Ketoximes, protonation

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

The reaction that normally occurs on treatment of a ketoxime with a Lewis or proton acid is the Beckmann rearrangement (18-17) fragmentations are considered side reactions, often called abnormal or second-order Beckmann rearrangements. Obviously, the substrates mentioned are much more susceptible to fragmentation than are ordinary ketoximes, since in each case an unshared pair is available to assist in removal of the group cleaving from the carbon. However, fragmentation is a side reaction even with ordinary ketoximes and, in cases where a particularly stable carbocation can be cleaved, may be the main reaction. ... 

Table 2. Activation energies for the reaction of protonated benzyl methyl ketoximes and their sulfur analogous systems calculated by MP2/6-31G. ... 

The use of compounds with activated methylene protons (doubly activated) enables the use of a mild base during the Neber reaction to 277-azirines. Using ketoxime 4-toluenesulfonates of 3-oxocarboxylic esters 539 as starting materials and a catalytic quantity of chiral tertiary base for the reaction, moderate to high enantioselectivity (44-82% ee) was achieved (equation 240). This asymmetric conversion was observed for the three pairs of Cinchona alkaloids (Cinchonine/Cinchonidine, Quinine/Quinidine and Dihydro-quinine/Dihydroquinidine). When the pseudoenantiomers of the alkaloid bases were used, opposite enantioselectivity was observed in the reaction. This fact shows that the absolute configuration of the predominant azirine can be controlled by base selection. 

By analogy with the dehydration of aldoximes in the KOH/DMSO system, which certainly involves abstraction of the proton nearest to the oxime function, in the case ketoximes, one can expect 1,3-dehydration which leads to unstable intermediates such as the 1,3-dipole 82, azirine 83, vinylnitrene 84 or nitrile, or the stable rearrangement product of one of them (Scheme 42). 

Potassium hydroxide is taken in an equimolar ratio with respect to the initial ketoxime. The yield of 0-vinyloximes (92) amounts to 65% with 52-77% conversion of ketoximes. At present, this seems to be the only suitable route to 0-vinyloximes bearing no substituent in the vinyl group. The IR and H-NMR spectra of 0-vinyloximes resemble those of vinyl ethers in the position and shape of characteristic bands and proton signals of the vinyloxy group (80KGS1299). 

According to H-NMR spectra, the adducts 113 are of the Z-con-figuration (3J 6.5-6.7 Hz). Consequently, the reaction of ketoximes with diacetylene is stereospeciflc and follows a trans-addition scheme. Since the process is facilitated by the addition of water, one may assume that nucleophilic addition to the C=C bond also involves uptake of the proton delivered by the medium. 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. " Among these are oximes of a-diketones (illustrated above), a-keto acids,... 

The copper-specific extractants used to extract copper from other base metals in acidic sulfate liquors are known as hydroxyoximes, and the interaction is known as chelation. The basic structures of modem oxime extractants are shown in Figure 5.4, where A = H for aldoximes and A = CHj for ketoximes. The R-chain is usually C9H19 (occasionally C12H25). The complexation of copper by these extractants is shown schematically in Equation (5.1). Extraction of each copper ion releases two protons, thereby providing a useful source of acid for further leaching (see Figure 5.2). pH is an important parameter controlling the equilibrium position of this reaction. 

In aldoximes and ketoximes, the chemical shift difference between syn and anti protons at the a-CH groups, A5 = - 8anti> depends on the dihedral angle,... 

Ketoximes are known to behave in some cases as C-H acids, for example, they are metalated across the a-CHj and CH2 groups (Scheme 1.196) [278,281,401,402], RegioselecUve deprotonation of ketoxime methyl ethers, namely, proton abstraction from the cis-position relative to the methoxy group, has been noted (Scheme 1.197) [278]. 

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