Chromium oxide-pyridine, oxidation with

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. 

If homolytic reaction conditions (heat and nonpolar solvents) can be avoided and if the reaction is conducted in the presence of a weak base, lead tetraacetate is an efficient oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. The yield of product is in many cases better than that obtained by oxidation with chromium trioxide. The reaction in pyridine is moderately slow the intial red pyridine complex turns to a yellow solution as the reaction progresses, the color change thus serving as an indicator. The method is surprisingly mild and free of side reactions. Thus 17a-ethinyl-17jS-hydroxy steroids are not attacked and 5a-hydroxy-3-ket-ones are not dehydrated. 

In a typical Knof procedure, 3jS-hydroxyandrost-5-en-17-one acetate is epoxidized with perbenzoic acid (or m-chloroperbenzoic acid ) to a mixture of 5a,6a- and 5)5,6)5-epoxides (75) in 99 % yield. Subsequent oxidation with aqueous chromium trioxide in methyl ethyl ketone affords the 5a-hydroxy-6-ketone (76) in 89% yield. Baeyer-Villiger oxidation of the hydroxy ketone (76) with perbenzoic acid (or w-chloroperbenzoic acid ) gives keto acid (77) in 96% yield as a complex with benzoic acid. The benzoic acid can be removed by sublimation or, more conveniently, by treating the complex with benzoyl chloride and pyridine to give the easily isolated )5-lactone (70) in 40% yield. As described in section III-A, pyrolysis of j5-lactone (70) affords A -B-norsteroid (71). Knof used this reaction sequence to prepare 3)5-hydroxy-B-norandrost-5-en-17-one acetate, B-noran-... 

The intermediacy of dipolar species such as 186 has been demonstrated by reaction of enamines with 2-hydroxy-1-aldehydes of the aromatic series (129). The enamine (113) reacts in benzene solution at room temperature with 2-hydroxy-1-naphthaldehyde to give the crystalline adduct (188) in 91 % yield. Oxidation with chromium trioxide-pyridine of 188 gave 189 with p elimination of the morpholine moiety. Palladium on charcoal dehydrogenation of 189 gave the known 1,2-benzoxanthone (129). 

D. Oxidation with Chromium Trioxide-Pyridine Complex General Procedure... 

By monitoring the intensity of the carbonyl absorption it was observed that oxidation of methyl 4,6-0-benzylidene-2-deoxy-a-D-Zt/ ro-hexopyrano-side with chromium trioxide-pyridine at room temperature gave initially the hexopyranosid-3-ulose (2) in low concentration, but attempts to increase this yield resulted in elimination of methanol to give compound 3. However, when methyl 4,6-0-benzylidene-2-deoxy-a-D-Zt/ ro-hexo-pyranoside is oxidized by ruthenium tetroxide in either carbon tetrachloride or methylene dichloride it affords compound 2 without concomitant elimination. When compound 2 was heated for 30 minutes in pyridine which was 0.1 M in either perchloric acid or hydrochloric acid it afforded compound 3, but in pyridine alone it was recoverable unchanged (2). Another example of this type of elimination, leading to the introduction of unsaturation into a glycopyranoid ring, was observed... 

Oxidation of 2-deoxyglycosides with the chromium peroxide-pyridine... 

OXIDATION WITH THE CHROMIUM TRIOXIDE-PYRIDINE COMPLEX PREPARED in situ ... 

CHROMIUM TRIOXIDE-PYRIDINE COMPLEX, preparation in situ, 55, 84 Chrysene, 58,15, 16 fzans-Cinnamaldehyde, 57, 85 Cinnamaldehyde dimethylacetal, 57, 84 Cinnamyl alcohol, 56,105 58, 9 2-Cinnamylthio-2-thiazoline, 56, 82 Citric acid, 58,43 Citronellal, 58, 107, 112 Cleavage of methyl ethers with iodotri-methylsilane, 59, 35 Cobalt(II) acetylacetonate, 57, 13 Conjugate addition of aryl aldehydes, 59, 53 Copper (I) bromide, 58, 52, 54, 56 59,123 COPPER CATALYZED ARYLATION OF /3-DlCARBONYL COMPOUNDS, 58, 52 Copper (I) chloride, 57, 34 Copper (II) chloride, 56, 10 Copper(I) iodide, 55, 105, 123, 124 Copper(I) oxide, 59, 206 Copper(ll) oxide, 56, 10 Copper salts of carboxylic acids, 59, 127 Copper(l) thiophenoxide, 55, 123 59, 210 Copper(l) trifluoromethanesulfonate, 59, 202... 

This complex, formerly called pyridine perchromate and now finding application as a powerful and selective oxidant, is violently explosive when dry [1], Use while moist on the day of preparation and destroy any surplus with dilute alkali [2], Preparation and use of the reagent have been detailed further [3], The analogous complexes with aniline, piperidine and quinoline may be similarly hazardous [4], The damage caused by a 1 g sample of the pyridine complex exploding during desiccation on a warm day was extensive. Desiccation of the aniline complex had to be at ice temperature to avoid violent explosion [4]. Pyridinium chlorochromate is commercially available as a safer alternative oxidant of alcohols to aldehydes [5], See Chromium trioxide Pyridine Dipyridinium dichromate See Other AMMINECHROMIUM PEROXOCOMPLEXES... 

Oxidation, of primary alcohols to aldehydes, 52, 5 of terminal olefins with chromyl chloride, 51, 6 of 2,4,4-trimethyl-1-pentene with chromyl chloride, 51, 4 with chromium trioxide-pyridine complex, 52, 5... 

Thiochromenes (e.g., 15) are converted to thiocoumarins by oxidation with chromium trioxide in pyridine. In a similar way thiochromylium salts (e.g., 16) are converted to thiocoumarins by oxidation with either active... 

Oxidation of carbinols with chromium trioxide-pyridine... 

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