Some ab Initio Calculations on Indole, Isoindole, Benzofuran, and Isobenzofuran J. Koller and A. Ažman Chemical Institute “Boris Kidric” and Department of Chemistry, University of Ljubljana, P.O.B. 537, 61001 Ljubljana, Slovenia, Yugoslavia N. Trinajstić Institute “Rugjer Boskovic”, Zagreb, Croatia, Yugoslavia (Z. Naturforsch. 29 a. 624 — 632 [1974] ; received January 9, 1974) Ab initio calculations in the framework of the methodology of Pople et al. have been performed on indole, isoindole, benzofuran. and isobenzofuran. Several molecular properties (dipole moments, n. m. r. chemical shifts, stabilities, and reactivities) correlate well with calculated indices (charge densities, HOMO-LUMO separation). The calculations failed to give magnitudes of first ionization potentials, although the correct trends are reproduced, i. e. giving higher values to more stable iso­ mers. Some of the obtained results (charge densities, dipole moments) parallel CNDO/2 values. Introduction as positional isomers 4 because they formally differ Indole (1), benzofuran (3) and their isoconju­ only in the position of a heteroatom. Their atomic gated isomers: isoindole (2) and isobenzofuran (4) skeletal structures and a numbering of atoms are are interesting heteroaromatic molecules1-3 denoted given in Figure 1. 13 1 HtKr^nL J J L / t hü H 15 U (3) U) Fig. 1. Atomic skeletal structures and numbering of atoms for indole (1), isoindole (2), benzofuran (3), and isobenzofuran (4). Reprint requests to Prof. Dr. N. Trinajstic, Rudjer Boskovic Institute, P.O.B. 1016, 41001 Zagreb I Croatia, Yugoslavia. Dieses Werk wurde im Jahr 2013 vom Verlag Zeitschrift für Naturforschung This work has been digitalized and published in 2013 by Verlag Zeitschrift in Zusammenarbeit mit der Max-Planck-Gesellschaft zur Förderung der für Naturforschung in cooperation with the Max Planck Society for the Wissenschaften e.V. digitalisiert und unter folgender Lizenz veröffentlicht: Advancement of Science under a Creative Commons Attribution Creative Commons Namensnennung 4.0 Lizenz. 4.0 International License. J. Koller, A. Azman, and N. Trinajstic • Some Initio Calculations 625 The difference in the position of a heteroatom Computational Details reflects rather strongly the differences in physical Indole, isoindole, benzofuran, and isobenzofuran and chemical properties of positional isomers4-6. have been studied by an ab initio (Hartree-Fock - Theoretical studies 7 using the Dewar’s variant 8 of Roothaan) LCAO-SCF-MO procedure37. The main the Pople’s SCF MO9 (variable ß) 10 procedure problem in ab initio calculations are, of course, the predicted the geometries of 1, 2, 3, and 4, respec­ difficulties in the evaluation of the multicenter elec­ tively. These results can be summarized as follows: tron repulsion integrals over the Slater-type orbitals the benzene ring in indole and benzofuran is un­ (STO). Several research workers 38-42 have shown affected by the attachment of the N- or O-polyenoid that the difficulties of integral evaluation can be moiety whereas isoindole and isobenzofuran have overcome by simulating each STO (<£„) as a linear a quinonoid structure, because in these molecules combination of K 1 s and 2 p Gaussian-type orbitals the six-membered ring has lost the benzene-like (GTO) gltk: geometry becoming a cyclopolyenoid C6 moiety. K These quinonoid-like structures are very reactive in = Z cMk guk. the case of (4 m + 2) -rings u . Thus, while 1 and 3 A = 1 were first prepared a century ago 12-14 and possess Hehre, Stewart, and Pople41 have optimized the a considerable aromatic stabilization [the DRE and GTO exponents (and have found that these do not REPE values 15 being (1) 23.8 kcal/mole, (3) 20.3 depend on the size of the basis set) and have de­ kcal/mole, (1) 0.047/?, and 0.036 ß, respective­ termined the expansion coefficients cßk by a least- ly] 7’ 165 2 and 4 are of more recent date 6i 17“ 22 and squares fit of the STO’s using expansions where K possess a lower aromatic stabilization [the DRE ranges from 2 to 6 (termed STO-K G expansions). and REPE values being (2) 11.6 kcal/mole, (4) Pople and co-workers41,42 have found in their 2.4 kcal/mole, (2) 0.029 ß, and (4) 0.002 ß, re­ studies that the three-gaussian representation spectively] 7’16. (STO-3G) set is very economical to use (gives re­ sults — atomic population, dipole moments, bar­ Indole and benzofuran also appear as the funda­ riers to rotation around the single bond — close to mental constituent parts of many biologically active the STO limit) and as a minimal (Is, 2 s, 2 p) molecules3,23,24, e.g.: indole-3-acetic acid (the natu­ basis can be applied to larger molecules. Therefore, ral plant growth hormone), tryptamine (the hallu­ following their experience the STO-3G basis func­ cinogenic