OXIDATION OF PRIMARY ALCOHOLS AND ALDEHYDES

Oxidation of primary alcohols produces aldehydes, and oxidation of aldehydes produces carboxylic acids. For these oxidation reactions KMn04 and K2Cr207 solutions are used in acidic medium. 

If an excess amount of oxidizing agent is used, primary alcohols are oxidized to carboxylic acids directly. 

Benzoic acid is prepared by the oxidation of alkyl benzenes. For the oxidizing agent, a hot, acidic solution of KMn04 or K2Cr207 is used. The number of carbon atoms attached to the aromatic structure, doesn t change the product. 

Organic acids can be prepared in many ways, four of which are described here (1) oxidation of primary alcohols or aldehydes, (2) oxidation of alkyl side chains on aromatic rings, (3) reaction of Grignard reagents with carbon dioxide, and (4) hydrolysis of alkyl cyanides (nitriles). 

The oxidation of primary alcohols (Sec. 7.12) and aldehydes (Sec. 9.13) to carboxylic acids has already been mentioned. It is easy to see that these are oxidation reactions because going from an alcohol to an aldehyde to an acid requires replacement of C—H bonds by C—O bonds. 

The most commonly used oxidizing agents for these purposes are potassium permanganate (KMnOJ, chromic acid anhydride (Cr03), nitric acid (HNO3), and, with aldehydes only, silver oxide (Ag20). For specific examples, see eqs. 7.37, 9.37, 9.38, and 9.41. 

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Oxidation of primary alcohols and aldehydes RCH2OH JSU RCHO RC02H... 

Carboxylic acids can be prepared by the oxidation of primary alcohols, and aldehydes. An oxidizing agent such as KMnO can accomplish these conversions. 

Carbojqrlic acids can be prepared by oxidation of primary alcohols and aldehydes. Problems 17.18-17.24, Treating a Grignard reagent with carbon dioxide (CO2) gives the magnesium 17.42,17.48 salt of a carboxylic acid, which, upon protonation with aqueous acid, gives a carboxylic acid. 

The oxidation of primary alcohols and aldehydes to carboxylic acids by aqueous Cr(VI) was described in Sections 8-6 and 17-4. This section presents two additional reagents suitable for this purpose. It is also possible to introduce the carboxy function by adding a carbon atom to a haloalkane. This transformation can be achieved in either of two ways the carbonation of organometaUic reagents or the preparation and hydrolysis of nitriles. 

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

To the synthetic chemist the most important of the reactions m Table 17 1 are the last two the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones Indeed when combined with reactions that yield alcohols the oxidation methods are so versatile that it will not be necessary to introduce any new methods for preparing aide hydes and ketones in this chapter A few examples will illustrate this point... 

We ve already discussed two methods of aldehyde synthesis oxidation of primary alcohols and oxidative cleavage of alkenes. 

Dipyridiue-chromium(VI) oxide2 was introduced as an oxidant for the conversion of acid-sensitive alcohols to carbonyl compounds by Poos, Arth, Beyler, and Sarett.3 The complex, dispersed in pyridine, smoothly converts secondary alcohols to ketones, but oxidations of primary alcohols to aldehydes are capricious.4 In 1968, Collins, Hess, and Frank found that anhydrous dipyridine-chromium(VI) oxide is moderately soluble in chlorinated hydrocarbons and chose dichloro-methane as the solvent.5 By this modification, primary and secondary alcohols were oxidized to aldehydes and ketones in yields of 87-98%. Subsequently Dauben, Lorber, and Fullerton showed that dichloro-methane solutions of the complex are also useful for accomplishing allylic oxidations.6... 

Compared with ketoreductases, the synthetic application of alcohol oxidases has been less explored. However, selective oxidation of primary alcohols to aldehydes is superior to the chemical methods in terms of conversion yields, selectivity, and environmental friendliness of reaction conditions. In addition, coupling of alcohol oxidase with other enzymes provides a tremendous opportunity to develop multi-enzyme processes for the production of complex molecules. Therefore, a growing impact of alcohol oxidases on synthetic organic chemistry is expected in the coming years. 

Oxidation of ascorbate (reduction of 02 to H20) Oxidation of primary alcohols to aldehydes in sugars (reduction of 02 to 11202) Removal of amines and diamines Electron-transfer... 

A better reagent for oxidation of primary alcohols to aldehydes in good yield is pyridinium chlorochromate (PCC), a complex of chromium trioxide with pyridine and HCl. 

