Jones reagent, oxidation alcohols

Jones reagent. Oxidation of the alcohol (1) with Jones reagent does not give the expected ketone, but the 8-lactone (2). The -methaxy group was shown to be essential for this oxidation of a methyl group. The expected ketone is obtained under Oppenauer conditions. 

Primary alcohols are cleanly oxidized to aldehydes (not to carboxylic acids as with Jones reagent), secondary alcohols yield ketones, and tertiary alcohols are again unre-active. Therefore, a Swem oxidation accomplishes the same transformations as PCC. Hence, in Example 10.11, the same products would be obtained with a Swern oxidation as with the application of PCC. 

Selective oxidation of secondary alcohols to ketones is usually performed with CrOj/HjSO, I I in acetone (Jones reagent) or with CrOjPyj (Collin s reagent) in the presence of acid-sensitive groups (H.G. Bosche, 1975 C. Djerassi, 1956 W.S. Allen, 1954). As mentioned above, a,)S-unsaturated secondary alcohols are selectively oxidized by MnOj (D.G. Lee, 1969 D. Arndt, 1975) or by DDQ (D. Walker, 1967 H.H. Stechl, 1975). 

When a solution of chromic and sulfuric acids in water is added at 0-20° to an alcohol or formate dissolved in acetone, a rapid oxidation takes place with the separation of the green chromium III reduction product as a separate layer. This system is commonly known as Jones reagent. The rate of oxidation is so fast that it is often possible to run the reaction as a titration to an... 

Secondary bicyclic alcohols are quantitatively oxidized by Jones reagent however rearranged products are obtamed [5f ] (equation 47)... 

With a secure route to pentacyclic amine 2, the completion of the total synthesis of 1 requires only a few functional group manipulations. When a solution of 2 in ethanol is exposed to Pd-C in an atmosphere of hydrogen, the isopropenyl double bond is saturated. When a small quantity of HCI is added to this mixture, the hydro-genolysis of the benzyl ether is accelerated dramatically, giving alcohol 15 in a yield of 96%. Oxidation of the primary alcohol in 15 with an excess of Jones reagent, followed by Fischer esterification, gives ( )-methyl homosecodaphniphyllate [( )-1] in an overall yield of 85 % from 2. 

Various experimental conditions have been used for oxidations of alcohols by Cr(VI) on a laboratory scale, and several examples are shown in Scheme 12.1. Entry 1 is an example of oxidation of a primary alcohol to an aldehyde. The propanal is distilled from the reaction mixture as oxidation proceeds, which minimizes overoxidation. For secondary alcohols, oxidation can be done by addition of an acidic aqueous solution containing chromic acid (known as Jones reagent) to an acetone solution of the alcohol. Oxidation normally occurs rapidly, and overoxidation is minimal. In acetone solution, the reduced chromium salts precipitate and the reaction solution can be decanted. Entries 2 to 4 in Scheme 12.1 are examples of this method. 

The synthetic sequence, which shows only the succesful solutions adopted in every step, is outlined in Scheme 13.1.11. Reaction of l Chloroadamantan-4-one (39) [15] with sodium-potassium alloy in ether gave a mixture of ketonic and hydroxylated material which upon oxidation with Jones reagent gave 7-methylenebicyclo[3.3.1]nonan-2-one (40) in 75% yield. Reduction of 40 with sodium borohydride gave the alcohol 41 which could be also obtained in better yields from l-chloroadamantan-4-one with a large excess of sodium-potassium... 

Finally, the remaining steps were accomplished by methylation of 26a with methyl fluorosulphonate in ether to give the methylammonium salt 25, reductive cleavage of the N-0 bond with LAH and oxidation of the resulting alcohol with Jones reagent. The yields of the last three steps are almost quantitative and the overall yield of the seven steps synthetic sequence leading to optically pure (+)-luciduline (1) is 33%. 

This preparation illustrates a general and convenient way of oxidizing secondary alcohols to ketones in high deld. This procedure, usually called the Jones oxidation or oxidation by use of the Jones reagent, offers the advantage of almost instantaneous... 

The oxidation of a secondary alcohol to a ketone can also occur through the use of a variety of oxidizing agents. Figure 3-22 illustrates the oxidation of a secondary alcohol using Jones reagent. 

The compound in which the 3-keto group is reduced to a hydrocarbon interestingly still acts as an orally active progestin. The preparation of this compound starts with the hydrolysis of dihydrobenzene (13-2) to afford 19-nortestosterone (15-1). Reaction with ethane-1,2-thiol in the presence of catalytic acid leads to the cyclic thioacetal (15-2). Treatment of this intermediate with Raney nickel in the presence of alcohol leads to the reduced desulfurized derivative (15-3). The alcohol at 17 is then oxidized by any of several methods, such as chromic acid in acetone (Jones reagent), and the resulting ketone (15-4) treated with hthium acetylide. There is thus obtained the progestin lynestrol (15-5) [18]. 

Any oxidizing reagents, including H2Cr04, Jones reagent or PCC, can be used to oxidize 2° alcohols to ketones. However, the most common reagent used for oxidation of 2° alcohols is chromic acid (H2Cr04). 

Jones reagent is used to oxidize the aldehyde here to an acid. In general only the first two reagents listed in the Tips oxidi/e aldehydes to acids. TPAP can be used for oxidation of alcohols to aldehydes, ketones, or acids. The others are used for oxidizing alcohols to aldehydes or ketones.27... 

The mechanism of the oxidation of alcohols with Jones reagent is often depicted as given below.4... 

Some successful oxidations of secondary alcohols to ketones, using Jones reagent, are listed bellow ... 

In fact, it has been reported34 that benzyl ethers can react with Jones reagent, resulting in the formation of ketones and benzoates. This happens under relatively harsh conditions, and nonnally no interference from benzyl ethers is observed during the oxidation of alcohols with Jones reagent. 

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