Nucleophiles ion pairs

Phase-transfer catalytic (PTC) conditions, which are specific for anionic reactions (and anionic activation) are perfectly well tailored for microwave activation, because after ion exchange between a substrate and catalyst, the resulting nucleophilic ion pair is a highly polar species especially prone to interaction with microwaves [32]. Eventually, the mixture of neat reagents in an open vessel can lead to a reaction under microwave conditions provided that one of the reagents is liquid or a low melting solid that couples well with microwaves. On the other hand, even a small amount of a good microwave absorber (e.g,. H20, DMF for example, see Table 1.3) added to reaction mixtures that consist of substrates that do not absorb microwaves in the solid state can initiate an increase of reaction mixture temperature and then chemical reaction. 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

Amines also react with diacyl peroxides by nucleophilic displacement on the oxygen—oxygen bond forming an ion pair iatermediate (187) ... 

For continuing polymerization to occur, the ion pair must display reasonable stabiUty. Strongly nucleophilic anions, such as C/ , are not suitable, because the ion pair is unstable with respect to THE and the alkyl haUde. A counterion of relatively low nucleophilicity is required to achieve a controlled and continuing polymerization. Examples of anions of suitably low nucleophilicity are complex ions such as SbE , AsF , PF , SbCf, BE 4, or other anions that can reversibly coUapse to a covalent ester species CF SO, FSO, and CIO . In order to achieve reproducible and predictable results in the cationic polymerization of THE, it is necessary to use pure, dry reagents and dry conditions. High vacuum techniques are required for theoretical studies. Careful work in an inert atmosphere, such as dry nitrogen, is satisfactory for many purposes, including commercial synthesis. 

Substituted 2-haloaziridines are also known to undergo a number of reactions without ring opening. For example, displacement of chlorine in (264) with various nucleophilic reagents has been found to occur with overall inversion of stereochemistry about the aziridine ring (65JA4538). The displacements followed first order kinetics and faster rates were noted for (264 R = Me) than for (264 R = H). The observed inversion was ascribed to either ion pairing and/or stereoselectivity. 

The ionization and direct displacement mechanisms can be viewed as the extremes of a mechanistic continuum. At the 8 1 extreme, there is no covalent interaction between the reactant and the nucleophile in the transition state for cleavage of the bond to the leaving group. At the 8 2 extreme, the bond formation to the nucleophile is concerted with the bondbreaking step. In between these two limiting cases lies the borderline area, in which the degree of covalent interaction between the nucleophile and the reactant is intermediate between the two limiting cases. The concept of ion pairs is important in the consideration of... 

Attack by a nucleophile or the solvent can occur at either of the ion pairs. Nucleophilic attack on the intimate ion pair would be expected to occur with inversion of configuration, since the leaving group would still shield the fiont side of the caibocation. At the solvent-separated ion pair stage, the nucleophile might approach fiom either fece, particularly in the case where solvent is the nucleophile. Reactions through dissociated carbocations should occur with complete lacemization. According to this interpretation, the identity and stereochemistry of the reaction products will be determined by the extent to which reaction occurs on the un-ionized reactant, the intimate ion pair, the solvent-separated ion pair, or the dissociated caibocation. 

If it is assumed that ionization would result in complete randomization of the 0 label in the caihoxylate ion, is a measure of the rate of ionization with ion-pair return, and is a measure of the extent of racemization associated with ionization. The fact that the rate of isotope exchange exceeds that of racemization indicates that ion-pair collapse occurs with predominant retention of configuration. When a nucleophile is added to the system (0.14 Af NaN3), k y, is found to be imchanged, but no racemization of reactant is observed. Instead, the intermediate that would return with racemization is captured by azide ion and converted to substitution product with inversion of configuration. This must mean that the intimate ion pair returns to reactant more rapidly than it is captured by azide ion, whereas the solvent-separated ion pair is captured by azide ion faster than it returns to racemic reactant. 

The concept of ion pairs in nucleophilic substitution is now generally accepted. Presumably, the barriers separating the intimate, solvent-separated, and dissociated ion pairs are quite small. The potential energy diagram in Fig. 5.4 depicts the three ion-pair species as being roughly equivalent in energy and separated by small barriers. 

