Anchimeric assistance, also

Summary This is an example of anchimeric assistance (also called neighbouring group participation) in nucleophilic substitution reactions... 

Table 15 shows that peroxyester stabiUty decreases for the alkyl groups in the following order tert — butyl > tert — amyl > tert — octyl > tert — cumyl > 3 — hydroxy — 1,1 dimethylbutyl. The order of activity of the R group in peroxyesters is also observed in other alkyl peroxides. Peroxyesters derived from benzoic acids and non-abranched carboxyUc acids are more stable than those derived from mono-a-branched acids which are more stable than those derived from di-a-branched acids (19,21,168). The size of the a-branch also is important, since steric acceleration of homolysis occurs with increasing branch size (236). Suitably substituted peroxyesters show rate enhancements because of anchimeric assistance (168,213,237). 

Recently, anchimeric assistance was also reported in the solvolysis of dialkyl-j3-thiovinyl sulfonates (184). In particular, vinyl ester 221 reacts 3.8 X 10 times faster and vinyl ester 222, 4.2 x 10 times faster, respectively, than model compound 223 in 9 1 CH3N03 CH3 0H at 25°. The large anchimeric effects, 10 to 10, in the solvolysis of dialkyl- 3-thiovinyl sulfonates... 

Rearrangement across the double bond and possible anchimeric assistance involving carbon also has been investigated. Rappoport and Gal (134) have reported that the solvolysis of l-anisyl-2,2-diphenyl bromide, 224, in aqueous ethanol as well as in formic acid gave a,a-diphenyl-p-methoxyacetophenone, 225, as the only product i.e., no rearrangement product 226 was observed. 

Cleavage of 8-0-4-ethers in alkaline pulping is also facilitated by HS as used in kraft pulping.98 The major mechanisms (Fig. 12.8b) are via addition to the quinone methide QM1 to give adduct 19, followed by anchimerically assisted fragmentation via a thioepoxide 20. 

Dimethylaminoethane-2-ol (20) is a compound that, by virtue of its nucleophilic center (Me2NH+C2H40), is employed to convert protected segments bound to supports as benzyl esters into acids by transesterification into dimethylaminoethyl esters [C(=0)0C2H4NMe2] that are hydrolyzable by a dimethylformamide-water (1 1) mixture. Compound 20 readily forms esters from acid chlorides. The hydrolysis and esterification are facilitated by anchimeric assistance by the adjacent nitrogen atom (see Section 2.10). The amino alcohol also reacts with dichloromethane. 

The type of anchimeric assistance encountered in the trans-1,4-cyclohexanediol dehydration had also been shown in solvolytic reactions of noncyclic diols (6, 70) and of 1,4-cyclohexanediol system 71). 

Anchimeric assistance may also explain slight changes in mechanism resulting from the presence of a neighboring group. One likely case is the acid-catalyzed hydrolysis of phenylglycosides. Raftery s group" found that the secondary kinetic isotope effect (/tr/ d) was 1.13 for acid hydrolysis of phenyl-4-0-(2-acetamido-2-deoxy-j8-D-glu-... 

Anchimeric assistance by the aUcoxyl oxygen lone pair promotes heterolytic S v 1 and reactions at nitrogen as well as homolysis of the N—Cl bond. A-Haloamides are also amidyl radical sources" but their heterolytic reactivity is known to involve positive, rather than negative, halogen ... 

Halogen displacement from 2-halo-tetrahydropyrans and -hexahydropyrimidines is extremely easy, being assisted, in the SnI process, by the electron pairs on the heteroatom (equation 124). 3-Halohexahydropyridines can also show accelerated halogen displacement (anchimeric assistance from nitrogen equation 125). Apart from these and other (normal) substitutions, eliminations of H—Hal are also commonly found. 

The initial work on the bicyclo[3.1.0]hexenyl system was reported by de Vries135 and Winstein and Battiste in I960136. It was shown that acetolysis of the tosylate 55 occurred with a 10 °-fold acceleration over neopentyl tosylate. The ionization of 55 was found to be anchimerically assisted with the predominant kinetic product of the reaction being the homofulvene 56. Small amounts of the acetate 57 were also present. Pentamethylbenzene, the anticipated product, was notably absent under kinetic control conditions. 

Winstein also found that the rate is highly dependent on the electron-donating ability of R—much more so than the rates of other intramolecular rearrangements (see Table 6.3). He therefore postulated that the migrating alkyl group provides anchimeric assistance to the departure of the nitrobenzoate anion and that the transition state for the rearrangement can be represented by a bridged structure such as 130. 

In connection with the methoxy participation, the gas-phase pyrolytic elimination of 4-chloro-1 -butanol was investigated177. The products are tetrahydrofuran, propene, formaldehyde and HCl. It is implied that the OH group provides anchimeric assistance from the fact that, besides formation of the normal unstable dehydrochlorinated intermediate 3-buten-l-ol, a ring-closed product, tetrahydrofuran, was also obtained. The higher rate of chlorobutanol pyrolysis with respect to chlorethanol and ethyl chloride (Table 27) confirmed the participation of the OH group through a five-membered ring in the transition state. 

To limit the scope of this review and to reduce overlap with other reviews, some related topics will only be discussed briefly. The addition of salts can affect both the rate and the course of solvolytic reactions and provides very important evidence for ion-pair intermediates. A full discussion of this topic has been published recently (Raber etal., 1974) additional comments are given onpp. 27,32. Also, we have generally excluded solvolyses known to proceed by competitive nucleophilically solvent-assisted and anchimerically assisted pathways. These solvolyses are very common (e.g. even n-propyl tosylate yields 87% of rearranged product during trifluoroacetolysis Reich et al., 1969), but a detailed account has been published recently (Harris, 1974). Recognition that solvolytic reactions could proceed by these two competitive, assisted pathways provided the key to the solution of the controversial phenonium ion problem (Lancelot et al., 1972 Brown et al., 1970), as well as inspiring the reinvestigation of the mechanisms of solvolyses of simple secondary substrates discussed in Section 2. 

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