Carboxylic acids Sodium chlorite

Many of the oxidants employed to prepare aldehydes from primary alcohols may be used to further oxidize the aldehyde initially formed to the corresponding carboxylic acid. The most common oxidants for this purpose include KMn04," chromic acid, sodium chlorite,silver oxide," and PDC in DMF. °... 

Oxidation of the aldehyde groups of SVI-IO4 with weakly acidic sodium chlorite " for various times gave products (see 17, SVI-IO4-BH4-CIO2) in which from 16 to 81% of the aldehyde groups had been oxidized, and which showed decreasing precipitation in anti-Pn VI horse and rabbit sera with increasing content of carboxylic acid groups. The product from the con-... 

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

One feature of this oxidation system is that it can selectively oxidize primary alcohols in preference to secondary alcohols, as illustrated by Entry 2 in Scheme 12.5. The reagent can also be used to oxidize primary alcohols to carboxylic acids by a subsequent oxidation with sodium chlorite.34 Entry 3 shows the selective oxidation of a primary alcohol in a carbohydrate to a carboxylic acid without affecting the secondary alcohol group. Entry 5 is a large-scale preparation that uses NaC102 in conjunction with bleach as the stoichiometric oxidant. 

This methodology provides a general synthesis of L-amino acids in 92-96% ee and in chemical yields of about 40-60%. Thus reaction of 3 (X = Br) with NaN3 under phase-transfer conditions provides 6, which is homologated to the 1-chloro-2-azidoboronate 7. This product is oxidized by sodium chlorite directly to an azido carboxylic acid (8). Hydrogenation of 8 provides L-amino acids (9). 

Effective conditions for oxidation of aldehydes to carboxylic acids with KMn04 involve use of t-butanol and an aqueous NaH2PC>4 buffer as the reaction medium.173 Buffered sodium chlorite is also a convenient oxidant.174 175 An older reagent for carrying out the aldehyde — carboxylic acid oxidation is silver oxide. 

Benzo[ ]perimidinone carbaldehyde and carboxylic acid derivatives have also been prepared by alkyl oxidation. Thus, treatment of the 2-methyl derivative 588 with selenium dioxide at reflux in dioxane gave the aldehyde 589, which then gave carboxylic acid 590 on reaction with sodium chlorite <2001JME2004>. 

For the synthesis of amino acids, the reaction of an a-haloalkyl boronic ester 4 with sodium azide and a phase-transfer catalyst in dichloromethane/water requires a large excess of azide in order to form the a-azidoalkyl boronic ester 5 with only 1-2% epimer34. With the exception of R1 = benzyl, where epimerization of 4 is relatively rapid, bromoalkyl boronic esters are preferred. Chloroalkyl boronic esters react so slowly that the azide and dichloromethane may generate hazardously explosive diazidomethane65,66. Chain extension of 5 to 6 proceeds normally. Sodium chlorite, which is known to oxidize aldehydes to carboxylic acids67-69, also oxidizes a-chloroalkyl boronic esters to carboxylic acids34. The azido acid is hydrogenated to the amino acid. 

Oxidation of a,p-enals. Sodium chlorite is superior to other reagents for oxidation of oc,/l-unsaturated aldehydes to the corresponding carboxylic acid, particularly of aldehydes containing an ct-methylene group. In addition, the oxidation is stereospecific. 2-Methyl-2-butene2 was used as the chlorine scavenger. 

Immobilized TEMPO has been used for the one-pot oxidation of alcohols to carboxylic acids as well.26 For this purpose TEMPO resin 1 was combined with two ion-exchange resins loaded with chlorite anions and hydrogen phosphate in the presence of catalytic amounts of potassium bromide and sodium hypochlorite in solution. The reaction required work-up for the removal of salts, but tolerated several protecting schemes and afforded pure products in good to excellent yields. The reaction is initiated by catalytic TEMPO oxidation of alcohols to aldehydes driven by dissolved hypochlorite followed by oxidation to the carboxylic acids effected by chlorite. 

Fig. 17.17. Sodium chlorite oxidation of aliphatic or aromatic aldehydes to form a carboxylic acid. The extra additive destroys the reduction product of the oxidant, i.e., sodium hypochlorite or hypochloric acid.

Sodium chlorite is a mild oxidizing agent for the oxidation of aldehydes to carboxylic acids. 

A further oxidation is then performed to establish the carboxylic acid moiety at C-1, which will form the macrolactone later in the synthesis. Sodium chlorite is commonly used as an oxidizing agent and is often applied for saturated and aromatic aldehydes. Hypochloric acid (HOCl) and sodium hypochlorite (NaOCl) are formed as byproducts and have to be destroyed before they can attack the substrate or the product, because they are stronger oxidizing agents. In this case, 2-methyl-2-butene (43) is added to the reaction mixture forming a chlorohydrin 44. 

In the final stages of the total synthesis of ustiloxin D, M.M. Joullie and co-workers had to install the amide side-chain onto the already assembled macrocycle.To achieve this goal, the macrocyclic primary alcohol was treated with the Dess-Martin periodinane to generate the corresponding aldehyde, which was subsequently treated with sodium chlorite to afford the carboxylic acid. The carboxylic acid was then coupled with the benzyl ester of glycine to complete the installation of the side-chain in 66% yield for three steps. 

Raach, A., Reiser, O. Sodium chlorite-hydrogen peroxide, a mild and selective reagent for the oxidation of aldehydes to carboxylic acids. J. Prakt. Chem. 2000, 342, 605-608. 

Dalcanale, E., Montanari, F. Selective oxidation of aldehydes to carboxylic acids with sodium chlorite-hydrogen peroxide. J. Org. Chem. 1986,51,567-569. 

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. ... 

Oxidation of an aldehyde group to a carboxyl group has often been used for identification of the compounds. As far as can be judged from the results, such oxidations, using chromium trioxide/acetic acid, bromine-water, - peroxy acids, - or chlorite, have not been accompanied by any important side-reactions. Hypoiodite titration, using the iodine in sodium bicarbonate-sodium carbonate procedure, has sometimes been used, giving almost stoichiometric aldehyde determinations. - - Reduction by the Meerwein-Ponndorf reaction, with borohydride - - ... 

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