Oxidations to carboxylic acids

Thiazolecarboxaldehydes are very easily oxidized to carboxylic acids by most oxidizing agents, the most common being KMn04 in cold pyridine or boiling acetone. Thiazolecarboxylic acids are obtained in 50% yield (29). Other oxidizing agents such as Ag 0 in dioxane and water (29, 103), chromic acid, and so forth are also used. 

Aldehydes are easily oxidized to carboxylic acids under conditions of ozonide hydroly SIS When one wishes to isolate the aldehyde itself a reducing agent such as zinc is included during the hydrolysis step Zinc reduces the ozonide and reacts with any oxi dants present (excess ozone and hydrogen peroxide) to prevent them from oxidizing any aldehyde formed An alternative more modem technique follows ozone treatment of the alkene m methanol with reduction by dimethyl sulfide (CH3SCH3)... 

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 readily oxidized to carboxylic acids by a number of reagents including those based on Cr(VI) in aqueous media... 

Section 17 15 Aldehydes are easily oxidized to carboxylic acids... 

Pyridazine aldehydes and ketones with the carbonyl group at the ring or in a side chain react in the usual manner. They form hydrazones, semicarbazides, oximes, etc. Side-chain aldehydes can be easily oxidized to pyridazinecarboxylic acids with silver nitrate and side-chain ketones are oxidized to carboxylic acids by treatment with potassium permanganate or hydrogen peroxide. 

Methyl groups in pyridopyrazines (64IMC240) and pyridopyrazinones (71TH21500) are oxidized to carboxylic acids with potassium permanganate. Aryl carbinol substituents are also very readily oxidized to benzoyl derivatives in alkaline conditions (76CPB238). Bromina-tion of 2,3-dimethylpyrido[3,4-f ]pyridazine gives the 2,3-bisbromomethyl derivative, whilst... 

Ruthenium tetroxide is a potent oxidant, however, and it readily attacks carbon-carbon double bonds.19 Primary alcohols are oxidized to carboxylic acids, methyl ethers give methyl esters, and benzyl ethers are oxidized to benzoate esters. 

Aldehydes can be oxidized to carboxylic acids by both Mn(VII) and Cr(VI). Fairly detailed mechanistic studies have been carried out for Cr(VI). A chromate ester of the aldehyde hydrate is believed to be formed, and this species decomposes in the rate-determining step by a mechanism similar to the one that operates in alcohol oxidations.209... 

A total synthesis of O-methylarnottianamide (223) was performed by Falck et al. (177) (Scheme 34). The regio- and stereospecific cycloaddition of the 2,4-dinitrophenyl (DNP) salt of 6,7-methylenedioxyisoquinoline (218) with a-methoxystyrene 219 resulted in 220. Compound 220 was hydrolyzed, then aromatized, and the resultant aldehyde was oxidized to carboxylic acid 221. Curtius rearrangement of the appropriate azide yielded urethane 222, which... 

Oxidation of —CHtOH — —CHO (cf., 12,479-480). This oxidation can be effected in high yield with sodium hypochlorite (slight excess) in buffered H20/ CH2C12 with this nitroxyl radical and KBr as the catalysts.1 The oxidation is exothermic, and the temperature should be maintained at 0-15° with a salt-ice bath. Saturated primary alcohols are converted to aldehydes in 88-93% yield yields are lower in the case of unsaturated substrates. Addition of quaternary onium salts permits further oxidation to carboxylic acids. 

Aldehydes are oxidized to carboxylic acids. A major enzyme responsible for this oxidation is aldehyde dehydrogenase (see Aldehyde Dehydrogenases section in this chapter) (79) however, other enzymes such as AO and cytochromes P450 can also mediate the oxidation of aldehydes as discussed (discussed earlier in this chapter). Ketones are not substrates for aldehyde dehydrogenase for the same reason that tertiary alcohols cannot be oxidized by ALD. Unlike the oxidation of alcohols, the oxidation of aldehydes is irreversible. Aldehydes are usually toxic and therefore there are aldehyde dehydrogenases in virtually all cells and in most compartments within cells. 

Aldehydes and ketones are readily reduced back to primary and secondary alcohols, respectively. In the case of ketones, although the reduction is reversible, ketoreductase utilizes NADPH, the concentration of which is higher than NADP+, and this drives the reaction toward the secondary alcohol. A good example is warfarin as shown in Figure 5.3 (19). However, aldehydes are further oxidized to carboxylic acids and carboxylic acids are not reduced back to aldehydes thus eliminating the aldehyde. Reductive metabolism of esters and amides also does not generally occur. 

The reduction of aldehydes is not usually apparent because aldehydes are generally rapidly oxidized and oxidation to carboxylic acids is basically an irreversible process. Aldehydes with electron-withdrawing groups, however, such as trifluoroacetaldehyde, are more readily reduced since they are less readily oxidized and therefore this pathway is more evident. 

Several examples have been reported of the use of palladium-mediated oxidation reactions of alcohols and alkyl halides. Palladium(II) acetate in the presence of iodobenzene converts primary and secondary alcohols into carbonyl compounds under solid-liquid two-phase conditions [20], However, other than there being no further oxidation to carboxylic acids, the procedure has little to commend it over other methods. It is relatively slow with reaction times in the order of 2 days needed to achieve yields of 55-100%. 

Deisopropylation (Cunninghamella echinulata, Gliocladium deliquescens) and oxidation to carboxylic acid (G. deliquescens)... 

C-1 Aromatic hydro-xylation 1,2-epoxidation and hydrolysis to the trans 1,2-dihydro-diol primary alcool oxidation to carboxylic acid... 

Terminal methyl hydroxylation and oxidation to carboxylic acid aromatic hydroxylation... 

Allylic methyl group hydroxylation and oxidation to carboxylic acid Beauveria bassiana) Allylic methyl group hydroxylation and lactate ester formation glucosidation Cunninghamella echinulata)... 

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