SN2 mechanism transition state

The mechanism of phosphate ester hydrolysis by hydroxide is shown in Figure 1 for a phosphodiester substrate. A SN2 mechanism with a trigonal-bipyramidal transition state is generally accepted for the uncatalyzed cleavage of phosphodiesters and phosphotriesters by nucleophilic attack at phosphorus. In uncatalyzed phosphate monoester hydrolysis, a SN1 mechanism with formation of a (POj) intermediate competes with the SN2 mechanism. For alkyl phosphates, nucleophilic attack at the carbon atom is also relevant. In contrast, all enzymatic cleavage reactions of mono-, di-, and triesters seem to follow an SN2 

It has to be assumed that these processes are occurring on the boundary between SN1(P) and SN2(P) mechanisms in whose transition states considerable P—0(—Ar) bond cleavage takes place. The lifetime of the resulting, more or less free metaphosphate anion 102 then depends upon the nucleophilicity of the surrounding solvent. With pyridine, for example, a very fast reaction occurs so that the overall process approaches an SN2 reaction. Acceleration of the reaction by amines such as 2,6-lutidine, which are disqualified from acting as nucleophiles by steric hindrance, or by solvents such as dioxane, whiche are presumably too 

Steric hindrance raises the energy of the Sjv-2 transition state, increasing AG- and decreasing the reaction rate (Figure 11.7a). As a result, SN2 reactions are best for methyl and primary substrates. Secondary substrates react slowly, and tertiary substrates do not react by an S -2 mechanism. 

Two reaction mechanisms, such as SN1 and SN2 mechanisms, seem to be possible for explaining formations of 158a-c (Scheme 25). The former requires a resonance-stabilized indolyl cation 165 as an intermediate, while the latter indicates the presence of a transition state like 167. The introduction of a methoxy group into the 5 position of 165 should stabilize the corresponding cation 166, in which nucleophilic substitution on indole nitrogen would become a predominant pathway. 

The greater the contribution of 4 to the transition state, the more firmly the system is placed in the N category likewise a large contribution from 5 is characteristic of the Lim category. Bentley and Schleyer state that the essential difference between the SnI and Sn2 mechanisms depends upon whether nucleophilic attack 

No single mechanism accounts for all the reactions. One pathway involves a concerted one-step process involving a cyclic transition state. This of necessity affords a c -product. Another possibility, more favoured in polar solvents, involves a cationic 5-coordinate intermediate [IrX(A)(CO)L2]+, which undergoes subsequent nucleophilic attack by B-. Other possibilities include a SN2 route, where the metal polarizes AB before generating the nucleophile, and radical routes. Studies are complicated by the fact that the thermodynamically more stable isolated product may not be the same as the kinetic product formed by initial addition. 

E.Z-Selectivity in the insertion by unsymmetrical carbenoid 24, is specifically indicative of the transition state of the stepwise mechanism. Based on the evidence that carbenoid 24, which is generated from 42 or 43 (E Z = 84 16), exists nearly exclusively in the -configuration under the equilibrium even at —95°C,29 the observed stereoselectivity for E-isomers in the insertion products verifies that hydride abstraction takes place via an Sn2-like transition state 52 with inversion of configuration at the carbenoid carbon, followed by the recombination of menthone 40 and carbanion 53 (Scheme 19). 

Rate IS governed by stability of car bocation that is formed in loniza tion step Tertiary alkyl halides can react only by the SnI mechanism they never react by the Sn2 mecha nism (Section 8 9) Rate IS governed by steric effects (crowding in transition state) Methyl and primary alkyl halides can react only by the Sn2 mecha nism they never react by the SnI mechanism (Section 8 6) 

Hughes and Ingold interpreted second-order kinetic behavior to mean that the ratedetermining step is bimolecular, that is, that both hydroxide ion and methyl bromide are involved at the transition state. The symbol given to the detailed description of the mechanism that they developed is Sn2, standing for substitution nucleophilic bimolecular. 

The Sn2 mechanism is believed to describe most substitutions in which simple primary and secondary alkyl halides react with anionic nucleophiles. All the exanples cited in Table 8.1 proceed by the Sn2 mechanism (or a mechanism very much like Sn2— remember, mechanisms can never be established with certainty but represent only our best present explanations of experimental observations). We ll examine the Sn2 mechanism, particularly the stnacture of the transition state, in more detail in Section 8.5 after-first looking at some stereochemical studies cariied out by Hughes and Ingold. 

In the critical area of (1-mannoside synthesis [317-321], the evidence strongly suggests that a-mannosyl triflate serves as a reservoir for a transient contact ion pair (CIP), which is the glycosylating species (Scheme 4.37), although the possibility of an SN2-like mechanism with an exploded transition state cannot be completely excluded [135]. In view of the probable operation of the contact ion-pair mechanism 

For each reaction, plot energy (vertical axis) vs. the number of the structure in the overall sequence (horizontal axis). Do reactions that share the same mechanistic label also share similar reaction energy diagrams How many barriers separate the reactants and products in an Sn2 reaction In an SnI reaction Based on your observations, draw a step-by-step mechanism for each reaction using curved arrows () to show electron movements. The drawing for each step should show the reactants and products for that step and curved arrows needed for that step only. Do not draw transition states, and do not combine arrows for different steps. 

The possible mechanisms for solvolysis of phosphoric monoesters show that the pathway followed depends upon a variety of factors, such as substituents, solvent, pH value, presence of nucleophiles, etc. The possible occurrence of monomeric metaphosphate ion cannot therefore be generalized and frequently cannot be predicted. It must be established in each individual case by a sum of kinetic and thermodynamic arguments since the product pattern frequently fails to provide unequivocal evidence for its intermediacy. The question of how free the PO ion actually exists in solution generally remains unanswered. There are no hard boundaries between solvation by solvent, complex formation with very weak nucleophiles such as dioxane or possibly acetonitrile, existence in a transition state of a reaction, such as in 129, or SN2(P) or oxyphosphorane mechanisms with suitable nucleophiles. 

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