Monosubstituted benzenes conformations

After a paper devoted to GIAO/B3LYP calculations of 13 monosubstituted benzenes and 21 1-substituted pyrazoles [148] that allowed discussion of some structural problems (such as conformation, tautomerism, and structure of salts) we have continued to use this combination of experimental (in solution and in the solid state, CPMAS NMR) and calculated values as a very useful exploratory technique. For instance, we have used II, 13C, and 15NNMR spectroscopy to study compounds 149-154. In para-disubstituted derivatives 149,151,152,153, in the solid state (no free rotation) the signals of the ortho carbons are split (one is close to N2) and, thanks to the calculated values, they can be assigned [149],... 

Norskov-Lauritsen, L., and Biirgi H.-B. Cluster analysis of periodic distributions application to conformational analysis. J. Comput. Chem. 6,216-228 (1985). Domenicano, A., Murray-Rust, P., and Vaciago, A. Molecular geometry of substituted benzene derivatives. IV. Analysis of variance in monosubstituted benzene rings. Acta Cryst. B39, 457-468 (1983). 

A key paper on monosubstituted benzenes, which represents the basis of the more recent work reported here, is that by Hehre, Radom, and Pople (6). It contains a detailed analysis at the STO-3G level of substituent ring interactions in monosubstituted benzenes, and encompasses charge distributions, stabilities, and conformations of 35 substrates. Relevant results are more fully detailed in Section IV. 

A detailed account, at the STO-3G level, of conformations, charge distributions and stabilities of 35 monosubstituted benzenes, including 10 of our representative set, has been presented by Hehre et al. (6). Corresponding results for the remaining members (Li, 0", NH, and NHa ) have been obtained more recently (67,10,11). We reproduce here some of the key results for all of the substituents which will be relevant to our subsequent discussion of di- and polysubstituted benzenes. Calculated total energies and dipole moments are listed in Table 1, and Mulliken charges and overlap populations are listed in Table 2. Where more than one conformation is possible, unless otherwise specified, the energy data listed are for the most stable conformation. 

Figure 6 HOMO coefficients for monosubstituted benzenes. Data for toluene and anilinium ion are for the conformation in which a C—H or N—H bond is orthogonal to the ring. Data for aniline refer to planar N. Data for orthogonal and planar nitrobenzene refer to the level below the HOMO. The HOMOs in both cases are mainly localized on the two oxygen atoms.

The HOMO and LUMO orbitals of a monosubstituted benzene where the substituent, X (= NH2, OH or F), is a neutral rr-donor, may be obtained through interaction of the benzene HOMO and LUMO orbitals with the substituent lone pair according to the principles discussed in Section III.B. Being an occupied orbital, the lone pair orbital will be closer in energy to the occupied benzene orbitals than the unoccupied ones (Fig. 8). As a result, it will interact mainly with the occupied orbital of appropriate symmetry, to give two new orbitals. The antibonding o)mbination of this interaction now becomes the HOMO and may be seen to conform to the quantitative data in Fig. 6. The LUMOs for aniline, phenol, and fluorobenzene are the essentially unaffected benzene LUMO, in agreement with the quantitative data (Fig. 7). 

Hehre WJ, Radom L, Pople JA (1972) Molecular orbital theory of the electronic structure of organic compounds. Xn. conformations, stabilities, and charge distributions in monosubstituted benzenes. J Am Chem Soc 94(5) 1496-1504. doi 10.1021 a00760a011... 

Conformational constraints induced by various ortho-substitutents in 1-aUyloxy-2-azidomethylbenzenes (97) were used to accelerate intramolecular cycloadditions of the azide group to alkenes (21) (Scheme 9.21). For the unsubstituted azide 96, high temperature was required for the cycloaddition and the yield of the cycloadduct 100 was low. The monosubstituted azide 97 underwent cycloaddition in refluxing benzene in 10 h to give the cycloadduct 101 in good yield. Disubstituted azides 98 and 99 underwent 1,3-dipolar cycloaddition in 5-7 h to give the triazolines 102 and 103. 

This question could be answered more easily if we knew that the C6C3 units conformed with the principle of additivity. This principle can be formulated as follows. If the introduction of each of two substituents alters the free energy of activation at a particular position by amounts x and y, the presence of both substituents would alter the free energy of activation by an amount (x + y). If this relationship holds, it allows one to predict the reactivities of the individual positions in disubstituted benzene derivatives from the rate data obtained for the corresponding monosubstituted ones. The partial rate factor for a given position of a... 

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