Carboxylic acids primary alcohol oxidations

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... 

Using appropriate reactants, alcohols can be oxidized into aldehydes, ketones, and/or carboxylic acids. Primary alcohols can be oxidized into aldehydes, which can then be oxidized into carboxylic acids. Secondary alcohols can be oxidized into ketones. Tertiary alcohols do not undergo this type of oxidation. Give the structure of the product(s) resulting from the oxidation of each of the following alcohols. 

Carboxylic acids. Primary alcohols are oxidized to acids (secondary alcohols to ketones) using catalytic amount of CrOj and excess HjIOg in wet MeCN. By this procedure there is very little racemization of the products bearing a chirality center adjacent to the emerging carbonyl group. Therefore this method is useful for the preparation of chiral a-amino acids. 

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. 

Perhaps the most valuable reaction of alcohols is their oxidation to yield car-bony compounds—the opposite of the reduction of carbonyl compounds to yield alcohols. Primary alcohols yield aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols don t normally react with most oxidizing agents. 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

The most characteristic reaction of butadiene catalyzed by palladium catalysts is the dimerization with incorporation of various nucleophiles [Eq. (11)]. The main product of this telomerization reaction is the 8-substituted 1,6-octadiene, 17. Also, 3-substituted 1,7-octadiene, 18, is formed as a minor product. So far, the following nucleophiles are known to react with butadiene to form corresponding telomers water, carboxylic acids, primary and secondary alcohols, phenols, ammonia, primary and secondary amines, enamines, active methylene compounds activated by two electron-attracting groups, and nitroalkanes. Some of these nucleophiles are known to react oxidatively with simple olefins in the presence of Pd2+ salts. Carbon monoxide and hydrosilanes also take part in the telomerization. The telomerization reactions are surveyed based on the classification by the nucleophiles. 

Primary and secondary alcohols are oxidized slowly at low temperatures by benzyltriethylammonium permanganate in dichloromethane primary alcohols produce methylene esters (60-70%), resulting from reaction of the initially formed carboxylate anion with the solvent, with minor amounts of the chloromethyl esters and the carboxylic acids. Secondary alcohols are oxidized (75-95%) to ketones [34] the yields compare favourably with those obtained using potassium permanganate on a solid support. 1,5-Diols are oxidized by potassium permanganate under phase-transfer catalytic conditions to yield 8,8-disubstituted-8-valerolactones [35] (Scheme 10.1). 

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... 

Chromic acid test. This test is able to distinguish primary and secondary alcohols from tertiary alcohols. Using acidified dichromate solution, primary alcohols are oxidized to carboxylic acids secondary alcohols are oxidized to ketones tertiary alcohols are not oxidized. (Note that in those alcohols which are oxidized, the carbon that has the hydroxyl group loses a hydrogen.) In the oxidation, the brown-red color of the chromic acid changes to a blue-green solution. Phenols are oxidized to nondescript brown tarry masses. (Aldehydes are also oxidized under these conditions to carboxylic acids, but ketones remain intact see Experiment 31 for further discussion.)... 

Chromium (VI), permanganate ion, or silver oxide can all be used to oxidize an aldehyde to a carboxylic acid Cr6+ also oxidizes primary alcohols to carboxylic acids... 

R—CH2 primary alcohol [oxidizing agent] —Tit R—C—H aldehyde [over-oxidation] [O] R—C—OH carboxylic acid... 

Primary alcohols afforded the corresponding carboxylic acids via further oxidation of the aldehyde intermediate, e.g. 1-hexanol afforded 1-hexanoic acid in 95% yield. It is important to note, however, that this was achieved without the requirement of one equivalent of base to neutralize the carboxylic acid product (which is the case with supported noble metal catalysts). In contrast, when 1 mol% TEMPO (4 equivalents per Pd) was added, the aldehyde was obtained in high yield, e.g. 1-hexanol afforded 1-hexanal in 97% yield. Under cosolvent conditions using water/ethylene carbonate, Pd-neocuproine was found to be even more active (Fig. 4.65) [174]. This system is exceptional because of its activity (TOF 500h-1 could be reached for 2-octanol) and functional group tolerance, such as C=C bonds, C = C bonds, halides, a-carbonyls, ethers, amines etc. Thereby this system is expected to have a broad synthetic utility. 

Primary alcohols react with C1O3 in aqueous acid to form carboxylic acids, secondary alcohols yield ketones, and tertiary alcohols are unreactive to oxidation. Of the eight alcohols in the previous problem, only 2-methyl-2-butanol is unreactive to C1O3 oxidation. 

