Journal of Molecular Structum (Theoche.n), 121(1985) 173-183 Eisevier Science Publishers B.V., Amsterdam - Printed in The Netherlands

AB INITIO CALCULATIONS ON 4B-PYRANd-ONE AND ITS SULPHUR ANALOGUES

COLIN THOMSON and COLIN EDGE

Regional Workshop of the National Foundation for Cancer Research, Department of Chemistry, University of St. Andnzws, St. Andrews. Fife (Great Britain)

(Received 2 July 1984)

ABSTRACT

Ab initio calculations on 4H-pyran-4-one and its three sulphur analogues are described. The geometries were fully optimised at the Hartree-Fock level, using a 3-2ig basis set. The electrostatic potentials were calculated in four planes around the molecule.

The e9;entiaIly non-aromatic nature of these molecules is demonstrated by considering the resultant geometries, wave functions and electrostatic potential maps.

INTBODUCTION

4H-Pyran-4one and its sulphur analogues (Fig. 1) have received consider- able attention recently as the parent molecules of many new compounds of biological interest (e.g., [1, 21) and as participants in new syntheses (e.g., 13,41).

4H-pyran-4one was first suggested to be of aromatic character in the 1920s by Arndt et al., 153 who suggested that its unusual properties could be explained in terms of mesomerism involving interaction between the two oxygen atoms and the carbon double bonds in the molecule. Since then there has been much controversy over the degree of aromaticity displayed by these compounds, but nuclear magnetic resonance (NMR) and microwave studies have made it obvious that they are essentially non-aromatic [S-11]. On the other hand, they do not behave as simple ketones or even lactone vinylogues. For instance, nitration in 4.?I-pyran-4-one gives the 3-nitro- derivative: this appears to be an aromatic electrophilic substitution, but the mechanism is uncertain and the yield of the reaction is only 1%. In contrast, the double bonds between C2 and C4 are not easy to reduce and bromination occurs by substitution rather than addition, which seems to point to aromatic properties of the ring. Also, the carbonyl group is remarkably unreactive and does not show typical carbonyl reactions [ 121. The high dipole moments measured 111, 131 also suggest contributions from zwitterionic canonical forms promoting aromatic ring stability (Fig. 2). This is over-emphasized as evidence for aromatic structure: the theoretical dipole moment of structure (c) is 22 debye, whereas that of (a) is 2.8 debye; thus very little contribution from ionic forms is needed to account for the experiment value of 4 debye.

0166-1280/85/$03.30 0 1985 Elsevier Science Publishers B-V.

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- x7

HI0

Fig. 1. 4Hpyran-4-one and its sulphur analogues: (X6 = 0, X7 = 0) 4H-pyran-4-one; (X6 = 0, X7 = S) 4H-ppran-4-thione; (X6 = S, X7 = 0) 4H-thiapyran-4-one; (X6 = S, X7 = S) 4H-thiapyran-4-thione.

a b C d e

Fig. 2. Canonical forms of the pyrones.

There have been no previous ab initio molecular orbital calculations on these compounds, despite their intriguing properties. This paper presents ab initio calculations using a 3-21G basis set to predict the molecular geom- etries of these four molecules, and an analysis of the resultant wave functions.

METHOD OF CALCTJLATION

Optimised geometries were calculated using a 3-21G basis set 1141 with the GAUSSIAN 80 package of ab initio molecular orbital programs 115 J on a VAX 11/780 computer at St. Andrews University. The GAUSSIAN 80 pro- gram package has been modified [IS] to enable electrostatic potentials [ 171 to be calculated across various planes through the molecules using the opti- mised wave function. These were: (1) in the plane of the molecule; (2) 1.6 A above the plane of the molecule; (3) perpendicular to this plane through the principal axis and (4) perpendicular to the plane of the molecule through the C2-C4 pi bond. Theseresults were converted into pictorial contour diagrams by the SURFACE II facility [lS] on the same computer.

RESULTS

Molecular geometries

The geometries obtained using the 3-21G basis set are very close to the experimental results (Table 1). The bond lengths are all within 0.05 A (error

175

TABLE 1

Geometry results

Bond MO Experimentala

4H-pymn-4-one Cl-C2 c2-C4 C6--06 Cl--o7 C2-H8 C4-HlO

4H-p ymndihione Cl-C2 C2--c4 C4-06 Cl-67 C2-H8 C4-HlO

4H-thiapymwkwze Cl-C2 C2-C4 C4-S6 Cl-07 C2-H8 C4-HlO

4H-fhiapymn-4~fhione Cl-C2 C2-C4 C4-S6 Cl-s7 C2-H8 C4-HlO

1.4689 l-4627* 0.0010 1.3209 1.3438* 0.0010 1.3733 1.35832 0.0009 1.2194 l-2261* 0.0010 1.0651 1.0791* 0.0009 1.0703 1.0818 f 0.0010

1.442 1.431* 0.004 1.330 1.357 f 0.002 1.364 1.363 + 0.003 1.694 1.665 * 0.002 1.068 1.082 * 0.002 1.066 1.082= 0.002

1.471 1.318 1.797 1.219 1.072 1.070

1.445 1.327 1.785 1.692 1.071 1.070

-b

- - -

1.406~ 0.004 1.342 * 0.004 1.759* 0.004 1.6712 0.002 - -

*Ref. [ll]. bNoexperimentalvaluesavailable.

