Hydrogenolysis of carboxylic acids

Hydrogenolysis of carboxylic acid thioesters over Ra-Ni deactivated by boiling in acetone is one of the classic syntheses of aldehydes.405-408 Without deactivation the Ra-Ni hydrogenolyzes the thioesters to alcohols. 

Hydrogenolysis of carboxylic acid esters COOR -> COOH... 

N-Decarbobenzoxylation with hydrogenolysis of carboxylic acid p-nitrobenzyl esters and replacement of nitro groups by hydrogen... 

In addition to the preparation of l-alkenes, the hydrogenolysis of allylic compounds with formate is used for the protection and deprotection of carboxylic acids, alcohols, and amines as allyl derivatives (see Section 2.9). 

Hydrogenolyses of carboxylic acids and esters to the corresponding aldehydes seems very attractive due to their simplicity. Copper chromites are the most widely used catalysts.15 Raney copper and zinc oxide-chromium oxide have also been used for this process.16-18 The hydrogenolysis of methyl benzoate to benzaldehyde was studied on various metal oxides at 300-350°C. ZnO, Zr02 and Ce02 presented high activities and selectivities (Scheme 4.8). 

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. 

The hydrogenolysis of the thiol esters of carboxylic acids offers a delicate method for reducing an acid to the corresponding aldehyde or alcohol application of this method to the sugar series has been made by Wolfrom and Karabinos who reduced D-ribonyl chloride tetraacetate (LXXV) to aldehydo-D-ribose tetraacetate (LXXVII) in 22% yield via ethyl thiol-D-ribonate tetraacetate (LXXVI). The desulfurization of the thiol ester (LXXVI) was carried out with a somewhat aged sample of Raney nickel" which doubtless had less activity than the... 

Diphenylmethyl (benzhydryl) esters.3 These esters can be cleaved either by acid hydrolysis or hydrogenolysis. They have been prepared by reaction of carboxylic acids with diphenyldiazomethane, generated in situ by oxidation of ben-... 

Esterification. One use for the reagent is for esterification of carboxylic acids, either for protection of the carboxyl function or preparation of characterizing derivatives. Carboxylic acids, even hindered tertiary acids, react with diphenyidiazomethane to give benzhydryl esters the protective group is removed when required by hydrogenolysis.° Acetylsalicylic acid reacts with 1.5 equiv. of reagent in refiuxing... 

Rhenium catalysts. H. Smith Broadbent and co-workers have reported the preparation of a number of oxides of rhenium (RcbOt. ReOj, ReOa, ReO), which are effective hydrogenation catalysts, particularly for the reduction of carboxylic acids to primary alcohols. Kor the reduction of aromatic, olefinic. carbonyl, and nitro groups they are less aclivc than nickel or plutimim calalysts hence selective hydrogenation is possible. Bcn/ylic hydroxyl groups are stable to hydrogenolysis. 

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. 

Hydrogenolysis of the diallyl alkylmalonate 757 with formic acid in boiling dioxane affords the monocarboxylic acid 758. Allyl ethyl malonates are converted into ethyl carboxylates[471]. The malonic allyl ester TV-allylimide 759 undergoes smooth deallylation in refluxing dioxane to give the simple imide 760(472]. The allyl cyanoacetate 761 undergoes smooth decarboxylation to give... 

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... 

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. 

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