Deuterium isotope effects product dependence

The ratio of products (36) and (37) from VNS of hydrogen (Pe) and substimtion of halogen (Px), respectively (Scheme 4), will depend on the strength and concentration of base, provided that the elimination is a kinetically important step in the VNS reaction, namely Pr/Px = kikE[B]/k-ikx. The influence of base will decrease until a constant value Ph/Px = k /kx is reached as kslB] k i. This has been demonstrated for 4-chloronitrobenzene, which undergoes exclusive substimtion of chlorine unless strong base is present to favour the VNS process. The deuterium isotope effect for VNS hydroxylation by Bu OOH, determined as me ratio of H versus D substitution of l-deutero-2,4-dinitrobenzene, varied from 7.0 0.3 to 0.98 0.01 as the base in NH3 was changed from NaOH to Bu OK me former value is consistent with a rate determining E2 process. 

Molecular orbital calculations of the w-electron distribution in pyridine predict that more 4- than 2-aminopyridine should be formed in the Tschitschibabin reaction.4 The fact that no 4-aminopyridine can be detected when the two positions are allowed to compete for a deficiency of sodamide (see, e.g., Abramovitch et al 268) has led to the suggestion that the observed orientation in this reaction depends on the relative ease of elimination of a hydride ion from C-2 and C-4 and not upon the initial mode of addition (which, by implication, must take place predominantly at C-4 as predicted by the molecular orbital calculations).4 This hypothesis necessitates that the addition step be rapidly reversible and that the second stage, the elimination of hydride ion, be the rate-determining one (Scheme VII). Although it seems reasonable to assume that the hydride ion eliminations are the slow steps in this reaction, the fact that no deuterium isotope effect was observed in the reaction of 3-picoline-2d and of pyridine-2d with sodamide implies that the first stage must be virtually irreversible,268 as was found also in the case of the addition of phenyllithium to pyridine.229 The addition stage must, therefore, be the product-... 

Large primary kinetic isotope effects have been measured for the H-atom transfer steps from substrate to dAdo and from dAdo to the product radical in a number of AdoCbl-dependent enzymes as indicated in Table 19.1. In methylmalonyl-CoA mutase, the steady-state deuterium isotope effect is 5-6 in the forward direction, and the intrinsic isotope effect of step (i) in Scheme 19.3 is masked by the kineti-cally coupled but slower later steps [37-39]. The steady-state tritium kinetic isotope effect kii/kj) in the forward direction has been reported to be 3.2 [38]. Note that the experiments with deuterium were performed with a fully deuterated methyl group, while those with tritium were carried out at the trace level and correspond to a single isotopic atom therefore these two isotope effects should not be directly compared. For the reverse reaction, the deuterium kinetic isotope effect is also par-... 

Interestingly, due to the competition between the two reaction pathways, a deuterium isotope effect on the enantioselectivity in the hydrogenation of 94 and some other enamides was observed. For example, hydrogenation of a-(o-methoxyphenyl)enamide 94 with H2 gave 50%-57% ee (R) depending on the reaction conditions. The same hydrogenation with HD and D2 afforded the product with 24% ee (R) and 5% ee (S),... 

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

Thermolysis of l,l-difluoro-2,3-diphenylcyclopropane in supercritical CO2 has allowed the rate of geometrical isomerization [i.e. cis-( 109) to /ra/M-(109)] and racemization [i.e. (/< )-( 109) to (S)-( 109)] to be determined from O2 dependence of the trapping rate of the postulated intermediate 1,3-biradical.246 Above 150 °C, the formation of 2,2-difluoroindane and its decomposition products is reported. A similar thermally induced equilibrating series of stereomutations has been observed with the analogous non-fluorinated cyclopropane in which rate constants and deuterium exchange isotope effects are reported.247 Theoretical studies of this isomerization have focused on classical248 and quasi-classical trajectories.249... 

The pattern of deuterium distribution in isotope exchange products of 1,8-nap-hthyridine and its methyl-, hydroxyl-, amino- and nitro derivatives indicates that the rate and pathway of this process depend on the pH of the medium as well as the nature and position of substituent (1988ACH267). In neutral D20 and a D20-DC1 mixture, hydrogen atoms are replaced with deuterons exclusively at positions 2 and 7. In D20 solutions containing NaOD, hydrogen atoms are replaced with deuterons in all positions of the naphthyridine system. In neutral D20, the replacement of the protons in monomethyl-substituted 1,8-naphthyridines occurs predominantly in the ortho positions with respect to the nitrogen atoms (positions 7 and 2, 7). The high reactivity of these positions is determined by the inductive effect of the substituent. 

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