Chromic acid oxidation of alcohols

Aldehydes are oxidized easily by moist silver oxide or by potassium permanganate solution to the corresponding acids. The mechanism of the permanganate oxidation has some resemblance to the chromic acid oxidation of alcohols (Section 15-6B) ... 

Interestingly, very few examples involving other organic solvents, apart from acetone, acetic acid or diethyl ether, are found in the literature in chromic acid oxidations of alcohols. Rarely used organic solvents include ethyl acetate,350 benzene,351 chlorobenzene,352 dioxane353 and DMSO.354... 

An interesting variation of the chromic acid oxidation of alcohols to aldehydes was discovered by Oppenauer and Oberrauch.411 When dissolved in tert-butyl alcohol and an organic solvent, alcohols are dehydrogenated to aldehydes by tert-butyl chromate in 90% yield. Experimental details are given in Houben-Weyl s reference work.ln... 

The PIE model was also applied successfully to the chromic acid oxidation of alcohols in micelles of sodium dodecyl sulfate (SDS) [81]. In these systems the medium chain length alcohols act as cosurfactants. However, as noted above, key assumptions of the PIE treatment are the constancy of a and the one-to-one ion exchange, which are reasonably satisfactory for aqueous micelles but are less reliable for cosurfactant-modified micelles and O/W microemulsions, where a is relatively large and sensitive to both ionic and nonionic solutes. 

The oxidation of cyclohexanol by concentrated nitric acid is mechanistically complex. A reasonable mechanistic route to the dicarboxyUc acid is given here. The first stage of the oxidation is considered to proceed by a mechanism similar to that found in chromic acid oxidations of alcohols (see Experiment [33]).The reaction here involves the initial formation of a nitrate ester intermediate, which, under the reaction conditions, cleaves by proton abstraction to form the ketone. This reaction is accompanied by reduction of the nitrate to nitrite. The proton transfer may involve a cyclic intramolecular rearrangement during the oxidation-reduction cleavage step. A likely mechanism is outlined below ... 

The mechanism of chromic acid oxidations of alcohols has been investigated thoroughly. It is interesting because it shows how changes in oxidation states occur in a reaction between an organic and an inorganic compound. The first step is the formation of a chromate ester of the alcohol. Here we show this step using a 2° alcohol. 

FIGURE 15.4 A mechanism for chromic acid oxidation of an alcohol. 

Chromic acid oxidations of 2° alcohols generally give ketones in excellent yields if the temperature is controlled. 

In chromic acid oxidation of isomeric cyclohexanols, it is usually found that axial hydroxyl groups react more rapidly than equatorial groups. For example, trans-4-t-butylcyclohexanol is less reactive (by a factor of 3.2) than the cis isomer. An even larger difference is noted with cis- and trans-3,3,5- trimethylcyclohexanol. The trans alcohol is more than 35 times more reactive than the cis. Are these data compatible with the mechanism given on p. 748 What additional detail do these data provide about the reaction mechanism Explain. 

Chromic acid oxidation of saturated hydrocarbons starts with hydrogen abstraction to give a caged radical pair.113,114 The collapse of the latter leads to a chromium(IV) ester, which hydrolyzes to the product tertiary alcohol. The postulation of the caged pair was necessary to explain the high degree of retention in oxidation of (+)-3-methylheptane 113... 

The above criteria apply in the case of isolated hydroxyl groups but when additional polar substituents are placed in the vicinity of the substrate hydroxyl the oxidation rate can be expected to change. Allylic hydroxyls are generally oxidized more rapidly than their saturated counterparts. Burstein and Rin-gold have studied the chromic acid oxidation of steroidal allylic alcohols in some detail and have found that the quasi-equatorial 3)3-isomer is oxidized more... 

A Cr(VI)-catalyst complex has been proposed as the reactive oxidizing species in the oxidation of frans-stibene with chromic acid, catalysed separately by 1,10-phenanthroline (PHEN), oxalic acid, and picolinic acid (PA). The oxidation process is believed to involve a nucleophilic attack of the olefinic bond on the Cr(VI)-catalyst complex to generate a ternary complex.31 PA- and PHEN-catalysed chromic acid oxidation of primary alcohols also is proposed to proceed through a similar ternary complex. Methanol- reacted nearly six times slower than methanol, supporting a hydride transfer mechanism in this oxidation.32 Kinetics of chromic acid oxidation of dimethyl and diethyl malonates, in the presence and absence of oxalic acid, have been obtained and the activation parameters have been calculated.33 Reactivity in the chromic acid oxidation of three alicyclic ketoximes has been rationalized on the basis of I-strain. Kinetic and activation parameters have been determined and a mechanism... 

M. Rhaman and J. Rocek, Chromium(IV) oxidation of primary and secondary alcohols, J. Am. Chem. Soc., 93 (1971) 5455-5462 Mechanism of chromic acid oxidation of isopropyl alcohol. Evidence for oxidation, ibid., 93 (1971) 5462-5464. 

Chromic acid oxidation of an alcohol (Section 11-2A) occurs in two steps formation of the chromate ester, followed by an elimination of H+ and chromium. Which step do you expect to be rate-limiting Careful kinetic studies have shown that Compound A undergoes chromic acid oxidation over 10 times as fast as Compound B. Explain this large difference in rates. 