agent), lysergic acid diethylamine (the tions have been also used in the present work. most potent hallucinogen), serotonin (the effect on The LCAO coefficients are obtained solving the the blood vessels), indomethacin (the potent anti­ Hartree-Fock-Roothaan equations. The Mulliken inflammatory agent), medmain (the potent serotonin gross population 43 of the atomic orbital 0 U is cal­ antagonist), 5-methoxy-6,7-dimethyl benzofuran (the culated from the expression: aroma-constituent of greek tabacco), 2-methyl benzo­ furan (the aroma constituent of coffee), etc. Indole g U = P f i l l“t” Z P ß V ^ f I V and benzofuran have been found in cigarette smoke20 V ( + , « ) and tested on chemical carcinogenecity26,27 showing where PßV is a first-order density matrix (P^v = occ. no carcinogenic activity. On the other hand, the 2 2 c^i c„j). The electric dipole moments are evalu- corresponding isoconjugated isomers have never i been detected to our knowledge as parts of bio­ ated from the formula: logical molecules. fx (D) = 2.5416 { 2 ZArA - S P.r r j A In the past, the theoretical studies7’16, 28-36 on where 1, 2, 3, and 4 in their ground and excited states iV = /<Z>^r <Z>„dF. have been performed in the framework of the ap­ The geometries of studied molecules are needed proximate molecular orbital methods. We have de­ for the input data. Unfortunately, the experimental cided to study these molecules using an ab initio geometries of indole, isoindole, benzofuran, and iso­ LCAO-SCF-MO approach and to compare our re­ benzofuran are not known as yet. The experimental sults with some previously obtained by semi-empiri­ bond lengths in the 3-methylindole-trinitrobenzene cal methods. complex 44 and the crystal structure of indole 45 are, 626 J. Koller, A. Azman, and N. Trinajstic • Some Initio Calculations so far, determined only. Since these data 44, 45 ai*e However, the correct trends are »obtained when not very helpful for our purpose we have used the the total energies of indole and benzofuran are com­ standard bond lengths as suggested by Pople and pared with those of their isoconjugated isomers: Gordon46 to construct the geometrical models of isoindole and isobenzofuran, the former being large. 1, 2, 3, and 4, respectively. Thus, the ab initio calculations prefer indole and All calculations are carried out on a CDC 6400 benzofuran over isoindole and isobenzofuran, and computer of the University of Ljubljana. Table 2. Dipole moments (D). Results and Discussion Indole Average exp. value a 2.08 Total energies and the electronic populations of CNDO/2 value48 1.86 indole, isoindole, benzofuran, and isobenzofuran VESCF value 49 1.76 Ab initio value 1.77 are given in Table 1 and Fig. 2, respectively. Isoindole Ab initio value 2.20 Benzofuran Experimental value b 0.79 Molecule Etot (a. u.) VESCF value 49 0.52 Ab initio value 0.64 Isobenzofuran Ab initio value 0.38 Indole — 357.028678 Isoindole -357.001836 Benzofuran -376.544474 a This value is a average of values taken from the following Isobenzofuran -376.519020 Table 1. works: E. G. Cowley and J. R. Partington, J. Chem. Soc. Total energies. 1936, 47; E. G. Cowley, J. Chem. Soc. 1936, 45; E. F. J. We shall not comment on the values of the total Janetzky and M. C. Lebret, Rec. Trav. Chim. 63, 123 [1944]. energies because the ab initio method is not very b E. A. Schott-L’vova and Y. K. Syrkin, J. Phys. Chem. USSR reliable in this respect 4‘. 12.479 [1938]. + 56 1) ( 2 ) + 62 H ♦ 67 -220 62 (3) ( 4 ) Fig. 2. Electron population for indole (1), isoindole (2), benzofuran (3), and isobenzofuran (4) (10 3 electron). J. Koller, A. Azman, and N. Trinajstic • Some Initio Calculations 627 this is in agreement with earlier theoretical predic­ and the VESCF value49 for benzofuran are also tions 7’16 and experimental findings6. Electronic included in Table 2. The agreement between the ex­ densities have been used for the calculation of perimental and theoretical values is satisfactory. dipole moments. The calculated and available ex­ The gross orbital charges in indole, isoindole, perimental dipole moments are given in Table 2. benzofuran, and isobenzofuran are summarized in The CNDO/2 and VESCF values 48,49 for indole Table 3. These results are interesting and worth Table 3. Gross orbital charges. (1) Indole N 1 s = 1.9947 2 p 0 = 2.1845 2 p = 3.9010 II II II - 0 .6 1 1 5 s1.43 p2.18 2 s = 1.4323 2 p 71 = 1.7165 0.2835 2 px = 1.0915 - 0 .3 2 8 0 2 py = 1.7165 2 p * = 1.0930 C, 1 s = 1.9929 2 p 0 = 1.8222 2 p = 2 .8 5 6 4 (5(0) = 0.0739 gl.ll pi.82 2 s = 1.1110 2 p;t = 1.0342 8 (ji) = -0 .0 3 4 2 2 Px = 0.9540 8= 0.0397 2 p2/ = 1.0342 2 p2 = 0.8682 C3 l s = 1.9927 2 p ö= 1.8903 2 p = 2.9876 8(o) = - 0 .0 0 6 9 s1.12 p i.89 2 s = 1.1239 2 p w = 1.0973 8 (tt) = - 0 .0 9 7 3 2 Px = 0.9271 8=