Substitution, nucleophilic, unimolecular reactions

A large number of radical reactions proceed by redox mechanisms. These all require electron transfer (ET), often termed single electron transfer (SET), between two species and electrochemical methods are very useful to determine details of the reactions (see Chapter 6). We shall consider two examples here - reduction with samarium di-iodide (Sml2) and SRN1 (substitution, radical-nucleophilic, unimolecular) reactions. The SET steps can proceed by inner-sphere or outer-sphere mechanisms as defined in Marcus theory [19,20]. 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

Alkyl halides undergo nucleophilic substitution reactions by unimolecular (S l) and bimolecular (S 2) pathways. The substitution reactions of alkyl halides, and of derivatives of alcohols, utilize oxygen, nitrogen, sulfur and carbon nucleophiles. 

Substitution reactions of t-butyl halides, you will recall from Chapter 15, invariably follow the S l mechanism. In other words, the rate-determining step of their substitution reactions is unimolecular—it involves only the alkyl halide. This means that, no matter what the nucleophile is, the reaction goes at the same rate. You can t speed this S l reaction up, for example, by using hydroxide instead of water, or even by increasing the concentration of hydroxide. You d be wasting your time, we said (see p. 332). 

This chain reaction is analogous to radical chain mechanisms for nucleophilic aliphatic nucleophilic substitution that had been suggested independently by Russell and by Komblum and their co-workers. The descriptive title SrnI (substitution radical-nucleophilic unimolecular) was suggested for this reaction by analogy to the SnI mechanism for aliphatic substitution. The lUPAC notation for the SrkjI reaction is (T -t- Dm -t- An), in which the symbol T refers to an electron transfer. When the reaction was carried out in Ihe presence of solvated electrons formed by adding potassium metal to the ammonia solution, virtually no aryne (rearranged) products were observed. Instead, reaction of 95c produced only 98 (40%) and 94 (40%) but no 99, and reaction of 96c produced 99 (54%) and 94 (30%) with only a trace of 98. ... 

Gas-phase SN2 nucleophilic substitution reactions are particularly interesting because they have attributes of both bimolecular and unimolecular reactions.1 As discovered from experimental studies by Brauman and coworkers2 and electronic structure theory calculations,3 potential energy surfaces for gas-phase SN2 reactions of the type,... 

The reaction is unimolecular => SnI reaction (Substitution, Nucleophilic, Unimolecular). 

So the tertiary halide reacts by a different mechanism, which we call SnI- It s still a nucleophilic substitution reaction (hence the S and the N ) but this time it is a unimolecular reaction, hence the 1 . The rate-determining step during reaction is the slow unimolecular dissociation of the alkyl halide to form a bromide ion and a carbocation that is planar around the reacting carbon. 

FIGURE 2.10 Differentiation of SN1 (substitution nucleophilic unimolecular, first order) and SN2 (substitution nucleophilic bimolecular, second order) reactions. 

SnI reaction means substitution nucleophilic unimolecular. The SnI reaction occurs in two steps, with the first being a slow ionization reaction generating a carbocation. Thus, the rate of an S l reaction depends only on the concentration of the alkyl halide. First, the C—X bond breaks without any help from the nucleophile, and then there is quick nucleophilic attack by the nucleophile on the carbocation. When water or alcohol is the nucleophile, a quick loss of a proton by the solvent gives the hnal product. For example, the reaction of t-butylbromide and methanol gives t-butyl methyl ether. 

We note that in Eq. 13-11 we have introduced the El (elimination, unimolecular) reaction, which commonly competes with the SN1 reaction provided that an adjacent carbon atom carries one or several hydrogen atoms that may dissociate. We also note that similar to what we have stated earlier for nucleophilic substitution reactions, elimination reactions may occur by mechanisms between the E2 and El extremes. 

One of the most common reasons for lowyields is an incomplete reaction. Rates of organic reactions can vary enormously, some are complete in a few seconds whereas rates of others are measured on a geological timescale. Consequently, to ensure that the problem of low yields is not simply due to low reactivity, reaction conditions should be such that some or all of the starting material does actually react. If none of the desired product is obtained, but similar reactions of related compounds are successful, the mechanistic implications should be considered. This situation has been referred to as Limitation of Reaction, and several examples have been given [32 ] the Hofmann rearrangement, for example, does not proceed for secondary amides (RCONHR ) because the intermediate anion 28 cannot form (Scheme 2.11). Sometimes, a substrate for a mechanistic investigation may be chosen deliberately to exclude particular reaction pathways for example, unimolecular substitution reactions of 1-adamantyl derivatives have been studied in detail in the knowledge that rear-side nucleophilic attack and elimination are not possible and hence not complications (see Section 2.7.1). 

The second type of mechanism is an S 1 mechanism. This mechanism follows first-order kinetics (the reaction rate depends on the concentration of one reactant), and its intermediate contains only the substrate molecule and is therefore unimolecular. The terminology S 1 stands for substitution nucleophilic unimolecular. ... 

Apart from overcoming coulombic repulsions, 8 2 reactions also proceed with inversion in the face of steric hindrance. By comparison, the stereochemical result of unimolecular nucleophilic substitution SN1 is variable. In fact, nucleophilic substitutions at carbon with retention invariably follow other than SN2 paths. In its broad outlines, the Hughes-Ingold approach swept away the confusions of the period 1895-1933 and has not ceased to stimulate and provoke ideas in the area of substitution reactions. Surprisingly enough, the theoretical foundations of the SN2 process require reexamination and modification, as we shall see. 

The fact that the rate law depends only on the concentration of tert-butyl chloride means that only tert-butyl chloride is present in the transition state that determines the rate of the reaction. There must be more than one step in the mechanism because the acetate ion must not be involved until after the step with this transition state. Because only one molecule pert-butyl chloride) is present in the step involving the transition state that determines the rate of the reaction, this step is said to be unimolecular. The reaction is therefore described as a unimolecular nucleophilic substitution reaction, or an SN1 reaction. 

Sisl reaction or unimolecular nucleophilic substitution reaction (Section 8.6) A reaction in which the nucleophile replaces the leaving group at an sp3-hybridized carbon in a two-step mechanism that proceeds through a carbocation intermediate. 

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