Alkyl benzyl ethers

Irradiation of 1,2,3-triphenylaziridine (98) in various alcohols has been reported to give benzaldehyde acetals and N-benzylaniline (68T2193). Competitive fragmentation to give N-(benzylidene)aniline and phenylcarbene, which is trapped as the alkyl benzyl ether, also appears to occur. 

Catalytic hydrogenolysis of an O-benzyl protective group is a mild, selective method introduced by Bergmann and Zervas to cleave a benzyl carbamate (>NC0-0CH2C6H5 —> >NH) prepared to protect an amino group during peptide syntheses. The method has also been used to cleave alkyl benzyl ethers, stable compounds prepared to protect alkyl alcohols benzyl esters are cleaved by catalytic hydrogenolysis under neutral conditions. 

SnBr2, AcBr, CH2CI2, rt, 5-24 h, 76-86% yield. These conditions convert a benzyl ether to the acetate and are effective for alkyl benzyl ethers as well. ... 

Schollkopf and colleagues have reported that the rearrangement of the enantiopure forms of a-chiral alkyl benzyl ethers 8 followed by oxidation affords ketone 9 of the predominantly retained configuration at the migrating carbon in 20% ee (R = H) and ee (R = Ph) (equation 7)". 

Cleavage conditions for alkyl benzyl ethers prepared from acid-labile benzyl alcohols are similar to those for the corresponding benzyl esters (Table 3.30). Aryl benzyl ethers, however, are generally cleaved more easily by acidolysis than esters or alkyl ethers. Phenols etherified with hydroxymethyl polystyrene, for instance, can even be released by treatment with TFA (Entry 1, Table 3.31). It has also been shown that Wang resin derived phenyl ethers are less stable than Wang resin derived esters towards refluxing acetic acid [29]. Alternatively, boron tribromide may be used to cleave aryl ethers from hydroxymethyl polystyrene [573],... 

Examples of the preparation of alkyl benzyl ethers by the Williamson synthesis are included in Section 5.6.2, p. 583. An example of an alkyl phenyl ether is provided by the synthesis of phenacetin (Expt 6.109) where p-aminophenol is first converted into its Af-acetyl derivative by reaction with slightly more than one equivalent of acetic anhydride. Treatment of the product with ethanolic sodium ethoxide solution followed by ethyl iodide then yields the ethyl ether of AT-acetyl-p-phenetidine (phenacetin). This compound is biologically active and has been widely employed for example as an antipyretic and analgesic however, owing to undesirable side reactions, its use is now restricted. 

This stability order has been used in a reevaluation of the mechanism of the Wittig rearrangement of alkyl benzyl ethers (Eq. (82)). The migration... 

Reactions of this type are relatively few, in comparison to those of DIB. Alkyl benzyl ethers afforded benzaldehyde and alkyl trifluoroacetates in a potentially useful reaction for the deprotection of benzylated alcohols under oxidative conditions, since trifluoroacetates are hydrolysed very easily [53] ... 

Nonactivated esters are reduced only slowly if at all in strongly acidic medium at a lead cathode [45], whereas alkyl benzoates are reduced to a mixture of benzyl alcohol and alkyl benzyl ether [45,46], and alkyl 4-imidazolecarboxylates similarly are reduced to a mixture of the corresponding alcohol and ether [76]. Phenyl and benzyl benzoate give predominantly esters [23,34], as do also ethyl o-chloro- and m-bromobenzoate [46]. 

Aryl benzyl ethers are cleaved more easily than are alkyl benzyl ethers. The presence of an amine hinders the hydrogenolysis of alkyl benzyl ethers but has no effect on the cleavage of aryl benzyl ethers. - Because of this the benzyl ether is selectively hydrogenolyzed in compounds containing both a benzyl amine and an aryl benzyl ether (Eqn. 20.24)55 but the benzyl amine is selectively cleaved in compounds having both a benzyl amine and an alkyl benzyl ether (Eqn. 20.25).53,54,56... 

The preparation of benzyllithium from benzyl halides and alkyllithiums is not feasible because the benzyllithium initially formed reacts with the starting benzyl halides, producing 1,2-diphenylethane. Metalation of toluene with n-BuLi in the presence of TMEDA at 30 °C results in a 92 8 ratio of benzyllithium and ring metalated products. Metalation of toluene with n-BuLi in the presence of potassium rert-butoxide, and treatment of the resultant organopotassium compound with lithium bromide, affords pure benzyllithium in 89% yield. Alternatively, benzyllithiums are accessible by cleavage of alkyl benzyl ethers with lithium metal. " ... 

Both singlet and triplet photosensitization of (Z)-cyclooctene (50) produces the (E)-cyclooctene enantiomers [(—)-(/ )-51 and ( I )-(.S )-51 Scheme 6.14]. High enantio-differentiation (Special Topic 6.1) has been achieved with singlet excited chiral polyalkyl benzenepolycarboxylates, whereas triplet sensitization (e.g. with chiral alkyl benzyl ethers) gives low optical yields only. For example, when a chiral tetra[(—)-bomyl]oxycarbonyl singlet sensitizer 52 was used at —88 °C, ( )-(R)-5 was obtained in 9% chemical yield and 41% optical purity at 12% conversion. The effect is attributed to specific interactions within an exciplex formed between sensitizer and alkene. 

The methods discussed above all require chemically aggressive reagents. Freudenberg and his co-workers,41 however, found that benzyl ethers can also be cleaved by catalytic hydrogenation alkyl benzyl ethers can be converted into toluene and an alcohol by hydrogenation under very mild conditions in presence of platinum metals or Raney nickel reductive cleavage of aryl benzyl ethers is best carried out in presence of palladium-charcoal. 

Some ethers react with metallic lithium in the same way as alkyl and aryl halides e.g., benzyllithium is obtained in good yield from alkyl benzyl ethers in tetrahydrofuran.49... 

Alkyl-benzyl-ether werden in etherischer Losung durch Alkalimetalle glatt gespalten349 (vgl. Bd. XIII/1, S. 161) die Carboxylierung liefert in Abhangigkeit von der Temperatur Phenyl-essigsauren oder -malonsauren (vgl. Bd. XIII/1, S. 622) ... 

In addition, a catalytic amount of pyridine or ammonium acetate also suppresses the hydrogenolysis of aliphatic 0-benzyl protective group. " Cleavage of phenoUc benzyl ethers, which are more labile than alkyl benzyl ethers, can also be prevented by the addition of 2,2 -dipyridyl (Scheme 83). ° ... 

Schafer M, Dreiocker F, Budzikiewicz H. Collision-induced loss of AgH from Ag adducts of alkylamines, aminocarboxylic acids and alkyl benzyl ethers leads exclusively to thermodynamically favored product ions. J Mass Spectrom. 2009 44 278-84. 

The a, P-mode is not confined to ammonium salts. It is also observed with ethers, in particular, alkyl benzyl ethers. Strong bases such as propylsodium metalate benzyl ethyl ether at the benzylic site (as attested by the loss of its deuterium label) before the resulting intermediate 245 disintegrates by intramolecular proton abstraction from the ethyl group (Scheme 1-189). ... 

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