Dynamic NMR Study of the Interference between Cyclic Proton Exchange, Selfassociation and Hindered Rotation of Diphenylformamidine in Tetrahydrofuran

Abstract

Chcriiicd KineticsThc 90 M H z ' H N M R spectra of '5N,'sN'-dipentadeutcrophenylformamidine (DPFA), a nitrogen analogue of formic acid, dissolved in tetrahydrofuran-d8 (THF) have been measured as a function of concentration, deuterium fraction in the 'H-I5N sites, and of temperature. The spectra show characteristic changes, from which thermodynamic and kinetic information on hindered rotation, hydrogen bond association and proton exchange of DPFA in THF are obtained by NMR lineshape analysis. DPFA forms two conformers A and B in THF, to which s-trans and s-cis structures have been assigned. At low concentrations both DPFA conformers are located in a hydrogen bond to the solvent molecules. However, as a result of the different structure, only A is able to selfassociate to any observable extent. This effect leads to concentration dependent A/B populations. Higher selfassociates or mixed AB associates are not observed. Whereas B is not able to exchange protons, A is subject to a very fast proton transfer. By measuring proton lifetimes as a function of concentration and of the deuterium fraction in the labile proton sites, it was established that two protons are transferred in every exchange process. Thermodynamic data of the association process obtained by the analysis of the chemical shifts, of the A/B populations and the proton lifetimes as a function of concentration agreed very well. These results are evidence that A forms only selfassociated hydrogen bonded dimers with a cyclic structure in which the double proton transfer takes place. The observation of a kinetic HH/HD isotope effect of 20 at 178 K establishes this transfer as the rate limiting step of the overall proton exchange. Rate constants of the double proton transfer in the cyclic dimer were obtained as a function of temperature from which an activation energy of about 19 kJ mol-' was obtained. In addition, the rates of interconversion between the two conformers were determined as a function of temperature. Details of the reaction mechanism and differences to the related carboxylic acids are discussed. Thus, it is shown that dynamic NMR spectroscopy can be a useful tool for elucidating elementary steps of complex reaction networks.

NMR Stratagems for the Study of Multiple Kinetic Hydrogen/Deuterium Isotope Effectsof Proton Exchange. Example: Di-p-fluorophenylformamidine/THF

“…Unauthenticated Download Date | 5/10/18 3: 29 PM still remains because the vibrational frequencies of transition states cannot be observed spectroscopically and because of proton tunneling, which also affects kinetic hydrogen/deuterium isotope effects [1], In order to check the validity of the RGM we have, for a number of years, been studying kinetic isotope effects of well characterized multiple symmetric pro ton transfer reactions by dynamic NMR spectroscopy in non aqueous liquids [17,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and, recently, also in the solid state [35][36][37][38][39][40][41][42]. Large deviations from (2) were observed for the intramolecular HH migrations in meso-tetraphenylporphine [17] and azophenine [17,32,33] as well as for proton exchange between acetic acid and methanol in tetrahydrofuran (THF) [17,21], as replacement of the first H atom by D resulted in a larger decrease in the rate constants than replacement of the second H atom by D. These results have been useful in elucidating kinetic results of enzyme reaction mechanisms [ 10,11 ].…”

“…In order to measure the above mentioned multiple kinetic isotope effects, NMR proton inventory tech niques [17,21,29,31,32] had to be designed that involve dynamic NMR measurements as a function of the deuterium fraction D in the mobile proton sites. When the chemical shifts of the jumping protons or deuterons are altered during the exchange, kinetic constants can be derived by a combination of !H and 2H NMR spectroscopy [17,21].…”

“…The use of the modulation of a scalar spin-spin interaction between the mobile hydrogen isotopes L and "re mote" spins in the residual group A of a molecule AL is only a partial solution to the problem because of the following circumstance. Although kinetic HH/HD isotope effects can be obtained from the analysis of A -H splitting patterns by *H NMR experiments [17,28,29,31,33,34], scalar A -D coupling is not strong enough to obtain kinetic HD/DD isotope effects by 2H NMR spectroscopy because of the smaller gryomagnetic ratio of the 2H nucleus. Therefore, kinetic HH/DD isotope effects of several intramolecular dou ble proton transfer reactions were obtained by per forming NMR experiments on remote spins such as 13C [17,33].…”

“…Exchange processes of N,N'-diarylamidines in THF as identified by NMR spectroscopy [31]. The species in square brackets were identified only indirectly.…”

“…Borisov et al also reported that N,N'-diarylformamidines exist in tetrahydrofuran (THF) in an s-trans form A and an s-cis form B, which show different exchange characteristics. In a recent dynamic NMR study of 15N,15N'-dipentadeuterophenylformamidine (DPFA) in THF [31] we have established the complex reaction network shown in Figure 1. The 15N label had to be introduced in order to avoid 14N quadrupole effects on the mobile proton signals, which obscure the kinetic information on proton ex change.…”