Oxidations of Ketones and Aldehydes

Aldehydes undergo facile autoxidation (see Fig. 4.78), which is frequently used to form peracids in situ. The peracid itself will react with aldehydes in a Baeyer-Villiger (BV) reaction to form carboxylic acids [6]. 

The reaction is used commercially in the oxidation of acetaldehyde to peracetic acid [234], acetic anhydride [235] and acetic acid [236], respectively (Fig. 4.79). In the production of acetic anhydride, copper(II) salt competes with dioxygen for the intermediate acyl radical affording acetic anhydride via the acyl cation. 

Also heterogeneous catalysts can be employed, such as Pd or Pt on carbon [237]. Recently, it was found that gold supported on a mesoporous Ce02 matrix 

Ketones are oxidized by strong oxidizing agents such as alkaline KMn04. HNO3 also oxidizes ketone to carboxylic acid with fewer carbon atoms than the original ketone. 

The cyclic ketones on treatment with an alkaline or acidic KMn04 give dicarboxylic acid. Adipic acid is commercially prepared by the oxidation of cyclohexanone. The oxidizing agent attacks on an enol form. 

Silver oxide The mild oxidizing agent silver(I) oxide (Ag20) also oxidizes aldehyde to 

The use of silver(II) oxide is less common because of its cost and limited availability. Corey converted an benzaldehyde into the corresponding benzoic acid in 97% yield with 

Selenium dioxide (SeOi) oxidation Selenium dioxide is an excellent oxidizing agent for the oxidation of allylic and benzylic C-H fragments to allylic or benzylic alcohol. It also oxidizes the aldehydes and ketones to 1,2-dicarbonyl compounds (i.e. oxidation of active methylene groups to carbonyl groups). 

Among the most useful reactions of this type is that between an acid chloride and a diorganocopper reagent. We ll discuss this subject in more detail in Section 21.4. 

Problem 19,4 How would you carry out the following reactions More than one step may be required. 

Aldehydes are readily oxidized to yield carboxylic acids, but ketones are generally inert toward oxidation. The difference is a consequence of structure Aldehydes have a -CHO proton that can be abstracted during oxidation, but ketones do not. 

Many oxidizing agents, including KMn04 and hot HNO3, convert aldehydes into carboxylic acids, but CrOs in aqueous acid is a more common choice in the laboratory. The oxidation occurs rapidly at room temperature and results in good yields. 

Bernhard Tollens (1841 -1918) was born in Hamburg, Germany, received his Ph.D. at the University of Gottingen, and then became professor at the same institution. 

One drawback to this Cr03 oxidation is that it takes place under acidic conditions, and sensitive molecules sometimes undergo side reactions. In such cases, the laboratory oxidation of an aldehyde can be carried out using a solution of silver oxide, Ag30, in aqueous ammonia, the so-called Tollens reagent. Aldehydes are oxidized by the Tollens reagent in high yield 

Aldehydes easily oxidize to carboxylic acids or to carboxylates. In fact, preventing the oxidation of an aldehyde is difficult. Ketones oxidize with difficulty, since a change in the backbone must first take place. 

Aldehydes are easy to oxidize They slowly oxidize in the presence of air thus, in the laboratory, many old open bottles of aldehydes are acidic. In practice, the oxidation of an aldehyde may employ several reagents. 

Aldehydes are easy to oxidize, but ketones are more challenging. The two important oxidation reactions of ketones are the oxidation with a strong oxidant and the iodoform test. 

A number of procedures are available for the oxidation of aldehydes to the corresponding carboxylic acids in aqueous and organic media. 

Aromatic aldehydes have been conveniently oxidized by aqueous performic acid obtained by addition of H2O2 to HCOOH at low temperature (0-4 

The carboxylic acids precipitate out of the reaction mixture and can be isolated by filtration. Even the hetroaromatic aldehydes like formyl pyridines, formyl quinolines and formylazaindoles can be oxidised by the above procedure to the corresponding carboxylic acids in this procedure, the formation of N-oxides is avoided. 

Chemoselective oxidation of formyl group in presence of other oxidizable groups can be carried out in aqueous media in presence of a surfactant. For example, 4-(methylthio)benzaldehyde is quantitatively oxidised to 4-(methylthio)benzoic acid with TBHP in a basic aqueous medium in presence of cetyltrimethyl ammonium sulphate. 

