Benzyl ethyl ether, hydrogenolysis

Most experimental data are reported on the use of Pd-Ti02 catalysts in the hydrogenation. As equation 24 shows, product distribution is considerably affected by the para substituent. The formation of benzyl alcohols is favorable on nonacidic supports while acidic supports promote hydrogenolysis. Hydrogenolysis can also be avoided under strongly acidic conditions in the presence of ethanol. In this case, the product benzyl alcohol readily undergoes dehydration to form benzyl ethyl ether. 

Ethyl lactate can be protected as a BOM ether for subsequent nucleophilic additions to the corresponding aldehyde with high diastereoselectivity. A synthesis of zoapatanol used selective protection of a diol (eq 3). Primary alcohols can be protected selectively in the presence of secondary hydroxy groups, and secondary hydronyls react more quickly than tertiary ones with benzyl chloromethyl ether and base. Removal of this protecting group can be carried out by hydrogenolysis over Pd. 

Catalytic hydrogenation in acetic anhydride-benzene removes the aromatic benzyl ether and forms a monoacetate hydrogenation in ethyl acetate removes the aliphatic benzyl ether to give, after acetylation, the diacetate. Trisubstituted aDcenes can be retained during the hydrogenolysis of a phenolic benzyl ether. ... 

V-(9-Fluorenylmethoxycarbonyl)-0-(2,3,4-tri-0-benzoyl- 3-D-xylopyranosyl)-L-serine 15. The Fmoc O-xylosyl serine benzyl ester 13 (1.0 g, 1.2 mmol) is stirred in methanol (40 mL) at room temperature and subjected to hydrogenolysis for 18 h under atmospheric pressure using palladium-charcoal (0.2 g, 5%) as the catalyst. The educt 13 dissolves slowly. The catalyst is filtered off, and the solvent evaporated in vacuo. If the residue is not pure according to thin-layer chromatography (TLC), it is dissolved in 2 mL of ethyl acetate and purified by chromatography on a short column of silia gel 60. The byproducts are eluted with petroleum ether-ethyl acetate the product 15 with methanol yield 0.85 (92%) mp 109°C, [cr]D -12.6° (c 0.3, CH3OH) Rf 0.64 (toluene-ethanol, 1 2). 

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). 

When the solvent is or contains an alcohol, it is often incorporated in the ozonation products For example, Kratzl et al (1976) obtained about one mole of ethyl formate per mole of veratrole ozonized when the solvent was 10% ethanol in chloroform Tanahashi et al (1975) obtained methyl esters and, on hydrogenolysis of some ozomde/methanol adducts, methyl benzyl ethers using... 

Catalytic hydrogenolysis of BOM ethers is typically accomplished with Pd/C in ethanol, ethyl acetate or THF. At the close of a synthesis of FR-900482, a phenolic benzyl ether and a benzyloxy BOM ether were hydrogenolysed without... 

A useful application of an enolate-oxime ether condensation, described by Weeks, Volkmann and co-woricers, is found in the synthesis of 6-aminomethylpenicillin derivative (218), a potent -lactamase inhibitor. As shown in Scheme 45, the sensitive penicillin Grignard (216) is condensed with ethyl formaldoxime at -80 C in the presence of Bp3-OEt2 to afford adduct (217). The use of Bp3-OEt2 is critical because it allows the reaction to proceed at the low temperature required for the stability of enolate (216). Hydrogenolysis of (217) simultaneously results in removal of the ethoxy, bromo and benzyl groups, affording (218). 

Several syntheses are available to the 13,14-dihydroprostaglandins, some of which are metabolites of the E and F series. The first of these routes [143, 144] started from the formyl derivative (LVII) of the enol ether of cyclo-pentan-l,3-dione which on reaction with ethyl 6-bromosorbate and tri-phenylphosphine followed by selective catalytic reduction afforded the ester (LVIII). A second formylation followed by elaboration with n-hexanoyl-methylenetriphenylphosphonium chloride 1 to the ketone (LIX) which on reduction of the exocyclic double bond and acid-catalysed solvolysis in benzyl alcohol afforded the benzyl ether (LX) and its isomeric enol ether. Reduction with lithium tri-t-butoxyaluminium hydride to the corresponding 15-hydroxy-compound and palladium-charcoal catalysed hydrogenolysis followed by prolonged catalytic hydrogenation with rhodium-charcoal led to ( )-dihydro-PGEi ethyl ester. 

Similarly Klotzer [24-26] has used the same two ethers of hydroxyurea for the preparation of iV-alkoxy and A-hydroxy derivatives of uracil, barbituric acid, cytosine, thymine, and 5-fluorouracil by condensation reactions catalyzed with sodium ethoxide. Thus, for example, the reaction of N-benzyloxyurea with ethyl cyanacetate gave l-benzyloxy-6-aminouracil which was debenzylated by heating it with hydrogen bromide in acetic acid [24]. In syntheses of 1- and 3-hydroxycytosine [24] and of l-hydroxy-5-fluorouracil the O-benzyl protective group was removed by hydrogenolysis in presence of palladium [25, 26]. 

Preparation by hydrogenolysis of 6-(benzyloxy)-3-chloro-2,2, 4,4 -tetramethoxy-6 -methyl-benzo-phenone (SM) with hydrogen in ethyl acetate/tetrahydrofuran in the presence of 10% Pd/C at 25°. SM was obtained by condensation of 2,4-dime-thoxy-6-methylbenzoic anhydride with 4-chloro-3,5-dimethoxyphenol benzyl ether in the presence of trifluoroacetic anhydride in methylene chloride under nitrogen for 10 min (47%) [1179]. 

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