Ketone from secondary alcohols

A common step in the metabolism of alcohols is carried out by alcohol dehydrogenase enzymes that produce aldehydes from primary alcohols that have the -OH group on an end carbon and produce ketones from secondary alcohols that have the -OH group on a middle carbon, as shown by the examples in Reactions 7.3.6 and 7.3.7. As indicated by the double arrows in these reactions, the reactions are reversible and the aldehydes and ketones can be converted back to alcohols. The oxidation of aldehydes to carboxylic acids occurs readily (Reaction 7.3.8). This is an important detoxication process because aldehydes are lipid soluble and relatively toxic, whereas carboxylic acids are more water soluble and undergo phase n reactions leading to their elimination. 

No more complete study of a single catalysed reaction has ever been published than that of Palmer and Constable,2 extending over eight years, on the dehydrogenation of alcohols by heated copper surfaces. Aldehydes are formed from primary and ketones from secondary alcohols by this reaction. The work has resulted in a considerable increase in our knowledge of the mode of formation and properties of the active centres on the surface of copper, and much of it may be applicable also to other metallic catalysts. The reactions are... 

Sarett and coworkers discovered that the complex (1) prepared by the addition of chromium(VI) oxide to pyridine (CAUTION—reverse order of addition may cause the mixture to inflame) is an efficient oxidizing agent for the preparation of ketones from secondary alcohols. The reagent, as prepared by Sarett, is moderately soluble in pyridine, but is only sparingly soluble in standard organic solvents. Thus the normal procedure is to add a solution of the dcohol in pyridine to three equivalents of the complex, also in pyrictoe. This procedure is also useful for the preparation of aromatic and a, -unsaturated aldehydes, but the use of pyridine as solvent prohibits the oxidation of volatile, saturated primary alcohols. ... 

Hou, C.T., Patel, R., Laskin, A.I., Barnabe, N., Barist, I. (1983) Production of methyl ketones from secondary alcohols by cell suspensions of C2 to C4 n-alkane-grown bacteria. Appl. Environ. Microbiol. 46, 178-184. 

The 1-hydroxyethyl radical may be further oxidized, to form aldehydes from primary alcohols, and ketones from secondary alcohols. The only tertiary alcohol to he studied in detail gave the corresponding ketone on irradiation. 

A simple and convenient method of obtaining very pure ketones from secondary alcohols has been described by Brown and Garg.437... 

Based on studies of the RuCls-catalyzed disproportionation of iodine(III) species to iodobenzene and iodylbenzene [53, 94-96], a mild and efficient tandem catalytic system for the oxidation of alcohols and hydrocarbons via a Ru(in)-catalyzed reoxidation of ArlO to ArI02 using Oxone as a stoichiometric oxidant has been developed [53, 96, 97]. In particular, various alcohols are smoothly oxidized in the presence of catalytic Phi and RuCls in aqueous acetonitrile at room temperature to afford the respective ketones from secondary alcohols, or carboxylic acids from primary alcohols, in excellent isolated yields (Scheme 4.59) [97]. 

Ketones from secondary alcohols by Swern oxidation and other methods (discussed in Section 12.4) ... 

Like PDC and PCC, dimethyl sulfoxide in the presence of oxalyl chloride and trimethylamine gives aldehydes from primary alcohols and ketones from secondary alcohols. 

The accelerating effect of MW irradiation in the synthesis of ketones from secondary alcohols with TBHP as oxidant was also reported. 

A facile, efficient and selective solvent-free synthesis of ketones from secondary alcohols with tert-butylhydroperoxide (TBHP) as the oxidant under microwave irradiation has been achieved, where the copper (II) 2,4-alkoxy-l,3,5-triazapenta-dienato complexes (CATAPD) worked as efficient catalysts providing high yields (even upto 100%) (Figiel et al, 2010). 