< 5%) of the most precise experimental values [11] and the great majority are within 0.02 A (error < 2%).

The bonds of most interest are the C2-C4 and Cl-X7 bonds; i.e., to determine whether or not they are “double bonds”. As can be seen from Table 3, the C2-C4 bond is shorter than a normal single bond; in fact, the C2-C4 distances for the molecules are all slightly shorter than the ethylene double bond (1.339 II) [19]. The Cl-C2 bonds are much longer than the C2-C4, implying a non-delocalised, diene structure for the ring.

The Cl-X7 bond lengths are also shorter. The C=O bonds in pyran-kne and thiapyran-4-one are very close to the experimental value of the same bond in acrolein (1.219 A) 1201. The C-S distances for pyran-4-thione and thiapyran-4~thione are 1.694 and 1.692 A. respectively.

176

The C4-06 distances in pyran-4-one and pyran-4-thione are 1.37 and 1.36 A respectively, and are comparable to the same bond in furan (1.362 A) 1211. The C-S bond length for thiophene is 1.714 A [ZZ] which compares favourably with the corresponding lengths of 1.80 and 1.79 A for thiapyran- 4-one and thiapyran-4-thione.

Generally, it is considered more reliable to match the trends evident for a series of MO calculations with those of experiment rather than give direct comparisons. It is interesting to study these trends on the replacement of oxygen by sulphur in these molecules.

On the introduction of sulphur atom, the ring shape is obviously modified by its greater bulk compared to the oxygen atom. The internal carbon atom angles all become shallower as the ring widens to accommodate the larger atom. The sulphur atom is located further away from the ring centre than the oxygen atom on the corresponding pyran derivative. If the e3tu orrygen is replaced by sulphur, the Cl<2 bond length decreases by about 0.02 A and the C2-Cl-C3 angles flatten, bringing the carbon of the thionyl group closer to the ring centre. The rest of the molecular structure remains fairly constant, except for the obvious difference in length between the carbonyl and tbionyl bonds. The C2-C4 distances increase by about 0.01 A, as do the C4-X6 lengths, but the overall shape of the half of the ring opposite the thionyl group is very similar to the corresponding carbonyl derivative. These changes are paralleled reasonably closely in the available structural findings [ 111. (The structural data on thiapyran-4-one are not as comprehensive as that for the other analogues.)

The dipole moments are not as constant as the Stark-effect measured values [11] but do show the same numerical ordering; they are 2.90, 3.64, 4.46 and 5.36 debye for thiapyran-4-one, pyran-4-one, thiapyran6thione and pyran-4-thione, respectively. Dipole moment calculations are quite dependent on the choice of basis set and this goes some way to explaining why the results have such a large spread compared with experiment.

Wave function analysis

The eigenvalue coefficients for the highest bound state (HOMO) show a definite pattern of carbonyl group and double bond, as opposed to an aromatic structure (Table 2). The coefficients for C2, C3, C4 and C5 are of opposite sign to the rest of the atoms, implying double bonds between C2 and C4 and between C3 and C5. The HOMO contains contributions from just the px orbitals of the atoms (these are the atomic orbitals perpendicular to the plane of the molecule). The largest contributions are those due to C2, C3, X6 and X7. The “sausage and baboon” picture of the HOMO can be drawn thus (Fig. 3).

The numbers extracted from the MuIliken population analysis 1141 are shown in Table 3. These show au interesting difference between the pyrans and the thiapyrans: the pyrans have alternate charges on the ring atoms C2

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TABLE2

HOMO eigenvaluecoefficients

4H-pymn-4-one Cl 2P (1)

2P (0) c2 2P (1)

2P (0) c4 2P CI)

2P (0) 06 2P (1)

2P (0) 07 2P (I)

2P (0)

4H-tkiapymn-4-one Cl 2P (1)

2P (0) c2 2P (1)

2P (0) C4 2P (1)

2P (0) S6 2P

3PII) 3P(O)

07 2P(I) 2P(O)

0.02818 0.11412

-0.20754 -0.30030 -0.13657 -0.12416 0.23568 0.31776 0.26544 0.32745

4.00904 -0.07025 0.18596 0.26159 0.11023 0.12744 0.18308

-0.39631 -0.42282 +A20692 -0.26078

4H-pyran-4-tkione Cl 2P (1)

2P (0) c2 2P (1)

2P (0) c4 2P (1)

2P (0) 06 2P (1)

2P (0) s7 2P

3P (1) 3P (0)

4H-tkiapyrandtkione Cl 2p II)

2P (0) c2 2P (1)

2P (0) c4 2P (1)

2P (0) S6 2P

3P (1) 3P (0)

57 2P 3P (I) 3P (0)

0.08421 0.17594

-0.13709 -0.21524 -0.11405 -0.11788 0.16038 0.22602

-0.20149 0.41484 0.44719

0.06541 0.14396

-0.14021 -0.20844 -0.11297 -0.14065 -0.12813 0.27866 0.31178

4.18276 0.37620 0.40960

Fig. 3. RepresentationofHOMO ofthepyrones.

and C4 whereas the C2 and C4 carbons of total atomic charges.

