Conformational energy differences

Sources, which compare the accuracy of various levels of theory for describing conformational energy differences, are... 

For 1,3-dithiolanes the ring is flexible and only small energy differences are observed between the diastereoisomeric 2,4-dialkyl derivatives. The 1,3-oxathiolane ring is less mobile and pseudoaxial 2- or 5-alkyl groups possess conformational energy differences (cf. 113 114) see also the discussion of conformational behavior in Section 4.01.4.3. 

Calculations on larger molecules have been carried out using molecular mechanics techniques and the Merck force field.- This method has proven to be suitable for the calculation of equilibrium geometries and conformational energy differences. 

Topol, I. A., and S. K. Burt. 1993. The calculations of small molecular conformation energy differences by density functional method. Chem. Phys. Lett 204,611. 

The actual Fock-matrix elements between orthogonalized ctch and ctc H orbitals are too small to account for appreciable conformational energy differences in the actual geometry of ethane (as can be seen from the small numerical values of /fsteric in Fig. 3.57). 

It might be anticipated that computational models would provide good accounts of conformational energy differences and rotation/inversion... 

All conformational energy differences and errors in conformational energy differences will be reported in kcal/mol. 

A comparison of calculated and experimentally measured conformational energy differences for a small selection of singlerotor acyclic systems is provided in Table 8-1. The experimental data for some systems are subject to large uncertainties, and too much weight should not be placed on quantitative comparisons. 

SYBYL molecular mechanics is completely unsatisfactory for describing conformational energy differences in acyclic systems, and should not be employed for this purpose. On the other hand, the MMFF mechanics model provides a good account of all systems examined. In fact, the performance of MMFF is significantly better than any of the semi-empirical models, and in the same league as the best of the Hartree-Fock, local density, density functional and MP2 models (see discussion following). 

Except for systems where the difference in energy between the conformers is very small, even the STO-3G Hartree-Fock model properly assigns ground-state conformation. However, conformational energy differences from STO-3G calculations show large errors in some cases. Results from 3-2IG calculations are generally even worse, and the simplest Hartree-Fock model to provide a reliable (and for the most part quantitative) account of conformational energy differences is the 6-3IG model. Except for formic acid and methyl... 

Table 8-1 Conformational Energy Differences in Acyclic Molecules... 

MNDO, AMI and PM3 models are unsatisfactory for assignment of ground-state conformer and for calculation of conformational energy differences in acyclic systems. While this could have been anticipated, given the poor performance of semi-empirical models for other isodesmic processes (see discussion in Chapter 6), it is nevertheless disappointing. In many cases, semi-empirical models either yield the... 

As with acyclic systems, semi-empirical models provide a poor account of the ground-state conformation and conformational energy differences in cyclic systems. While all three models typically yield reasonable results for hydrocarbons, results for other systems are not acceptable. The performance of the PM3 model with regard to the... 

Table 8-2 Conformational Energy Differences in Cyclic Molecules (2)... 

Closely related to conformational energy differences are barriers to single-bond rotation and to pyramidal inversion. Here the experimental data are restricted to very small systems and derive primarily from microwave spectroscopy, from vibrational spectroscopy in the far infrared and from NMR, but are generally of high quality. Comparisons with calculated quantities are provided in Table 8-3 for single-bond rotation barriers and Table 8-4 for inversion barriers. The same models considered for conformational energy differences have been surveyed here. 

As with conformational energy differences, SYBYL and MMFF molecular mechanics show marked differences in performance for rotation/inversion barriers. MMFF provides a good account of singlebond rotation barriers. Except for hydrogen peroxide and hydrogen disulfide, all barriers are well within 1 kcal/mol of their respective experimental values. Inversion barriers are more problematic. While the inversion barrier in ammonia is close to the experimental value, barriers in trimethylamine and in aziridine are much too large, and inversion barriers in phosphine and (presumably) trimethylphosphine are smaller than their respective experimental quantities. Overall,... 

Compilations of experimental data relating to conformational energy differences and rotation/inversion barriers may be found in (a) T. A. Halgren andR.B. Nachbar,/. ComputationalChem., 17, 587 (1996) (b) T.A. Halgren,... 

Using Approximate Equilibrium Geometries to Calculate Conformational Energy Differences... 

Conformational energy differences for a small selection of acyclic and cyclic molecules obtained from 6-31G, EDF1/6-31G, B3LYP/ 6-3IG and MP2/6-31G models are provided in Tables 14-2 to 14-5, respectively. Results from exact geometries are compared with those obtained using structures from MMFF, AMI and 6-3IG calculations. 

MMFF geometries appear to be suitable replacements for exact structures for obtaining conformational energy differences. For all four calculation methods, the mean absolute error is essentially unchanged, and individual conformational energy differences change by a few tenths of a kcal/mol at most. 

Effect of Choice of Geometry on Conformational Energy Differences. 6-31G Model... 

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