Primary alcohols oxidations to aldehydes

Primary alcohols oxidize to aldehydes, which, in turn, oxidize to carboxylic acids. Secondary alcohols oxidize to ketones. In each case, the reverse process is called re- duction... 

Among the aliphatic alcohols, oxidation of methanol has been studied most extensively [122-125]. At a platinum anode in acidic aqueous solutions, methanol oxidizes completely to CO2. Higher primary alcohols oxidize to aldehydes and acids under these conditions, though detailed mechanistic studies are lacking [126,127]. Anodic oxidation of secondary alcohols in aqueous acid leads to the corresponding ketones in high yield, but the reaction has received little attention over the years [126,128]. Indirect oxidation methods employing mediators are of considerable interest in this area and are treated elsewhere. 

The most characteristic reactions of alcohols are their oxidation to aldehydes and ketones, which may undergo further oxidation, producing carboxylic acids. While primary alcohols oxidize to aldehyde, secondary alcohols produce ketones ... 

Primary alcohols oxidize to aldehydes, which in turn may readily oxidize further to the corresponding carboxylic acids. 

Oxidation of primary alcohols leads to aldehydes and oxidation of secondary alcohols leads to ketones. This oxidation also involves the loss of two hydrogen atoms. However, unlike the oxidations discussed so far in this chapter that are mediated almost exclusively by cytochromes P450, the major enzyme involved in the oxidation of ethanol is ALD (discussed earlier in this chapter) (74). Although ALD is the major enzyme involved in the oxidation of ethanol and most other low molecular-mass alcohols, cytochromes P450, especially 2E1, can also oxidize ethanol and this enzyme is induced in alcoholics. Although comprehensive studies have not been published, it appears that cytochromes P450 are often the major enzymes involved in the oxidation of higher molecular mass alcohols. 

As mentioned above for RuO (1.2.7.10) and [RuO ]" (1.3.4.6) there are reports of Ru-catalysed oxidations for which the nature of the active catalyst or catalyst precursor is unclear but is probably predominantly [RuO ]. Electronic and Raman spectroscopy have been used to establish the nature of the catalytic species, but incorrectly fran.y-[Ru(0H)2(0)3] " rather than [RuO ] " was the formula ascribed to the ruthenate solute [212, 222]. Examples in which [RuO ] is the catalytic species include oxidations of nucleosides by RuCl3/K3(S20g)/aq. M KOH (Fig. 2.11) [547], and of primary alcohols oxidised to aldehydes RuClj or Ru03/Na(C10)/aq. base [551]. 

Reaction of the C-0 and O-H Bonds Primary alcohols oxidize to carboxylic acids secondary alcohols oxidize to ketones with chromium trioxide or sodium dichromate. Tertiary alcohols do not oxidize under mild conditions. With pyridinium chlorochromate (PCC) the oxidation of primary alcohols can be stopped at aldehydes. 

Oxidation of primary alcohols leads to aldehydes in moderate to good yield. Aldehydes are relatively easy to oxidize to the corresponding carboxylic acid. In most cases, the oxidation stops at the aldehyde, but small amounts of the acid are a common byproduct. Heating and long reaction times lead to increased amounts of the acid, and in some cases, the aldehyde is the minor product. Where feasible, removal of the aldehyde as it forms will minimize side reactions. When the reaction is pushed to give the carboxylic acid, there are at least two reasonable mechanistic rationales for this conversion-44 These two approaches involve formation of a chromate ester such as 13. Removal of the a-hydrogen (analogous to the alcohol to aldehyde conversion)... 

Aristeromycin 5 -aldehyde has been prepared, and was shown to be a potent inhibitor of SAH hydrolase this study indicated that the fluoromethylene compounds (Vol. 26, p. 247), which are also inhibitors, do not act as precursors of the aldehyde. 2-Halo-derivatives 39 (X=F, Cl) of neplanocin A have been prepared, as have the equivalent structures lacking the CH2OH group and the analogue 40. Neplanocin analogues with the primary alcohol oxidized to the carboxylic acid level have also been made by oxidation, and aristeromycin and its cytosine analogue (carbodine) have been incorporated into a hammerhead ribozyme domain. ... 

Collins reagent (Cr03 2 pyridine) A complex of chromium trioxide with pyridine, used to oxidize primary alcohols selectively to aldehydes, (p. 465)... 

When we come to study synthesis, we will find that oxidation of alcohols by chromium(VI) compounds is an important reaction. Primary and secondary alcohols can both be oxidized under appropriate conditions, and by controlling the conditions, we can oxidize primary alcohols either to aldehydes or carboxylic acids (Figure 10.42). Pyridinium chlorochromate (PCC) [pyHj+lCrOjCl] can be, and often is, used instead of the CrOj/pyridine combination. Because this reaction is an elimination, it is necessary that there is a hydrogen atom attached to the carbon bearing the OH group to be oxidized. Therefore, tertiary alcohols are not oxidized under these conditions. 

When chlorine is passed into boiling ethanol, both chlorination of the methyl group and oxidation of the primary alcohol group to an aldehyde occur, giving trichloro-acetaldehyde or chloral ... 