Phenols undergo oxidation, but they give different types of products from those seen with aliphatic alcohols. Chromic acid oxidation of a phenol gives a conjugated 1,4-diketone called a quinone. In the presence of air, many phenols slowly autoxidize to dark mixtures containing quinones. 

Controlled oxidation of a primary alcohol with a mixture of sulfuric and chromic acids gives the corresponding aldehyde. In the preparation of low-molecular-weight aldehydes, an aqueous medium is used and the product is removed by steam distillation, thus preventing further oxidation. This procedure is well illustrated by the preparation of propion-aldehyde (49%) and isovaleraldehyde (60%). Certain benzyl alcohols are dissolved in aqueous acetic acid for chromic acid oxidation. Ole-finic aldehydes are produced by a rapid low-temperature (5-20°) oxidative procedure, as illustrated by the preparation of 2-heptenal (75%) from 2-heptenol. Aldehyde ethers such as methoxyacetaldehyde and ethoxy-acetaldehyde have been prepared by the chromic acid oxidation of the corresponding alcohols in 17% and 10% yields, respectively. ... 

Oxidation of primary alcohols in acid media is often accompanied by esterification. By the use of the proper proportions of reactants, fair yields of esters may be obtained directly from the alcohols e.g., -butyl n>butyrate (47%) by chromic acid oxidation of n-butyl alcohol. Aqueous acid chlorate solutions in the presence of vanadium pentoxide have been used for this purpose. ... 

Carboxypyrazine catalyzes the chromic acid oxidation of primary and secondary alcohols (1305). The first-order, specific rates of reduction of Co(III) by Fe(ll) in complexes of the type [(NHj)(4ors)CoLFe(CN)sl with L as chelating 2-carboxylatopyrazine, pyrazine, and 2-methylpyrazine are 1.3 x 10", 5.5 x 10 , and 30 x 10 /sec, respectively, at 25°, pH 6-7, and fi = 0.15A/(1306). Complexes from 2-carboxypyrazine and lanthanide basic carbonates (1307) and from 2,3-dicarboxypyrazine and transition metals (1308) and its pentaamminechromium(III) complexes have been prepared (1309). 

Walker, B. H. Effect of manganese on the chromic acid oxidation of secondary-tertiaryvicinal glycols. J. Org. Chem. 1967, 32, 1098-1103. Collins, J. C., Hess, W. W., Frank, F. J. Dipyridine-chromium(VI) oxide oxidation of alcohols in dichloromethane. Tetrahedron Lett. 1968, 3363-3366. 

Hofmann degradation of dihydrocodeinone methiodide affords dihydrocodeinone methine [Lvm] [55] which can also be prepared by the hydrolysis of dihydrothebaine methine [lix] [78], and by the catalytic rearrangement of a-codeimethine [lx] by boiling with Raney nickel in alcohol [79]. It can be reduced to the dihydromethine, available by the hydrolysis of dihydrothebaine dihydromethine and by the chromic acid oxidation of a-tetrahydrocodeimethine [lxi] [78]. The cyclic ether link of the methine [lviii] and dihydromethine can be opened by aluminium amalgam reduction in wet ether, giving dihydrothebainone methine [lxii] and dihydromethine respectively [78]. 

The known bicyclo[3.1. Ojhexene 167 was hydroborated and oxidized to afford anti alcohol 168 in up to 80% yield. Chromic acid oxidation of 168 was followed by p elimination of malonate anion with EtaN to produce enone 169 (86%). Initial deprotonation of 169 followed by the addition of cuprate 166 afforded an 82% yield of 170. As expected, Michael addition to the enone occurred anti to the malonate unit. Reduction of ketone 170 with LiBH4 gave a 4 1 mixture of Cy alcohols, the major product being the desired a-hydroxy isomer. Chromatographic separation of the alcohols, followed by protection and ester cleavage, then gave the diacid 171. 

This was accomplished by anaerobic reduction with Sporotrichum exile in which the 4a(S),8a(R)-enantiomer 51 is reduced six times more rapidly than the other enantiomer. This process in combination with chromic acid oxidation of the derived alcohol gave approximately 70% optically pure enantiomers. Resolution was completed by recrystallization from benzene in which the racemic form is significantly more soluble. The absolute configurations and optical purity of these enantiomeric ketones were confirmed by obtaining the 4a(S),8a(R)-enantiomer 51 from naturally occurring cinchonine (45) via meroquinene... 

Sodium Borohydride Reduction of an Aldehyde or Ketone 653 Acid-Catalyzed Formation of Diethyl Ether from Ethyl Alcohol 660 Chromic Acid Oxidation of 2-Propanol 665... 

Mechanism 15.3 outlines the mechanism of chromic acid oxidation of 2-propanol to acetone. The alcohol reacts with chromic acid in the first step to give a chromate ester. A carbon-oxygen double bond is formed in the second step when loss of a proton from carbon accompanies cleavage of the bond between oxygen and chromium. The second step is rate-determining as evidenced by the fact that (CH3)2CHOH reacts 6.7 times faster than (CH3)2CDOH. If the second step were faster than the first, no deuterium isotope effect (Section 5.17) would have been observed. 

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