Oxidation of Primary Alcohols to Carboxylic Acids

The conversion of primary alcohols into carboxylic acids is not a difficult task. Often, the same oxidant that has been used to oxidize alcohols to aldehydes is applicable to the oxidation to acids when used in appropriate amounts, in different solvents, at higher temperatures, or at longer reaction times. An example is the oxidation of primary alcohols with air or oxygen with platinum-on-charcoal or, better still, platinum dioxide as catalyst (equation 228) [56]. 

Electrolytic oxidation with nickel anodes and stainless steel cathodes and sodium hydroxide or potassium hydroxide as the electrolyte converts saturated, unsaturated, acetylenic, and aromatic alcohols into acids at 25-75 in yields ranging from 51 to 92% (equation 229) [116]. 

Potassium hydroxide can act as an oxidant at higher temperatures. Heating heptadecyl alcohol with 3 times its weight of powdered potassium hydroxide for 15 min at 240-250 °C results in a 76% yield of heptadecanoic acid [484. Under much milder conditions, benzyl alcohol is converted into benzoic acid in a 75% yield on heating for 10-60 min at 25-80 °C with an excess of powdered potassium hydroxide in aqueous ferf-butyl alcohol and carbon tetrachloride [954.  

Vanillyl alcohol yields 93% of vanillic acid on heating with aqueous sodium hydroxide and silver oxide for a few minutes at 75 C. The oxidation most probably involves a Cannizzaro-type reaction [366]. 

The oxidation of primary alcohols to acids has been accomplished with nitric acid. Concentrated nitric acid d 1.42) at 25-30 °C oxidizes 3-chlo-ropropanol to 3-chloropropanoic acid in 78-79% yield after several hours [469] and converts 6-bromohexanol into 6-bromohexanoic acid in 91% yield after heating for 45 min at 100 °C [465]. 

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Figure 3-5. The search for a) oxidations of primary alcohols to carboxylic acids will obtain reaction b) as a hit, although this reaction is in reality a hydrolysis of an ester, c) The correct specification of the query to obtain reactions invoivingthe oxidation of aicohols to carboxyiic acids.

OXIDATION OF PRIMARY ALCOHOLS TO CARBOXYLIC ACIDS WITH SODIUM CHLORITE CATALYZED BY TEMPO AND BLEACH 4-METHOXYPHENYLACETIC ACID... 

Oxidation of Primary Alcohols to Carboxylic Acids or Carboxyiic Esters... 

Scheme 34 Oxidation of primary alcohols to carboxylic acids with nickel(lll) as mediator.

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... 

In general, the oxidation of primary alcohols to carboxylic acids using T)2-dioxygen metal complexes is rare. To our knowledge, only one report (134) communicates such a process. 

Scheme 7. The steps in the oxidation of primary alcohols to carboxylic acids mediated by the peroxo complex [(triphos)IrCl(T)2-02)]. Although not isolated, experimental evidence indicates that an intermediate with the proposed structure indicated by A in the scheme is present.

A special construction, called Swiss-Roll cell [13] (Fig. 22.12), is used for the application of the NiOOH electrode in the oxidation of primary alcohols to carboxylic acids. 

Anelli s TEMPO-mediated oxidation can be accelerated by the addition of a quaternary ammonium salt, like Aliquat 336, acting as a phase transfer catalyst. This can be advisable in the oxidation of hindered secondary alcohols but can encourage the over-oxidation of primary alcohols to carboxylic acids.16... 

Swiss-roll cell — This cell was developed in Switzerland in 1982, and it is used on industrial-scale in case of the NiOOH electrode for the oxidation of primary alcohols to carboxylic acids, as, e.g., in vitamin C production. The electrolyte solution flows axially through the cell (see Figure), which is made up of rolled meshes of the nickel net anode and steel net cathode, separated from each other by polypropylene spacers, around the central current feeder rod. 

The heterobimetallic complexes [N(n-Bu)4] [Os(N)R2(/u.-0)2Cr02] catalyze the selective oxidation of alcohols with molecular oxygen. A mechanism in which alcohol coordinates to the osmium center and is oxidized by B-hydrogen elimination (see -Hydride Elimination) is consistent with the data. The hydroxide adduct of OSO4, [0s(0H)204], with ferric cyanide and other co-oxidants catalyzes the oxidative dehydrogenation of primary aromatic and aliphatic amines to nitriles, the oxidation of primary alcohols to carboxylic acids, and of secondary alcohols to ketones. Osmium derivatives such as OsCb catalyze the effective oxidation of saturated hydrocarbons in acetonitrile through a radical mechanism. ... 

Oxidation. This reagent effects the oxidation of primary alcohols to carboxylic acids under alkaline conditions. Exposure of the hydroxy carboxylate salt derived from 1 to sodium ruthenate in 1 (V sodium hydroxide solution afforded the diacid 2, in which the substituent at Ce had epimerized to the thermodynamically favored 8-configuration. ... 

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. 

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. 

Zhao, M. Li,J. Mano, E. Song, Z. T chaen, D. M. Grabowski, E.J.J. Reider, P.J., Oxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite Catalyzed by TEMPO and Bleach. ... 

Recently, Giacomelli and co-workers have reported an efficient oxidation of primary alcohols to carboxylic acids through a TEMPO-catalyzed procedure. The procedure is based on the addition of 2 molar equiv of TCCA to an acetone solution of the alcohol followed by catalytic amounts (0.1 equiv) of TEMPO, NaBr, and then 1 equiv of aq. NaHCOs (Equation 65). This system operates at room temperature, the oxidation of the primary alcoholic group being practically quantitative. Secondary alcohols are oxidized to ketones. The mild conditions of this procedure and the total absence of any transition metal make this reaction suitable for safe laboratory use <2003JOC4999>. 

G. and Fernandez, M. (2010) Oxidation of Primary Alcohols to Carboxylic Acids, Springer, New York. 

Yakura and coworkers have developed bifunctional catalysts bearing TEMPO and iodobenzene moieties (stmctures 110 and 111, Eigure 4.3), which are useful for the environmentally benign oxidation of primary alcohols to carboxylic acids. Reaction of primary alcohols with a catalytic amount of catalyst 111 in the presence of peracetic acid as the terminal oxidant under mild conditions affords the corresponding carboxylic acids in excellent yields [91]. 

Huang LJ, Teumelsan N, Huang XF (2006) A facile method for oxidation of primary alcohols to carboxylic acids and its application in glycosaminoglycan syntheses. Chem Eur J 12 5246-5252... 

Cobalt complexes have frequently been used as catalysts for the oxidation of alcohols. Secondary alcohols were oxidized to ketones in the liquid phase in the presence of mixtures of Co(II) and Co(III) acetates at 60 C in nearly 80% yield [312]. Primary alcohols, on the other hand, gave high yields of the corresponding carboxylic acids in the presence of Co(OAc)3 [313]. Reaction proceeded stepwise through the aldehyde to the acid [314]. Chromium acetate could also be used to catalyze the oxidation of primary alcohols to carboxylic acids at temperatures below 100 °C but manganese and ferrous naphthenates were inactive under these conditions [314]. 

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