Alcohols, oxidizing reagents acids

A recently discovered (2) oxidizing system promises to become very important for the oxidation of acid-sensitive compounds. The reagent is chromium trioxide-pyridine complex, which may be isolated after preparation and employed in nonaqueous solvents (usually methylene chloride). A remarkable feature of the reagent is that good yields of aldehydes are obtained by direct oxidation of primary alcohols. The preparation of the reagent and its use are given. 

We have also found that BTMA Br3 can be used as a reagent for the oxidation of benzyl alcohols to benzoic acids. That is, the reaction of benzyl alcohols with 2-equiv. of BTMA Br3 in an aq. alkaline solution at room temperature or at 70°C afforded benzoic acids in good yields. Thus, we could selectively obtain the oxidation products, benzaldehydes and benzoic acids, from benzyl alcohols by using a stoichiometric amount of BTMA Br3 (Fig. 24) (ref. 32). 

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. 

One feature of this oxidation system is that it can selectively oxidize primary alcohols in preference to secondary alcohols, as illustrated by Entry 2 in Scheme 12.5. The reagent can also be used to oxidize primary alcohols to carboxylic acids by a subsequent oxidation with sodium chlorite.34 Entry 3 shows the selective oxidation of a primary alcohol in a carbohydrate to a carboxylic acid without affecting the secondary alcohol group. Entry 5 is a large-scale preparation that uses NaC102 in conjunction with bleach as the stoichiometric oxidant. 

In order to overcome these two issues, we reversed the order of the reaction sequence, as summarized in Scheme 1.20. We took advantage of the alcohol functional group in 50. Oxidation ofpMB of 50 with DDQ proceeded smoothly to form cyclic aminal 52 (as a mixture of a and P = 11.5 1) in toluene at 0-10 °C. The resulting DDQH, which is insoluble in toluene, was filtered off, and isolated DDQH could be recycled as we demonstrated in the Proscar process (see p. 92) [32]. Thus, this process minimizes the impact to the environment from an oxidizing reagent. Cyclic aminal 52 was solvolyzed with NaOH in MeOH at 40 °C. The resulted anisaldehyde was reduced in situ to pMBOH 43 by addition of NaBH4 and the desired amino alcohol 53 was isolated by direct crystallization from the reaction mixture, upon neutralization with acetic acid, in 94% yield and >99.9% ee after crystallization from toluene-heptane. 

Later, Torii et al. found that the tin-aluminum-mediated allylation can be carried out with the less expensive allyl chloride, instead of allyl bromide, when a mixture of alcohol-water-acetic acid was used as the solvent.77 When combined with stoichiometric amounts of aluminum powder, both stoichiometric and catalytic amounts of tin are effective. As reported by Wu et al., higher temperatures can be used instead of aluminum powder.78 Under such a reaction condition, allyl quinones were obtained from 1,4-quinones, followed by oxidation with ferric chloride. Allylation reactions in water/organic solvent mixtures were also carried out electrochemically, with the advantage that the allyltin reagent could be recycled.79... 

The characteristic end point orange color can be demonstrated by addition of a slight excess of the chromic acid oxidizing reagent to a few milliliters of acetone containing a few drops of isopropyl alcohol. 

Nickel(lll) oxide, prepared from a nickel(ii) salt and sodium hypochlorite, is used for the oxidation of alkanols in aqueous alkali [46]. Residual nickel(Ii) oxide can be re-activated by reaction with sodium hypochlorite. Nickel oxides have also long been used in the manufacture of the positive pole in the Edison nickel-iron rechargeable battery, now largely superseded by die lead-acid accumulator, and in the Jungner nickel-cadmium batteries used as button cells for calculators [47]. Here, prepared nickel oxide is pressed into a holding plate of perforated nickel. Such prepared plates of nickel(lli) oxide have been proposed as reagent for the oxidation, in alkaline solution, of secondary alcohols to ketones and primary alcohols to carboxylic acids [48]. Used plates can be regenerated by anodic oxidation. 

Common alcohol oxidation methods employ stoichiometric amounts of toxic and reactive oxidants like Cr03, hypervalent iodine reagents (Dess-Martin) and peracids that pose severe safety and environmental hazards in large-scale industrial reactions. Therefore, a variety of catalytic methods for the oxidation of alcohols to aldehydes, ketones or carboxylic acids have been developed employing hydrogen peroxide or alkyl hydroperoxides as stoichiometric oxygen sources in the presence of catalytic amounts of a metal catalyst. The commonly used catalysts for alcohol oxidation are different MoAV(VI), Mn(II), Cr(VI), Re(Vn), Fe(II) and Ru complexes . A selection of published known alcohol oxidations with different catalysts will be presented here. 

Materials. Chemically pure solvents and reagent grade ceric ammonium nitrate were used as received. Cumene hydroperoxide was purified via the sodium salt. Lucidol tert-butyl hydroperoxide was purified by low temperature crystallization. Tetralin hydroperoxide, cyclohexenyl hydroperoxide, and 2-phenylbutyl-2-hydroperoxide were prepared by hydrocarbon oxidation and purified by the usual means. 1,1-Diphenyl-ethyl hydroperoxide and triphenylmethyl hydroperoxide were prepared from the alcohols by the acid-catalyzed reaction with hydrogen peroxide (10). 

Preparation of alcohols Organometallic reagents (RMgX, RLi) are powerful nucleophiles. They attack epoxides at the least hindered carhon, and generate alcohols. For example, propylene oxide is an unsymmetrical epoxide, which reacts with methyl magnesium bromide to produce 2-butanol, after the acidic work-up. 

Primary alcohols are oxidized either to aldehydes or to carhoxylic acids, depending on the oxidizing reagents and conditions used. 

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). 

Metallic oxidants, namely, chromic acid and potassium permanganate, may be used to oxidize alkanes to alcohols or ketones, but these reagents have only limited synthetic value. Alkaline KMnC>4 is rather ineffective, mainly because of the insolubility of alkanes in the aqueous solution of the reagent. Oxidations in acidic solutions such as aqueous CF3COOH,108 or the use of special reagents such as benzyltriethylammonium permanganate109 may give better results. 

Uhromic acid, in a variety of acidic media, has been used extensively for the oxidation of primary alcohols to aldehydes Itul. rarely has provided aldehydes in greater than 50% yield.5 Uhromium trioxide in pyridine was introduced as a unique, hniiacidic reagent for alcohol oxidations and has been used extensively to prepare ketones, but has been applied with only limited success to the preparation of aldehydes. While o-metlmxybenzaldehyde was obtained in 89% yield, 4-nitro-beir/.uldehyde and n-heptanal were obtained in 28% and 10% yields, respectively.7... 

Ru04 is a very reactive reagent that is employed not only for the oxidation of secondary alcohols to ketones and primary alcohols to carboxylic acids,36 but also to perform the following transformations ... 

---