Chromium reagents aqueous acetic acid

A common way to change reaction conditions for the oxidation of alcohols is to modify the acid that is added to the medium. Indeed, chromium trioxide will have different oxidizing abilities in different acids. Since most organic compounds are insoluble in water, a cosolvent is usually required to dissolve not only the chromium reagent but also the alcohol substrate. This solvent must be resistant to oxidation, and acetic acid or acetone are commonly used. For the alcohol - carbonyl conversion several Cr(VI) reagents can be used, including chromium trioxide in water or aqueous acetic acid catalyzed by mineral acid, sodium dichromate in aqueous acetone catalyzed by mineral acid, sodium dichromate in acetic acid, the Cr03 pyridine complex, and err-butyl chromate.Both primary and secondary alcohols can be oxidized to the aldehyde or ketone, respectively. Aldehydes may be oxidized to the carboxylic acid under some conditions. 

Oxidations of hydroxy ketones to diketones occur frequently in steroidal alcohols. If the alcoholic group, usually secondary, is remote enough from the keto group, its oxidation takes place independently and is achieved by the same reagents that are used for the oxidation of alcohols. A solution of chromium trioxide in aqueous sulfuric acid oxidizes 5-pregnen-3p-ol-20-one in acetone solution at room temperature within 2-5 min to 5-pregnen-3,20-dione in 90% yield [579]. Similarly, lip-hydroxytestosterone 17-acetate is transformed by chromium trioxide in 80% acetic acid at room temperature in 30 min into 11-ketotestosterone 17-acetate in 92% yield [807]. 

The immediate outcome of the Hantzsch synthesis is the dihydropyridine which requires a subsequent oxidation step to generate the pyridine core. Classically, this has been accomplished with nitric acid. Alternative reagents include oxygen, sodium nitrite, ferric nitrate/cupric nitrate, bromine/sodium acetate, chromium trioxide, sulfur, potassium permanganate, chloranil, DDQ, Pd/C and DBU. More recently, ceric ammonium nitrate (CAN) has been found to be an efficient reagent to carry out this transformation. When 100 was treated with 2 equivalents of CAN in aqueous acetone, the reaction to 101 was complete in 10 minutes at room temperature and in excellent yield. 

The precipitate is soluble in free mineral acids (even as little as is liberated by reaction in neutral solution), in solutions containing more than 50 per cent of ethanol by volume, in hot water (0.6 mg per 100 mL), and in concentrated ammoniacal solutions of cobalt salts, but is insoluble in dilute ammonia solution, in solutions of ammonium salts, and in dilute acetic (ethanoic) acid-sodium acetate solutions. Large amounts of aqueous ammonia and of cobalt, zinc, or copper retard the precipitation extra reagent must be added, for these elements consume dimethylglyoxime to form various soluble compounds. Better results are obtained in the presence of cobalt, manganese, or zinc by adding sodium or ammonium acetate to precipitate the complex iron(III), aluminium, and chromium(III) must, however, be absent. 

---