Oxidations with Cr VI

Another reagent that has applicability to oxidation 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. This is a potent oxidant, however, and it readily attacks carbon-carbon double bonds.  

The alcohol functional group is not rapidly attacked by oxygen or peroxides. Alcohols are attacked by ozone, but no major preparative procedures have been developed. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed that involve dimethyl sulfoxide (DMSO) and any one of a number of electrophilic molecules, particularly dicyclohexylcarbodiimide, acetic anhydride, and sulfur trioxide. The initial work involved the DMSO-dicyclo-hexylcarbodiimide system. The utility of the method has been greatest in the oxidation of molecules that are highly sensitive to more powerful oxidants and therefore cannot tolerate alternative methods. The mechanism of the oxidation involves formation of intermediate A by nucleophilic attack of DMSO on the carbodiimide, followed by reaction of this species with the alcohol. A major portion 

The role of activating DMSO toward the nucleophilic addition step can be accomplished by other electrophilic species. A method that appears to have certain advantages of convenience is use of the pyridine complex of A mechanism 

Other reagents that have been found capable of activating DMSO toward nucleophilic attack include acetic anhydride and phosphorus pentoxide.  

SECTION 10.1. OXIDATION OF ALCOHOLS TO ALDEHYDES, KETONES, OR CARBOXYLIC ACIDS 

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The effective oxidant in the TPAP oxidation of alcohols is the perrathenate ion, a Ru(VII) compound. This compound is employed in catalytic amounts only but is continuously replenished (see below). The mechanism of the alcohol —> aldehyde oxidation with TPAP presumably corresponds to the nonradical pathway of the same oxidation with Cr(VI) (Figure 14.10, top). Accordingly, the key step of the TPAP oxidation is a /3-elimination of the ruthenium(VII) acid ester B. The metal is reduced in the process to ruthenium(V) acid. 

This unsaturated alcohol is perfectly stable until it is oxidized with Cr(VI) it then immediately cyclizes to the product shown. Explain. 

When Ireland wanted to introduce a cyclopropane ring stereoselectively into a pentacyclic system containing an enone, he first reduced the ketone to an alcohol (DIBAL gave only the equatorial alcohol) that controlled the stereochemistry of the Simmons-Smith reaction. Oxidation with Cr(VI) put back the ketone. 

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. 

There is evidence that oxidation with Cr(VI) in aqueous acetic acid involves an epoxide intermediate Roc ek, J. Drozd, J.C. ]. Am. Chem. Soc. 1970, 92, 6668. 

Pioneering work in the synthesis of 8,12-eudesmanolides from santonin was carried out by Yamakawa and coworkers [47], These authors reported an allylic oxidation, with Cr(VI)-based oxidants, of methyl 3-oxoeudesm-1,4,6-trienoate (291) to give the corresponding 8-oxo-compound 294. Compound 291 was prepared from santonin (1) in a multi-step synthesis in 20% overall yield. Subsequent allylic oxidation of 291 with chromium reagents proceeded in low yield and the 8-oxo-compound (294) obtained in this way presented further difficulties when reduction of the carbonyl group at C(8) into a hydroxyl group was attempted. 

Both the syntheses in Schemes 11.8 and 11.9 use a two-step oxidation sequence to effect the required oxidation of the allylic methyl group. The first step is a singlet oxygen oxidation to a mixture of hydroperoxides with oxygen bound mainly at carbon atom 2. The mixture is reduced to the corresponding alcohols which were then subjected to oxidation with Cr(VI). The overall yield of this transformation is rather low. 

The oxidation by Cr(VI) of aliphatic hydrocarbons containing a tertiary carbon atom has been studied by several groups of workers. Sager and Bradley showed that oxidation of triethylmethane yields triethylcarbinol as the primary product with a primary kinetic isotope effect of about 1.6 (later corrected by Wiberg and Foster to 3.1) for deuterium substitution at the tertiary C-H bond. Oxidations... 

Also important is the choice of a suitable redox system for the indirect electroreaction of particular substrates. For instance, toluene can be oxidized with Mn(III) or Ce(IV) to benzaldehyde, whilst with Cr(VI) benzoic acid is obtained. On the other hand, anthraquinone is commercially prepared from anthracene by employing chromic acid oxidation. 

Since the stable product of oxidation by Cr(VI) is Cr(III) we are necessarily involved with three-electron reactions, with their attendant interests and eomplications. For inorganic reductants, R oxidized to O, the reaction scheme (1.118) holds... 

