Ketones, derivatives, oxidation

Under oxidative stress conditions, primary and secondary hydroxyls can be oxidized to the corresponding aldehyde and ketone derivatives. Oxidation of a secondary hydroxyl to a ketone (4 -oxolactone) is observed for the API lovastatin (Fig. 82) (123). 

Derivative Formation. Hydrogen peroxide is an important reagent in the manufacture of organic peroxides, including tert-huty hydroperoxide, benzoyl peroxide, peroxyacetic acid, esters such as tert-huty peroxyacetate, and ketone derivatives such as methyl ethyl ketone peroxide. These are used as polymerization catalysts, cross-linking agents, and oxidants (see Peroxides and peroxide compounds). 

Some unsaturated ketones derived from acetone can undergo base- or acid-catalyzed exothermic thermal decomposition at temperatures under 200°C. Experiments conducted under adiabatic conditions (2) indicate that mesityl oxide decomposes at 96°C in the presence of 5 wt % of aqueous sodium hydroxide (20%), and that phorone undergoes decomposition at 180°C in the presence of 1000 ppm iron. The decomposition products from these reactions are endothermic hydrolysis and cleavage back to acetone, and exothermic aldol reactions to heavy residues. 

The formation of a-acetoxyketones by oxidation of enamines with thallic acetate has been studied in detail (27) and found to be of preparative value (80 % yields) particularly in five- and six-membered-ring ketone derivatives. Enamines of linear or seven-membered-ring ketones were oxidized also, but at very much slower rates. Enamines of aldehydes with a-hydrogen substituents underwent self-eondensations during the oxidation reactions. Lead tetraacetate was less satisfactory as an oxidizing agent. 

The well-known condensation between 2-furaldehyde and acetone in a basic medium yields what is usually called furfurylidene acetone monomer composed of a mixture of 2-furfurylidene methyl ketone, di-2-furfurylidene ketone, mesityl oxide and other oligomers derived from further condensation reactions135. This mixture is then polymerized by the action of an acidic catalyst in the first phase of the reaction a polymer of low molecular weight is produced which on further treatment cross-links to a black insoluble and heat-resistant material136. ... 

The first synthesis of stable 3-hydroperoxy-sultams (24) which are a new class of sultam with oxidising properties, was reported. The synthesis involved oxidation of the isothiazolium salts (23) with hydrogen peroxide in acetic acid. Reduction of (24) with aqueous sodium bisulphite afforded the corresponding novel 3-hydroxysultams whereas thermolysis in ethanol resulted in the elimination of water to give 3-ketone derivatives, which are versatile as dieneophiles <96T783>. 

VNS products derived from a-chloroalkyl sulfones are converted into the corresponding aldehydes or ketones via oxidation (Eq. 9.42).70... 

A study of the reactions of halogeno-phosphines with ketone derivatives has been extended to (44), which forms a heterocycle (45a) with dichloro(phenyl)phosphine38 under neutral conditions. The analogous oxide (45b) has already been isolated from... 

Adlerol, i.e. l-(3,4-dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propan-l-ol, is a well-established dimeric model compound of lignin and, as such, its oxidation to the ketone-derivative Adlerone, i.e. l-(3,4-dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphen-oxy)propan-l-one, has been taken as a benchmark reaction (Scheme 20) to evaluate the efficiency of several chemo-enzymatic procedures. 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

According to the Cd 18-90 AOCS ° official method, the ANV is 100 times the optical density measured in a 1 cm cell, at 350 nm, of a solution containing 1.00 g of oil in 100 ml of the test solution. The measured absorbance is due to Schiff bases (167) formed when p-anisidine (166) undergoes condensation reaction with carbonyl compounds, according to equation 55. The carbonyl compounds are secondary oxidation products of lipids, such as a, S-unsaturated aldehydes and ketones derived from the hydroperoxides (see Scheme 1 in Section n.A.2.c), and their presence points to advanced oxidation of the oil. 

A general oxidative cleavage reaction of ketone-derived SAMP-hydrazones can be realized without racemization by reaction with magnesium monoperoxyphthalate (MMPP) hexahydrate in methanol or in methanol/pH 7 phosphate buffer within 2 hours26. 

Thiadiazolyl-5-hydrazines show the expected reducing action towards ammoniacal silver nitrate, and yield ketonic derivatives.176 3-Methylthio-5- (to -phenylhydrazino)-l,2,4-thiadiazole (290) is oxidized by yellow mercuric oxide in ethanol to the azo compound 291.198... 

The flavor of blue cheese is produced by a combination of free fatty acids and methyl ketones derived from fatty acids. The partial oxidation of fatty acids to methyl ketones occurs via the /3-oxidation pathway (Kinsella and Hwang 1976A). 

ASYMMETRIC OXIDATION OF KETONE-DERIVED ENOLATES USING (+)-(2R,8aS)-10-(CAMPHORYLSULFONYL)OXAZIRIDINE... 

As with aldehydes, production of ketones by nonredox processes is not a common synthetic approach. Ketone derivatives having the same oxidation level are usually produced from ketones themselves. Several examples of enol and acetal ketone derivatives are shown below. All are prepared from ketones, all can be readily hydrolyzed back to the ketone in the presence of acidic water, and, with the exception of vinyl acetates, all are very stable to strong bases and nucleophiles. Acetals are often used as ketone (and aldehyde) protecting groups while enol derivatives are versatile synthetic intermediates. 

The CD spectra of six derivatives (60-65) of cedran-10-one devoid of a C(8)-C(i3) oxide bridge exhibit negative Cotton effects near 290 nm in accordance with the octant rule and a chair conformation of the six-membered ring151. The corresponding ketones with oxide bridge show a preference for a boat-like conformation and exhibit positive n —> jr Cotton effects152. 

Oxidation of 3-butyryl diazepinanthrone (R = -Bu) 31 with MnOa gives the ketone derivative 32. The relative resistance of the ring carbon to oxidation is shown in 4-phenyl diazepinanthrone (R = Ph) 31, which does not react to give 33 under identical conditions <2000TL771> (Scheme 7). 

The benzyl hydroxyl containing API cyclandelate undergoes oxidation to the corresponding ketone, 3,3,5-trimethylcyclohexyl phenylglyoxalate (143). Low level benzylic oxidation is observed for the API ibuprofen. Oxidation to form the ketone derivatives at both benzylic sites to yield isobutyl acetophenone and 2-(4-isobutyrylphenyl)-propionic acid has been reported (144). 

Oxidation of non-conjugated thienyl tetrayne derivatives followed by cycloaroma-tization of the corresponding ketone derivatives give indenothiophenone derivatives (Scheme 119).176... 

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