Aromatic aldehydes having hydroxyl group in ortho or para position to the formyl groups can be oxidised with alkaline (Dakin reaction) in low yields. This reaction has been recently carried out in high yields using sodium percarbonate (SPC Na COj, 1.5 H O ) in H, 0-THF under ultrasonic irradiation. Using this procedure following aldehydes have been oxidised in 85-95% yields o-hydroxybenzaldehyde p-hydroxybenzaldehyde 2-hydroxy-4-methoxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde and 3-methoxy-4-hydroxybenzaldehyde. 

Compared with the oxidation of alcohols the oxidation of aldehydes and ketones by peroxodisulphate is generally slow. Formaldehyde and acetaldehyde are oxidised to the corresponding acids, viz. 

Subbaraman and Santappa studied the oxidations of formaldehyde and acetaldehyde in de-aerated solutions, both in the presence and absence of silver ions. When the concentration of aldehyde is much less than that of peroxodisulphate, the rate equation for reaction in absence of silver ions is 

With excess formaldehyde the rate equation becomes 

Oxygen inhibits the oxidations of both aldehydes. Subbaraman and Santappa suggest that the hydrated forms of the aldehydes react via chain mechanisms similar to those proposed for alcohols. Edwards et u/. in their study of the oxidation of ethanol (section 2.2.2) proposed a mechanism for the oxidation of acetaldehyde involving the non-hydrated form, viz. reactions (42)-(44). 

Acetone and cyclohexanone are oxidised at an appreciable rate only when silver ions are present. Acetone is oxidised to acetic acid and carbon dioxide, and the process is first-order with respect to both peroxodisulphate and silver ions, and zero-order with respect to acetone (Subbaraman and Santappa , Bekier and Kijowski ). The former workers observed that de-aeration has little effect on the rate, and suggested a chain mechanism involving CH3COCH2 radicals. Cyclohexanone is oxidised about 50 % more rapidly than acetone (Subbaraman and Santappa ). 

In both the Ni(acac)2-[bmim][PF6] and fluorous biphasic systems, catalyst leaching is very low and several further batch oxidation reactions may be carried ont with similar results to those obtained in the first run. In the fluorous biphasic system, the yield of 4-chlorobenzoic acid dropped from 87 % to 70 % by the sixth reaction cycle using [bmimJpFe] as a solvent, the yield was essentially the same after four uses, and no catalyst was found to leach into the organic phase. 

Oxidation reactions are not limited to those that occur at a carbon centre. The perfluorinated Ni(F-acac)2-benzene-C8FnBr system described above was also active for the oxidation of sulfides to sulfoxides and sulfones [28]. A sacrificial aldehyde is required as co-reductant, but the reaction may be tuned by changing the quantity of this aldehyde. If 1.6 equivalents of aldehyde are used, the sulfoxide is obtained, whereas higher quantities (5 equivalents) lead to sulfones. Fluorous-soluble transition metal porphyrin complexes also catalyse the oxidation of sulfides in the presence of oxygen and 2,2-dimethylpropanal [29]. 

For all of these kinds of carbonyl-containing compounds (aldehydes, ketones, carboxylic acids, etc.), some properties of which are provided for some of the more simple members in Table 9.2, it might be anticipated that protonation of the non-bonded electrons (Chapter 1) on oxygen would increase the electron deficiency at the carbon of the carbonyl and facilitate attack at that carbon by nucleophiles. It might further be expected that, since the carbon of the carbonyl is positive, protons on the carbon adjacent to the carbon of the carbonyl (i.e., the a-carbon) would be particularly acidic (relative to protons on carbon not in such a position). In addition, it might be anticipated that the positive carbon of the carbonyl would exert an influence on sites of unsaturation (both double and triple bonds) that were conjugated with the carbonyl (i.e., a,P-unsaturated). 

PART I. ALDEHYDES AND KETONES A. OXIDATION OF ALDEHYDES AND KETONES 

Aldehydes are more easily oxidized than ketones, but, as with other organic compounds, complete combustion in the presence of oxygen produces carbon dioxide (CO2) and water (H2O) (assuming, of course, that halogen, etc., are absent). 

In the presence of a suitable initiator, which might be triplet oxygen ( 02) or a radical source, the controlled oxidation of aldehydes by oxygen results in the abstraction of the hydrogen attached to the carbon of the carbonyl to produce an acyl radical (Equation 9.1)  

TABLE 9.2. Representative Examples of Aldehydes, Ketones, Carboxylic Acids, and Derivatives of the Latter  

In addition to those methods already discussed, ketones can also be prepared from certain carboxylic acid derivatives, just as aldehydes can. Among the most useful reactions of this sort is that between an acid chloride and a lithium diorganocopper reagent such as we saw in Section 10.7. We ll discuss this reaction in more detail in Section 21.4. 

