Chromium trioxide oxidation, acetylated

The anomeric configurations of the sugar residues were determined by chromium trioxide oxidation [14], Oxidation of the fully acetylated polysaccharide and subsequent monosaccharide analysis by GLC indicated that the D-Xyl units are P-linked (oxidized more rapidly) and that die D-GlcA are a-linked (Table II). 

An improved route has been described for the degradation of cholesterol to dehydroepiandrosterone,68,69 in which cholesterol is first acetylated and then bromi-nated to give the 5a,6/8-dibromide. This protected cholestane is then isomerized to the 5/3,6a-dibromide prior to chromium trioxide oxidation and zinc debromination. The yield of dehydroepiandrosterone (isolated from the reaction mixture as a 5a,6/3-dibromide) is 20%. 

Chromium trioxide oxidation of fully acetylated aldopyranosides has been generally used for the determination of anomeric configurations, as the equatorial aglycones (the -anomer) are preferentially degraded (Angyal and James, 1970). However, the work of Hoffman and Lindberg... 

A novel diacetal of L-xi/lo-3-hexulose has been isolated in the course of studies on a general method for the synthesis of 3-hexuloses by oxidation of fully acetylated, hexitol monoacetals with chromium trioxide. Oxidation of l,2,5,6-tetra-0-acetyl-3,4-0-methylene-D-glucitol with chromium trioxide in acetic acid yielded principally l,2,5,6-tetra-0-acetyl-4-0-formyl-D-nbo-3-hexulose. The material remaining in the mother liquors was saponified with sodium methoxide in methanol and the product treated with acetone containing concentrated sulfuric acid a di-O-isopropylidene derivative, presumably l,2 3,4-di-0-isopropylidene-j8-L-xj/lo-3-hexulofuranose (116), was obtained. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Appropriate pyrido[2,3-d]pyrimidin-5-ones with formyl groups in the 6-position have been oxiized to piromidic (68) and pipemidic (69) acids, or to intermediates for these, using moist silver oxide, chromium trioxide (potassium dichromate), potassium permanganate or, alternatively, sodium chlorite/hydroxylamine-O-sulfonic acid. 6-Acetyl groups have been similarly oxidized using sodium hypobromite in aqueous dioxane, whilst 2-acetyl groups give dimethylaminomethylene derivatives en route to 2-pyrazolylpyrido[2,3-d]pyrimidines. 

Oxidation of PI with chromium trioxide. Fraction PI was twice acetylated as described above. The peracetylated polysaccharide (75 mg), together with 20 mg of mannitol hexacetate as internal standard was dissolved in 1.5 mL of HCCI3, and treated with 1.89 mL of glacial acetic acid and 189 mg of chromium trioxide, at 50°C. Aliquots were removed at zero, 30, 60 and 120 min, water then added, and the material recovered by extraction with chloroform, hydrolyzed and analysed by GLC of derived alditol acetates. 

The methyl substituent of 2-methyl-4,8-dihydrobenzo[l,2- 5,4-. ]dithiophene-4,8-dione 118 undergoes a number of synthetic transformations (Scheme 8), and is therefore a key intermediate for the preparation of a range of anthraquinone derivatives <1999BMC1025>. Thus, oxidation of 118 with chromium trioxide in acetic anhydride at low temperatures affords the diacetate intermediate 119 which is hydrolyzed with dilute sulfuric acid to yield the aldehyde 120. Direct oxidation of 118 to the carboxylic acid 121 proceeded in very low yield however, it can be produced efficiently by oxidation of aldehyde 120 using silver nitrate in dioxane. Reduction of aldehyde 120 with sodium borohydride in methanol gives a 90% yield of 2-hydroxymethyl derivative 122 which reacts with acetyl chloride or thionyl chloride to produce the 2-acetoxymethyl- and 2-chloromethyl-4,8-dihydrobenzo[l,2-A5,4-3 ]-dithiophene-4,8-diones 123 and 124, respectively. 

An interpretation of the oxidation of acetals by chromium trioxide is summarized in Scheme 1 the reagent could initially remove a proton from the acetalic carbon atom, to give a dioxolan-(or dioxan-)2-ylium ion, rapidly hydrolyzed to an ester (formyl, acetyl, or benzoyl) of an a-alcohol, which would be further oxidized to a ketone [see Scheme 1, path (a)] in the case of methylene acetals, in the presence of acetic anhydride (which acts as a water scavenger), the intermediate is further oxidized, probably through a chromic ester. 

This oxidation has been used to determine the anomeric nature of sugar residues in oligosaccharides.153 The oligosaccharide is reduced to the alditol, this is acetylated, and the ester is treated with chromium trioxide in acetic acid in the presence of an internal standard. From the sugar analysis of the product, the residues that have survived (and, consequendy, are a-D-linked) may be identified. The... 

I. Hoffman, B. Lindberg, and S. Svensson, Determination of the anomeric configuration of sugar residues in acetylated oligo- and poly-saccharides by oxidation with chromium trioxide in acetic acid, Acta Chem. Scand., 26 (1972) 661-666. 

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