Intramolecular kinetics

Bunsen. Discussion on Intramolecular processes Ber. Bunsenges. Phys. Chem. 92 209 50 Bunsen. Discussion on Unimolecular reactions Ber. Bunsenges. Phys. Chem. 101 304-635 Faraday Discuss. Chem. Soc. 1983 Intramolecular kinetics. No 75... 

B2.5.8 INTRAMOLECULAR KINETICS FROM HIGH-RESOLUTION SPECTROSCOPY... 

Oxidative ring opening of isoxazolidines leads to nitrones. Thus, bicyclic isox-azolidines (50) and (51), treated with m-CPBA, afford nitrones (52), (53), (54), and (55) (Scheme 2.19). Conformational analysis has confirmed the key role of the nitrogen lone pair with respect to regioselectivity of the reaction and of the intramolecular kinetic deprotonation of the intermediate oxoammonium derivative (125). 

Notes i) The isotope effects dealt with in mass spectrometry are usually intramolecular kinetic isotope ejfects, i.e., two competing fragmentations only differing in the isotopic composition of the products exhibit different rate constants k and k, . [69] ii) The kinetic isotope effect is called normal if k k, > 1 and inverse if k ko < 1. iii) Isotope effects can also be observed on KER, [52,70] e.g. the KER accompanying H2 loss from methylene immonium ion varies between 0.61 and 0.80 eV upon D labeling at various positions. [52]... 

Photochemical Activation. Photochemical processes have been used to produce catalytic metallic nuclei in three ways, each characterized by a different kinetic scheme photoelectrochemical, photoelectron, or intramolecular kinetic. These processes have... 

KINETIC ISOTOPE EFFECT EQUILIBRIUM ISOTOPE EFFECT SOLVENT ISOTOPE EFFECT HEAVY ATOM ISOTOPE EFFECT INTRAMOLECULAR KINETIC ISOTOPE EFFECT... 

Attempts to use intermolecular and intramolecular kinetic isotope effects (KIE s) to identify a complexation step during ortholithiation have so far been inconclusive. Both intramolecular and intermolecular KIE s for the deprotonation of 2 and 3 by s-BuLi... 

The intramolecular kinetic isotope effect determined in reaction of BTNO with p-MeO-C6H4CH(D)0H gave a h/ d ratio of 5.6 in MeCN , consistent with a rate-determining H-abstraction step. Additional determinations gave a h/ d of 7 with PhCH(D)OH, and 12 for the intermolecular competition of fluorene vs. 9,9-dideuteriofluorene. The latter value supports the contribution of tunnelling already commented on for reaction of PINO with various C—H donors ( h/ d values in the 11-27 range) . ... 

Zelent, B., Veklich, Y., Murray, J., Parkes, J. H., Gibson, S., and Liebman, P. A. (2001). Rapid irreversible G protein a subunit misfolding due to intramolecular kinetic botdeneck that precedes Mg2+ lock after GTP/GDP exchange. Biochemistry 40, 9647-9656. 

The 2,6-dichloropyridine /V-oxidc-Ru(IV)(TMP)Cl2 (TMP = tetramesitylporphy-rinato) system converts /V-acyl cyclic amines to N-acylamino acids via oxidative C-N bond cleavage. The kinetic isotope effect was measured using N-benzoyl [2,2-di Ipyrrolidine. The intramolecular kinetic isotope effect in the oxidation of was found to be 9.8 0.2, strongly suggesting that the rate-determining step is hydrogen abstraction and not one-electron oxidation.75... 

HO radicals [26]. These results were also consistent with intramolecular kinetic isotope effect measurements on typical Gif oxygenations of l,3-d2-adamantane to... 

RELATIONSHIP BETWEEN INTRAMOLECULAR ISOTOPE EFFECTS ON ION ABUNDANCES AND INTRAMOLECULAR KINETIC ISOTOPE EFFECTS... 

There is one obvious difficulty in determining intramolecular kinetic isotope effects with the present PIPECO techniques for metastable ions (Sect. 3.2.1), which is that peaks for product ions from isotopically labelled molecules will overlap. Indeed, peaks for ions separated by only one mass unit will typically be largely superimposed. The time-of-flight technique is, in effect, measuring velocity and what is required is measurement of mass and translational energy in separate analysers. The problem... 