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

On the other hand, the production of desired compounds through reduction of starting material requires the electron donors to be oxidized (reductant). Alcohols are often used not only as a solvent but as the donor to produce useful compounds, e.g., anilines from nitrobenzenes,22) alcohols from aldehydes,23) and secondary amines from the corresponding Schiff bases.24) From the organic synthetic point of view, however, the separation of undesired products, aldehydes or ketones, from the alcohols is necessary unless subsequent reaction processes consume them25,26) or they are easily removed by distillation or other procedures. A recent report has shown that water acts as the electron donor and is converted into 02 in the photocatalytic regio-selective reduction of terpenes mixed with aqueous suspension of Ti02.27,28) It is notable that isolation of the desired product from the reaction mixture is simple in this type of photocatalytic reduction. 

Primary alcohols possess a considerably less congested environment than secondary ones. Therefore, it may seem contradictory that a certain oxidant could be able to perform the selective oxidation of secondary alcohols. On the other hand, the oxidation potential of aldehydes is generally higher than the one of ketones (see page 257). This means that thermodynamics usually favor the oxidation of secondary alcohols over primary ones and mild oxidants have a tendency to react quicker with secondary alcohols. Other factors that promote the selective oxidation of secondary alcohols include the intermediacy of alkyl hypohalides, which are less stable when derived from secondary alcohols, and the operation of a mechanism involving a hydride transfer, leaving a carbocation located at the a position of an alcohol that possesses a higher stability in secondary alcohols. 

The periodinane (10) may also be prepared from o-iodobenzoic acid by oxidation with potassium bromate and then treatment with acetic anhydride18 (see Expt 6.36 for detailed formulation). It should be noted that the organic derivatives of pentacoordinate iodine(v) are termed periodinanes.18b This compound (the systematic name is l,l,l-triacetoxy-2,l-benzoxiodol-3(3//)-one) has found use as an oxidant of primary alcohols to aldehydes and alicyclic ketones to secondary alcohols it is claimed to have advantages over the chromium-based oxidation reagents. 

Oxidation.1 Hydrated copper permanganate oxidizes alcohols in CH2C12 rapidly and in high yields. Ketones are obtained from secondary alcohols, and carboxylic acids from primary and benzylic alcohols. Primary or secondary allylic alcohols are also oxidized efficiently. Anhydrous reagent is much less active. 

This ligand, in combination with a rhodium complex prepared in situ from Rh(NBD)2+C104 (NBD = norbomadiene), can be used for an enantioselective hydrogenation of prochiral ketones to secondary alcohols (equation IV).5... 

Formation of aldehydes and ketones. The oxidation of alcohols can lead to the formation of aldehydes and ketones. Aldehydes are formed from primary alcohols, while ketones are formed from secondary alcohols. 

The Corey-Kim Oxidation allows the synthesis of aldehydes and ketones from primary alcohols and secondary alcohols, respectively. 

Recently, comprehensive World Wide Web (Internet) databases have been established on insect pheromones and semiochemicals The Pherolist , a database of chemicals identified from sex pheromone glands of female lepidopteran insects and other chemicals attractive to male moths (Am et al., 1999) and The Pherobase , a database of pheromones and semiochemicals for Lepidoptera and other insect orders (El-Sayed, 2006). These large databases on behavior modifying chemicals have extensive cross-linkages for animal taxa, indexes of compounds and source (reference) indexes. The indexes include those compounds cited in this chapter and many more with pheromone and semiochemical function acetate esters, diols, epoxides, ethers, ketones and secondary alcohols. For example, The Pherolist reports approximately 90 epoxy derivatives of C17-C23 of n-alkancs, mono-alkenes and di-alkenes as insect semiochemicals. 