Aldehyde oxidations occur through intermediate 1,1-diols, or hydrates, which are formed by a reversible nucleophilic addition of water to the carbonyl group. Even though formed to only a small extent at equilibrium, the hydrate reacts like any typical primary or secondary alcohol and is oxidized to a carbonyl compoimd (Section 17.7). 

Ketones are inert to most oxidizing agents but undergo a slow cleavage reaction of the C-C bond next to the carbonyl group when treated with hot alkaline KMn04. The reaction is not often used and is mentioned here only for completeness. 

Thomson OW Click Organic Interactive to use a web-based palette to predict products from a variety of oxidation reactions involving aldehydes and ketones. 

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For a review of metal ion-catalyzed oxidative cleavage of alcohols, see Trahanovsky, W.S. Methods Free-Radical Chem. 1973, 4, 133. For a review of the oxidation of aldehydes and ketones, see Verter, H.S. in Zabicky The Chemistry of the Carbonyl Group, pt. 2 Wiley NY, 1970, p. 71. 

Hassall, C. W., The Baeyer-Villiger oxidation of aldehydes and ketones. Organic Reactions. 9, 73-106, 1957. 

C. H. Hassall, The Baeyer-Villiger Oxidation of Aldehydes and Ketones, Organic Reactions 9, 73 (1957). 

Iodine-catalysed hydroperoxidation of cyclic and acyclic ketones with aqueous hydrogen peroxide in acetonitrile is an efficient and eco-friendly method for the synthesis of gem -dihydroperoxides and the reaction is conducted in a neutral medium with a readily available low-cost oxidant and catalyst.218 Aryl benzyl selenoxides, particularly benzyl 3,5-bis(trifluoromethyl)phenyl selenoxide, are excellent catalysts for the epoxidation of alkenes and Baeyer-Villiger oxidation of aldehydes and ketones with hydrogen peroxide.219 Efficient, eco-friendly, and selective oxidation of secondary alcohols is achieved with hydrogen peroxide using aqueous hydrogen bromide as a catalyst. Other peroxides such as i-butyl hydroperoxide (TBHP), sodium... 

TEMPO has a double role - it generates the oxoamonium salt, responsible for the oxidation (Scheme 1), and inhibits the further oxidation of aldehydes and ketones, which occurs instead via free-radical chain processes under the same conditions, but in the absence of TEMPO [5a], Thus, this catalytic system is highly effective for one of the most demanding transformations, the selective synthesis of aldehydes from benzylic and nonbenzylic alcohols. 

Several research groups have tested a number of other secondary amines (3c-f) for this important transformation [18]. Derivative 3c was found to be a very efficient catalyst for the a-oxidation of aldehydes and ketones, as the same high yields and enantioselectivities could be obtained in the case of both aldehydes and ketones, but with a lower catalyst loading and shorter reaction times. 

One drawback for the direct organocatalytic a-oxidation of aldehydes and ketones is the use of nitrosobenzene, which is an expensive oxygen source . This has led to further investigations in order be able to use other oxidants. Recently, Cordova et al. [20] reported that r-a-methyl proline could incorporate O2 in the a-position of an aldehyde. The presence of tetraphenylporphyrin (TPP) as sensitizer was necessary to promote the formation of singlet 02 as the electrophilic species. Although, the enantioselectivities obtained were only moderate (54-66% ee), this represents undoubtedly a very intriguing alternative to the use of nitrosobenzene in this type of reaction. 

The domain of oxidations with silver oxide includes the conversion of aldehydes into acids [63, 206, 362, 365, 366, 367 and of hydroxy aromatic compounds into quinones [171, 368, 369]. Less frequently, silver oxide is used for the oxidation of aldehyde and ketone hydrazones to diazo compounds [370, 371], of hydrazo compounds to azo compounds [372], and of hydroxylamines to nitroso compounds [373] or nitroxyls [374] and for the dehydrogenation of CH-NH bonds to -C=N- [375]. Similar results with silver carbonate are obtained in oxidations of alcohols to ketones [376] or acids [377] and of hydroxylamines to nitroso compounds [378]. 

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