Unimolecular nucleophilic reactions

LIMITING UNIMOLECULAR NUCLEOPHILIC REACTIONS. KINETICS AND STEREOCHEMISTRY1... 

Section 4.9 The potential energy diagrams for separate elementary steps can be merged into a diagram for the overall process. The diagram for the reaction of a secondary or tertiary alcohol with a hydrogen halide is characterized by two intermediates and three transition states. The reaction is classified as a unimolecular- nucleophilic substitution, abbreviated as SnI. 

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

The abbreviation SnI conveys the information sub-stitution-nucleophilic-unimolecular . The reaction achieves much the same result as the Sn2 reaction, i.e. the replacement of a leaving group by a nucleophile, but is mechanistically different. It is unimolecular, since kinetic data indicate that only one species is involved in the rate-determining step ... 

Shafizadeh5 has suggested that a unimolecular (SNO reaction is operative. In this type of reaction, the rate-determining step would be the formation of a carbonium ion, with the removal of the ethylthio group subsequent attack on this ion by the nucleophile would be rapid. In an SNj reaction, the removal of the ethylthio group and the attack by the nucleophile would be simultaneous. The SNi reaction seems more probable here. 

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). 

Because the slowest step of this reaction only involves t-butyl bromide, the overall rate of reaction only depends on the concentration of this species. This is therefore a unimolecular nucleophilic substitution, or SN1, reaction. 

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 gas-phase base-induced elimination reaction of halonium ions was thoroughly investigated in radiolytic experiments22. Radiolytically generated acids C/JH5+ (n = 1,2) were allowed to react at 760 Torr with selected 2,3-dihalobutanes to form the halonium intermediates which, in the presence of trimethylamine, undergo base-induced bimolecu-lar elimination as shown in Scheme 6. This elimination reaction occurs in competition with unimolecular nucleophilic displacement to the cyclic halonium ion and subsequent rearrangement. Isolation and identification of the neutral haloalkenes formed and kinetic treatment of the experimental results indicated that 3-halo-1 -butene is formed preferentially with respect to the isomeric 2-halo-2-butenes and that the bimolecular elimination process occurs predominantly via a transition state with an anti configuration22. 

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. 

The activation mechanism of phosphosulfate linkages (P—O —S)has been studied to understand the chemistry of biological sulfate-transfer reactions of phosphosul-fates of adenosine (APS and PAPS). Several phosphosul-fates were prepared and subjected to several nucleophilic reactions including hydrolysis. In general, phosphosulfates are stable in neutral aqueous mediay but become labile under acidic conditions, resulting in selective S—O fission. This S—O fission appears to occur by unimolecular elimination of sulfur trioxide, which can react with a nucleophilic acceptor, leading to a sulfate-transfer reaction. This process can be accelerated by Mg2+ ion when the solvent is of low water content. Under neutral conditions, divalent metal ions also were found to catalyze nucleophilic reactions, but these occurred on phosphorus to result in exclusive P-O fission. 

In unimolecular surface reactions, a single reactant species is adsorbed and reacts on the surface. A good example is given by catalysed nucleophilic solvolyses discussed further in Sect. 2.1. The reaction scheme may then be written... 

S[sjl reaction (Section 11.4) A unimolecular nucleophilic substitution reaction. 

In the preceding Section, the poly-O-acylglycosyl halides have been discussed with particular reference to the effect of their structure on the reactivity of the halogen atom and on the configuration of the product resulting from the unimolecular, nucleophilic substitution. In the present Section is given a general account of the reactions of the halides which refers more to the type of product which may be obtained from these compounds. 

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