Electrosiatic potential results

the thiapyrans both have negative

The electrostatic potential 1171 at a given point is the electrostatic inter- actions energy between the molecule and a point charge at that point. It is an observable physical parameter which is useful in predicting reaction

178

TABLE3

MuUikenpopulationanalysis:totaietomicchsrges

4H-pyrandone Cl 0.561573 c2 -0.415744 c4 0.221118 06 -0.704308 07 -0.615425 H8 0.280113 HlO 0.293593

4H-thiapyran-4-one Cl 0.486918 c2 -0.239502 c4 -0.589393 S6 0.611260 07 -0.600846 HS 0.286547 H10 0.293684

4H-pyrandthione Cl -0.366421 c2 -0.330011 c4 0.235080 06 -0.696451 s7 0.055106 H8 0.296698 HlO 0.302116

4H-thiapymrd-thione Cl -0.467245 c2 -0.142917 c4 -0.598976 S6 0.661248 57 0.089539

0.296698 0.300637

characteristics. This approach has its faults, however (for instance, the inter- action calculated is for an inflexible molecular geometry which cannot react to the point charge) but it produces a simple pictorial viewpoint which is valuable in the over-numerate discipline of high-level molecular orbital caI- eulation.

The contour maps of the electrostatic potentials were calculated in four different planes through the molecule (Figs. 4-7). The in plane maps show an extensive negative region around the carbonyl oxygen or thionyl sulphur and a much smaller negative region near the endo heteroatom (Fig. 4). The negative potential area around the carbonyl or thionyl group extends over that half of the ring with spurs of more concentrated negative potential above the CZ-C4 bonds. The pyrones do not have complete rings of negative potential above and below the ring-atoms as benzene does; in fact, the maps 1.6 A above the molecular plane (Fig. 5) show distinct positive areas above the C4-X6 bond of 0.010 to 0.020. Thus the attack by electrophiles at C2 and C3 (and X7) and the attack by nucleophiles at C4 and C5 is in keeping with the electrostatic potential diagrams obtained. This is shown by the potential contour maps along the C2-C3 bond of the molecules, perpendi- cular to the molecular plane; two examples of which are given in Fig. 6. These show that C2 is surrounded by a negative sheath on three sides (in this plane), whereas C4 is only “half-covered” and so is susceptible to nucleophilic attack.

The electrostatic potential maps perpendicular to the molecular plane, intersecting the principal axis (Fig. 7) show some differences between the molecules. &I-pyran-4-one and the two thione compounds have a similar pattern of negative and positive regions, modified only by the lone-pair structures of the sulphur or oxygen atoms: that is, a large negative area

Fig. 4. Electrostatic potential maps in the plane of the pyrones.

“capping” the thionyl/carbonyl end of the molecule and one or two distinct smaller regions of negative potential for the oxygen/sulphur lone pairs of the endo heteroatom. However, 4H-thiapyran A-one is completely encircled by negative charge in this plane, albeit a very small negative potential around the middle of the molecule. This is due to the combined effect of the large negative potential arising from the carbonyl oxygen and the proximity of the sulphur lone pairs to this, whereas, in the case of 4H-pyran4-one itself, the e&o-oxygen lone pairs are too far away to interact.

Fig. 5. Electrostatic potential maps 1.6 A above the plane of the pyrones.

CONCLUSIONS

As mentioned before, the microwave spectra point towards a non-aromatic diene structure (or la&one vinylogue) for these compounds. The molecular orbital calculations support this because first, the optimised geometry data confirm that there is a noticeable difference in bond length between the “single” bond Cl-C2 and the “double” bond C2=C4. Tt is also evident that the carbonyl/thionyl bond length Cl-X7 is short. Second, the eigenvalue coefficients show the presence of carbon-carbon double bonds also; the 2px orbit& of C2, C3, C4 and C5 are in the opposite direction to the other orbit&, forming a pi-bond instead of a delocalised structure. Third, the electrostatic potential maps do not show rings of negative potential above

181

Fig. 6. Electrostatic potential maps along the n-bond of 4H-pyran-4-thione and 4H- thiapyran-4-one.

and below the molecules as they do for aromatic molecules, but instead have broken rings. The attack of electrophiles and nucleophiles at different carbon atoms is well illustr&ed by maps along the pi-bonds.

Thus, these calculations support the contemporary view of these molecules as being essentially non-aromatic and give a good insight into the electronic properties of them.

Fig. 7. Electrostatic potential maps along the axis of the pyrones.

ACKNOWLEDGEMENTS

We are indebted to the National Foundation for Cancer Research for financial support, and to Professor J. A. Pople for a copy of GAUSSIAN 80. We also wish to thank Mr. C. A. Reynolds and Dr. J. R. Ball for their assist- ance with the development of the electrostatic potential plotting programs, and Dr. J. Tomasi for a copy of his electrostatic potential program.

183

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