Oxidation of alcohol 8 to ketone

Protocol 4 describes the oxidation of alcohol 8 by dimethylsulfoxide (DMSO) and acetic anhydride at room temperature.20 This Albright-Goldman method is more economical and simpler to perform on a large scale than other 

Caution Carry out all procedures in a well-ventilated hood, and wear disposable vinyl or latex gloves and chemical-resistant safety goggles. 

Set up the magnetic stirrer, round-bottomed flask with stirrer bar, heating mantle, thermometer with adaptor, and nitrogen inlet adaptor. 

Flush the flask with N2. Add the 5-benzylidene-1,2,3,4,5,6,7,8-octahydro-acridin-4-ol and the anhydrous DMSO. Place the ground glass stopper in the third neck of the flask and stir the mixture at room temperature under N2 until all of the solid has dissolved. 

Add the acetic anhydride. Replace the ground glass stopper and stir the resulting solution under N2 at 39-40°C for 6 h. Allow the reaction mixture to cool slowly to room temperature, stirring under N2. 

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Pyridinium chlorochromala 1 or Cr03-dimelhylpyrazola 4 for oxidation of alcohols to ketone or aldehydes... 

In Table 9-5 we have listed a large number of reaction types. For many of these reaction types you may be able to think of examples from central metabolism. For example, the oxidation of alcohols to ketones is a very commonly encountered reaction. Thus ... 

Another reagent that finds application of oxidations of alcohols to ketones is ruthenium tetroxide. The oxidations are typically carried out using a catalytic amount of the ruthenium source, e.g., RuC13, with NaI04 or NaOCl as the stoichiometric oxidant.16 Acetonitrile is a favorable solvent because of its ability to stabilize the ruthenium species that are present.17 For example, the oxidation of 1 to 2 was successfully achieved with this reagent after a number of other methods failed. 

Oxidations for oxidation of alcohols to ketones employs dimethyl sulfoxide (DMSO) and any... 

Owing to the efficient oxidation of alcohols to ketones, alcohols can be used as the starting materials in oxidative cleavages. The conditions required are more vigorous than for the alcohol to ketone transformation (see Section 12.1.1). 

Oxidation. DMSO activated by P205 (1 equiv.) and in combination with triethylamine is useful for oxidation of alcohols to ketones and aldehydes, particularly in cases where the Swern reagent results in chlorinated byproducts. Yields are typically 80-85%. 

Early electrochemical processes for the oxidation of alcohols to ketones or carboxylic acids used platinum or lead dioxide anodes, usually with dilute sulphuric acid as electrolyte. A divided cell is only necessary in the oxidation of primary alcohols to carboxylic acids if (he substrate possesses an unsaturated function, which could be reduced at the cathode [1,2]. Lead dioxide is the better anode material and satisfactory yields of the carboxylic acid have been obtained from oxidation of primary alcohols up to hexanol [3]. Aldehydes are intermediates in these reactions. Volatile aldehydes can be removed from the electrochemical cell in a... 

Another reagent that finds application in oxidations of alcohols to ketones is ruthenium tetroxide. For example, the oxidation of 1 to 2 was successfully achieved with this reagent after a number of other methods failed. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed which involve DMSO and any one of several electrophilic reagents, such as dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, or... 

Convenient new methods for the preparative scale oxidation of alcohols to ketones and carboxylic acids are always welcome. T. Punniyamurthy of the Indian Institute of Technology Guwahati reports (Tetrahedron Lett. 44 6033, 2003) that 30% aqueous H,02 catalyzed by a Co salen complex effects this transformation. 

Hydrogen peroxide is an inexpensive oxidant, but it requires a catalyst to effect oxidation of an alcohol to the ketone. Removal of the catalyst then becomes an issue. Ronny Neumann of the Weizmann Institute of Science reports (J. Am. Chem. Soc. 2004,126, 884) the development of a hybrid organic-tungsten polyoxometalate complex that is not soluble in organic solvents, but that nonetheless catalyzes the hydrogen peroxide oxidation of alcohols to ketones. The solid catalyst is removed by filtration after the completion of the reaction. The catalyst retained its activity after five recyles. 

In several cases A-hydroxyphthalimide has been used as an organic mediator for the oxidation of alcohols to ketones, of benzyl ethers to benzoates , of alkyl aromatics to aryl ketones , and of 4-phenyl-l,3-dioxolanes to unprotected ketones... 

Oxidation of the TV-aryl azanols under controlled conditions yields nitroso compounds. This reaction is not unlike the oxidation of alcohols to ketones (Section 15-6B) ... 

A milestone in the routine employment of perruthenate in the oxidation of alcohols was established with the publication by Griffith, Ley et al. in 1987 on the catalytic use of tetra- -propylammonium perruthenate (TPAP).11 The presence of the tetra- -propylammonium cation renders this compound soluble in apolar media and allows the existence of a high concentration of perruthenate ion in organic solvents. The tetra- -propylammonium perruthenate is easily prepared and can be employed catalytically in CH2CI2 solution in the oxidation of alcohols to ketones and aldehydes, using /V-methyl morpholine A-oxide (NMO) as the secondary oxidant. 

