Benzyl ethers bonding

Benzyl esters of carboxylic acids are frequently used in organic synthesis for the protection of carboxyl groups. The C-O bond in benzyl esters can be cleaved more easily than the corresponding benzyl ether bond. The hydrogenolysis of an ester leads to carboxylic acid and toluene. Examples of debenzylation of benzyl esters of carboxylic acids on Pd/C catalysts are summarized in Table 4.4. 

Cleavage of a benzyloxy bond was also accomplished by treatment with sodium in liquid ammonia [640] or by refluxing with sodium and butyl alcohol [641]. On the other hand, aluminum amalgams reduced a nitro group but did not cleave benzyl ether bond in dibenzylether of 2-nitrohydroquinone [642]. 

Since 1995, Tietze et al. [26-32] have studied the use of norpseudoephedrin derivative 61 as a chiral auxiliary in order to perform a diastereocontrolled SMS reaction. Further cleavage of the benzylic ether bond of 62 by Na/NH3 led to optically active homoallylic alcohol 26 with good yields and selectivity (Scheme 13.25). 

There are different methods to cleave benzyl ether bonds. The most common one is hydrogenolysis with palladium on carbon or platinum as catalysts under H2 atmosphere. The standard solvents are ethanol or ethyl acetate. Pd is the preferred and milder one, because the use of Pt at any rate results in aromatic ring hydrogenation. Also a number of methods have been developed in which hydrogen is generated in situ, e. g. from cyclo-hexene, -hexadiene or formic acid (see Chapter 7). 

The hydroxy-tempo derivative 11 is first reacted with p-chloromethyl styrene to give a Tempo capped polymerizable styrenic compound 12. Copolymerization of 12 with styrene gives the multifunctional initiator 13, which has a PS backbone with attached Tempo groups. Reaction of 13 with styrene at 130 °C gives the grafted copolymer 14. After cleavage of the benzyl ether bonds, a Mn of 23000 is determined with a Mw/Mn value of 1.20. 

Azuma and Koshijima [52-55] found that benzyl ether bonds in nonpheno-lic structural units are effectively and selectively cleaved by (DDQ) dichlorodi-cyanoquinone oxidation and proposed this treatment for the analysis of benzyl ether-type LCC bonding structure. 

The ozonation method has provided novel insight into the stereo structure of lignin side chains. It has other important biological and industrial outcomes, such as the analysis of benzylic ether bonds established between lignins and polysaccharides [112],... 

The bonds that are stable to alkaline hydrolysis are more difficult to characterize, but model compound studies indicate that benzyl ether bonds can be cleaved by acid hydrolysis and are resistant to alkaline hydrolysis [153], Nonphenolic benzyl alkyl ether model compounds are stable even under alkaline pulping conditions [154], Watanabe... 

B Kosikova, D Joniak, L Kosakova. On the properties of benzyl ether bonds in the lignin-saccharidic complex isolated from spruce. Holzforschung 33 11-14, 1979. 

The formation of the deuterated hydrocarbon, 54, on irradiation of the methyl ether, 53, in acetonitrile/water, Eq. (25), suggests homolytic cleavage of the benzylic-ether bond followed by disproportionation of the in-cage radical pair [87]. Finally, orf/io-nitrobenzylic chromophores have been used to photorelease carbohydrates from the corresponding ethers [76]. 

Amines derived from p-alkoxybenzyl-type linkers, despite not being acid cleav-able, still have synthetic utility. Anilines anchored to Wang resin, once converted into carboxamides or sulfonamides by reaction with the appropriate electrophile, can be cleaved with TFA (Figure 14.6) [34]. Sulfonamides of aliphatic amines may also be cleaved with TFA [36]. Stronger acids are generally required for acyl derivatives of amines but this can cause cleavage of the linker benzylic ether bond, leading to formation of p-hydroxybenzylated by-products. 

Reduction of the product of this last reaction, 27-6, with lithium and tert-butanol in liquid ammonia proceeds to the corresponding dihydrobenzene. The (9-benzyl ether bond is cleaved reductively under those conditions to free the... 

It was anticipated that the C(4) benzylic ether bonds in proteraca-cinidins (39)-(42) would be susceptible to solvolysis in aqueous medium. The very same conditions which are applied universally for the formation of C(sp )—>C(sp ) interflavanyl linkages 40 would hence be less applicable to the generation of the ether bonds in compounds (39)-(42). We thus opted to enhance the electrophilicity at C(4) of one of the flavan-3,4-diol methyl ethers, e.g. (43) by formation of the 4-chloroflavan-3-ol derivative (44) in order to permit the formation of the crucial ether bond at near a neutral pH value. 

For example, in phenyl ether dendrimer, the terminal benzyl ether bond can be replaced with a variety of other functional groups. 

There is at least one other main issue that has to be cited. It has been observed that traces of linear PEG are found in final products after cleavage because of the weak benzyl ether bond that links the PEG to the polyst5Tene backbone. 

However, one of the drawbacks of using this type of cross-linker is that PEG is connected to the polystyrene backbone by a benzyl ether bond that could be cleaved by the use of Lewis or protic acids. Meldal reported the synthesis and the use of an alternative cross-linker containing a three-carbon spacer between the PEG chain and the polystyrene backbone (85) (Fig. 13). 

---