Benzylic halides cleavage

Primary amines can be prepared from alkyl halides by the use of hexamethylenetetramine followed by cleavage of the resulting salt with ethanolic HCl. The method, called the Delepine reaction, is most successful for active halides such as allylic and benzylic halides and a-halo ketones, and for primary... 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

In the case of halocarbon matrices, the SOMO is of the a type and the cleavage is facilitated by the antibonding nature of the SOMO. In other ions, a or a orbitals of scissile bonds interact with a ti or 7i orbital, causing them to be weakened. Accordingly, radical anions of benzyl halides may generate benzylic radicals with loss of a halide ion. Conversely, benzylsilane radical cations may form benzylic radicals with loss of a silyl cation (Fig. 6.15). 

Several research groups ha ve been involved in the study of ET reactions from an electrochemically generated aromatic radical anion to alkyl halides in order to describe the dichotomy between ET and polar substitution (SN2). The mechanism for indirect reduction of alkyl halides by aromatic mediators has been described in several papers. For all aliphatic alkyl halides and most benzylic halides the cleavage of the carbon-halogen bond takes place concertedly with the... 

Organonickel(II) species are believed to be formed during the reaction between [Ni(TMC)] and primary alkyl halides, and subsequently undergo hydrolysis with cleavage of the Ni—C bond. Kinetic data measured in the presence of excess alkyl halide indicate a rate law -dlNi1 (TMC)+]/cft = MNi (TMCr][RX]. The rate constants increase for R and X in the order methyl < primary < secondary < allyl < benzyl halides and Cl < Br < I (133, 140). This suggests that the rate-determining step is electron transfer from the Ni(I) complex to R—X via an inner-sphere atom-transfer mechanism (143). 

Benzyl Halides The molecular ion peak of benzyl halides is usually detectable. The benzyl (or tro-pylium) ion from loss of the halide (rule 8, Section 2.7) is favored even over /3-bond cleavage of an alkyl substituent. A substituted phenyl ion (a-bond cleavage) is prominent when the ring is polysubstituted. 

The indirect electrochemical cleavage of halides has been studied in detail by Lund and Simonet et al. -272) course of the reaction is strongly influenced by the structure of the substrates. Thus, aryl and benzyl halides do not form alkylation products of the mediators. The products Of the perturbed redox catalysis are, however, favored in the case of aliphatic halides. Primary halides give predominantly monoalkylation products, while tertiary halides favor the formation of dialkylation products. 

Illustrative examples of cleavage reactions of /V-arylbenzylaminc derivatives are listed in Table 3.25. Aromatic amines can be immobilized as /V-bcnzylanilincs by reductive amination of resin-bound aldehydes or by nucleophilic substitution of resin-bound benzyl halides (Chapter 10). The attachment of the amino group of 5-aminoin-doles to 2-chlorotrityl chloride resin has been reported [486]. Anilines have also been linked to resin-bound dihydropyran as aminals [487]. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

As mentioned in Sec. 15.2.3, benzylic radicals are obtained also from the cleavage of a nucleofugal group from the radical anion. This may lead again to benzylation, and it has been shown that irradiation of 1,4-dimethoxynaphthalene in the presence of substituted benzyl halides leads to benzylated naphthalenes (mainly in position 2) via benzyl radical/arene radical cation combination, which is analogous to the benzyl radical/radical... 

The radical anions of / -nitrobenzyl chloride, bromide and iodide203, of p-nitrocumyl bromide203, of 28, X = Br, I204 and of 29, X = Cl, Br205 postulated as reactive intermediates in the S l reactions of these compounds, have been observed by ESR spectroscopy, and so have the radicals formed by C—Br bond cleavage of the radical anions of / -nitrocumyl bromide and 29, X = Br. The radical anions of the primary homocyclic benzyl halides were stable under the reaction conditions used to generate them (y-irradiation, 77 K, THF or MeOH matrix) and so were the radical anions of 28 and 29, X = Cl. 

Irradiation of NADH model compounds in the presence of benzyl bromide or p-cyanobenzyl bromide in acetonitrile brings about reduction of the benzyl halides to the corresponding toluene compounds114. Like the S l substitution reaction, this photoreduction also occurs via an electron-transfer chain mechanism. Unlike in that case, though, here an electron transfer from the excited state of the NADH compound is solely responsible for the initiation step. In the propagation, the benzyl radical produced by C—Br bond cleavage in the radical anion abstracts hydrogen from the NADH compound. This yields a radical intermediate, from which electron transfer to benzyl bromide occurs readily (equations 39-42). 

It is believed that the electrochemical reductive of aliphatic halides [58], benzyl halides and aryldialkylsulfonium salts [89] are concerted, i.e., electron acceptance is concomitant with bond cleavage, due in part to the a nature of the LUMO as well as the instability of the anion-radical species and stability of the products. If the anion-radical is not a discrete chemical entity back ET cannot take place. Therefore, the efficiency of PET bond cleavage reactions would be expected to be greater for the reasons mentioned above. However, due to the localized nature of the a molecular orbitals the probability for intermolecular and intramolecular ET, for example, to a a MO may be quite low. However, the overall efficiency of PET concerted bond cleavage reactions may approach unity provided that ET to the This topic clearly requires further consideration and research using fast kinetic laser spectrophotometric techniques to go beyond the qualitative discussion provided here. 

As with preparing allyl of benzyl halides and alkali useful route to benzylalkali R-R coupling. Benzylalkali prepared by (1) addition of arylalkenes, (2) cleavage of benzyl ethers (equation 28), (3) transmetallation (equations 29-31), and (4) metallation of methyl substituted aromatics. a, a -Bis(trimethylsilyl)benzyl potassium can be prepared by metallation with a mixture of butyllithium and potassium 3-methyl-3-pentanolate in THF. ... 

The mechanism of this reaction has been investigated in some detail. RX must be an activated halide, such as a benzyl halide, a-halo ether, or a 1,1-dihalocarbon where at least one of the halides is Br or L Simple halocarbons do not react, nor does methylene chloride. Reaction with chloroform is slow, while reaction with carbon tetrachloride is instantaneous at room temperature. The (pseudo) first-order rate constant is linearly correlated to the polarographic reduction potential of the halide thus electron transfer from (38) to RX (equation 57) is the rate-determining step, followed by rapid cleavage of the RX radical anion into R and X . 

The benzyl ethers of serine and threonine are stable under the acidic conditions used in the Boc strategy. Cleavage of the benzyl ethers is performed with HF under normal conditions or with nnixtures of super adds. Especially in the case of large peptides with many benzyl ether groups, side reactions result from the intermediate benzyl halides that can react with unprotected functionalized side chains scavengers are added to avoid such side reactions. A modified TMSBr method has also been developed. ... 

Primary, secondary and tertiary benzylic halides are cleaved with zinc dust in acetic acid or under basic conditions (equations 80 and 81). Benzylic C—N bonds can also be cleaved (equation 82)," with particular ease when quaternary ammonium salts are reduced (equation 83).There has also been a recent report of cyclopropane cleavage with zinc metal and zinc chloride (equation 84). ... 

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