Stepwise nucleophilic substitution concerted reactions

The authors of this review article suggest that the results indicated in Schemes 34, 35 and 36 are consistent with a stepwise nucleophile substitution mechanism (64JA107) as outlined in Scheme 37. When Z is nitrogen the driving force for the reaction is the ease of cleavage of the N—S bond by a soft nucleophile with a concerted elimination of phenylcyanamide. In the thiazole (Z = CH), however, the stable C—S bond precludes ring fission by a nucleophilic attack at sulfur and the initial adduct (79) (presumably trans) is obtained as a stable product. 

Reactions and reactivity of nucleophiles with thiolsulfonates 137 Nucleophilic substitutions of sulfenyl derivatives general considerations 139 Bimolecular substitution at sulfenyl sulfur stepwise or concerted 140 Reversibility in reactions of nucleophiles with cyclic thiolsulfonates 145 Other reactions of thiolsulfonates 147... 

Similar qualitative relationships between reaction mechanism and the stability of the putative reactive intermediates have been observed for a variety of organic reactions, including alkene-forming elimination reactions, and nucleophilic substitution at vinylic" and at carbonyl carbon. The nomenclature for reaction mechanisms has evolved through the years and we will adopt the International Union of Pure and Applied Chemistry (lUPAC) nomenclature and refer to stepwise substitution (SnI) as Dn + An (Scheme 2.1 A) and concerted bimolecular substitution (Sn2) as AnDn (Scheme 2.IB), except when we want to emphasize that the distinction in reaction mechanism is based solely upon the experimentally determined kinetic order of the reaction with respect to the nucleophile. 

Students of reaction mechanism will recognize intuitively that the difference between the narrow and broad borderline regions observed for nucleophilic substitution of azide ion at secondary and tertiary carbon (Fig. 2.2) is due to the greater steric hindrance to bimolecular nucleophilic substitution at the tertiary carbon. This leads to a large difference in the effects of an a-Me group on (s ) for the stepwise solvolysis and s ) for concerted bimolecular nucleophilic... 

The change from a stepwise preassociation mechanism through a triple ion intermediate to an uncoupled concerted reaction occurs as the triple ion becomes too unstable to exist in an energy well for the time of a bond vibration ( 10 s). The borderline between these two reaction mechanisms is poorly marked, and there are no clear experimental protocols for its detection. These two reaction mechanisms cannot be distinguished by experiments designed to characterize their transition states, which lie at essentially the same position in the inner upper right hand corner of Figure 2.3. Only low yields of the nucleophilic substitution product are obtained from both stepwise preassociation and uncoupled concerted reactions, because for formation of the preassociation complex in water is small... 

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. 

Generally, only a single stepwise or concerted pathway for aliphatic nucleophihc substitution is detected by experiment because of the very different activation barriers for formation of the respective reaction transition states for these reactions. The description of the borderline between stepwise and concerted nucleophilic substitution reactions presented in this chapter has been obtained through a search for those rare substrates that show comparable barriers to these two reactions and through the characterization of the barrier for nucleophile addition to the putative carbocation intermediate of the stepwise reaction in the region of this change in mechanism. 

The description of the borderline between stepwise and concerted nucleophilic substitution remains murky in cases where there is no significant stabilization of the transition state for the concerted reaction through the coupling of bond cleavage and formation. The reason is that there are no simple experimental protocols to detect the point at which the energy well for the carbocation intermediate of the stepwise reaction in the upper right hand corner of Figure 2.3 is transformed into... 

The action of a catalytic amount of MeONa on methoxymethyldisilane gives o,a>-dimethoxypermethylpolysilanes or cyclic polysilanes, depending on the reaction time (55b). It was concluded that the mechanism involves a concerted nucleophilic substitution with base-assistance or stepwise substitution by silyl anion a silylene mechanism is ruled out. 

Fig. 4.7. Two-dimensional reaction energy diagram showing concerted, ion pair intermediate, and stepwise mechanisms for nucleophilic substitution.

A kinetic study of the nucleophilic substitution reaction of substituted phenyl diphenylphosphinates (530a) and diphenylphosphinothioates (530b) with alkali-metal ethoxides (MOEt M = Li, Na, K) in anhydrous ethanol has been reported (Scheme 178). Experimental studies revealed the wide-ranging and important effects of structural change P=0 to P=S bond on reactivity, mechanisms (concerted versus stepwise), and on... 

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