Benzylic systems

Examples of effects of reactant stmcture on the rate of nucleophilic substitution reactions have appeared in the preceding sections of this chapter. The general trends of reactivity of primaiy, secondary, and tertiaiy systems and the special reactivity of allylic and benzylic systems have been discussed in other contexts. This section will emphasize the role that steric effects can pl in nucleophilic substitution reactions. 

The Sn2 rates for allylic and benzylic systems are also increased (see Table 10.3), probably owing to resonance possibilities in the transition state. Evidence for this in benzylic systems is that the rate of the reaction was 8000 times slower than the rate with (PhCH2)2SEf. The cyclic 84 does not have the proper geometry for conjugation in the transition state. 

In para-substituted benzyl systems, steric effects have been removed, but resonance and field effects are still present. However, Holtz and Stock °. studied a system that removes not only steric effects but also resonance effects. This is the 4-substituted bicyclo[2.2.2]octylmethyl tosylate system (88). In... 

The increase of the exocyclic C—C bond stretching frequency from 1208 cm in toluene to 1264 cm in the benzyl radical and the simultaneous decrease of the C—C ring bond stretching frequencies (from 1494 and 1460cm to 1469 and 1446cm , respectively) result from electron density delocalization in the benzyl system. Furthermore, the force constant value for the C—C bond in the C6H5CH2 radical (5.5 X 10 N m ) is between the values for the ordinary C—C bond (4.5 x 10 N m ) and the double C=C bond (9.0 X 10 N m ) and is close to the corresponding force constant in the allyl radical (5.8 x 10 N m ). 

This reaction type has been intensely studied °. The application of highly polar solvents, catalysis with tertiary amines" or with acids mesomeric stabilization of intermediate carbenium ions " (allylic and benzylic systems propargylic systems" ) as well as derivatives of sulfinic acids with increasing acidity - usually indicate an ionic pathway (intra- and/or inter-molecular) ... 

Wakselman, M. 1,4 and 1,6-Eliminations from hydroxy- and amino-substituted benzyl systems chemical and biochemical applications. Nouv J. Chim. 1983, 7, 439 147. 

The proximity of carbon-carbon double or triple bonds or a phenyl substituent, as in allylic, propargylic, or benzylic systems, has very little impact upon a fluorine substituent s chemical shift (Scheme 3.53). Note that one would not expect allyl fluoride and methallyl fluoride to have the same chemical shift. 

Some typical proton and carbon chemical shift and coupling constant data for allylic and benzylic systems are given in Scheme 3.54. An alkenyl substituent or a phenyl substituent on either a CH2F or a —CHF- group has virtually no effect upon that carbon s chemical shift, and they also only affect the proton chemical shift by about 0.5 ppm. 

Electrophilic catalysis may play an important role in the case of the similar benzylic carbon, too. For an O-benzyl system, it was found in a 1997 experiment that palladium oxide is a much more effective catalyst than palladium metal when the catalyst has been prereduced with chemical reducing agents. This finding shows very clearly that the electrophilic character of the unreduced metal ions plays an important role in the hydrogenolysis of the benzyl C—O bonds. Additional support for this mechanism is the fact that a small amount of butylamine can inhibit the hydrogenolysis of the benzyl C—O bond. 

It was found in the case of O-benzyl systems that palladium oxide is much more effective than palladium metal. No such effect was observed with the N-benzyl system.8 It is possible that the N-compounds can poison the electrophile metal ions, and the hydrogenolysis of the N-benzyl bond can take place only by the hydrogenolytic cleavage instead of the insertion mechanism. This is supported by the experimental finding that the product amine can inhibit the catalyst, and this can be minimized by buffering at a pH less than 4. 

Hydrogenation of silyl enol ethers with the DIOP catalyst followed by hydrolysis [Eq. (52)] has yielded a route to optically active alcohols with low optical purities, 7% ee NMDPP (12) and MePhPR (R = n-Pr, Et, benzyl) systems were less effective (299). 

