Temperature coefficient of NH chemical shifts of thioamides and amides in relation to structure

NH chemical shift temperature coefficients have been measured in a large series of N-substituted-3-piperidinethiopropionamides in which the N· · ·N distances are short but of varied length, as well as in a couple of the corresponding amides and in some simpler amides and thioamides. Geometries are calculated by means of ab initio DFT methods. The N-substituted-3-piperidinethiopropionamides show in most cases strong intramolecular N–H· · ·N hydrogen bonds according to IR spectra and ab initio calculations. For compounds with rather short N· · ·N distances the SyC–N–H moiety is non-planar. Dihedral angles as small as 1608 are found. The NH chemical shift coefficients measured in non-polar solvents in all the N-substituted-3-piperidinethiopropionamides are more negative (28 to 217 ppb/K) than in nonhydrogen bonded thioamides. For the latter in non-polar solvents like CDCl3 and toluene the temperature coefficients are as small as 21 to 24 ppb/K. The large negative effects can be related not only to the non-planarity of the thioamide group in a way that the more pronounced the non-planarity the more negative the temperature coefficients, but also to strong hydrogen bonding and the fact that the acceptor is a nitrogen. For similar amides with non-planar amide groups and nitrogen acceptor large negative temperature coefficients are likewise seen. In polar solvents like DMF the effects in simple thioamides are uniform and close to 26 ppb/K, whereas in the more complex compound like 4p(t) the temperature coefficient is close to 0. An essential feature of measuring temperature coefficients of compounds without strong intramolecular hydrogen bonds in non-polar solvents and at low temperatures is to keep the concentration low enough to avoid dimerisation. q 2004 Elsevier B.V. All rights reserved.