Aldehyde to Acid Oxidation State

The reaction has traditionally been run with 90% trifluoroacetic peracid or 90% H202, but the explosive nature of these reagents, as well as the availability of safer 

A clean vessel was charged with water (20 gal), sodium hydrogen phosphate (25 kg, 183.5 mol), 5-(2-formyl-pyridin-2-yloxy)-benz[l,2,5]oxadiazole (15 kg, 62 mol), and tert-butyl alcohol (99 gal). The mixture was stirred for 1 h, and then a solution of sodium chlorite (34 kg, 379 mol) in water (40 gal) was added at a rate to keep the internal temperature 35 °C. The reaction was quenched with a solution of sodium bisulfite (90 kg) in water (99 gal) at a rate to keep the temperature 25 °C. The tert-butyl alcohol was stripped at slightly below atmospheric temperature (to control the bisulfite fumes released) until the head temperature was 80 °C. After cooling to 20 °C, the solids were stirred for 5.5 h, filtered, and washed with water (10 gal). The wet cake was reslurried in water (30 gal) for 1 h at 80 °C. After cooling to 20-25 °C, the solids were slurried for 2 h, filtered, and washed with water (5 gal). The solids were dried in a vacuum oven at 45-55 °C until the KF was 0.5%, yielding 14.3 kg (89%) of the desired product. 

---

Oxidation states of alcohols. An alcohol is more oxidized than an alkane, yet less oxidized than carbonyl compounds such as ketones, aldehydes, and acids. Oxidation of a primary alcohol leads to an aldehyde, and further oxidation leads to an acid. Secondary alcohols are oxidized to ketones. Tertiary alcohols cannot be oxidized without breaking carbon-carbon bonds. 

Disulfides are good soft acceptors. They are reduced to thiols by hydro-selenide ion (90). The utilization of dimethyl disulfide as an indirect oxidant during conversion of aldehyde to acid derivatives via the dithiane synthesis has been reported (91). The alkylation of the lithiodithiane derived from cinnam-aldehyde occurs exclusively at the heterocyclic carbon. This may be indicative of symbiotic stabilization of the transition state and the product. 

The hydrogenation of functionalities in the carboxylic acid oxidation state can also be useful for small- or large-scale syntheses. For example, the hydrogenation of adiponitrile generates hexamethylenediamine that is one of the two monomers in the production of nylon. This reaction is conducted with a heterogeneous catalyst, but homogeneous catalysts for the reduction of nitriles to amines would be convenient for the conversion of nitriles to amines on a laboratory scale. The hydrogenation of esters to aldehydes would... 

The syntheses we have examined thus far do not take into account enantios-electivity. The Hannesian group described a synthesis that used quinic acid (165) as an enantiopure starting material. The idea was to prepare reserpine (79) from / mr -substituted cyclohexane 162. The incipient C3 was to come from an intermediate with that carbon at the aldehyde oxidation state (to be derived from reduction of the lactone). The incipient C21 was to be introduced at the carboxylic acid oxidation state. This plan avoids issues with formation of inside isomers as we saw in the Wender and Martin syntheses. Lactone 162 was to come via a radical cyclization of an intermediate of type... 

Three noteworthy procedures for the oxidation of an aldehyde to the acid oxidation state were recently reported. Jonathan M. J. Whhams of the University of Bath demonstrated Chem. Commun. 2008, 624) that crotonitrile could serve as the hydrogen acceptor in the oxidation of an aldehyde 7 to the methyl ester 8. Note that isolated alkenes were stable to these conditions. Vikas N. Telvekar the University Institute of Chemical Technology, Mumbai improved Tetrahedron Lett. 2008, 49, 2213) the oxidative amination of an aldehyde 9 to the nitrile 10. G. Sekar of the Indian Institute of Technology Madras effected... 

Vigorous oxidation leads to the formation of a carboxylic acid but a number of meth ods permit us to stop the oxidation at the intermediate aldehyde stage The reagents most commonly used for oxidizing alcohols are based on high oxidation state transition met als particularly chromium(VI)... 

A third access to isocorroles was found7 when a tetrapyrrole 11 having an acrylaldehyde side chain was cyclized in presence of copper(II) or cobalt(II) salts. In this case isocorrole-9-carb-aldehydes 12 are formed with copper and cobalt in the oxidation state + III. The copper compound can easily be demetaled by hydrochloric acid to yield the metal-free isocorrole. In contrast, the cyclization of the tetrapyrrole in the presence of palladium(II) gives the isopor-phycene (see Section 1.7.1.). 

The pyridoxal amino acid analog (Pal) was stereoselectively synthesized from a readily available pyridoxol derivative and the residue was incorporated into peptides at the alcohol oxidation state in protected form. Oxidation of the 4 -alcohol group to the desired aldehyde was achieved post-synthetically on free. 

Hydroxylamine is used as a reducing agent in many inorganic and organic synthetic reactions. Other applications of this compound include purification of aldehydes and ketones dehairing of hides as an antioxidant for fatty acids to stabilize lower oxidation states of metal ions for analysis and in photography. 

When the C—H bond to be oxidized is proximate to a functional group, as we have stated already, its reactivity depends on the type of functional group. In the case of the hydroxy group, especially in secondary alcohols, these are more prone to dioxirane oxidation than their alkane precursors and, consequently, usually carbonyl products are obtained as the final product. Primary alcohols are less reactive, but may still be converted slowly to the corresponding aldehydes or carboxylic acids (due to the facile further oxidation of aldehydes)The functional-group transformation of the alcohols to ethers or acetals reduces the oxidative reactivity " but these C—H bonds are still more reactive than unfunctionalized ones. Thus, dioxirane oxidation of benzyl ether or acetal may... 

Steps I and 2 constitute an oxidation by the ionic pathway by Cr(VI), and steps 6 and 7 a similar oxidation by Cr(V), which is produced by an electron-transfer process. Either Cr(VI) (step 3) or Cr(IV) (step 4) (Cr(IV) is produced in step 2] may abstract a hydrogen and the resulting acyl radical is converted to carboxylic acid in step 5. Thus, chromium in three oxidation states is instrumental in oxidizing aldehydes. Still another possible process has... 

An important distinction between dimerization and acrolein formation is that the selectivity of the former is evidently connected with a partially reduced state of the catalyst. It is commonly accepted, therefore, that cations like Bi3+, Sn4+, etc. play a role, presumably by adsorbing the allyl radical intermediate. Several authors assume that this is the case for allylic oxidation in general and that the role of a second oxide component is to promote dimerization byi stabilization of the allyl radical, or to direct the oxidation to aldehyde formation via a cationic allyl complex. Seiyama et al. [285] further suggest that the acidity of the promoting oxides is an important factor in this connection, and may, in part, explain why acidic oxides like Mo03 direct the oxidation to aldehydes, while basic compounds favour dimerization. 

---