Benzylic substrate

Parenthetically we might also note that primary allylic and benzylic substrates are particularly reactive in S 2 reactions as well as in SN-1 reactions. 

Unsaturation at the p Carbon. The SnI rates are increased when there is a double bond in the P position, so that allylic and benzylic substrates react rapidly (Table 10.5). The reason is that allylic (p. 221) and benzylic (p. 222) cations are stabilized by resonance. As shown in Table 10.5, a second and a third phenyl group increase the rate still more, because these carbocations are more stable yet. It should be remembered that allylic rearrangements are possible with allylic systems. 

SN1 Very strong effect reaction favored by polar solvents Weak effect reaction favored by good nucleophile/weak base Strong effect reaction favored by good leaving group Strong effect reaction favored by 3°, allylic, and benzylic substrates... 

The secondary a-tritium KIEs in these reactions, on the other hand, are small and normal. Benzyl substrates have looser SN2 transition states than methyl substrates (vide infra) and thus, the benzyl substrate reactions would be expected to have slightly larger (normal) KIEs rather than the inverse KIEs... 

The authors concluded that the transition states for the Menshutkin reactions of the benzyl substrates were early (reactant-like) with nitrogen-alpha carbon bond formation lagging behind alpha carbon-oxygen bond rupture. The transition states for the Menshutkin reactions with the methyl and ethyl substrates, on the other hand, are tight (product-like) with nitrogen-alpha carbon bond formation greater than alpha carbon-oxygen bond rupture. 

Finally, it is worth noting that the substituent effects are different on the two types of Menshutkin reactions as well. For the benzyl substrates, changing to a better nucleophile, i.e. changing the substituent on the nucleophile from the meta-nitro to a para-methoxy substituent, leads to a later, more product-like transition state with more inverse secondary incoming nucleophile deuterium kinetic isotope effects. Flowever, the same change in nucleophile in the reactions with the methyl and ethyl substrates leads to an earlier transition state and less inverse secondary incoming nucleophile deuterium kinetic isotope effects. 

The reaction is even more general and applicable to ketones bearing an a-methylene. Yields up to 90% of the corresponding dimethyl esters are obtained in the case of benzylic substrates (Scheme 4.19). 

Poor to modest yields of trinitromethyl compounds are reported for the reaction of silver nitroform with substituted benzyl iodide and bromide substrates. Compounds like (36), (37), and (38) have been synthesized via this route these compounds have much more favourable oxygen balances than TNT and are probably powerful explosives." The authors noted that considerable amounts of unstable red oils accompanied these products. The latter are attributed to O-alkylation, a side-reaction favoured by an SnI transition state and typical of reactions involving benzylic substrates and silver salts. Further research showed that while silver nitroform favours 0-alkylation, the sodium, potassium and lithium salts favour C-alkylation." The synthesis and chemistry of 1,1,1-trinitromethyl compounds has been extensively reviewed. The alkylation of nitronate salts has been the subject of an excellent review by Nielsen." ... 

As shown in the last section, the arene-catalyzed lithiation of mesylates has the limitation that it only proceeds for allylic and benzylic substrates. This drawback has been... 

Besides having smaller oxidation potential values than substituted benzyl alcohols (E° > 1.4 V/NHE), the DMAs have larger energy values (90-92 kcalmoD ) for the NC—H bond with respect to C—H bond energies around 75-85 kcalmoD of the benzyl alcohols (Scheme 12). Both factors disfavour the operation of the radical HAT route for PINO with the DMAs, and cause a mechanistic changeover to the ET route, as opposed to the reactions with the benzylic substrates listed in Table 4. 

These systems are also described as normal copper proteins due to their conventional ESR features. In the oxidized state, their color is light blue (almost undetectable) due to weak d-d transitions of the single Cu ion. The coordination sphere around Cu, which has either square planar or distorted tetrahedral geometry, contains four ligands with N and/or 0 donor atoms [ 12, 22]. Representative examples of proteins with this active site structure (see Fig. 1) and their respective catalytic function include galactose oxidase (1) (oxidation of primary alcohols) [23,24], phenylalanine hydroxylase (hydroxy-lation of aromatic substrates) [25,26], dopamine- 6-hydroxylase (C-Hbond activation of benzylic substrates) [27] and CuZn superoxide dismutase (disproportionation of 02 superoxide anion) [28,29]. 

The benzylic substrates X-l-Y and X-2-Y have provided a useful platform for examining the changes in reaction mechanism for nucleophilic substitution that occur as the lifetime of the carbocation intermediate is decreased systematically by varying the meta- and para- aromatic ring substituents. When X is strongly resonance electron-donating, X-l-Y and X-2-Y react by a stepwise mechan-... 

Unsaturation at the 3 carbon. SnI rates are increased when there is a double bond in the 0 position, so that allylic and benzylic substrates react rapidly (Table 10.5).261 The... 

Scheme4.26. Nucleophilic substitution at sterically demanding benzylic substrates [118, 119],...

LiBr has been reported to catalyse the dihydroxylation of alkenes (1) to afford syn-and anh -diols (2/3) with excellent diastereoselectivity, depending on the use of NaKTt (30 mol%) or PhI(OAc)2 (1 equiv.), respectively, as the oxidant.28 The authors claim that oxidation of non-benzylic halides was achieved for the first time to afford the corresponding diols in excellent yields 28 is not really justified as the development of the silver-free Prevost-Woodward dihydroxylation for non-benzylic substrates had... 

Unfortunately, two equivalents of the copper complex have to be used to achieve good conversions and the system is severely limited to benzylic substrates. Aliphatic alcohols proved to be either unreactive or underwent competing C-C bond cleavage (9). 

Suitable alkylbenzene side chains are oxidized at the benzylic position under the action of mCPBA, air, and NaHC03 to generate the corresponding ketones. The oxygen-centered radical formed from mCPBA, abstracts the benzylic hydrogen atom of the benzylic substrate (68) to form a benzylic radical, and then it reacts with molecular oxygen... 

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