Debenzylation of carboxylic esters

Table I. Debenzylation of Carboxylic Esters on Alumina Surface...

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. 

An efficient solvent-free debenzylation process for the cleavage of carboxylic esters on an alumina surface has been developed by Varma and colleagues (Scheme... 

Preferential debenzylation of carboxylic acid esters s. 16,621 COOCHgCeHs COOH... 

Simultaneous debenzylation of carboxylic and phosphoric acid esters... 

Treatment of some substituted o-benzyloxy-ketones with hydrochloric acid in acetic acid gives, e.g., the carboxylic ester (130, R = COOMe), then the corresponding benzofuran (130, R = H) through debenzylation, ring closure, hydrolysis, and decarboxylation.331... 

A different approach was adopted in the synthesis by Justoni and Pessina (111). The Japp-Klingemann reaction of p-benzyloxyphenyl-hydrazine with cyclopentanone carboxylic ester gave the p-benzyloxy-phenylhydrazone of a-ketoadipic acid (XIV) Fischer cyclization of the corresponding dimethyl ester then yielded 5-benzyloxyindole-2-car-boxylic-3-jS-propionic acid (XV). Decarboxylation of XV followed by Curtius degradation and debenzylation eventually afforded 5-hydroxy-tryptamine. 

Among procedures for the synthesis of 1,7-naphthyridines, four-component condensation of l-benzyl-3-hydroxy-5-piperidone 101 with 2,3-dichloro-6-fluorobenz-aldehyde, acetoacetic esters and ammonium acetate giving rise to 1,4,5,6,7-hexahydro-l,7-naphtyridin-5-one-3-carboxylic esters 102 attracts attention due to its simplicity. The compounds 102 and their N-debenzylation products 103 exhibit hypotensive activity (1985USP4596873, 1985USP4618678). 

Piperidine 141 was synthesized from the Barton-McCombie reaction <75JCSP11574> of 142 which gave the expected amido-ester (96 %) as a 3 2-mixture of diastereomers. The mixture was hydrolyzed to the corresponding carboxylic acid which, upon thermal decarboxylation, gave the desired /V-bcnzyl lactam (85% overall yield) as a single diastereomer whose structure was unequivocally established by a single-crystal X-ray analysis. Reduction of the lactam with LiAlH4 (81%) followed by debenzylation via... 

During a synthesis of the protein kinase C inhibitor Balanol. Lampe and co-workers77 found that deprotection of the tert-butyl ester 30.1 [Scheme 6.30] with trifluoroacetic or formic acid was accompanied by substantial quantities of a debenzylated by-product. The same side reaction accompanied thermolytic cleavage of the terf butyl ester in neutral solvents presumably due to add catalysis by the carboxylic acid product 30.2. Thermolysis in quinoline at 205 °C led cleanly to the desired benzophenone carboxylic acid 30.2 in 68% yield. 

The total synthesis of the lichen diphenyl ether epiphorellic acid 1 was achieved in the laboratory of J.A. Elix using the Smiles rearrangement as the key step. The diaryl phenolic ester substrate was heated in dry DMSO in the presence of potassium carbonate, which brought about the rearrangement. The resulting carboxylic acid was converted to the methyl ester with diazomethane and was debenzylated under catalytic hydrogenation conditions. 

Poly((3-malic acid) is the most simple carboxylated polyester [47-49]. It is prepared by ring opening polymerization of the mono-benzyl ester (3-lactone of malic acid and subsequent debenzylation. It has been explored as drug carrier. Reaction of itaconic anhydride with PCL with hydroxy terminals results in polyesters with carboxylic and C=C double bond functional terminals, suitable for further reactions to form networks and gels, (5) and (6) [50,51]. 

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