Ketones, reaction with chromyl chloride

Etard reagents (chromyl chloride and some derivatives) suffer from the problem that occasionally they can exhibit a lack of selectivity and low yields. They are useful in the selective oxidation of aromatic side-chains to a carbonyl group, aldehyde or ketone but in many instances, the formation of the initial complex is slow and yields are low because of difficulties in the work-up which lead to undesired over-reaction. Attempts have been made to solve the problems by the use of sonication [134]. A simple preparation of the liquid reagent was proposed and the Etard reaction itself together with the hydrolytic step were conducted under sonication, with some success (Scheme 3.25). 

Oxidation with chromium(VI) oxide, t-butyl chromate or chromyl chloride may also take place at the allylic position with the formation of unsaturated ketones. The alkene may enhance the rate of displacement of an allylic halide, and the reaction may even take place with the participation of the double bond, so leading to an allylic rearrangement (Scheme 3.25). 

The success of the method appears to be the use of acetone as solvent. Addition of zinc dust to the crude reaction mixture results in reduction to the corresponding ketone. Yields of chloroketones arc highest if the reaction is carried out at - 70°, but are still reasonable at reaction temperatures of - 5 to 3°. Thus oxidation of cyclododecene at — 75° with chromyl chloride gave a-chlorocyclododecanone in 79% yield the yield of the chloroketone was 69% from a reaction conducted at — 5. ... 

The reaction of chromyl chloride with alkenes gives epoxides, chlo-rohydrins, chloroketones, and ketones [668, 667, 668, 669, 670] or aldehydes (in the presence of zinc) [671, 672]. Benzene homologues are oxidized to aldehydes [667, 668] or ketones [666, 668, 673], Primary alcohols are converted into aldehydes [674, 675], and trimethylsilyl ethers of enols are transformed into a-hydroxy ketones [676]. 

Chromyl chloride can also produce ketones, but a common side reaction is formation of an a-chloro ketone, as in the conversion of cyclododecene to a-chlorocyclododecanone (401) in 79% yield. In a subsequent reaction, the chloride moiety in 401 was reduced to give cyclododecanone in 95% yield with zinc and acetic acid. Chromyl chloride also reacts with alkenes to give a trans-chlorohydrin rather than a carbonyl compound (see sec. 2.10.C for the preparation of chlorohydrins), as in the conversion of cyclohexene to tran5-2-chlorocyclohexanol. 5 It is interesting that in this particular case (the temperature was maintained at -78°C in dichloromethane), the cis-chlorohydrin was formed. ... 

A hydroxyl group may be introduced a- to a ketone group by the reaction of chromyl chloride with the ketone silyl enol ether in dichloromethane at low temperature, No a-chloro-ketones were observed as by-products. Alternatively, an alkoxy-group may be introduced by the reaction of the silyl enol ether with alkyl hypochlorites, catalysed by tetrakis(triphenylphosphine)palladium. ... 

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