Alcohol oxidation reactivity

Although the fate of Cr(IV) is uncertain, (cf. the alcohol oxidation), some characteristics of the intermediate chromium species have been obtained by Wiberg and Richardson from a study of competitions between benzaldehyde and each of several substituted benzaldehydes. The competition between the two aldehydes for Cr(VI) is measured simply by their separate reactivities that for the Cr(V) or Cr(IV) is obtained from estimation of residual aldehyde by a C-labelling technique. If Cr(V) is involved then p values for oxidation by Cr(VI) and Cr(V) are 0.77 and 0.45, respectively. An isotope effect of 4.1 for oxidation of benzaldehyde by Cr(V) was obtained likewise. 

Wilkinson s catalyst has also been utilized for the hydroboration of other alkenes. Sulfone derivatives of allyl alcohol can be hydroborated with HBcat and subsequently oxidized to give the secondary rather than primary alcohol. This reactivity proves to be independent of substituents on the sulfur atom.36 Similarly, thioalkenes undergo anti-Markovnikoff addition to afford a-thioboronate esters.37 The benefits of metal-catalyzed reactions come to the fore in the hydroboration of bromoalkenes (higher yields, shorter reaction times), although the benefits were less clear for the corresponding chloroalkenes (Table 3).38,39 Dienes can be hydroborated using both rhodium and palladium catalysts [Pd(PPh3)4] reacts readily with 1,3-dienes, but cyclic dienes are more active towards [Rh4(CO)i2].40... 

Since for an endothermic reaction the activation energy E > AH, all such reactions cannot explain the experimental value of the activation energy (see Chapter 4). The following mechanism seems to be the most probable now. Hydrogen peroxide is protonized in a polar alcohol solution. Protonization of H202 intensifies its oxidizing reactivity. Protonized hydrogen peroxide reacts with alcohol with free radical formation. 

The concentration of the spin trap is usually not critical, although care must be exercised in quantitative studies (next Section). When reactive radicals are being trapped in competition with attack on substrate, the scavenger concentration may have to be adjusted in order to detect substrate-derived radicals. In these experiments the variation of the scavenger concentrations can give useful information, as in the example of alcohol oxidation discussed earlier. 

Oxidation of ethyl alcohol was one of the two important commercial routes to acetaldehyde until the 1950s, The other, much older route was the hydration of acetylene. The chemical industry was always after a replacement of acetylene chemistry, not just for acetaldehyde production, but all its many applications. Acetylene was expensive to produce, and with its reactive, explosive nature, it was difficult to handle. In the 1950s, acetylene chemistry and the ethyl alcohol oxidation route were largely phased out by the introduction of the liquid phase direct oxidation of ethylene. Almost all the acetaldehyde produced uses the newer process. 

Crystalline packing is an important parameter for auto-oxidation in the sohd state, as molecular oxygen must be able to access susceptible moieties in the molecule. Lyn et al. [63] showed that only one (hexagonal form) of the five different polymorphic forms of prednisolone tert-butylacetate were susceptible to oxidation, yielding the 11-ketone product. The authors attributed this oxidative reactivity to channels in the crystal structure allowing access to the labile 11-alcohol position. Bryn et al. [64] also identified a similar phenomenon in the photo-mediated oxidation of 21-cortisol tert-butylacetate to the corresponding ketone. 

Of the Ru(IV) complexes recorded here most are mono-oxo species which, despite the strong axial distortion brought about by the terminal oxo ligand, are probably all paramagnetic. Semi-empirical molecular orbital calculations (INDO/1) for epoxidations effected by oxo-Ru(IV) complexes have been reported (a non-concerted [1 h- 2] pathway was preferred) [642], [643] and for alcohol oxidations by octahedral species containing an Ru" (0) unit [644]. The reactivity of high oxidation-state polypyridyl complexes of osmium and Ru, with particular emphasis on Ru(IV) and Os(IV) oxo species, has been reviewed [43]. 

Common alcohol oxidation methods employ stoichiometric amounts of toxic and reactive oxidants like Cr03, hypervalent iodine reagents (Dess-Martin) and peracids that pose severe safety and environmental hazards in large-scale industrial reactions. Therefore, a variety of catalytic methods for the oxidation of alcohols to aldehydes, ketones or carboxylic acids have been developed employing hydrogen peroxide or alkyl hydroperoxides as stoichiometric oxygen sources in the presence of catalytic amounts of a metal catalyst. The commonly used catalysts for alcohol oxidation are different MoAV(VI), Mn(II), Cr(VI), Re(Vn), Fe(II) and Ru complexes . A selection of published known alcohol oxidations with different catalysts will be presented here. 

Nickel-containing polyfluorometalated [Ni(H20)H2FeNaWi7055] was capable of catalytic activation of hydrogen peroxide for allylic alcohol oxidation in biphasic conditions (catalyst substrate ratio 1 1000). Homoallylic alcohols are significantly less reactive than allylic homologues and cis > trans reactivity is found also in this case. 

When the C—H bond to be oxidized is proximate to a functional group, as we have stated already, its reactivity depends on the type of functional group. In the case of the hydroxy group, especially in secondary alcohols, these are more prone to dioxirane oxidation than their alkane precursors and, consequently, usually carbonyl products are obtained as the final product. Primary alcohols are less reactive, but may still be converted slowly to the corresponding aldehydes or carboxylic acids (due to the facile further oxidation of aldehydes)The functional-group transformation of the alcohols to ethers or acetals reduces the oxidative reactivity " but these C—H bonds are still more reactive than unfunctionalized ones. Thus, dioxirane oxidation of benzyl ether or acetal may... 

Results of oxidation of unsaturated alcohols are shown in Table 3. Both 2-penten-1 -ol and 3-methyl-2-buten-1 -ol exhibited higher reactivity than cyclohexene. A decrease around 20-50% in catalytic activity of organically functionalized samples has been observed. This is probably due to the inhibition of access of the rather hydrophilic substrates to the Ti-active sites surrounded by the organic groups of increased hydrophobicity. It is noteworthy that the epoxidation was favorable for the organically functionalized samples whereas the alcohol oxidation was retarded. 

Iodine(V) reagents such as Dess-Martin periodinane (DMP) and o-iodoxyben-zoic acid (IBX) are known as general reagents for oxidation of alcohols and have been utilized widely for natural product syntheses. Besides their general use for alcoholic oxidation, recently, the active studies on novel utilization of iodine( V) reagents such as DMP and IBX have been pursued mainly by Nicolaou and coworkers [26]. In particular, the versatile reactivities of anilides (62) with IBX or DMP are interesting and involve unprecedented features as follows. o-Imido-quinones (63) are prepared from 62 by the action of DMP and water. This reaction has been investigated extensively and was found to lead to p-quinones (64)... 

If we do the same disconnection at the alcohol oxidation level 27 the reagent for the a2 synthon might be an epoxide 29. More reactive enolates such as lithium enolates are now all right. 

Oxidation of alcohols. The reactivity of PDC is increased by acetic anhydride. Primary and secondary alcohols are oxidized efficiently with 0.6-0.7 equiv of PDC and 3 equiv. of Ac.O in CfLCl, at 40°. Addition of DMF in the oxidation of primary alcohols retards further oxidation to the carboxylic acid. Acid-sensitive groups are stable to the conditions. 

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