Oxidation of primary alcohols to aide hydes (Section 15 10) Pyridinium di chromate (PDC) or pyridinium chloro chromate (PCC) in anhydrous media such as dichloromethane oxidizes primary al cohols to aldehydes while avoiding over oxidation to carboxylic acids... 

Aldehydes are more easily oxidized than alcohols which is why special reagents such as PCC and PDC (Section 15 10) have been developed for oxidizing primary alco hols to aldehydes and no further PCC and PDC are effective because they are sources of Cr(VI) but are used m nonaqueous media (dichloromethane) By keeping water out of the reaction mixture the aldehyde is not converted to its hydrate which is the nec essary intermediate that leads to the carboxylic acid... 

The reaction of aldoses with nitric acid leads to the formation of aldaric acids by oxidation of both the aldehyde and the terminal primary alcohol function to carboxylic acid groups Aldaric acids are also known as saccharic acids and are named by substi tutmg aric acid for the ose ending of the corresponding carbohydrate... 

The use of silver (II) salts, particularly argentic picolinate, as reagents for hydroxyl oxidation has also been disclosed recently. The reaction may be run in acid, neutral or basic media in aqueous or polar organic solvents at room or slightly elevated temperatures. Primary alcohols may be oxidized to aldehydes or acids depending on the conditions used. Amines and trivalent phosphorous compounds are more sensitive to oxidation with this reagent than are hydroxyl groups. 

The S >ern oxidation is a preparatively important reaction which allows for the oxidation of primary and secondary alcohols 1 to aldehydes and ketones 2, respectively, under mild conditions, using activated dimethyl sulfoxide (DMSO) as the oxidizing agent. 

Most other oxidizing agents, such as chromium trioxide (0rO3) in aqueous acid, oxidize primary alcohols directly to carboxylic acids. An aldehyde is involved as an intermediate in this reaction but can t usually be isolated because it is further oxidized too rapidly. 

Perhaps the most important reaction of alcohols is their oxidation to carbonyl compounds. Primary alcohols yield either aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols are not normally oxidized. Pyridinium chlorochromate (PCC) in dichloromethane is often used for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones. A solution of Cr03 in aqueous acid is frequently used for oxidizing primary alcohols to carboxylic acids and secondary alcohols to ketones. 

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... 

Another factor complicating the situation in composition of peroxyl radicals propagating chain oxidation of alcohol is the production of carbonyl compounds due to alcohol oxidation. As a result of alcohol oxidation, ketones are formed from the secondary alcohol oxidation and aldehydes from the primary alcohols [8,9], Hydroperoxide radicals are added to carbonyl compounds with the formation of alkylhydroxyperoxyl radical. This addition is reversible. 

Fig. 11.3. Comparison of a) hydrolytic dehalogenation and b) oxidative dehalogenation. The products of Reaction a (an alcohol) and Reaction b (a carbonyl) may be interconverted by de-hydrogenation/hydrogenation (Reaction c). When these products are a primary alcohol and an aldehyde, further oxidation to the acid is possible (Reaction c).

You learned earlier that primary alcohols are oxidized to aldehydes, and secondary alcohols are oxidized to ketones. You can think of the reduction of aldehydes and ketones as the reverse of these reactions. Aldehydes can be reduced to produce primary alcohols. Ketones can be reduced to produce secondary alcohols. 

Varieties of primary and secondary alcohols are selectively oxidized to aldehyde or carbonyl compounds in moderate to excellent yields as summarized in Table 3. As can be seen, /(-substituted benzyl alcohols (e.g., -Cl, -CH3, -OCH3, and -NO2) yielded > 90% of product conversion in 3-4 h of reaction time with TOP in the range of 84-155 h (entries 2-5, Table 3), Heterocyclic alcohols with sulfur- and nitrogen-containing compoimds are found to show the best catalytic yield with TOP of 1517 and 902 h for (pyrindin-2-yl)methanol and (thiophene-2-yl) methanol, respectively (entries 9 and 10, Table 3). Some of aliphatic primary alcohols (long chain alcohols) and secondary alcohols (cyclohexanol, its methyl substituted derivatives and norboman-2-ol) are also selectively oxidized by the membrane catalyst (entries 11-14 and 15-17, Table 3) with TOP values in the window of 8-... 

An alternative approach is to oxidize both the carbonyl and primary alcohol functions to carboxylic acids, then selectively reduce that corresponding to the required aldehyde. This may be achieved by... 

Early electrochemical processes for the oxidation of alcohols to ketones or carboxylic acids used platinum or lead dioxide anodes, usually with dilute sulphuric acid as electrolyte. A divided cell is only necessary in the oxidation of primary alcohols to carboxylic acids if (he substrate possesses an unsaturated function, which could be reduced at the cathode [1,2]. Lead dioxide is the better anode material and satisfactory yields of the carboxylic acid have been obtained from oxidation of primary alcohols up to hexanol [3]. Aldehydes are intermediates in these reactions. Volatile aldehydes can be removed from the electrochemical cell in a... 

Both primeiry and secondary alcohols can be oxidized, but tertiary alcohols won t undergo simple oxidation. Oxidation of a primary alcohol gives an aldehyde however, preventing further oxidation of the aldehyde to a carboxylic acid is difficult. Secondary alcohols oxidize to a ketone without the problem of additional oxidation occurring. 

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