Ethers with chromium trioxide

Oxidation of that compound with chromium trioxide in sulfuric acid leads cleanly to the desired ketone (67). Treatment with hydrobromic acid serves to demethylate the phenolic ether function (68). Direct... 

The synthesis of napelline was completed from compound 285. Hydrolysis of the ketal 285 by treatment with aqueous acetic acid yielded compound 287. The latter was reduced with lithium aluminium hydride to afford a trihydroxyamine, which was acetylated to give compound 290 in 20% yield. The dihydroxyacetate 291 was prepared in 45% yield by hydrolysis of 290 with potassium carbonate in aqueous methanol. Acetylation of 291 afforded 292, which on oxidation with chromium trioxide in methylene chloride gave 293. Bromination of 293 with bromine in a mixture of ether and chloroform containing HC1 yielded the bromoketone 294. The latter was... 

Methoxy-2-tetralone was methylated by the Stork method to yield 337. The latter was treated with sodium hydride and benzyl chloromethyl ether to furnish compound 338 in 60% yield. Ketalization of 338 afforded the ketal 339 which was hydrogenated with palladium on calcium carbonate to give the alcohol 340 in a yield of 92%. The alcohol 340 was oxidized with chromium trioxide in pyridine to afford the aldehyde 341 in quantitative... 

Enmein was converted to 20-hydroxykaur-6-en-15a-pyranylether (382), which was oxidized with chromium trioxide in pyridine to afford the aldehyde 383. The latter was converted with hydroxylamine to the oxime 384. The nitrone 385 was prepared by treatment of 384 with bromine azide. Photolysis of 385 gave the desired compound 381 in 46% yield. This intermediate possesses several useful functionalities (e.g., carbinolamine ether linkage), which may be of interest for synthesis of C20-diterpenoid alkaloids after minor changes in this scheme. 

The relative reactivity of primary and secondary positions adjacent to oxygen can be strongly dependent on the nature of the oxidant. For example, treatment of the methyl ethers (8) and (10) with chromium trioxide in acetic acid leads to the formation of the formates (9) and (11), respectively (equations 13 and 14). In direct contrast, n-decyl methyl ether is oxidized exclusively to methyl n-decanoate (83% yield) by ruthenium tetroxide (equation 11). Under similar reaction conations, 3 -cholestanol methyl ether gives cholestan-3-one as the mqjor product, togedier with traces of the corresponding formate. Therefore, at least in the case of ruthenium tetroxide, primary positions appear to be more reactive than tertiary. 

The main applications of oxidation with chromium trioxide are transformations of primary alcohols into aldehydes [184, 537, 538, 543, 570, 571, 572, 573] or, rarely, into carboxylic acids [184, 574], and of secondary alcohols into ketones [406, 536, 542, 543, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584]. Jones reagent is especially successful for such oxidations. It is prepared by diluting with water a solution of 267 g of chromium trioxide in a mixture of 230 mL of concentrated sulfuric acid and 400 mL of water to 1 L to form an 8 N CrOj solution [565, 572, 579, 581, 585, 556]. Other oxidations with chromic oxide include the cleavage of carbon-carbon bonds to give carbonyl compounds or carboxylic acids [482, 566, 567, 569, 580, 587, 555], the conversion of sulfides into sulfoxides [541] and sulfones [559], and the transformation of alkyl silyl ethers into ketones or carboxylic acids [590]. 

A solution of chromium trioxide in dilute sulfuric acid used in aqueous acetone is called Jones reagent [572]. Other solvents of chromium trioxide are ether [535] and hexamethylphosphoric triamide (HMPA) [543. Oxidations are also carried out with chromium trioxide adsorbed on Celite (diatomaceous earth) [53S], silica gel [537], or an ion exchanger such as Amberlyst A26 (a macroreticular quaternary ammonium salt anion exchanger) [571, 617]. Such oxidations often take place at room temperature and can be used not only for saturated alcohols but also for unsaturated and aromatic alcohols (equations 208 and 209). 

Oxidations with chromium trioxide (chromic oxide or chromic anhydride) and with chromic acid are carried out in different solvents, usually by adding solutions of chromic oxide or chromic acid to the solutions of the alcohols. When chromium trioxide dissolved in 80% acetic acid is added to a stirred solution of cis-2-phenylcyclohexanol in acetic acid at 50 °C and the mixture is allowed to stand at room temperature for 1 day, an 80% yield of 2-phenylcyclohexanone is obtained [576], Other solvents used are dimethylformamide [542], hexamethylphosphoric triamide (HMPA) [543], acetone [578, 5 i], ether [55 ], dichloromethane [555, 617], and benzene [571] (equation 249). 

The addition of chromium trioxide to solutions of alcohols in ether and dichloromethane in the presence of Celite furnishes ketones in 71-93% yields after 35 min at room temperature [535]. Oxidation can also be performed by refluxing the alcohols in solvents such as chloroform, ether, hexane, or benzene with chromium trioxide on an anion exchanger, Am-berlyst A26 [571]. Very good results are obtained when chromium trioxide is converted into tetrabutylammonium chromate by addition of catalytic amounts of tetrabutylammonium chloride in dichloromethane [617. ... 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

Oxidation of the trihydroxypropyl compound 7 or the aldehydes 38 and 40 with chromium trioxide in acetic acid or 50% sulfuric acid furnishes the 3-carboxylic acids, which readily decarboxylate to the 3-unsubstituted compounds at their melting points. " In contrast, the 3-methyl-l-phenyl compoimd is not appreciably attacked by chromiiun trioxide, potassium permanganate, or selenium dioxide. Chromyl chloride oxidation of 7 does not give the aldehyde 38 but apparently provides the tetraflavazolyl ether 41. The inertness of the 3-methyl group is emphasized by its stability toward bromine and its lack of reaction with benzaldehyde." ... 

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