The formation of methyl ketones can be rationalized by a modified f-oxidation of fatty acid precursors (18). This process, caused by some moulds, mainly deteriorates short chain fatty acids and leads to the so-called "ketonic-rancidity". Kinderlerer et al. (19-21) demonstrated the formation of methyl ketones and secondary alcohols by some xerophilic fungi isolated from coconuts. After deacylation and decarboxylation of the f-ketoacyl-CoA-intermediates the last step of the biogenetical sequence is the reduction of the corresponding methyl ketones. 

Enantioselective Reduction ofa,P-Ynones. Oxazaborolidine ligands 1 are among the most effective catalysts for the enantioselective reduction of ketones to secondary alcohols. Substitution of the methyl or butyl group on boron by a trimethylsilylmethyl group led to a much improved catalyst for the catecholborane mediated reduction of a, 3-ynones. For example, the enantioselectiv-ities for the reduction of an a, 3-ynone was improved from 60% to 98.5% when the nature of the R group was modified (eq 1). ... 

Acetals from aldehydes or ketones and secondary alcohols. The synthesis of ketone di-rcc-alkyl acetals ordinarily proceeds in low yield. Roelofsen and van Bekkum report that such acetals can be prepared in 70 90% yield by use of type 5A molecular sieves to absorb selectively the water formed. p-Toluenesulfonic acid is used as the acid catalyst. 

Introduction. The controlled oxidation of primary and secondary alcohols yields compounds which have less hydrogen on the carbon atom to which the hydroxyl group is attached. The oxidation products of primary alcohols are represented by the general formula RCHO and are called aldehydes, the products from secondary alcohols have the general formula RjCO and are called ketones. Both compounds have the carbonyl (CO) group as a functional group. 

Many oxidative processes (e.g., benzylic, allylic, alicyclic, or aliphatic hydroxylation) generate alcohol or carbinol metabolites as intermediate products. If not conjugated, these alcohol products are further oxidized to aldehydes (if primary alcohols) or to ketones (if secondary alcohols). Aldehyde metabolites resulting from oxidation of primary alcohols or from oxidative deamination of primary aliphatic amines often undergo facile oxidation to generate polar carboxylic acid derivatives." As a general rale, primary alcoholic groups and aldehyde functionalities are quite vulnera-... 

Trialkyltin alkoxides prepared by evacuation of methanol from a mixture of an alcohol and trialkyltin methoxide are easily oxidized by bromine in the presence of trialkyltin alkoxide as HBr scavenger, producing the desired aldehyde and ketone efficiently [324]. This oxidation is more feasible on organotin alkoxides derived from secondary alcohols than those from primary alcohols, and enables regioselective oxidation of polyols [325]. The regioselectivity in oxidation of vicinal secondary alcohols was also examined [326], and the empirical informative results were invoked for access to namenamicin A-C disaccbarides (Scheme 12.177) [327]. 

There are, however, numerous organic precendents. The Cannizzaro reaction, in which two equivalents of a nonenolizable aldehyde such as bezaldehyde are reacted with hydroxide to form a primary alcohol and the salt of a carboxylic acid, is thought to involve hydride transfer to one aldehyde carbonyl from the carbonyl-addition product of the other aldehyde and hydroxide. The Leuckart reaction, formation of a tertiary amine from formic acid, a primary amine and either a ketone or an aldehyde, seems to procede via hydride transfer from formate to an iminium ion. And the Meervein-Ponndorf-Verley-Oppenauer reaction, the reversible transfer of hydrogen between ketones and secondary alcohols in the presence of excess aluminum isopropoxide, is almost certainly a hydride-transfer reaction. This latter process is of particular interest to us because it requires a metal, just as GI does. The aluminum acts as a Lewis acid, coordinating the carbonyl oxygen and... 

OxidationThe reagent oxidizes primary alcohols in good yield to aldehydes it can also oxidize aldehydes further to carboxylic acids. Ketones are obtained in high yield from secondary alcohols. Oxidation is most rapid in DMSO but proceeds satisfactorily in water. Hydroquinone is oxidized to p-benzoquinone in 89% yield. 

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