The most important applications of peroxyacetic acid are the epoxi-dation [250, 251, 252, 254, 257, 258] and anti hydroxylation of double bonds [241, 252, the Dakin reaction of aldehydes [259, the Baeyer-Villiger reaction of ketones [148, 254, 258, 260, 261, 262] the oxidation of primary amines to nitroso [iJi] or nitrocompounds [253], of tertiary amines to amine oxides [i58, 263], of sulfides to sulfoxides and sulfones [264, 265], and of iodo compounds to iodoso or iodoxy compounds [266, 267] the degradation of alkynes [268] and diketones [269, 270, 271] to carboxylic acids and the oxidative opening of aromatic rings to aromatic dicarboxylic acids [256, 272, 271, 272,273, 274]. Occasionally, peroxyacetic acid is used for the dehydrogenation [275] and oxidation of aromatic compounds to quinones [249], of alcohols to ketones [276], of aldehyde acetals to carboxylic acids [277], and of lactams to imides [225,255]. The last two reactions are carried out in the presence of manganese salts. The oxidation of alcohols to ketones is catalyzed by chromium trioxide, and the role of peroxyacetic acid is to reoxidize the trivalent chromium [276]. 

The spectrum of applications of potassium permanganate is very broad. This reagent is used for dehydrogenative coupling [570], hydrox-ylates tertiary carbons to form hydroxy compounds [550,831], hydroxylates double bonds to form vicinal diols [707, 296, 555, 577], oxidizes alkenes to a-diketones [560, 567], cleaves double bonds to form carbonyl compounds [840, 842, 552] or carboxylic acids [765, 841, 843, 845, 852, 869, 872, 873, 874], and converts acetylenes into dicarbonyl compounds [848, 856, 864] or carboxylic acids [843, 864], Aromatic rings are degraded to carboxylic acids [575, 576], and side chains in aromatic compounds are oxidized to ketones [566, 577] or carboxylic acids [503, 878, 879, 880, 881, 882, 555]. Primary alcohols [884] and aldehydes [749, 868, 555] are converted into carboxylic acids, secondary alcohols into ketones [749, 839, 844, 863, 865, 886, 887], ketones into keto acids [555, 559, 590] or acids [559, 597], ethers into esters [555], and amines into amides [854, 555] or imines [557], Aromatic amines are oxidized to nitro compounds [755, 559, 592], aliphatic nitro compounds to ketones [562, 567], sulfides to sulfones [846], selenides to selenones [525], and iodo compounds to iodoso compounds [595]. 

Finally, Cr(VI)-reagents should be mentioned for example the Jones reagent (H2S04/Cr03 in acetone) for the oxidation of primary alcohols to carboxylic acids and the oxidation of secondary alcohols to the corresponding ketones. The main problem with these chromium reagents is their high toxicity. 

Secondary alcohols give the respective ketones as products, regardless of the reaction conditions. Primary alcohols, however, can produce either aldehydes or carboxylic acids. Commonly, these oxidations are run in basic aqueous media. Under these conditions, the aldehydes that are formed initially react with the water to form a hydrate and this is oxidized further to the acid. Aldehydes, particularly aryl aldehydes, are the primary product only when the reaction is run in a neutral, preferably non-aqueous, medium such as a hydrocarbon solvent and usually with controlled oxygen uptake. 3,62... 

For example, an aldehyde prepared by the oxidation of a primary alcohol (Sec. 16.8) may very well be contaminated with the carboxylic acid this acid can be simply washed out with dilute aqueous base. The carboxylic acid prepared by oxidation of an alkylbenzene (Sec. 12.10) may very well be contaminated with unreacted starting material the carboxylic acid can be taken into solution by aqueous base, separated from the insoluble hydrocarbon, and regenerated by addition of mineral acid. 

Besides ruthenium tetroxide, other ruthenium salts, such as ruthenium trichloride hydrate, may be used for oxidation of carbon-carbon double bonds. Addition of acetonitrile as a cosolvent to the carbon tetrachloride-water biphase system markedly improves the effectiveness and reliability of ruthenium-catalyzed oxidations. For example, RuCl3 H20 in conjunction with NaI04 in acetonitrile-CCl4-H20 oxidizes (Ej-S-decene to pentanoic acid in 88% yield. Ruthenium salts may also be employed for oxidations of primary alcohols to carboxylic acids, secondary alcohols to ketones, and 1,2-diols to carboxylic acids under mild conditions at room temperature, as exemplified below. However, in the absence of such readily oxidized functional groups, even aromatic rings are oxidized. 

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. 

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