Factors influencing the chemical shift a case study with a, a,-DI-tert butylthioaceric esters

Abstract

The assignment of structures to two forms of ?,? di tert butylthioacetic esters, detected by NMR, is the subject matter of this thesis entitled “Factors Influencing the Chemical Shift - A Case Study with ?,? Di tert butylthioacetic Esters.” Rotation about formal single bonds can never be considered as absolutely “free” since the presence of any barrier, however low, has the effect of perturbing the populations of all of the rotational states?¹?. The value of a barrier separating two rotamers is the resultant of the action of a number of factors: electron delocalisations, classical steric effects, dipolar electric influences, internal hydrogen bonding, solvent effects, etc., and as a result, the barriers may vary over a wide range. Yet, stabilisation of particular forms (rotational isomers), to a degree that enables their detection at ordinary temperature by a suitable technique, is encountered comparatively rarely. An instance of this rare type is found with ?,? di tert butylthioacetic esters (E). Esters E exhibit doubling into components of unequal intensity of salient resonances, notably the resonances of ? protons, in their NMR spectra. The work of Elam² can be taken as having established conclusively that this doubling is not due to factors (presence of enolic form, thio ester form, dimer, etc.) other than the stabilisation of two rotational isomers about the C–?–C (ester) bond. Elam et al. did not specifically assign conformations to the detected rotational isomers. The present thesis is concerned with an assessment of influences that may determine the intensity ratio and the relative chemical shift of the H ? lines in the methyl ester E. After describing in detail the researches of Elam et al. in Chapter I, the possibility of one or both of the detected forms being a chiral entity is considered. An experiment, the results of which could be construed as establishing that neither of the detected stabilisations was chiral in the case of the ethyl ester E, carried out earlier in these laboratories, is described. This is followed by an account of a preliminary, but inconclusive, attempt to assign the doubled lines to specific rotational isomers, by relating the intensity of the components with the enthalpies of particular forms, calculated by employing a semi empirical approach. The main reason for the inconclusive nature of the results lay in not allowing for the effect of the rotation of the tert butyl groups of E in the calculations. In the next Chapter (Chapter III) is described an attempt that takes into account the effect of the rotation of tert butyl groups. After a brief discussion of the basic principles of quantum chemical approaches and a short discussion of the reliability of various such approaches in the calculation of enthalpies as reported by others with different systems, the reasons for the choice of the CNDO/2 method are given. The results of the application of this method to the case of methyl ester E, assuming various ? = 5 dihedrals and combinations of conformations (internal and external) of the tert butyl groups, are detailed. A salient item immediately emerging from data thus gathered has been that over widely different tert butyl conformations, the forms in which H ? is syn and anti periplanar to C=S are stabilised over other forms. The barriers separating these two forms, while high, are highly sensitive to the tert butyl conformations. Three possible procedures for weighted averaging were examined in order to take account of the rotation of tert butyl groups. Following the presentation of the results of applying these procedures, their relative merits are discussed. Overall, it has emerged that the difference in enthalpies of the syn and anti forms (shown as stabilised in the CNDO/2 approach after applying any of the averaging procedures) is too small for reliable assignment, since approximations implicit in the methods could have had a profound effect on the sign of the difference. It has, nevertheless, appeared from these calculations that a higher degree of librational freedom would be associated with the syn form than with the anti form. The entropy factor could, therefore, exert an effect on the outcome in that the syn form is rendered stabilised despite the fact that the anti form emerges as the somewhat more stabilised when the entropy factor is not considered. A second attempt at assignment was based on the possibility of ?s density at H ? changing in some specific manner on going over to the anti form from the syn form. Calculations, using again the CNDO/2 approach, showed that ?s density at H ? would be lower in the syn form than in the anti form. A parallel difference was found for analogously structured systems (e.g., ?,? disubstituted acetaldehydes, etc.), both by the INDO method (for amenable systems) and by the CNDO/2 method, thus increasing the confidence in the results with the esters E. Insofar as the assignment of the H ? line that occurs at lower field (and has the higher intensity) to the syn form (on the basis that ?s density at H ? in this form is lower) accorded with that form being the more stabilised if the entropy factor becomes decisive, the CNDO formalism could be taken as having output internally consistent results. This is the subject of Chapter IV wherein also are discussed the factors affecting the chemical shift and the scaling of electron density changes into chemical shift differences before presenting the results concerned with electron density calculations. The Chapter ends with a cautionary note on relying solely on electron density changes for assignments of the type attempted. The anisotropic magnetic properties of the thioester function could be an important factor in the change of chemical shift of H ? on proceeding from the syn to the anti form. Using the working hypothesis that the anisotropy of the thione function may resemble that of the carbonyl function, the possible ways in which the properties of the former are altered when it forms part of the thioester function are examined. This has required a fairly extensive review of what is known about the anisotropic magnetic properties of the carbonyl. The conclusions have been reached that the anisotropic effect of the thiocarbonyl, as forming part of a thioester function, is not likely to be large and that the assignment of the H ? lines on the basis of electron density change alone, qualitatively considered, can be relied upon. The work on the anisotropic magnetic properties of the carbonyl, reviewed in a section of the Chapter wherein the matters dealt with in the previous paragraph are discussed (Chapter V), has shown that its anisotropic properties arrived at on a semi empirical (statistical) basis? differ from those arrived at starting from quantum chemical principles?. A number of instances (example - ref. 5) were found in the literature where, in extending the anisotropic properties of the carbonyl to the thiocarbonyl, the latterly accepted anisotropic properties? have not been taken into proper account. These instances are re examined and a new mnemonic has been suggested whereby the effect of the thiocarbonyl can be explained even while considering that the statistically arrived at anisotropic properties of the carbonyl are validly extendible to the thione. In the final section, note is taken of the fact that rather poor agreement is found between values of chemical shift change calculated on the basis of the new geometry of the carbonyl anisotropy and observed changes in the chemical shifts of H ? in certain substituted aldehydes. An explanation based on the dependence of H ? shifts on the degree of branching of the ? substituents as well as on the dependence of ?s density at H ? on the H–C–C=O dihedral is suggested. Three appendices are included. The first deals with a study of the potential surface generated when simultaneous rotation about the C–?–C (ester) and C–?–C–t Bu bonds occurs in methyl tert butylthioacetate. The nature of this surface has been found to be indicative of an interesting phenomenon whereby these types of rotation become coordinated (gear effect). The results of a truncated Fourier analysis? of various ?,? disubstituted carbonyl systems and their thio analogues are presented in Appendix II. The analysis was undertaken in an attempt at an examination of the relative importances of electronic, steric, etc. factors in determining the ?,? enthalpies in the systems. In Appendix III possible methods of experimental verification of the assignment of structures to the rotational isomers of the esters E, suggested in the main body of the thesis, are set forth.