Sn2 Displacement Mechanism

Promotion of an SN2 displacement mechanism, and hence greater regioselectivity, may be effected by the addition of liquid bromine to a warm suspension of purified red phosphorus in the appropriate alcohol. The reaction is of general application with primary alcohols (isobutyl alcohol to hexadecan-l-ol) the yields are over 90 per cent of the theoretical, but with secondary alcohols the yields are in the range 50-80 per cent (Expt 5.55). This method is to be preferred to the direct use (rather than the in situ generation) of phosphorus tribromide which is the more hazardous reagent. The outline mechanism may be represented thus ... 

Another case for which ET could be expected as a viable alternative to the SN2 displacement mechanism concerns the reactions of CH3I and CC14 with the nitric oxide anion, NO-263. Because of the extremely low electron affinity of NO (0.024- 0.55 kcalmof1), an ET process to the halo-compounds would be exothermic. However, in neither case was the substrate radical anion observed, despite the fact that both have bound molecular anions. Both reactions yield only the halide ion, a product which can arise via dissociative ET (a) or S 2 (b) (Scheme 38). The mechanism could not be assigned. 

The normal "backside displacement geometry associated with an SN2 transition state is impossible to achieve at a carbon atom in a benzene ring. There is, in fact, no evidence to support the occurrence of the one-step SN2 displacement mechanism at a benzene carbon. 

Cobaloximes(I) and hydridocobaloximes can be arylated with aryl halides with electron-withdrawing substituents, consistent with both electron transfer and Sn2 displacement mechanisms. 

The mechanism for the Wenker aziridine synthesis is very straightforward. As depicted by conversion 2—>3, the transformation is a simple case of intramolecular Sn2 displacement process, in which the sulfate ester is the leaving group. 

Diethyl ether and other simple symmetrical ethers are prepared industrially by the sulfuric acid-catalyzed dehydration of alcohols. The reaction occurs by SN2 displacement of water from a protonated ethanol molecule by the oxygen atom of a second ethanol. Unfortunately, the method is limited to use with primary alcohols because secondary and tertiary alcohols dehydrate by an El mechanism to yield alkenes (Section 17.6). 

The selectivity decreases with increasing amide size. This may be due to steric hindrance which prevents the chiral ligand from approaching the reaction site or may reflect a change in the reaction mechanism going from an SN1 reaction (A-acylimine 2 as intermediate) to an SN2 displacement of benzotriazole11. 

However, if we consider the alternative nucleophilic displacement, it is known that nucleophilic processes are accelerated by ionic liquids, but more pertinent is the fact that the Sn2 displacement of iodide from alkyl iodide (Mel) by Rh(CO)2l2 is slightly accelerated by ionic liquids (7). Unfortunately, ionic liquids would also be expected to accelerate the nucleophilic displacement of iodide from ethyl iodide by propionic acid to form ethyl propionate (Reaction 8). In fact, as an Sn2 Type II displacement (the interaction of two neutral species), the ester formation from propionic acid and ethyl iodide would be expected to be significantly increased compared to the reaction of Rh(CO)2l2 with EtI. Therefore, by operating in iodide containing ionic liquids, we had set up a situation in which we suppressed the normally predominant hydride mechanism, slightly accelerated the alternative nucleophilic mechanism, but dramatically increased the ethyl propionate by-product forming pathway. 

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. 

It has been shown e that two mechanisms, elimination-addition (benzyne) and SN2 displacement, are operative in the liquid-phase hydrolysis of halogenatcd aromatic compounds. The formation of isomeric phenols as a result of the availability of the benzyne route makes the reaction of limited synthetic value. The incorporation of the copper-cuprous oxide system suppresses reaction via the benzyne route, so that the present method has general utility for the preparation of isomer-free phenols. For example, >-cresol is the only cresol formed from -bromotoluene under the conditions of this preparation. 

Okamoto and co-workers noted that N-phenylhydroxylamine gave predominately diphenylamine on treatment with benzene in TFA but mostly 4-aminobiphenyl and 2-aminobiphenyl in the stronger acid trifluoromethane-sulfonic acid (TFSA). Similar results were obtained if benzene was replaced by toluene or anisole. The authors suggested that the reaction in TFA proceeded through O-protonated hydroxylamine either via a direct Sn2 displacement on N by the aromatic nucleophile or via attack of the aromatic compound on the N of a nitrenium ion. In TFSA they favored a mechanism in which the diprotonated hydroxylamine lost water to generate an iminium-benzenium dication (11, Scheme 5), a protonated nitrenium ion. " This... 

Evidence for the SNl-type mechanism is provided by fluorodehydroxylation of diastereomeric benzylic alcohols both diastercomers give the same mixture of products which implies that bond breaking precedes bond making in precursors that readily form carbenium ions. Evidence for an SN2 displacement is based on the results of fluorodehydroxylation of epimeric a-amino-/ -hydroxypropanoic acids which proceeds with predominant inversion of configuration.40... 

The formation and the hydrolysis of acyclic and cyclic acetals have been studied in rather great detail [91]. Several reviews on this topic are available [92] and some comments have been made [13] concerning the carbohydrate series. We have shown in Schemes 1,2, and 3 that a common feature of this reaction seems to be the intermediacy of an oxocarbenium ion. However, the cyclization of such an intermediate has been questioned more recently [93] in the light of the Baldwin s rules for ring closure [94]. At least for the five-membered ring, an SN2-type displacement mechanism far the protonated form (B) of die hemiacetal (A) (favorable 5-exo-tet cyclization) has been proposed rather than the unfavorable 5-endo-trig cyclization of the oxocarbenium ion (C) (Scheme 5). Except when the formation of the enol ether (D) is structurally impossible, the intermediacy of such a compound remains feasible. 

A nucleophilic mechanism can be applied in reductions with complex hydrides of highly fluori-nated aliphatic and alicyclic fluoroalkenes with electron-deficient C = C bonds the hydride anion adds as a strong nucleophilic agent to the more electrophilic carbon atom the intermediate anion can then lose a fluoride ion either from the original C = C bond, or from the allylic position finishing an SN2 displacement of the fluorine. Thus, the reductions of vinylic C-F bonds with hydrides proceed by a nucleophilic addition-elimination mechanism. Displacement of fluorine in highly fluorinated aromatic compounds proceeds by the same mechanism ... 

ROH —> R —C—OR + HX, which overall is a nucleophilic displacement of the X group by the nucleophile ROH. However, the mechanism of displacement is quite different from the SN2 displacements of alkyl derivatives, R X + ROH — R OR + HX, and closely resembles the nucleophilic displacements of activated aryl halides (Section 14-6B) in being an addition-elimination process. 

This mechanism corresponds to an SN2 displacement of water from the methyloxonium ion by the acid. How could you distinguish between this mechanism and the addition-elimination mechanism using heavy oxygen (180) as a tracer ... 

Acidic conditions also can be used for the cleavage of oxacyclopropane rings. An oxonium ion is formed first, which subsequently is attacked by the nucleophile in an SN2 displacement or forms a carbocation in an SN1 reaction. Evidence for the SN2 mechanism, which produces inversion, comes not only from the stereochemistry but also from the fact that the rate is dependent on the concentration of the nucleophile. An example is ring opening with hydrogen... 

---