Ionization of the substrate

A reasonable mechanism for this observation assumes rate determining ionization of the substrate as the first step followed by a hydride shift that converts the secondary carbocation to a more stable tertiary one... 

The first step is a slow ionization of the substrate and is the rate-determining step. The second is a rapid reaction between the intermediate carbocation and the nucleophile. The ionization is always assisted by the solvent, since the energy necessary to break the bond is largely recovered by solvation of R" " and of X. For example, the ionization of f-BuCl to f-Bu" and Cl" in the gas phase without a solvent requires ISOkcalmol" (630kJmol" ). In the absence of a solvent such a process simply would not take place, except at very high temperatures. In water, this... 

The El mechanism is a two-step process in which the rate-determining step is ionization of the substrate to give a carbocation that rapidly loses a P proton to a base,... 

Ionization of the substrates to cation-radicals is affected by means of tris(4-bromophenyl) ammoniumyl hexachloroantimonate (see Section 1.7.11). Subsequent reduction of the cation-radicals is accomplished by tributyltin hydride. For example, l,l-di(anisyl)ethylene was efficiently (93%) reduced essentially at the time of mixing (less than 1 min). Scheme 7.4. 

The first reaction is the slow, or rate-determining, ionization of the substrate to form a carbocation intermediate. The products of this first step will tend to be stabilized best in polar solvents. The SnI type of reaction can also lead to the formation of ion pair intermediates, as shown in the following reaction scheme ... 

Nucleophilic Substitution at Benzyl Derivatives. The sharp break from a stepwise to a concerted mechanism that is observed for nucleophilic substitution of azide ion at X-l-Y (Figs. 2.2 and 2.5) is blurred for nucleophilic substitution at the primary 4-methoxybenzyl derivatives (4-MeO,H)-3-Y. For example, the secondary substrate (4-MeO)-l-Cl reacts exclusively by a stepwise mechanism through the liberated carbocation intermediate (4-MeO)-T, which shows a moderately large selectivity toward azide ion ( az/ s = 100 in 50 50 (v/v) water/ trifluoroethanol). The removal of an a-Me group from (4-MeO)-l-Cl to give (4-MeO,H)-3-Cl increases the barrier to ionization of the substrate in the stepwise reaction relative to that for the concerted bimolecular substitution of azide ion. The result is that both of these mechanisms are observed concurrently for nucleophilic substitution of azide ion at (4-MeO,H)-3-Cl in water/acetone solvents. These concurrent stepwise and concerted nucleophilic substitution reactions of azide ion with (4-MeO,H)-3-Cl show that there is no sharp borderline between mechanisms for substitution at primary benzylic carbon, but instead a region of overlap where both mechanisms are observed. 

In the gas phase, in the absence of solvent, entropy is little affected by ionization of the substrate.34,35 In the absence of solvation it is enthalpy that has the greatest effect on ionization (see Table 4). 

The distinction between electrophilic and electron-transfer mechanisms of addition reactions to vinyl double bonds of ArX—CH=CH2 (X = S, O, Se) has been achieved by studying substituent effects. Specifically, the effects of meta and para substituents on the rates of electrophilic additions correlated with Hammett radical cations correlates with statistical tests. The ofclcctrophilicj/o-1 (FT) dichotomy is in accord with the conventional paradigm for cr/cr+ correlations and further support has been found by ah initio calculations. Interestingly, the application of this criterion to the reactions of aryl vinyl sulfides and ethers with tetracyanoethylene indicates that cyclobutanes are formed via direct electrophilic addition to the electron-rich alkene rather than via an electron-transfer mechanism.12... 

As the ionization of the substrate occurs at atmospheric pressure and thus with a high collision frequency, it is very efficient. Furthermore the high frequency of collisions serves to thermalize the reactant species. In the same way, the rapid desolvation and vaporization of the droplets reduce considerably the thermal decomposition of the analyte. The result is production predominantly of ions of the molecular species with few fragmentations. 

The rate of enzyme-catalyzed reactions typically shows a marked dependence on pH (Figure 8-7). Many of the enzymes in blood plasma show maximum activity in vitro in the pH range from 7 to 8. However, activity has been observed at pH values as low as 1.5 (pepsin) and as high as 10.5 (ALP). The optimal pH for a given forward reaction may be different from the optimal pH found for the corresponding reverse reaction. The form of tlie pH-dependence curve is a result of a number of separate effects including the ionization of the substrate and the extent of dissociation of certain key amino acid side chains in the protein molecule, both at the active center and elsewhere in the molecule. Both pH and ionic environment will also have an effect on the three-dimensional conformation of the protein and... 

Several groups +have examined the influence of divalent cations, such as Mg2 and Mn2, in catalyzing the solvolysis of allylic pyrophosphates such as geranyl pyrophosphate (58-60). The results strongly suggest that the role of the metal ion in enzymatic transformations of allylic pyrophosphates is to neutralize the negative charge of the pyrophosphate moiety and thus assist in the ionization of the substrate to produce the allylic cation. 

The pH-rate profiles have been determined for many ASs, and show a bell-shaped dependence that implies the participation of acid-base catalysis. " ASs fall into two groups according to their pH optima for T ax/ K. Such pH-rate profiles reflect ionizable groups on free enzyme and free substrate that are important for binding and catalysis. Ionizations of the substrate will not appear in the pH profiles of sulfatases because of the very low pZ value of the sulfuryl group, which is approximately —3. As a result, only the anion is present in solution under normal experimental conditions. 

No. The rate of an SnI reaction depends only on the rate of ionization of the substrate. The second step will be fast for all nucleophiles. 

If the solvent is water, or contains water, the bimolecular (collision) processes between a neutral substrate and a charged nucleophile (such as nucleophilic acyl addition reactions and nucleophilic displacement with alkyl halides) are generally slow due to solvation effects and unimolecular processes may be competitive. A H unimolecular process involves ionization of the substrate, usually to a carbocation (sec. 2.7.B.1). If the solvent is anything but water, the faster bimolecular processes probably dominates., which is obviously an assumption. 

The possibility of the 5, 1 mechanism was recognized very early in the study of reaction mechanisms at carbon since stereochemical information indicated that Walden inversion does not occur at tertiary centres but racemization does occur during substitution. The kinetics of the substitution process were also consistent with rate-determining ionization of the substrate. When stable carbonium ion salts were isolated, characterized, and shown to be kinetically competent as reaction intermediates, the mechanism became solidly established. In the case of phosphorus compounds, kinetic evidence to distinguish the mechanisms is ambiguous and stereochemical studies were not available until recently. Extensive amounts of indirect evidence were used to support the possibility of an SnI mechanism in phosphate substitution. The isolation of a dissociatively generated intermediate remains elusive, however. Until such an intermediate is available for study, the significance of a truly dissociative mechanism will remain problematical. 

We came to this area quite by chance. Our interest in nucleophilic functionalization of aromatics led us to consider photochemical reactions for this purpose. In several cases, such reactions involve ionization of the substrate. Furthermore, we were impressed by the work of Arnold and his co-workers showing that SET often occurs upon photoexcitation yielding an ion radical pair. In view of this fact, one of the experiments we carried out involved irradiation of the photochemical oxidant 1,4-naphthalenedicarbonitrile (DCN) in the presence of toluene and cyanide in deareated acetonitrile. Arnold s work had shown that cation radicals of alkenes add nucleophiles under this condition, and we wanted to test whether a similar reaction with... 

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