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

Abstract

Dedicated to Professor Jacob Bigeleisen on the occasion of his 70th birthday Stratagems are presented for the determination of kinetic isotope effects of proton exchange reactions by dynamic NMR spectroscopy. In such experiments, lineshape analyses and/or polariza tion transfer experiments are performed on the exchanging protons or deuterons as well as on remote spins, as a function of the deuterium fraction in the mobile proton sites. These methods are NMR analogs of previous proton inventory techniques involving classical kinetic methods. A theory is developed in order to derive the kinetic isotope effects as well as the number of transferred protons from the experimental NMR spectra. The technique is then applied to the problem of proton exchange in the system 15N,15N'-di-p-fluorophenylibrmamidine, a nitrogen analog of formic acid, dissolved in tetrahydrofuran-d8 (THF). DFFA forms two conformers in THF to which s-trans and s-cis structures have been assigned. Only the s-trans conformer is able to dimerize and exchange protons. Lineshape simulations and magnetization transfer experiments were carried out at 189,2 K, at a concentration of 0.02 mol l-1, as a function of the deuterium fraction D in the 'H-15N sites. Using 1H NM R spectroscopy, a linear dependence of the inverse proton lifetimes on D was observed. From this it was concluded that two protons are transported in the rate limiting step of the proton exchange. This result is expected for a double proton transfer in an s-trans dimer with a cyclic structure. The full kinetic HH/HD/DD isotope effects of 233:11:1 at 189 K were determined through 19F NMR experiments on the same samples. The deviation from the rule of geometric mean, although substantial, is much smaller than found in previous studies of intramolecular HH transfer reactions. Possible causes of this effect are discussed.

Combined X-ray Diffraction and 15N CPMAS NMR Study of Molecular Structure and Proton Order/Disorder Phenomena in Cyclic N,N‘-Bisarylformamidine Dimers

“…Substituted amidines are the nitrogen analogs of carboxylic acids and have been studied by various spectroscopic techniques. − As shown by NMR, , both s- cis and s-trans conformers (Figure a) can be present in solution exhibiting different hydrogen-bond association patterns. Evidence was obtained that only the s-trans conformers are able to form cyclic hydrogen-bonded dimers (Figure b) in which fast double proton transfers can take place, in analogy to carboxylic acid dimers.…”

“…Substituted amidines are the nitrogen analogs of carboxylic acids and have been studied by various spectroscopic techniques. − As shown by NMR, , both s- cis and s-trans conformers (Figure a) can be present in solution exhibiting different hydrogen-bond association patterns. Evidence was obtained that only the s-trans conformers are able to form cyclic hydrogen-bonded dimers (Figure b) in which fast double proton transfers can take place, in analogy to carboxylic acid dimers. On the other hand, X-ray diffraction techniques (XRD) showed that neither substituted acetamidines nor benzamidines form cyclic dimers in the solid state. , These species have, however, finally been observed in recent years in the case of some N , N -bisarylformamidines with the aryl substituents phenyl ( I ), p -bromophenyl ( II ), and p -chlorophenyl ( III ) .…”

“…The observed twist angles result from the balance between the potential coupling of these two π-electron systems and the steric and other components of the crystal packing forces.

1 (a) The s-cis and s-trans conformers of N , N ‘-bisarylformamidines in solution according to refs and . (b) Double proton transfer in cyclic N , N ‘-bisarylformamidines dimers: N , N ‘-bisphenylformamidine ( I, type C), N , N ‘-bis( p -bromophenyl)formamidine ( II, type B), N , N ‘-bis( p -chlorophenyl)formamidine ( III, type B), N , N ‘-bis( p -methoxyphenyl)formamidine ( IV , type C), N , N ‘-bis( p -methylphenyl)formamidine ( V, type A), N , N ‘-bis( p -fluorophenyl)formamidine ( VI, type A), N , N ‘-bis( p -nitrophenyl)formamidine ( VII type A), N , N ‘-bis( m -bromophenyl)formamidine ( VIII, type A).

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Kinetic H/D/T Isotope and Solid State Effects on the Tautomerism of the Conjugate Porphyrin Monoanion

“…Various approaches have been made in order to calculate the reaction energy surface 8 that indicate a stepwise reaction mechanism as depicted in Figure a; moreover, as ab initio calculation methods have been improved, the calculated barrier energies 8e have substantially decreased and are now of the order of those found experimentally 4e. Progress has also been made in the measurement and interpretation of kinetic HH/HD/DD isotope effects of double proton transfer reactions. − These effects have recently been determined using dynamic 1 H NMR of unsubstituted 15 N-labeled porphyrin dissolved in organic liquids as well as for the polycrystalline compound using 15 N cross polarization, magic angle spinning (CPMAS) NMR spectroscopy 4e…”

NMR Studies of the Tautomerism of Cyclo-tris(4-R-2,6-pyridylformamidine) in Solution and in the Solid State

“…Averaged NMR signals were often obtained in usual solvents at ambient temperature. Limbach and co-worker investigated such equilibria in detailed NMR studies on N,N ‘ -bisarylformamidines in tetrahydrofuran . Two conformers, E-syn and E-anti , were assigned which form a hydrogen bond to the solvent molecules at low concentration.…”