Reactivity of ketones

In early studies our group observed some intrinsic kinetic selectivities in photooxidation of organic substrates by polyoxometalates which led us to 

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AH ahphatic aldehydes and most ketones react to form cyanohydrins. The lower reactivity of ketones, relative to aldehydes, is attributed to a combination of electron-donating effects and increased steric hindrance of the second alkyl group in the ketones. The magnitude of the equiUbrium constants for the addition of hydrogen cyanide to a carbonyl group is a measure of the stabiUty of the cyanohydrin relative to the carbonyl compound plus hydrogen cyanide ... 

Reductions by NaBKt are characterized by low enthalpies of activation (8-13kcal/mol) and large negative entropies of activation (—28 to —40eu). Aldehydes are substantially more reactive than ketones, as can be seen by comparison of the rate data for benzaldehyde and acetophenone. This relative reactivity is characteristic of nearly all carbonyl addition reactions. The reduced reactivity of ketones is attributed primarily to steric effects. Not only does the additional substituent increase the steric restrictions to approach of the nucleophile, but it also causes larger steric interaction in the tetrahedral product as the hybridization changes from trigonal to tetrahedral. 

Double bonds in conjugation with the carbon-hetero multiple bond also lower addition rates, for similar reasons but, more important, may provide competition from 1,4 addition (p. 977). Steric factors are also quite important and contribute to the decreased reactivity of ketones compared with aldehydes. Highly hindered ketones like hexamethylacetone and dineopentyl ketone either do not undergo many of these reactions or require extreme conditions. 

Several factors affect the reactivity of the boron and aluminum hydrides, including the metal cation present and the ligands, in addition to hydride, in the complex hydride. Some of these effects can be illustrated by considering the reactivity of ketones and aldehydes toward various hydride transfer reagents. Comparison of LiAlH4 and NaAlH4 has shown the former to be more reactive,63 which is attributed to the greater... 

Reactivity of Ketones in Reactions with Peroxyl Radicals... 

Like for aldehydes, two factors are important for the reactivity of ketones in reactions with peroxyl radicals reaction enthalpy and polar interaction. The enthalpy of the reaction of the peroxyl radical with ketone is AH = DC—a A> H- The BDE of the a-C—H bonds of ketones are lower than those of the C—H bonds of the hydrocarbons (see Table 8.11) and the BDEs of the O—H bonds in a-ketohydroperoxides are marginally higher than those of alkylhydroperoxides. Therefore, the enthalpies of R02 + RH reactions are lower than those of parent hydrocarbons (Table 8.15). 

In contrast to the lack of reactivity of ketones with PPN [HCr(CO)d, Brunet et al. reported different reactivity with K+ rather than PPN+ as the counterion. They found that K HGr(CO)5 reacts with cyclohexanone in the absence of acid [35]. Hydrolysis with acid led to a 50% yield of cyclohexanol. These results suggest assistance from the K+ cation ion-pairing in metal anions has been studied in detail by Darensbourg [36]. 

Binaphthol- and biphenyl-derived ketones (9 and 10) were reported by Song and coworkers in 1997 to epoxidize unfunctionalized alkenes in up to 59% ee (Fig. 3, Table 1, entries 9, 10) [37, 38]. Ketones 9 and 10 were intended to have a rigid conformation and a stereogenic center close to the reacting carbonyl group. The reactivity of ketones 9 and 10 is lower than that of 8, presumably due to the weaker electron-withdrawing ability of the ether compared to the ester. In the same year, Adam and coworkers reported ketones 11 and 12 to be epoxidation catalysts for several trans- and trisubstituted alkenes (Table 1, entries 11,12). Up to 81% ee was obtained for phenylstilbene oxide (Table 1, entry 25) [39]. 

As was the case for alkenes, alkyl substituents lower the enthalpy of the unsaturated molecule. Hence, ketones, with two R s, have lower enthalpies than aldehydes, with one R. The electron-releasing R s diminish the electrophilicity of the carbonyl C, lessening the chemical reactivity of ketones. Furthermore, the R s, especially large bulky ones, make approach of reactants to the C more difficult. 

There are still two other factors influencing the reactivity of ketones in the Norrish-Yang reaction. If functional groups with a relatively low oxidation potential (amino, alkenyl or aryl groups, thioethers) are present in the reactants, the excited state may be quenched by partial or complete charge transfer from these groups to the extited carbonyl group. The effects of such processes may vary from a complete loss of reactivity to an entirely new reaction mode - cyclization reactions ini-... 

The reactivity of ketones toward aryllead(iv) triacetates is quite different from the reaction of these ketones with lead(iv) tetraacetate, which gives the a-acetoxyketones. Under the usual conditions for arylation (pyridine, CHCI3), simple ketones remain unaffected. Only ketone enolates and some specially activated ketones have been successfully... 

This polarization of the carbonyl group contributes to the reactivity of ketones and aldehydes The positively polarized carbon atom acts as an electrophile (Lewis acid), and the negatively polarized oxygen acts as a nucleophile (Lewis base). 

Selectivity to Ketone Relative Reactivity of Ketone Intermediate Desorbed to Cresol... 

Imine enolates can be prepared without self-condensation, yet they will add rapidly to carbonyl compounds. This circumvents the low reactivity of ketones toward carban-ions derived from nonactivated methylene compounds and permits addition of aldehyde enolate equivalents to ketones. 

Figure 17 Schematic view of the reactivity of ketones and aldehydes...

Calculations at the B3LYP/6-31G level were used to show how hydrogen bond formation influences the chemical reactivity of ketones.70 The effect of the chloroform on the activation energies was modelled by means of discrete-continuum models. Explicit hydrogen bond formation to chloroform lowers the gas-phase activation barrier. A DFT analysis of the global electrophilicity of the reagents provided a sound explanation of the catalytic effects of chloroform (see Table 6 and Chart 3). The electrophilicity of acetone... 

Selective Generation and Unique Reactivities of Ketone F-Enolates... 

Ketones. The individual reactivities of ketones were measured in several irradiation chambers, including those of Battelle (4, 35) and LA-APCD (2, 3). In addition to the data given in Tables I to III for ketones in the steel chamber, we present Table V with experimental findings for ketone irradiations in the small glass chamber. Fairly good agreement exists between the relative chemical reactivities observed for several ketones in the different investigations. 

The chemical reactivities of ketones follow the order terf-butyl > ethyl > methyl, which is the stability order for the cations or radicals of these groups. This suggests that the mechanisms of ketone decomposition involve a rate-determining migration of an electrophilic alkyl moiety of the ketone, perhaps leading to the production of acyl and alkoxy radicals from some partially oxidized intermediate. 

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