Benzyl hydrogenolysis

Hydrogenolysis Benzyl methyl ether Toluene + methanol [157]... 

Palladium/carbon. 13, 230-232 15. 245 II Hydrogenolysis. Benzyl phenyl etli... 

Hydrogenolysis. Benzyl phenyl ethers and benzyl benzoates are stable to Pd/C-cyclohexene in refluxing benzene. This is a limitation as well as an exploitable selectivity. 1-Alkene oxides undergo C-0 bond scission to give secondary alcohols by treatment with Pd/C and HCOONH in ethanol at room temperature. 

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

Carboxyl groups of ammo acids and peptides are normally protected as esters Methyl and ethyl esters are prepared by Fischer esterification Deprotection of methyl and ethyl esters is accomplished by hydrolysis m base Benzyl esters are a popular choice because they can also be removed by hydrogenolysis Thus a synthetic peptide protected at both... 

Section 27 16 Carboxyl groups are normally protected as benzyl methyl or ethyl esters Hydrolysis m dilute base is normally used to deprotect methyl and ethyl esters Benzyl protecting groups are removed by hydrogenolysis... 

Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

Catalytic hydrogenolysis of an O-benzyl protective group is a mild, selective method introduced by Bergmann and Zervas to cleave a benzyl carbamate (> NCO—OCH2C6H5 > NH) prepared to protect an amino group during pep-... 

A benzyl carbonate was prepared in 83% yield from the sodium alkoxide of glycerol and benzyl chloroformate (20°, 24 h). It is cleaved by hydrogenolysis (H2/ Pd-C, EtOH, 20°, 2 h, 2 atm, 76% yield) and electrolytic reduction (-2.7 V, R4N X, DMF, 70% yield). A benzyl carbonate was used to protect the hy-droxyl group in lactic acid during a peptide synthesis. 

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol the 1,3-acetal is the preferred product. It has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared." ... 

Historically, simple Vz-alkyl ethers formed from a phenol and a halide or sulfate were cleaved under rather drastic conditions (e.g., refluxing HBr). New ether protective groups have been developed that are removed under much milder conditions (e.g., via nucleophilic displacement, hydrogenolysis of benzyl ethers, and mild acid hydrolysis of acetal-type ethers) that seldom affect other functional groups in a molecule. 

The 2,6-dimethylbenzyl ether is considerably more stable to hydrogenolysis than is the benzyl ether. It has a half-life of 15 h at 1 atm of hydrogen in the presence of Pd-C whereas the benzyl ether has a half-life of —45 min. This added stability allows hydrogenation of azides, nitro groups, and olefins in the presence of a di-methylbenzyl group. ... 

The 4-(dimethylaminocarbonyl)benzyl ether has been used to protect the phenolic hydroxyl of tyrosine. It is stable to CF3CO2H (120 h), but not to HBr/AcOH (complete cleavage in 16 h). It can also be cleaved by hydrogenolysis (H2/Pd-C). ... 

Aiyl esters, prepared from the phenol and an acid chloride or anhydride in the presence of base, are readily cleaved by saponification. In general they are more readily cleaved than the related esters of alcohols, thus allowing selective removal of phenolic esters. 9-Fluorenecarboxylates and 9-xanthenecarboxylates are also cleaved by photolysis. To permit selective removal, a number of carbonate esters have been investigated aryl benzyl carbonates can be cleaved by hydrogenolysis aryl 2,2,2-trichloroethyl carbonates, by Zn/THF-H20. 

Catalytic transfer hydrogenation (entries 2 and 3 below) can be used to cleave benzyl esters in some compounds that contain sulfur, a poison for hydrogenolysis catalysts. 

The 2,4,6-trimethylbenzyl ester has been prepared from an amino acid and the benzyl chloride (Et3N, DMF, 25°, 12 h, 60-80% yield) it is cleaved by acidic hydrolysis (CF COOH, 25°, 60 min, 60-90% yield 2 N HBr/HOAc, 25°, 60 min, 80-95% yield) and by hydrogenolysis. It is stable to methanolic hydrogen chloride used to remove A-o-nitrophenylsulfenyl groups or triphenylmethyl esters. ... 

H2/Pd-C, 10 h, 87% yield. A nitrobenzyl carbamate is more readily cleaved by hydrogenolysis than a benzyl carbamate it is more stable to acid-catalyzed hydrolysis than is a benzyl carbamate, and therefore selective cleavage is possible. 

Benzyl carbamates substituted with one or more halogens are much more stable to acidic hydrolysis than are the unsubstituted benzyl carbamates.For example, the 2,4-dichlorobenzyl carbamate is 80 times more stable to acid than is the simple benzyl derivative. Halobenzyl carbamates can also be cleaved by hydrogenolysis with Pd-C. The following halobeni yl carbamates have been found to be useful when increased acid stability is required. 

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