An elaboration of the ion-pair concept includes an ion sandwich in which a preassociation occurs between a potential nucleophile and a reactant. Such an ion sandwich might be a kinetic intermediate which accelerates dissociation. Alternatively, if a caibocation were quite unstable, it might always return to reactant unless a nucleophile was properly positioned to capture the caibocation. 

Fig. 5.7. Mote O Ferrall-Jencks diagtam showing concerted, ion-pair and stepwise mechanisms for nucleophilic substitution.

Entry 4 shows that reaction of a secondary 2-octyl system with the moderately good nucleophile acetate ion occurs wifii complete inversion. The results cited in entry 5 serve to illustrate the importance of solvation of ion-pair intermediates in reactions of secondary substrates. The data show fiiat partial racemization occurs in aqueous dioxane but that an added nucleophile (azide ion) results in complete inversion, both in the product resulting from reaction with azide ion and in the alcohol resulting from reaction with water. The alcohol of retained configuration is attributed to an intermediate oxonium ion resulting from reaction of the ion pair with the dioxane solvent. This would react until water to give product of retained configuratioiL When azide ion is present, dioxane does not efiTectively conqiete for tiie ion-p intermediate, and all of the alcohol arises from tiie inversion mechanism. ... 

The order of enolate reactivity also depends on the metal cation which is present. The general order is BrMg < Li < Na < K. This order, too, is in the order of greater dissociation of the enolate-cation ion pairs and ion aggregates. Carbon-13 chemical shift data provide an indication of electron density at the nucleophilic caibon in enolates. These shifts have been found to be both cation-dependent and solvent-dependent. Apparent electron density increases in the order > Na > Li and THF/HMPA > DME > THF >ether. There is a good correlation with observed reactivity under the corresponding conditions. 

Ionization is obviously important in the SnI mechanism of nucleophilic substitution, and indeed two ion pair intermediates have been invoked.These are related as in Eq. (8-19), where (s) represents the solvent. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

The pyrylium cation possesses, according to the substituents in positions 2, 4, and 6, a more or less pronounced electrophilic reactivity which enables it to add nucleophiles in these positions. According to the nucleophilic reactivity and the carbon basicity " of the anions, an ion pair (a substituted pyrylium cation and an anion halide, perchlorate, sulfate, fluoroborate, chloroferrate, etc.), or a covalently bonded 2H- or 4//-pyran may be formed. With the more basic anions... 

Evidence that the actual methylation of the anion can be divided into SnI, Eq. (3), and Sx2 types, Eq, (4), is provided by a whole series of investigations. " The terms S l and 8 2 must be taken to mean reactions with, respectively less or greater nucleophilic participation of the anion in the transition state. The importance of oriented ion pairs" in the solvents of low polarity frequently used in reactions involving diazomethanc, e.g., the ions formed by a diazoalkane and benzoic acid in ether, should be emphasized. The expression oriented ion pair means that, because of insufficient solvation, the ions are not individually solvated but exist as ion pairs within a solvent cage. The orientation within the ion pair is defined electrostatically, and this orientation fixes the path for the productdetermining step. Several indications (cf, foo otes 22-24) in the literature indicate the occurrence of carbonium ions and oriented ion pairs in Broensted-type equilibria of the type of Eq. (2). 

This aminium radical salt in aqueous solution in the form of solvated radical salt is very stable and will not polymerize acrylonitrile even with CeHsCOONa to form the corresponding benzoate. Therefore, we believe that in the nucleophilic displacement, there must be some intermediate step, such as intimate ion pair and cyclic transition state, which will then proceed the deprotonation to form the active aminium radical ion [14], as shown in Scheme 1. The presence of the above aminomethyl radical has also been verified [15] through ultraviolet (UV) analysis of this polymer formed such as PAN or PMMA with the characteristic band as the end group. 

Figure 11.11 Ion pairs in an S l reaction. The leaving group shields one side of the carbocation intermediate from reaction with the nucleophile, thereby leading to some inversion ol configuration rather than complete racemization.

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