C-Acylation s. a. Ketones

C-Acylation (s. a. Ketones, C-Photoacylation, Side chain acylation) 23, 852... 

C-Acetyl... s. Methyl ketones Acetylation s. a. Acylation N-Acetylation, selective, with ketene 24,326... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

The course of the reaction may involve either the acylation of the ketone to a -diketonic intermediate following thereupon the pathway in Section II, C, 2, a, or alternatively the condensation of two moles of ketone to yield an intermediate dypnone which then undergoes acylation following the pathway in Section II,C, l,a. Dilthey and Fischer thought the first alternative more plausible, on the basis of reaction yields, and this lead them to explore the pathway in Section II,C,2,a. Schneider and Ross and Diels and Alder believed that the second alternative operates. Both views are plausible since acylations of methyl ketones to S-diketones are known to take place in the conditions of this reaction, and dypnone ha.s been isolated from acetophenone on treatment with Friedel-Crafts catalysts, in the absence of an acid anhydride or chloride (an excess of catalyst... 

The s character of the aziridine nitrogen s lone pair has other effects too. The lone pair interacts very poorly with an adjacent carbonyl group, so N-acyl aziridines such as the one you saw on p. 1125 behave not at all like amides. The nitrogen atom is pyramidal and not planar, and the stretching frequency of the C=0 bond (1706 cm-1) is much closer to that of a ketone (1710 cm-1) than that of an amide (1650 cm-1). 

As an alternative to using dialkyl carbonates [(R0)2C=0] for a-acylation of ketones, the reaction of ketone enolates with alkyl cyanoformates (NC-CO2R, Mander s reagent) provides P-keto esters in good yields. Reaction of lithium enolates with acyl halides or anhydrides, however, usually leads to mixtures of O- and C-acylated... 

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