Alkoxy acids, cleavage

Unsubstituted aliphatic carboxylic acids are only very slowly further oxidized to the lower homologous acid in the oxidation of primary alkanols less than 2% of this acid are found. However, with substituted carboxylic acids the cleavage can become the main reaction. Thus anodic oxidation of phenylacetic acid at the nickel hydroxide electrode leads to 87% benzoic acid . Cleavages of similar to a lesser extent are observed with amino acids (Chapter 3.1) or P-alkoxy substituted acids (Chapter 2.4). 

Directed lithiations of alkoxy furans have potential in the synthesis of butenolides, and the tetramethyldiamidophosphate moiety has been successfully used to prepare 3-substituted furans (22). Acidic cleavage of the phosphorus residue then allows access to the corresponding 2-substituted butenolide (23), and the overall process becomes equivalent to using the anion (24) (Scheme 8). 

Lewis acid induced alkylation of 4-alkoxy-3,5-dialkyl-2-oxazolidinones with allylsilanes gives the 4-allyl derivatives with complete irons stereoselectivity114,115. Cleavage of the oxazolidi-none ring with aqueous sodium hydroxide in ethanol leads to vicinal twP -aminoalkanols. 

Details of the hydrolytic process are somewhat more complicated because the acid-catalyzed hydrolysis proceeds via the initial protonation of an alkoxy oxygen followed by bond cleavage. Because the protonation can involve the exocyclic or endocyclic alkoxy group, two different sets of initial products are possible. However, in both cases the ultimate degradation products remain the same. These two possible reaction paths are shown on page 130. 

After treatment of XXXVI with aqueous barium hydroxide, the liquor contained formic, methoxyacetic, and ethoxyacetic acids, methoxyacetone, and ethoxyacetone, produced by the two modes of cleavage XXXVIa and XXXVIb. Formic acid was converted with red mercuric oxide to carbon dioxide this was recovered as barium carbonate, the radioactivity of which was a measure of the C14 incorporated into Cl of kojic acid in the biosynthetic process. The alkoxyacetones were removed from the liquor by steam distillation, and converted to iodoform and a mixture of methoxy- and ethoxy-acetic acids. The iodoform was recovered by filtration its radioactivity indicated the proportion of C14 incorporated into C4. The alkoxy-... 

There are dozens of linkers available for synthesis, and nearly all of them, once acylated by a protected amino acid, provide a benzyl ester or a benzyl amide that has been sensitized to cleavage by acid by the presence of electron-donating moieties such as alkoxy, phenyl, or substituted phenyl. There are cases in which a peptide chain is bound to a support through two different linkers in series. This allows for versatility in synthesis. The distinction between designation of a moiety affixed to a support as a handle or linker is sometimes arbitrary. 

FIGURE 5.17 Resins and linkers for synthesis of peptides using Fmoc/tBu chemistry. The linkers are secured to supports by reaction with aminomethyl resins. A protected amino acid is anchored to the support as an ester by reaction with a hydroxyl or chloro group (italicized). The alkoxy and phenyl substituents render the benzyl esters sensitive to the cleavage reagents. 

A third possible fate of the alkoxy radical is shown in Scheme 18.3 (lower reaction) and was postulated by Grossetete et al. [11], In this reaction, the hydroxy radical in the cage from hydroperoxide cleavage yields an anhydride by extraction of the a-hydrogen to the radical. These workers cite IR evidence in support of this reaction which seems quite reasonable. In addition, the report by Valk et al. [21] of glycolic acid would seem to confirm this path as well. 

Although the conditions used to cleave the ether linkage are vigorous, we decided to attempt this reaction on the a -alkoxy N-nitrosamines. The cleavage of ethers with acetic anhydride in the presence of Lewis acids is well-known in the literature (12,13,14). Reaction of a -methoxy dimethylnitrosamine IV with Ac20 in the presence of BF3 etherate at 60° resulted in the cleavage not only of the C-0 bond but also the N-C bond (15,16). ... 

Also A H+ as measured in these acidic solutions was 4 to 30 times less than when it was measured at pH 4.5-7.5 (Ahmad el al., 1977, 1979). Therefore in the acidic solutions the alkoxy group must have been lost before the rate-determining step in the formation of 2-hydroxyethyl benzoate and this step must therefore be breakdown of the hemiorthoester [70]. At higher pH breakdown of the hemiorthoester [70], which is also base-catalysed, becomes very fast, and cleavage of the exocyclic C— bond of the starting material [69], which depends on R, is rate-determining. 

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