Alcohols oxidation with chromate, mechanism

Mechanism The mechanism of the alcohol oxidation with Cr(VI) is outlined in Scheme 7.1, and involves the formation of chromate ester. The base removes the proton and Cr species leaves in an intermolecular process (A) however, an intramolecular process (B) may also operate. The Cr(IV) ions in H2Cr03 or HCrOs" are converted back to Cr(III) ions. It is believed that part of alcohol molecules are oxidized by the free radical mechanism. 

The mechanism of the Sarett oxidation, Collins oxidation, with Corey s PCC and with PDC, follows a similar mechanism as shown in Scheme 7.1. The alcohol reacts with CrOs to give a chromate ester. Either a base (Py) removes a proton from the chromate ester to give an oxidized product (aldehyde or ketone) and HCrOs" or a proton is transferred by the intramolecular mechanism to give an aldehyde or ketone and H2Cr03. 

The mechanism for alcohol oxidation has two key parts formation of a chromate ester and loss of a proton. Mechanism 12.5 is drawn for the oxidation of a general 2° alcohol with Cr03. 

Cr produced by reaction of lower-valence states with hydroperoxides, can react with alcohols to produce chromate esters. These esters will, of course, decompose heterolytically, in the manner described above, to produce carbonyls and, for example, H2C1O3 [79]. A similar but somewhat altered mechanism of het-erolytic chromate ester decomposition has been proposed to explain differences noted among several alcohols in the oxidation of alcohols with Cr [81]. The use of chromium-containing catalysts to decompose hydroperoxides to carbonyls in reactions conducted without autoxidation has been frequently noted [82-85]. 

In either mechanism, a low value for the KIE is expected for non-linear hydrogen transfer, with non-linear transfer associated with similar enthalpies and diiferent energies of activation for the two isotopomers. The oxidation of benzyl alcohol by quinoxalinium dichromate is acid catalysed, being first order in dichromate, substrate and added / -toluenesulfonic acid, and the KIE for PhCD20H oxidation is 6.78. The latter is the product of a primary effect and a secondary a-deuterium effect if we assume the latter is around 1.2 (see Section 3.3.1), the reaction is a typical acid chromate oxidation with a linear... 

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. 

The requirement for the formation of a chromate ester in step 1 of the mechanism helps us understand why 1° alcohols are easily oxidized beyond the aldehyde stage in aqueous solutions (and, therefore, why oxidation with PCC in CH2CI2 stops at the aldehyde stage). 

The aldehyde initially formed from the 1° alcohol (produced by a mechanism similar to the one we have just given) reacts with water to form an aldehyde hydrate. The aldehyde hydrate can then react with HCr04 (and H+) to form a chromate ester, and this can then be oxidized to the carboxylic acid. In the absence of water (i.e., using PCC in CH2CI2), the aldehyde hydrate does not form therefore, further oxidation does not take place. 

Chromium compounds decompose primary and secondary hydroperoxides to the corresponding carbonyl compounds, both homogeneously and heterogeneously (187—191). The mechanism of chromium catalyst interaction with hydroperoxides may involve generation of hexavalent chromium in the form of an alkyl chromate, which decomposes heterolyticaHy to give ketone (192). The oxidation of alcohol intermediates may also proceed through chromate ester intermediates (193). Therefore, chromium catalysis tends to increase the ketone alcohol ratio in the product (194,195). 

The mechanisms by which transition-metal oxidizing agents convert alcohols to aldehydes and ketones are complicated with respect to their inorganic chemistry. The organic chemistry is clearer and one possible mechanism is outlined in Figure 15.4. The key intennediate is an alkyl chromate, an ester of an alcohol and chromic acid. 

Oxidation of isopropyl alcohol (H2R) by chromic acid has been studied in det ai by Westheimer and Novick , and it was found that acetone (R) is formed nearly quantitatively. The reaction proved to be first order with respect to hydrogen chromate and second order with respect to hydrogen ions. Measurements using 2-deutero-2-propanol under identical conditions as those for the oxidation of ordinary isopropyl alcohol showed the rate of reaction to be of that with the hydrogen compound. This fact is considered to prove that the secondary hydrogen atom is removed in the rate-controlling step and that the assumption of hydride-ion abstraction can be excluded. The data are consistent with the following mechanism... 

