Benzoylacetone, from acetophenone

Benzophenone, directed reaction with acetaldehyde, 50, 68 1,4-Benzoquinone, 2,3-dichloro-5,6-dicyano-, (DDQ), aroma-tization with, 54, 14 Benzoylacetone, from acetophenone and acetic anhydride,... 

Benzophenone, directed reaction with acetaldehyde, 50,68 Benzoylacetone, from acetophenone and acetic anhydride, 51, 93... 

Acylation of ketones with esters requires the presence of a strong base under anhydrous conditions. Ketones where only one unique mesomeric carbanion is formed (e.g. symmetrical ketones or alkyl aryl ketones) yield a single regio-isomer. The reaction is illustrated by the formation of benzoylacetone from acetophenone and ethyl acetate (Expt 5.103), and may be outlined mechanistically as follows ... 

Benzoylacetone. — C6H5.CO.CH2.CO.CH3 is prepared in an analogous way from acetophenone and ethyl acetate according to the procedure of Claisen, Ber., 1905, 38, 695. The yield may be as much as 75 per cent of the theoretical. The cheaper converse method—action of sodamide on ethyl benzoate and acetone—also succeeds in this case, although it fails when sodium or sodium ethoxide is used as condensing agent. In general the use of sodamide is to be preferred in the synthesis of 1 3-diketones. 

Method II.—25 gms. (excess) of ethyl acetate and 30 gms. of acetophenone (1 mol.) are dissolved in 200 c.cs. of anhydrous ether. To this is slowly added with gentle cooling 20 gms. (excess) of powdered sodamide. It is then set aside for 24 hours, when the sodium salt separates, and is poured on to a mixture of ice and water sufficient to dissolve it completely. The aqueous layer is separated, and the ether removed from it by passing air through. Acetic acid is then added until the solution is acid, the precipitated benzoylacetone being filtered off and washed with water. 

Benzoylacetone. Return the condenser (protected by the calcium chloride guard-tube) to the reflux position, surround the flask with ice and introduce 200 ml (2 mol) of pure, dry ethyl acetate (Section 4.1.24, p. 409). Start the stirrer and add 60 g (58 ml, 0.5 mol) of acetophenone from the dropping funnel the reaction commences with the separation of the sodium salt of... 

Acetylacetophenone (Benzoylacetone). To an ice cooled solution of 352 g (4 moles) ethylacetate and 100 g sodium ethoxide (1.47 mole) was added dropwise 240 mL of acetophenone (2 moles) extended over a period of one hour. After addition was completed the reaction mixture was allowed to warm to room temperature and let stand 20 hours. The reaction mixture was poured into 1.5 of water and stirred until solution. The aqueous solution was washed with two 250 mL portions of ethyl ether, and acidified with 100 mL of glacial acetic acid to precipitate a yellow solid which was collected and dried overnight. The yellow solid was crystallized from alcohol to afford 175.6 g (72.2%) of pale yellow needles, mp 54-55°C. The infrared spectra showed absorptions at 3450 (vO-H), 1615 (vC=0), and 3005 (vC-H). The proton NMR showed peaks at 2.56 singlet (3), 6.26 singlet (1), and 7.66 multiplet (5). Anal Calcd C, 74.07 H, 6.17. Found C, 73.86 H, 6.40. 

This type of reaction was first used by Dilthey and Fischer69 in connection with the mechanism of the type in Section II, D, 2. By analogy with the well-known formation of benzopyrylium salts from methyl(ene) ketones and o-hydroxybenzaldehyde or o-hydroxy-acetophenone,340 benzoylacetone (84, R = Me, R = H, R" = Ph) and acetophenone (85, RIV = Ph, R" = H) afforded in the presence of acetic anhydride and sulfuric acid, 2-methyl-4,6-diphenylpyrylium sulfoacetate. The interesting feature of this reaction is that a unique product is obtained (i.e., only the carbonyl group of the diketone adjacent to the phenyl enters the condensation, although two such groups are available) R and R" could be reversed, but they are not.69-69 Similarly, dibenzoylmethane (84, R = R" = Ph, R =H) afforded 2,4,6-triphenylpyrylium with acetophenone in 80% yield.69... 

If, however, R is an aryl and R an alkyl group, then cleavage affords almost exclusively the alkyl aryl ketone by reaction (0), e.g., acetophenone from benzoylacetone ... 

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