Alcohol Oxidation 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... 

Newer methods of alcohol oxidation (Swem, Dess-Martin) are introduced as environmentally preferable to the older chromium methods, including a description of a general, unifying mechanism of alcohol oxidation to aldehydes and ketones. TEMPO is shown as an oxidation catalyst to enhance hypochlorite oxidation. 

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 ... 

Alcohol oxidation to aldehydes is a dehydrogenation type process, which may occur both in the presence and absence of 0. Methanol... 

In 2013, Adimurthy and co-workers reported a TM-free NaOH-catalyzed N-alkylation reaction of 2-aminothiazoles, 2-aminobenzothiazoles, aminopyrimidines, and aminopyridines with benzyhc and heterobenzyhc alcohols under air (Scheme 43) [203]. In condition optimization, the authors found the model reaction of 2-aminobenzothiazole and 4-chlorobenzylalcohol under air afforded a higher yield of the product (93 %) than the one under nitrogen (90 %). Therefore, along with other results of mechanistic studies and the authors own previous work on based-catalyzed imine synthesis from alcohols and amines [204], they proposed that alcohol oxidation to aldehyde by air in the presence of bases is the initiation step of... 

Dibromothiophene (14) was also the starting material for the constmction of 2-formylthieno[3,4-h]thiophene (150) (Scheme 33). Lithiation enabled formation of aldehyde 147 then reacted with ethyl mercaptoacetate in the presence of CuO nanoparticles and K2CO3 to give 148, the ester group of which was reduced and the resulting alcohol oxidized to aldehyde [55]. 

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

HMF has been selectively converted into FDCA (99 mol% yield) in water, under mild conditions (65-130°C, 10 bar air) using gold nanoparticles on nanoparticulated ceria. ° As an alternative to FDCA, 2,5-dimethylfuroate (FDMC) has also been synthesized using the same catalyst in the absence of a base in methanol. The oxidation of HMF into FDCA or FDMC comprises two steps aldehyde oxidation and alcohol oxidation. Kinetic studies show that the rate-limiting step of the reaction is alcohol oxidation to aldehyde. Once the aldehyde is formed, the corresponding hemiacetal is obtained, which is rapidly oxidized into the acid or the ester (Fig. 13.5). 

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. 

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... 

Ten Brink et al. (2000) have shown how biphasic systems, sometimes with the sparingly soluble alcohols as one phase and an aqueous phase as the other phase, benefit from the strategy for air oxidation to aldehydes/ketones by using water soluble Pd complex of bathophenanthroline disulphonate. This is a nice example of green technology. 

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. 

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. 

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-... 

Alcohols are oxidized to aldehydes by the liver enzyme alcohol dehydrogenase, and aldehydes to carboxylic acids by aldehyde dehydrogenase. In mammals, monooxygenases can be induced by plant secondary metabolites such as a-pinene, caffeine, or isobornyl acetate. Reduction is less common and plays a role with ketones that cannot be further oxidized. Hydrolysis, the degradation of a compound with addition of water, is also less common than oxidation. 

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. 

Primary benzylic alcohols are oxidized to aldehydes in good yields without overoxidation (entry 1) lowering the pH from 5 to 3.5 increases the conversion, for reasons not fnUy understood yet (entry 2) . The aminoxyl radical is an electrophilic species" ... 

By suitable modification of reaction conditions, it was found possible to reduce 859 to keto alcohol 873 K The subsequent conversion of this intermediate to 874 proceeded without event. However, 874 could not be oxidized to aldehyde 875. Overoxidation to produce 876 or 877 (Jones conditions) invariably was observed due to the extreme sensitivity of874. This potentially expedient route to dodecahedrane therefore had to be abandoned and recourse made to blocking group methodology. 

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]. 

With the fully functionalized heterocyclic core completed, synthetic attention next focused on introduction of the 3,5-dihydroxyheptanoic acid side-chain. This required initial conversion of the ethyl ester of 35 to the corresponding aldehyde through a two-step reduction/oxidation sequence. In that event, a low-temperature DIBAL reduction of 35 provided primary alcohol 36, which was then oxidized to aldehyde 37 with TRAP. Subsequent installation of the carbon backbone of the side-chain was accomplished using a Wittig olefination reaction with stabilized phosphonium ylide 38 resulting in exclusive formation of the desired -olefin 39. The synthesis of phosphonium ylide 38 will be examined in Scheme 12.5 (Konoike and Araki, 1994). 

TABLE 30. Comparison of the results of metal-catalyzed alcohol oxidation to ketones, carboxylic acids or aldehydes using H2O2 or TBHP... 

Allylic and benzylic alcohols were oxidized to aldehydes or ketones with BnPhsPHSOs in refluxing CHsCN. The yield increased in the presence of bismuth chloride in a catalytic amount. Selective oxidation of various alcohols under solvent free conditions was also reported Interestingly, benzyl alcohols were oxidized selectively to benzaldehydes in very high yield (95-100%) when reacted with BnPhsPHSOs (1.2 eq.) and AICI3 (1 eq.) in the presence of an equimolar amount of 2-phenethyl alcohol, diphenyl carbinol or methyl phenyl sulfide (equation 72). 

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