Sn2 substitution mechanism

A variety of mechanisms have been found (3). Simple SN2 substitution mechanisms are most common, followed by free-radical pathways. The latter occur by two mechanisms (a) removal of X as an atom, followed by reactions of R and (b) single-electron transfer from MLn to RX, to give R . Hydride ion transfer reactions are also known (4). Reactions believed to be simple SN2 processes in which RX is methyl iodide are discussed here. 

In the synthesis of propargylic alcohols, we saw the reaction of an alkynyl nucleophile (either the anion RC=CNa or the Grignard RC CMgBr, both prepared from the alkyne RC CH) with a carbonyl electrophile to give an alcohol product. Such acetylide-type nucleophiles will undergo Sn2 reactions with alkyl halides to give more substituted alkyne products. With this two-step sequence (deprotonation followed by alkylation), acetylene can be converted to a terminal alkyne, and a terminal alkyne can be converted to an internal alkyne. Because acetylide anions are strong bases, the alkyl halide used must be methyl or 1° otherwise, the E2 elimination is favored over the Sn2 substitution mechanism. 

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. 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

For the Cl" + CH3Clb trajectories on PES1, direct substitution only occurs when the C-Cl stretch normal mode is excited with three or more quanta. For CH3Clb at 300 K, the probability of this vibrational excitation and the rate constant with vibrational excitation is too small to make direct substitution an important contributor to Cl + CH3Clb - ClaCH3 + Cl Sn2 nucleophilic substitution on PES1. However, the direct substitution mechanism may become more important if less... 

The existence itself of the Sn2 mechanism, the question of its concertedness, and the origin of its stereochemistry, have been matter of hvely debate for the last half-century. The controversy was continuosly sustained by the paucity of firm proofs of the Sn2 mechanism in solution and by the coincidence of the Sn2 products with those arising from alternative competing mechanisms, i.e., SnU unimolecular rearrangement of the starting alcohol before substitution and of its derivatives after Sn2 substitution, etc. 

Glucuronidation involves the transfer of D-glucuronic acid from UDP-a-glu-curonic acid to an acceptor compound. The family of enzymes which catalyze this reaction are the UDP-glucuronyl transferases [16]. The reaction proceeds by nucleophilic Sn2 substitution of the C-1 carbon of glucuronic acid, the product undergoing inversion of configuration. The mechanism is illustrated schematically in Figure 7.21. 

As noted in Section 4.2.1, the gas phase has proven to be a useful medium for probing the physical properties of carbanions, specifically, their basicity. In addition, the gas phase allows chemists to study organic reaction mechanisms in the absence of solvation and ion-pairing effects. This environment provides valuable data on the intrinsic, or baseline, reactivity of these systems and gives useful clues as to the roles that solvent and counterions play in the mechanisms. Although a variety of carbanion reactions have been explored in the gas phase, two will be considered here (1) Sn2 substitutions and (2) nucleophilic acyl substitutions. Both of these reactions highlight some of the characteristic features of gas-phase carbanion chemistry. 

Reactions of nitrenium ions with lifetimes in aqueous solution ns. It is clear from the work presented to date that these species react predominately by ion-pair or preassociation mechanisms, but the detailed processes are far from clear. The possible transition to a true bimolecular substitution mechanism (Sn2) has also not been systematically investigated. 

Several research groups ha ve been involved in the study of ET reactions from an electrochemically generated aromatic radical anion to alkyl halides in order to describe the dichotomy between ET and polar substitution (SN2). The mechanism for indirect reduction of alkyl halides by aromatic mediators has been described in several papers. For all aliphatic alkyl halides and most benzylic halides the cleavage of the carbon-halogen bond takes place concertedly with the... 

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