Alcohols secondary oxidation, ketones/lactones

The nickel oxide electrode is generally useful for the oxidation of alkanols in a basic electrolyte (Tables 8.3 and 8.4). Reactions are generally carrried out in an undivided cell at constant current and with a stainless steel cathode. Water-soluble primary alcohols give the carboxylic acid in good yields. Water insoluble alcohols are oxidised to the carboxylic acid as an emulsion. Short chain primary alcohols are effectively oxidised at room temperature whereas around 70 is required for the oxidation of long chain or branched chain primary alcohols. The oxidation of secondary alcohols to ketones is carried out in 50 % tert-butanol as solvent [59], y-Lactones, such as 10, can be oxidised to the ketoacid in aqueous sodium hydroxide [59]. 

The four reactions involved in this conversion are shown in figure 12.31. The first oxidation, catalyzed by glu-cose-6-phosphate dehydrogenase at C-1, converts the hemi-acetal derivative of the aldehyde group to the lactone of the corresponding acid, 6-phosphogluconic acid. After hydrolysis of the lactone, the second oxidation at C-3, converts the secondary alcohol to a ketone. The expected product, 3-keto-6-phosphogluconic acid, is decarboxylated yielding ribulose-5-phosphate. 

Where functional groups are present which are more readily oxidized than the ether group, multiple reactions can occur. For example, in their total synthesis of (-i-)-tutin and (-i-)-asteromurin A, Yamada et al. observed concomitant oxidation of a secondary alcohol function in the oxidation of the ether (30) with ruthenium tetroxide (equation 24). The same group successfully achieved the simultaneous oxidation of both ether functions of the intermediate (31) in their related stereocontrolled syntheses of (-)-picrotox-inin and (-i-)-coriomyrtin (equation 25). Treatment of karahana ether (32) with excess ruthenium tetroxide resulted in the formation of the ketonic lactone (33) via oxidation of both the methylene group adjacent to the ether function and the exocyclic alkenic group (equation 26). In contrast, ruthenium tetroxide oxidation of the steroidal tetral drofuran (34) gave as a major product the lactone (35) in which the alkenic bond had been epoxidized. A small amount of the 5,6-deoxylactone (17%) was also isolated (equation 27). This transformation formed the basis of a facile introduction of the ecdysone side chain into C-20 keto steroids. 

Oxidation. This complex is made by passing gaseous fluorine into aqueous acetonitrile. It converts secondary alcohols to ketones (note that unsaturated alcohols are selectively oxidized to epoxy alcohols) and eventually to lactones. Phenols and polycyclic arenes are rapidly oxidized to give quinones. ... 

The protection of quinic acid was accomplished by T lactone formation, benzyl ether formation at the least hindered secondary equatorial alcohol, and methylation of the remaining two alcohols. The secondary alcohol of the resulting 167 was deprotected (hydrogenolysis) and the alcohol was oxidized to provide ketone 168. A transesterification followed by a )3-elimination provided 169. Protection of the secondary alcohol provided intermediate... 

The slow oxidation of primary alcohols, particularly MeOH, is utilized for the oxidation of allylic or secondary alcohols with allyl methyl carbonate without forming carbonates of the alcohols to be oxidized. Allyl methyl carbonate (564) forms 7r-allylpalladium methoxide, then exchange of the methoxide with a secondary or allylic alcohol 563 present in the reaction medium takes place to form the 7r-allylpalladium alkoxide 565, which undergoes elimination of j3-hydrogen to give the ketone or aldehyde 566. The lactol 567 was oxidized selectively with diallyl carbonate to the lactone 568 without attacking the secondary alcohol in the synthesis of echinosporin[360]. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Halogens are frequently used as oxidation agents and, under two-phase conditions, they can either be employed as ammonium complex halide salts [3], or in the molecular state with or without an added quaternary ammonium catalyst [4]. Stoichiometric amounts of tetra-n-butylammonium tribromide under pH controlled conditions oxidize primary alcohols and low-molecular-weight alkyl ethers to esters, a,cyclic ethers produce lactones [3], and secondary alcohols yield ketones. Benzoins are oxidized to the corresponding benzils (80-90%) by the tribromide salts in acetonitrile in the presence of benzoyl peroxide [5]. 