SN1 reactions of benzylic systems. Perhaps the most interesting system to be examined using the variable oxygen probe is a series of derivatives [108] of 1-phenylethanol (Edwards et al., 1986b). By varying substituents in the aromatic ring of the R group of R-OX it was possible to monitor... 

Jones and Kirby s systematic examination of R-OX bond lengths originally suggested the generalization the longer the bond the faster it breaks (Kirby and Jones, 1979 Edwards et al., 1986b). We have seen that the linear relationship with pKHox disappears for the benzylic systems discussed in the... 

Thus the simplest rule that the longer the bond the faster it breaks is not general not only are bond lengths in different systems not necessarily a guide to relative reactivity, but exceptions are to be expected also in systems where the conformation about the centres of interest varies. In fact this latter restriction is probably itself limited to situations, as in the benzylic system, or in acetals, in which strong rr-type orbital overlap directly affects the C-OX bond there appears to be little dependence on torsion angle in the [Pg.166]

On the other hand, the relationship between the levels of stilbene and the two benzyl systems (e) follows a different pattern,... 

An unique result of the electronic structure of the nitrosamine function is that it can apparently stabilize a positive or negative charge at the carbon adjacent to the amino nitrogen in a manner similar to the benzylic system. Hie stereoelectronic control of electroj ilic substitutions at the Or-position, to be discussed later, requires an orbital interaction of the nitrosamine function with the anionic electrons. Hie reactiv-... 

Examination of the observed and predicted values for log (I/D50) in Table 5 reveals that there are at least four types of compounds that are apparently not well-described by equation 4. These include compounds with hydroxy groups (e.g. compounds 20, 21, 22), compounds with chemically reactive a-hydrogens (e.g., allylic or benzylic systems, No s 9, 14), and compounds with extensive branching at the a-carbon (No s 4, 11). Acyclic nitro-samines, with one or two apparent exceptions (12), appear to constitute a separate reaction series (29). 

Compared to the reaction of benzylic systems, the situation with allylic organometallic compounds is much more complicated. 

In the deuterated 9-methylffuorenyl system (46), Cram and co-workers found retention of configuration in tetrahydrofuran with ammonia or a primary amine as base.127 Streitwieser has obtained similar results with benzyl systems in cyclohexylamine with cyclohexylamide as base.128 Cram s proposed mechanism is shown in Scheme 6. In dimethylsulfoxide, the exchange and racemization... 

Shimizu and coworkers have extensively studied the solvolyses of /1-silyl benzyl systems. They observed a rate acceleration of 3 x 105 for solvolysis of l-phenyl-2-(trimethylsilyl) ethyl trifluoroacetate 26 compared to the corresponding /1-r-butyl system 27. This indicates that the solvolytic generation of the /3-silyl carbocation is about 7.5 kcal mol 1 more favourable52. 

Simpler benzylic systems have been studied only later. The resurgence of organic photochemistry in the sixties touched this field, in particular with a seminal paper by Zimmerman and Sandel in 1963 [13], where it was shown that photoinduced solvolysis in substituted benzylic derivatives underwent a different substituent effect with respect to the ground state reaction. Activation by a m-methoxy group was found and rationalized in terms of LCAO MO electron distribution in the first electronic excited state. 

Exceptions are the few secondary benzyllithiums which show configurational stability on the microscopic (but not macroscopic) timescale - in other words, they racemise slower than they react with electrophiles, though they still cannot be maintained in stereoisomerically pure form for periods of minutes or more. These are the carbamates 288 and the sulfones 289, discussed in sections 5.1.4 and 5.I.7.6 It is significant that both of these compound classes contain powerful lithium-coordinating oxygen atoms, which may hold the lithium counterion close to one face of the benzylic system.134-120... 

In the case of benzyl systems, added carbon dioxide resulted in the formation of benzyl benzoate, strongly implicating a carbanionic species (equations 12). 

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