11.7 1.375 0.971

- 11.3 1.246 1.066

38.5 1.697 1.332

41.9 1.663 0.999

- 25.72 1.372 0.973 3.617 2.74

-33.16 1.255 1.663

75.08 1.695 1.334 4.171

69.38 1.604 1.036

Dimer AH, r(C-X/C-X) r(X-H/N-H) r(X-H. **N) cal. r(N-H-*-X)

z?’ exp.

3.048 2.77

3.033 3.328

signs but the former method overestimates the predominance of 2-OH-pyridine. The AM1 calculations predict that, in the self-associated dimers of 2pyridone and 2-thiopyridone, the lactam forms are more stable than the lactim

188 TABLE 7 Ionization potentials, eV

la lc Id 2a 2c 2d 3a 3b 4a 4b Sa 6b SC Sd 6a Bb 6C

6d 7a 7c 8a 8C

9 10 11 12

AM1

MIND0/3

MNDO

8.96 9.44 9.51 8.63 9.38 9.44 8.94 9.93 8.42 9.77 9.25 9.28 9.39 9.50 9.12 9.14 9.23 9.33 8.83 8.81 8.54 8.53 8.78 8.31 9.78 9.50

8.55 8.55 8.55 8.03 8.42 8.45 8.52 8.57 7.75 8.40 8.47 8.49 8.52 8.50 8.39 8.36 8.37 8.39 8.48 8.46 7.98 8.00 8.45 7.13 8.52 8.35

8.91 9.24 9.30 8.75 9.33 9.37 8.90 9.75 8.54 9.78 9.13 9.16 9.24 9.31 9.19 9.21 9.26 9.34 8.87 8.85 8.70 8.69 8.85 8.50 9.67 9.65

Exp’”

9.2sb

8.92b

9.8gb 9.50b 8.82”,8.9Sb

8.24”,8.47b

8.41”, 8.58b 7.69”, 7.84b 8.20”, 8.4gb 7.6”, 7.54b 9.25” 8.73b

“From ref. 13a. bFrom ref. 14. “For 4-ethoxypyridine.

forms, which agrees well with the experimental data (Table 6). The RS for the 0x0 derivative is 7.44 kcal mol-’ and is comparable with 6.8 kcal mol-’ derived from the ab initio (3-21G) calculation [ 351. The observed changes of some bond lengths on going from the monomer to dimer are comparable with changes caused by a hydrogen bond. AM1 can thus be used successfully in RS predictions. Ionization potentials and dipole moments

The calculated ionization potentials obtained by the AM1 method are close to those found by the MNDO method (Table 7). In all cases ionization potentials calculated by the AM1 and the MNDO methods are overestimated (0.41.0 eV) in comparison with the experimental values. Satisfactory agreement between MIND0/3 and experimental data is observed; an exception is 4methoxypyridine.

189 TABLE 8 Dipole momenta AM1

la 10 2a 2c

3a 3b 4a 4b Sa Sb SC

Sd 6a 6b 6%

Bd 7a 7c

8a 8C

9

10 11 12

MIND0/3

3.21 1.37 5.77 1.80

4.12 0.64 7.64 2.39

6.29 1.98 7.91

6.89

1.65

0.80 0.80 3.15 3.08 1.33 1.30 3.39 3.32 3.73 3.77 5.64 5.66 6.65 8.40

2.54 2.19

2.03 10.53 2.37

0.79 0.76 2.03 2.01 2.02 1.94 3.77 3.68 3.95 4.01 7.59 7.51 6.60 10.39

1.57 2.23

MNDO 3.55 1.23 5.65 1.85 5.67 2.12 7.62 1.55 0.85 0.88 2.88 2.86 1.41 1.36 1.97 3.15 3.34 3.43 5.48 5.52 5.84 7.87

2.49 2.13

Ed

1.95

5.3

1.15

4.15

6.9

3.0

“From ref. lla.

The AM1 dipole moments are close to those from the MNDO calculation (Table 8). The experimental dipole moment for 2-hydroxypyridine is between that calculated (AMl) for 2-hydroxypyridine and 2-pyridone. For a mixture with K ,=0.5 the calculated dipole moment is N 2 D. The calculated dipole moments for methyl derivatives are lower ( N 0.4 D) than the experimental ones. The largest differences between calculated and experimental dipole moment is observed for C-pyridone, but the solubility of 4-pyridone in benzene is low and the experimental value may not be very accurate. Heats of formation and proton affinity The absolute values of heat of formation and proton affinity calculated with the AM1 method for the most stable tautomers are listed in Table 9. In most cases the calculated heats of formation are higher than the experimental data.

190 TABLEI 9 Heats of formation (kcal mol- ’ ) and proton affinity B

HB+

CaIc.&IF B

HB+ 141.2 141.2 194.2 199.2 137.4 137.4 192.1 192.1 144.2 187.3

2c

lo lc 2c 2e

3a

3b

3b 4a 4b 6b

3b 4b 4b Sd

-11.3 -11.7 41.9 38.5 -4.6 - 12.3 49.0 39.8 -5.6

6b

6d

34.3

7b

7b

8b 9 10

8b 9 10

46.8 0.5 53.9

11 12

11 12

-6.5 35.9

la lc

2a

wt.

-5.4

144.3

B

PA$

MF

HB+

talc.

131

214.7 214.3 214.9 211.1 225.3 217.5 224.1 214.9 217.4

177

214.2

125

217.5

-12 33 -20

197.6 139.6 194.3

140.7 185.7

“Ref.40.bRef.41.“Ref.42.dPA=367.2+&(B)

218.4 228.1 226.8

-3 37

135 177

220 217.4

expt.

217”

220.3” 217.9b 221.9” 217.4” 222.0’ 215.8b 220.2c 223.4” 228.5 - 230.4” 227.6” 223.4” 225.5”

-d&(B+H).

However,the differencesbetween calcuiated and experimentalPA are within experimentalerror. CONCLUSIONS

AM1 predictsrelativestabilities,PA, dipole moments and geometriesof oxoand thio-pyridines which are in fair agreementwith those found experimentally. Bond lengths and ionization potentials are, however, systematically overestimatedby AM1 in these compounds. MIND0/3 predicts ionizationpotentials close to the experimentaldata. Geometriesderivedby AM1 may serve as startingpoints for more comprehensiveoptimizations. ACKNOWLEDGEMENT

Tbis work was partly supportedby the Polish Academy of Sciences ( CPBP 01.12.8.5).

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