Mechanism. Chromic acid reacts with isopropanol to produce a chromate ester intermediate. An elimination reaction occurs by removal of a hydrogen atom from the alcohol carbon, and departure of the chromium group with a pair of electrons. The Cr is reduced from Cr (VI) to Cr (IV), and the alcohol is oxidized. 

A ketone, resulting from the normal oxidation of a secondary alcohol, is obtained along with an alkene, resulting from an opening of the cyclopropane. The secondary product can be explained by the intermediacy of either a chromate ester, or a protonated alcohol. Treatment of the starting alcohol with 10% HC1 leads to a 87% yield of the secondary product, suggesting a mechanism involving PCC as a proton donor. 

The oxidation of substituted /3-benzoylpropionic acids by PFC follows the Hammett relation with a negative reaction constant. A possible mechanism for the oxidation has been discussed.5 The oxidation of maleic, fumaric, crotonic, and cinnamic acids by PCC is of first order with respect to PCC and the acid. The oxidation rate in 19 organic solvents has been analysed by Kamlet s and Swain s multiparametric equations. A mechanism involving a three-centre transition state has been postulated.6 The relative reactivity of bishomoallylic tertiary alcohols toward PCC, to yield substituted THF products via the tethered chromate ester, is dependent only on the number of alkyl groups. This observation suggests a symmetrical transition state in this intramolecular Cr(VI)-alkene reaction.7 Mechanisms have been proposed for the oxidation of 2-nitrobenzaldehyde with PBC8 and of crotonaldehyde with tetraethylammonium chlorochromate.9... 

The mechanism starts with the formation of HCr04 ions, that is, Cr(VI), from dichromate ion in solution. In acid, these form chromate esters with alcohols. The esters (boxed in black) decompose by elimination of the Cr(IV) HCrO, which subsequently reacts with a Cr(VI) species to yield 2 x Cr(V). These Cr(V) species can oxidize alcohols in the same way, and are thereby reduced to Cr(III) (the final metal-containing by-product). Cr(VI) is orange and Cr(III) is green, so the progress of the reaction is easy to follow by colour change. 

Non-Reversible Processes. —Reactions of the non-reversible type, i.e., with systems which do not give reversible equilibrium potentials, occur most frequently with un-ionized organic compounds the cathodic reduction of nitrobenzene to aniline and the anodic oxidation of alcohol to acetic acid are instances of this type of process. A number of inorganic reactions, such as the electrolytic reduction of nitric acid and nitrates to hydroxylamine and ammonia, and the anodic oxidation of chromic ions to chromate, are also probably irreversible in character. Although the problems of electrolytic oxidation and reduction have been the subject of much experimental investigation, the exact mechanisms of the reactions involved are still in dispute. For example, the electrolytic reduction of the compound RO to R may be represented by... 

As mentioned earlier, the chromate oxidation mechanism first involves formation of a chromate ester with the alcohol. Then a molecule of H2Cr03 serves as a leaving group during the elimination step that generates the C=0 bond of the carbonyl compound. 

The rate is first order with respect to both [oxidant] and [alcohol] and is catalysed by H+. A kinetic isotope effect knlk-D = 5.01 is consistent with a ratedetermining C—H cleavage from the alcohol carbon. A protonated Cr " species is proposed as the reactant and a mechanism involving hydride ion transfer within a chromate ester is invoked, e.g. equation (2). The possibility of direct... 

Oxidation of a Primary Alcohol to a Carboxylic Acid (Section 10.8A) A primary alcohol is oxidized to a carboxylic acid by chromic acid. The mechanism involves initial formation of an alkyl chromate intermediate, followed by reaction with base to remove a proton, generating the carbonyl group of an aldehyde and simultaneously reducing the chromium(VI) to chromium(IV). An initially formed aldehyde adds water, generating an aldehyde hydrate, which is oxidized according to the same mechanism to give the carboxylic acid. 

Force-field calculations have been used to correlate the rates of oxidation of secondary alcohols with steric strain. The results indicate that the chromate ester transition state is substantially like the ketone product but suggest that the steric effect of the ketone is not fully developed. The temperature dependence of the kinetic isotope criterion has been applied to studies of the Cr oxidation of a variety of alcohols in an attempt to distinguish between three possible mechanisms ... 

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