Charge exchange will suffer the same problems with intramolecular kinetic isotope effects as PIPECO if single-focussing mass spectrometers are used. Charge exchange with a double-focussing mass spectrometer should, however, allow determinations of intramolecular kinetic isotope effects. 

Measurements of product ion abundances or rates of decomposition can, as has been discussed, provide reliable, even if not precise, information on intramolecular kinetic isotope effects. These isotope effects constitute a powerful probe of reaction mechanism. 

On the basis of eqn. (1), the intramolecular kinetic isotope effect is given by... 

Symmetry factors, o, do not appear in eqn. (28) because the numbers of equivalent pathways have been allowed for in the definition of the kinetic isotope effect. F0(d is the critical energy of the decomposition involving the lighter isotope and F0(II) that of the decomposition involving the heavier isotope. The density of states, N(E), of the reactant ion is, of course, common to both decompositions and does not affect the intramolecular kinetic isotope effect. The intramolecular kinetic isotope effect is, therefore, dependent only upon transition state properties. 

The consequence of the restrictions imposed by the product rule on vibrational frequencies of transition states and critical energies of decompositions is that there is generally very little leeway in the mechanistic interpretation of intramolecular kinetic isotope effects. There are tight constraints upon the type of transition state structure consistent with a given intramolecular kinetic isotope effect. 

The important conclusion is that intermolecular kinetic isotope effects are not a sensitive probe of transition state properties in the way that intramolecular kinetic isotope effects are, indeed the intermolecular effects can be effectively independent of transition state characteristics. 

Fig. 18. The expected percentages of various labelled products of the dioldehydratase reaction using 25 as substrate. The calculation was based on the following facts and assumptions (1) The enzyme does not differentiate between the enantiotopic hydrogen positions (conclusion from experiments with species 17 and 18 shown in Fig. 14) (2) in the competition between vicinal hydrogen atoms there is an intramolecular kinetic deuterium isotope effect of 2.6 (Fig. 15) (3) this effect is 10 for geminal hydrogen atoms (4) the migrating hydroxyl group substitutes one of the hydrogen atoms in the vicinal position stereospecifi-cally (i.e., with inversion).

Theoretical Treatments.— The contributions of the theoretical chemists to the Faraday Discussion on Intramolecular Kinetics were mentioned earlier. Marcusconsidered the relation between classical quasiperiodic and chao-... 

This methodology has been extended successfully to polymer-supported chiral (salen)Co complexes [88] and to intramolecular kinetic resolution of epoxy alcohols (with (R,R)-L Co OAc)) [82]. The ceiling of 50 % yield in kinetic resolution reactions can be extended if the starting material undergoes racemization under the reaction conditions. This has been shown to be possible with epichlorohydrin in reaction with TMSN3, the dynamic kinetic resolution process affording now a 76 % product yield (97 % ee) and 12 % each of the dichloro and diazido products [89]. 

Recall that we can never know the absolute values of U and H fui a species at a given state. 0(kj/mol) is the sum of the energies of motion of all 6.02 X10 molecules in one gram-mole of the species plus the intramolecular kinetic and potential energies of all the atoms and subatomic particles, which are quantities we cannot determine. Since H = H + PV and we cannot know the value of V, we also cannot know the value of H at a specified state. 

Systematics are also available for the 8 0-values of the compounds in queshon [56[ carboxyl and carbonyl functions in isotopic equilibrium with the surrounding water are, due to equilibrium isotope effects, enriched in 0 relative to this water by 19 and by 25 to 28%o, respectively. From here, the 8 0-values of natural alcohols, mostly descendants of carbonyl compounds, will have (maximally) similar 8 0-values, provided the precursors have attained isotopic equilibrium with water and their reduction has not been faster than their equilibration. Alcohols from addihon of water to C=C double bonds or from exchange of halogen functions by OH groups, typical for synthetic alcohols, will have 8 0-values close to or even below that of the water, due to kinetic isotope effects. The few available results [246, 289, 290] seem to confirm this expectation. The 8 0-values of natural (and also synthetic) esters and lactones can be, especially in the carbonyl group, extremely high (up to 50%o), probably as a consequence of an intramolecular kinetic isotope effect on the activation of the carboxyl function. 

RP Hanzlik, I< Hogberg, JB Moon, CM Judson. Intramolecular kinetic deuterium isotope effects on microsomal and chemical chlorination of toluene-OC-dl and toluene-OC, 0C-d2. J Am Chem Soc 107 7164—7167, 1985. 

---