Relative reactivities ketones

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

Aldehyde or ketone Relative reactivity Aldehyde or ketone Relative reactivity ... 

Some toxicological data for cyclic ketones are shown in Table 16. Interestingly, toxicity is shown to increase with ring size. This is in reverse order of relative reactivity. 

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. 

This equation implies that the relative reactivity is independent of the specific nucleophile and that relative reactivity is insensitive to changes in position of the transition state. Table 8.4 lists the B values for some representative ketones. The parameter B indicates relative reactivity on a log scale. Cyclohexanone is seen to be a particularly reactive ketone, being almost as reactive as cyclobutanone and more than 10 times as reactive as acetone. 

Table 8.4. Relative Reactivity of Some Ketones toward Addition of Nucleophiles...

The carbonyl carbon of a ketone bears two electron-releasing alkyl groups an aldehyde carbonyl group has only one. Just as a disubstituted double bond in an alkene is more stable than a monosubstituted double bond, a ketone carbonyl is more stable than an aldehyde carbonyl. We ll see later in this chapter that structural effects on the relative stability of carbonyl groups in aldehydes and ketones are an important factor in their relative reactivity. 

Giese and Kretzschmar7j found the rate of addition of hexenyl radicals to methyl acrylate increased 2-fold between aqueous tetrahydrofuran and aqueous ethanol, Salikhov and Fischer74 reported that the rate constant for /-butyl radical addition to acrylonitrile increased 3.6-fold between tetradecane and acetonitrile. Bednarek et al75 found that the relative reactivity of S vs MMA towards phenyl radicals was ca 20% greater in ketone solvents than it was in aromatic solvents. 

The relative reactivities of alkyltin compounds towards tert-butoxyl radicals, ketone triplets, and succinimidyl radicals are dominated by the steric effect of the alkyl ligands (R" > R"), but that towards bromine atoms follows the reverse sequence (R" < R ). 

Alkylation of enamines requires relatively reactive alkylating agents for good results. Methyl iodide, allyl and benzyl halides, a-halo esters, a-halo ethers, and a-halo ketones are the most successful alkylating agents. The use of enamines for selective alkylation has largely been supplanted by the methods for kinetic enolate formation described in Section 1.2. 

Relative reactivities of aldehydes, ketones, esters, acid chlorides and anhydrides. 

The C2-symmetric 2,6-bis(2-oxazolin-2-yl)pyridine (pybox) ligand was originally applied with Rh for enantioselective hydrosilylation of ketones [79], but Nishiyama, Itoh, and co-workers have used the chiral pybox ligands with Ru(II) as an effective cyclopropanation catalyst 31 [80]. The advantages in the use of this catalyst are the high enantiocontrol in product formation (>95 % ee) and the exceptional diastereocontrol for production of the trans-cyclopropane isomer (>92 8) in reactions of diazoacetates with monosubstituted olefins. Electronic influences from 4-substituents of pyridine in 31 affect relative reactivity (p = +1.53) and enantioselectivity, but not diastereoselectivity [81]. The disadvantage in the use of these catalysts, at least for synthetic purposes, is their sluggish reactivity. In fact, the stability of the intermediate metal carbene has allowed their isolation in two cases [82]. 

Experiments on the bromination of equilibrated ketone-acetal systems in methanol were also recently performed for substituted acetophenones (El-Alaoui, 1979 Toullec and El-Alaoui, 1979). Lyonium catalytic constants fit (57), but for most of the substituents the (fcA)m term is negligible and cannot be obtained with accuracy. However, the relative partial rates for the bromination of equilibrated ketone-acetal systems can be estimated. For a given water concentration, it was observed that the enol path is more important for 3-nitroacetophenone than for 4-methoxyacetophenone. In fact, the smaller the proportion of free ketone at equilibrium, the more the enol path is followed. From these results, it can be seen that the enol-ether path is predominant even if the acetal form is of minor importance. The proportions of the two competing routes must only depend on (i) the relative stabilities of the hydroxy-and alkyoxycarbenium ions, (ii) the relative reactivities of these two ions yielding enol and enol ether, respectively, and (iii) the ratio of alcohol and water concentrations which determines the relative concentrations of the ions at equilibrium. Since acetal formation is a dead-end in the mechanism, the amount of acetal has no bearing on the relative rates. Bromination, isotope exchange or another reaction can occur via the enol ether even in secondary and tertiary alcohols, i.e. when the acetal is not stable at all because of steric hindrance. 

TABLE 11.9 The Selectivities for the Formation of Cyclohexanone Intermediates in the Hydrogenation of Isomeric Cresols and the Relative Reactivities of the Ketone to Cresol over Ru, Rh, and Pd-C Catalystfti>... 

---