An alternative approach to the oxidation of alcohols to ketones was also reported by Shea et al., who incorporated a nitroxide catalyst into a polymeric matrix [56], A polymerisable 2,2,6,6-tetramethylpiperidine (90) was derivatised as /V-allyl-amine (91), which was removed after polymerisation, leaving a catalytically active nitroxide (92) able to form stable free radicals, thereby efficiently catalysing the reaction of oxidation with yields ranging from 55 to 88%. 

Anodic dehydrogenations, e.g., oxidations of alcohols to ketones, have been treated in Sect. 8.1 and formation of olefins by anodic elimination of C02 and H+ from carboxylic acids was covered in Sect. 9.1. Therefore this section is only concerned with anodic bisdecarboxylations of v/odicarboxylic acids to olefins. This method gives usually good results when its chemical equivalent, the lead tetraacetate decarboxylation, fails. Combination of bisdecarboxylation with the Diels-Alder reaction or [2.2] -photosensitized cycloadditions provides useful synthetic sequences, since in this way the equivalent of acetylene can be introduced in cycloadditions. 

ADHs catalyze the oxidation of alcohols to ketones with simultaneous reduction of NAD(P)+. Due to the reversibility of this reaction, ADH-catalyzed reactions can either be used for the synthesis of (chiral) compounds or for the regeneration of the coenzyme. The latter holds true, for example, in the case of substrate-coupled ADH-catalyzed reduction reactions using isopropanol or ethanol as the hydrogen donor. Several kinds of ADHs have already been described. ADHs of the EC 1.1.1.1 group are dependent on NAD+. They act on primary or secondary alcohols or on hemiacetals. In contrast, ADHs of the group EC 1.1.1.2 depend on NADP+. Some enzymes of this group oxidize only primary alcohols others act on secondary alcohols as well. 

Over the past 25 years, biomimetic model systems have been extensively studied and a wide variety of interesting oxidation processes such as the epoxidation of olefins, the hydroxylation of aromatics and alkanes, the oxidation of alcohols to ketones, etc., have been accomplished some of these are also known in enantioselective versions with spectacular ee s. The vast majority of these transformations were obtained using monooxygen donors such as those mentioned above as primary oxidants. The complexity of the catalysts and the practical impossibility to use dioxygen as the terminal oxidant have so far prevented the use of such systems for large industrial applications, but some small applications in the synthesis of chiral intermediates for pharmaceuticals and agrochemicals, are finding their way to market. 

The most important applications of peroxyacetic acid are the epoxi-dation [250, 251, 252, 254, 257, 258] and anti hydroxylation of double bonds [241, 252, the Dakin reaction of aldehydes [259, the Baeyer-Villiger reaction of ketones [148, 254, 258, 260, 261, 262] the oxidation of primary amines to nitroso [iJi] or nitrocompounds [253], of tertiary amines to amine oxides [i58, 263], of sulfides to sulfoxides and sulfones [264, 265], and of iodo compounds to iodoso or iodoxy compounds [266, 267] the degradation of alkynes [268] and diketones [269, 270, 271] to carboxylic acids and the oxidative opening of aromatic rings to aromatic dicarboxylic acids [256, 272, 271, 272,273, 274]. Occasionally, peroxyacetic acid is used for the dehydrogenation [275] and oxidation of aromatic compounds to quinones [249], of alcohols to ketones [276], of aldehyde acetals to carboxylic acids [277], and of lactams to imides [225,255]. The last two reactions are carried out in the presence of manganese salts. The oxidation of alcohols to ketones is catalyzed by chromium trioxide, and the role of peroxyacetic acid is to reoxidize the trivalent chromium [276]. 

The domain of oxidations with silver oxide includes the conversion of aldehydes into acids [63, 206, 362, 365, 366, 367 and of hydroxy aromatic compounds into quinones [171, 368, 369]. Less frequently, silver oxide is used for the oxidation of aldehyde and ketone hydrazones to diazo compounds [370, 371], of hydrazo compounds to azo compounds [372], and of hydroxylamines to nitroso compounds [373] or nitroxyls [374] and for the dehydrogenation of CH-NH bonds to -C=N- [375]. Similar results with silver carbonate are obtained in oxidations of alcohols to ketones [376] or acids [377] and of hydroxylamines to nitroso compounds [378]. 

Aqueous potassium permanganate is hardly ever used to tixidize secondary alcohols to ketones, because further oxidation of ketones to carboxylic acids occurs even under mild conditions (15-30 °C) [2247]. On the other hand, oxidations of alcohols to ketones are successfully accomplished... 

Oxidation of alcohols to ketones or carboxylic acids is normally achieved through stoichiometric oxidants in homogeneous phase. For fme-chemical synthesis a two-phase process which allows for easy catalyst separation would be highly desirable. Simple biphasic processes with high TOFs and air as the oxidant have been described (eq. (1) [1, 2]). 

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