Possible Mechanisms for Nucleophilic Substitution

Now that you know something about the general features of nucleophilic substitution, you can begin to understand the mechanism. 

Nucleophilic substitution at an sp hybridized carbon involves two o bonds the bond to the leaving group, which is broken, and the bond to the nucleophile, which is formed. To understand the mechanism of this reaction, though, we must know the timing of these two events that is, what 

This a bond is broken. This a bond is formed. 

---

The preceding discussion has generated two possible mechanisms for nucleophilic substitution a one-step mechanism in which bond breaking and bond making are simultaneous, and a two-step mechanism in which bond breaking comes before bond making. In Section 7.10 we look at data for two specific nucleophilic substitution reactions and see if those data fit either of these proposed mechanisms. 

Rate equations for two different reactions give us insight into the possible mechanism for nucleophilic substitution. 

The paper discussed possible mechanisms for nucleophilic substitution at a cyclopropane carbon with particular attention to retentive replacements. From the NMR spectra of the syn- and anti-bromides and acetates shown above, it was concluded that smooth stereospecific substitution of bromide by acetate had taken place under typical Sis 2-type conditions. For the anti-pair, comprising two solids (one member of the syn pair is an oil), this conclusion was confirmed by X-ray structure determination of both educt and product. 

There are two possible mechanisms for nucleophilic substitution. In a reaction the molecule first forms a carbonium ion for example ... 

Nomenclature Physical properties Interesting alkyl halides The polar carbon-halogen bond General features of nucleophilic substitution The leaving group The nucleophile Possible mechanisms for nucleophilic substitution Two mechanisms for nucleophilic substitution The S 2 mechanism Application Useful Snj2 reactions... 

Part of the evidence for the existence of two possible mechanisms for nucleophilic substitution reactions is the kinetic order of the reaction (Section 9.9). We know an Sj 2 mechanism is a one-step process in which the nucleophile attacks the substrate and the leaving group departs simultaneously. In this concerted, bimolecular process, the substrate and the nucleophile are both present in the transition state. The rate of the reaction depends on the concentrations of both the nucleophile and the substrate. 

This mechanism is exactly analogous to the allylic rearrangement mechanism for nucleophilic substitution (p. 421). The UV spectra of allylbenzene and 1-propenylbenzene in solutions containing NH2 are identical, which shows that the same carbanion is present in both cases, as required by this mechanism. The acid BH protonates the position that will give the more stable product, though the ratio of the two possible products can vary with the identity of BH". It has been shown that base-catalyzed double-bond shifts are partially intramolecular, at least in some cases. The intramolecularity has been ascribed to a conducted tour mechanism (p. 766) in which the base leads the proton from one carbanionic site to the other ... 

Phosphate esters have a variety of mechanistic paths for hydrolysis. Both C-O and P-0 cleavage are possible depending on the situation. A phosphate monoanion is a reasonable leaving group for nucleophilic substitution at carbon and so 8 2 or SnI reactions of neutral phosphate esters are well known. PO cleavage can occur by associative (by way of a pentacoordinate intermediate), dissociative (by way of a metaphosphate species), or concerted (avoiding both of these intermediates) mechanisms. 

Scheme4.3. Possible mechanism for stereospecific radical nucleophilic substitutions [15],...

Since thiols and thiyl radicals are known to readily undergo addition reactions at unsaturated carbon centers (199, 202, 204), a possible mechanism for this inactivation reaction is shown in Scheme 43. Addition of the active site nucleophilic or radical species followed by protonation or electron transfer, respectively, would yield the thioacrylate derivative and inactive enzyme. Of course, addition to C-2 of propargylic acid is also possible, forming a 2-substituted acrylate derivative instead. 

There are three possible mechanisms for a phosphoryl transfer reaction. We will illustrate them using the following nucleophilic acyl substitution reaction. 

The study of pseudorotation in five-co-ordinate phosphorus(v) compounds is undertaken not only out of intrinsic interest but also for its relevance to rearrangements in transition states for nucleophilic substitution at tetrahedral phosphorus(v) compounds (c/. pp. 118—120). Pseudorotation in the stable compound MeaN PF4 takes place via a square-pyramidal transition state. The variation of line widths with temperature for various lines in the n.m.r. spectrum permits a distinction to be drawn between possible processes involving simultaneous interchange of two pairs of fluorine atoms, as required for the Berry mechanism for pseudorotation, or of only one pair. Inversion or pseudorotation in... 

The possible mechanism for present investigation involves the nucleophilic attack of a bromide ion at the less substituted C-3 position of the spiro epoxide leading to the formation of an intermediate (II and 12). Further, as sulfur is abetter nucleophile than nitrogen, in the next step cyclization leads to formation of an oxathiolane ring (Scheme 8.57). 

The stereochemistry and mechanistic implication for nucleophilic substitution at silicon continue to receive attention, and have been the subject of a comprehensive reviewThe nucleophiles HMPA, DMSO, DMF, and PhaPO catalyze the hydrolysis of triorganochlorosilanes and also their racemization. Stable 1 1 ionic adducts of HMPA with MeaSiBr have been isolated in the past and suggested to be possible intermediates in the racemization process. However, it has now been shown that such ionic 1 1 adducts are not usually formed and that the reported example was a special case which should not be generalized into a mechanism involving displacement of halides by the nucleophile. The previously accepted mechanism involving the formation of five- and six-coordinate species still seems more feasible. 

For nucleophilic substitutions involving alkylor arylsulfonyl halides 8 possessing at least one a-hydrogen atom, a different reaction mechanism is possible as shown (Equation 10) ... 

Nucleophilic Substitution, Metallation, and Halogen-Metal Exchange.—Direct nucleophilic displacement of the 7-chloro-group of 7-chloro-3-methyl-benzo[b]thiophen has been achieved. 3-Bromobenzo[b]thiophen was reduced to the 3-deuterio-derivative by the reaction with sodium borodeuteride and palladium chloride. Meisenheimer complexes were formed in the reaction of methoxide ion with 2-methoxy-3-nitro- and 3-methoxy-2-nitrobenzo[b]thiophen. Rate and equilibrium data were determined in methanol at 25 C. On treatment of 2-bromobenzo[b]thiophen with potassium amide in liquid ammonia, bromine migration to the adjacent carbon atom was observed. Considerable evidence for the occurrence of an intermolecular transbromination was obtained. The reaction of 3-bromo-benzo[b]thiophen with piperidine has been reinvestigated and found to give primarily the normal, but also some of the cine-substitution product, which is the only product obtained in the reaction of 2-bromobenzo[b]thiophen. Possible mechanisms for some of these reacticms are suggested. 

---