In another procedure, oxidation is carried out in the presence of chloride ions and ruthenium dioxide [31]. Chlorine is generated at the anode and this oxidises ruthenium to the tetroxide level. The reaction medium is aqueous sodium chloride with an inert solvent for the alkanol. Ruthenium tetroxide dissolves in the organic layer and effects oxidation of the alkanol. An undivided cell is used so that the chlorine generated at the anode reacts with hydroxide generated at the cathode to form hypochlorite. Thus this electrochemical process is equivalent to the oxidation of alkanols by ruthenium dioxide and a stoichiometric amount of sodium hypochlorite. Secondary alcohols are oxidised to ketones in excellent yields. 1,4- and 1,5-Diols with at least one primary alcohol function, are oxidised to lactones while... 

Some lactol-to-lactone oxidations were effected by TPAP/NMO/PMS/CH Clj [498, 499], or TPAP/NMO/PMS/CH3CN [159]. The system RUCI3 or RuO / Na(Br03)/aq. M Na3(C03) generates [RuO ]" in aqueous solution and oxidised secondary alcohols to ketones in high yield (Table 2.2) [213]. Kinetics of the oxidation of benzhydrol and 9-fluorenol by TPAP/NMO/CH3CN/30°C were measured. 

Abstract This is one of the most important classes of oxidation effected by Ru complexes, particnlarly by RnO, [RuO ] , [RnO ] and RuCljCPPhj), though in fact most Ru oxidants effect these transformations. The chapter covers oxidation of primary alcohols to aldehydes (section 2.1), and to carboxylic acids (2.2), and of secondary alcohols to ketones (2.3). Oxidation of primary and secondary alcohol functionalities in carbohydrates (sugars) is dealt with in section 2.4, then oxidation of diols and polyols to lactones and acids (2.5). Finally there is a short section on miscellaneous alcohol oxidations in section 2.6. 

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... 

Primary and secondary alcohols are quantitatively oxidized by peroxydisulfate to the corresponding aldehydes and ketones. Thus benzyl alcohols give aldehydes, and in the presence of Ni(II) and ammonia they gives nitriles secondary alcohols give the corresponding ketones . Interestingly, isopropylbenzene reacts with acetates in the presence of peroxy disulfate/Fe(II) to give lactones (equation 18). ... 

Oxone has been successfully used in aprotic solvents for oxidation reactions by dispersing it on an alumina surface. Thus, the oxidation of secondary aliphatic, alicyclic and benzylic alcohols using Oxone/wet alumina oxide in CH2CI2 or CH3CN afforded ketones in good to excellent yields (70-96%). Similarly, the conversion of cycloalkanones to lactones is also reported. 

The reaction takes place in a two-phase medium. Secondary alcohols form ketones (90%), primary alcohols and aldehydes are oxidized to carboxylic acids (60-77%), 1,2-diols are cleaved to carboxylic acids (75%), 1,4- and 1,5-diols are transformed to lactones and keto acids (75 %). 

This very hindered secondary alcohol—located in a complex molecule—can be efficiently oxidized to the corresponding ketone in a biphasic system, using Ru04 generated from RuC13 and excess of NaI04. An additional oxidation of a cyclic ether to a lactone occurs under the reaction conditions. 

Lactonization of a,ia-diols. Diols of this type (1) are converted into lactones (2) when treated with NaBrO (3 equiv.). A primary, secondary diol is oxidized under these conditions to a hydroxy ketone a primary alcohol, RCH,OH, is converted to an ester, RCOOCHjR, in 70-95% yield. 

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