Chromium. The chemical properties of the two possible oxidation states Cr(VI) and Cr(III) are very different. Cr(VI) occurs as an anion, whereas Cr(III) is a strongly hydrolyzing cation with a strong tendency to bind to the surfaces of oxides and other particles (77). According to the thermodynamic sequence, the reduction of Cr(VI) to Cr(III) occurs in a pe range similar to that for the reduction of Mn(III,IV) to Mn(II) (Figure 2). 

They form more complicated ions with high oxidation states. For example, chromium forms the dichromate(vi) ion, Cr2072-, which contains chromium with a +6 oxidation state (Cr(vi)) and manganese forms the manganate(vu) ion, Mn04, which contains manganese with a +7 oxidation state (Mn(vn)). 

Oxidation of hydroquinone derivatives (p-dihydroxybenzenes) with Cr(VI) reagents is a method for preparing quinones. 

With a DGT device, Cr(III) can be bound to the chelex resin because of its cationic nature, whereas Cr(VI) is not bound to the resin (it has an anionic nature) but is present in the diffusive gel layer (as in a DET probe), reaching equilibrium with Cr(VI) in the aquatic system. Hence, Cr(VI) can be measured in the diffusive layer and Cr(III) in the resin layer.44 For Mn the same procedure can be adopted. The oxidized Mn(IV) species form colloids or even larger particles and will not be sampled by the DGT probe, whereas Mn(II) species are free or labile complexes. For Fe speciation, DGTs with open pores and with restricted pores are often used. Since in aquatic systems, Fe(III) is present mostly as a ligand complex or in colloidal form, the restrictive pore size excludes these forms and makes only Fe(II) species available to the restrictive DGT,45 whereas the open-pore DGT allows the passage of Fe(II) and small and labile Fe(III) complexes. In the case of arsenic speciation, As(III) and As(V) diffuse through the diffusive gel layer of the DGT, but only As(III) is immobilized on the chelating resin layer As(V) remains in the diffusive layer as an anionic compound. 

Thus, in the fine chemicals industry, reduction of ketones and aldehydes relies mainly on the use of complex metal hydrides that require time-consuming workup of reaction mixtures and produce significant amounts of inorganic and organic wastes. Similarly, the oxidation of alcohols into carbonyls is traditionally performed with stoichiometric inorganic oxidants, notably Cr(VI) reagents or a catalyst in combination with a stoichiometric oxidant [1]. 

Oxidation of alcohols is normally carried out with Cr(VI) reagents (Chapter 24) but these, like the Jones reagent (Na2Cr2C>7 in sulfuric acid), are usually acidic. Some pyridine complexes of Cr(Vl) compounds solve this problem by having the pyridinium ion (p Ta 5) as the only acid. The two most famous are PDC (Pyridinium DiChromate) and PCC (Pyridinium Chloro-Chromate). Pyridine forms a complex with CrO but this is liable to burst into flames. Treatment with HC1 gives PCC, which is much less dangerous. PCC is particularly useful in the oxidation of primary alcohols to aldehydes as overoxidation is avoided in the only slightly acidic conditions (Chapter 24). 

The redox environment can also determine some of the properties of metallic and non-metallic species. For example, the toxicity of arsenic when present in oxic (oxidizing) environments such as As( V) is very low, whereas its reduced form, As(III), is highly poisonous. The opposite occurs with Cr(VI) that is much more toxic than its reduced counterpart, Cr(III). 

In spite of the fact that numerous oxidation reactions are known, that lead to a-functionalization of ketones [159,160], in most cases enol radical cations are not involved in these transformations, and rigorous evidence for their formation through selective oxidation of the enol tautomer (Fig. 2, path 2) has only been obtained in a few cases. For example, it could be inferred from kinetic studies that in many cases enols are not intermediates in aqueous oxidation reactions with V(V), Co(III), Ce(IV) and Mn(III) [161-163], whereas in acetic acid Mn(III) was postulated to attack the enol form of ketones [164,165], but not by electron transfer [166]. On the other hand, oxidants as Cr(VI), Tl(III), Hg(II) and Mn(VII) [167] as well as Pb(IV) [168] definitely react with the enol form, but since with these inner-sphere oxidants electron transfer is assumed to occur in a bonded fashion, radical cation intermediates are most likely not implicated. 

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