The system (4- Bu-pyH)3[Ru(0)3Cl ]/NM0/PMS/CH2Cl3 catalysed the oxidation of primary alcohols to aldehydes and of secondary alcohols to ketones like TRAP (Tables 2.1 and 2.2), such oxidations did not attack double bonds. As stoich. trans-(PPh )2[Ru(0)2Cl ] -/CH3CN it is a two electron oxidant for alcohols [561]. For tran -[Ru(0)2Cy - in solution the effective oxidant or oxidant precursor is [Ru(0)2Cl3]", and this species is coordinatively unsaturated. That this is the case is suggested by the observation that addition of extra Cl" (as (PPh )Cl) to the green [Ru(0)2Cl3]" in solution (Eq. 1.4) generating the red franx-[Ru(0)3Cl ] ", a markedly less effective catalytic oxidant for alcohols than [Ru(0) Cl ]" [561]. 

Aerobic oxidation of primary alcohols to aldehydes and secondary alcohols to ketones was accomplished in ionic liquids (bmim, l-butyl-3-methyl-imidazolium cation) as RuCl2(PPh3)j/(bmim)V80°C RuClj or [RuCl Cp-cymene)] were also used... 

Abstract This is one of the most important classes of oxidation effected by Ru complexes, particnlarly by RnO, [RuO ] , [RnO ] and RuCljCPPhj), though in fact most Ru oxidants effect these transformations. The chapter covers oxidation of primary alcohols to aldehydes (section 2.1), and to carboxylic acids (2.2), and of secondary alcohols to ketones (2.3). Oxidation of primary and secondary alcohol functionalities in carbohydrates (sugars) is dealt with in section 2.4, then oxidation of diols and polyols to lactones and acids (2.5). Finally there is a short section on miscellaneous alcohol oxidations in section 2.6. 

Table 2.1 Oxidation of primary alcohols to aldehydes and carboxylic acids...

Typical examples are listed in Table 2.1. A few oxidations are effected by RuO but in general it is too powerful an oxidant for this purpose. The system RuCyaq. NaCl-CCy Pt anode oxidised benzyl alcohol to benzaldehyde and benzoic acid and p-anisaldehyde to p-anisic acid [24], and a wide range of primary alcohols and aldehydes were converted to carboxylic acids, secondary alcohols to ketones, l, -diols to lactones and keto acids from RuOj/aq. NaCl pH 4/Na(H3PO )/Pt electrodes (Tables 2.1-2.4). The system [RuO ] "/aq. K3(S303)/Adogen /CH3Cl3 oxidised benzyhc alcohols to aldehydes [30]. The oxidation catalyst TPAP (( Pr N)[RuO ]) (cf. 1.3.4) is extremely useful as an oxidant of primary alcohols to aldehydes and secondary alcohols to ketones without... 

For a synthesis of the anti-cancer drug taxol TPAP/NMO was used in three steps, two for oxidation of primary alcohols to aldehydes (by TPAP/NMO/PMS/ CHjClj) and one for a secondary alcohol to ketone (by TPAP/NMO/PMS/CHjClj-CHjCN) [66], cf. also [111] and for the SERCA inhibitor thapsigargin (two primary alcohol and one secondary alcohol oxidation steps) [112], This system was also used during synthesis of the cholesterol biosynthesis inhibitor 1233A [52], the antibiotic and anti-parasitic ionophore tetronasin [113, 114] and for the cytotoxic sponge alkaloids motopuramines A and B [115]. 

NOC1 and an alcohol 9-9 From ozonides 9-10 Oxidative cleavage of enol ethers 9-13 Reaction between carboxylic acids and lead tetraacetate 9-18 Oxidation of ethers 9-22 Oxidation of primary alcohols or aldehydes... 

Material 3 has been found to serve as a highly effective and clean catalyst for the oxidation of primary alcohols to aldehydes with a superior performance over that of the previously reported polymer based system (PSP). The oxidations, using our previously published protocol, produced the corresponding aldehydes in less than three hours using a 10 wt% of solid catalyst,22 significantly, the aldehydes were free of contaminants. 

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... 

The most widely used chromium(VI)-oxo reagents for synthetic use in organic chemistry are the Collins reagent, Cr03(py)2,273 and the Corey reagent, Cr03CrpyH+,297 with the latter being superior for the oxidation of primary alcohols to aldehydes.275... 

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