Acetophenone anhydride preparation

C9H10O, Mr 134.18, mp 28 °C, Z> ioi.3kPa 226 °C, df 1.0051, nf 1.5335, has been identified in Brazilian rosewood oil and in pepper. It occurs as colorless crystals with a flowery-sweet odor that is milder than that of acetophenone. 4-Methyl-acetophenone is prepared from toluene and acetic anhydride or acetyl chloride by... 

The ketones are readily prepared, for example, acetophenone from benzene, acetyl chloride (or acetic anhydride) and aluminium chloride by the Friedel and Crafts reaction ethyl benzyl ketones by passing a mixture of phenylacetic acid and propionic acid over thoria at 450° and n-propyl- p-phenylethylketone by circulating a mixture of hydrocinnamic acid and n-butyric acid over thoria (for further details, see under Aromatic Ketones, Sections IV,136, IV,137 and IV,141). 

Friedel-Crafts Acylation. The Friedel-Crafts acylation procedure is the most important method for preparing aromatic ketones and thein derivatives. Acetyl chloride (acetic anhydride) reacts with benzene ia the presence of aluminum chloride or acid catalysts to produce acetophenone [98-86-2], CgHgO (1-phenylethanone). Benzene can also be condensed with dicarboxyHc acid anhydrides to yield benzoyl derivatives of carboxyHc acids. These benzoyl derivatives are often used for constmcting polycycHc molecules (Haworth reaction). For example, benzene reacts with succinic anhydride ia the presence of aluminum chloride to produce P-benzoylpropionic acid [2051-95-8] which is converted iato a-tetralone [529-34-0] (30). 

Besides acetophenone, this reaction was also applied to p-chloro- andp-methoxyacetophenone, and even to an aliphatic ketone, acetone (although the yield was stated to be only half as large as that obtained from mesityl oxide, i.e., less than 30%, Dorofeenko and co-workers reported a 45% yield of 2,4,6-trimethylpyrylium perchlorate from acetone, acetic anhydride, and perchloric acid), and is the standard method for preparing pyrylium salts with identical substituents in positions 2 and 4. The acylating agent may be an anhydride in the presence of anhydrous or hydrated ferric chloride, or of boron fluoride, or the acid chloride with ferric chloride.Schneider and co-workers ... 

Acetophenones can be obtained by various routes such as by reacting acetic anhydride with the substituted benzene (Shirley-PREPARATION OF ORGANIC INTERMEDIATES, 1951, pg. 190) and may then be isomerized, if necessary, with aluminum chlonde (JCS 232(1944)). 

Acetyl chloride (54 g. =075 mole) is allowed to run drop by drop from a tap funnel on to 80 g. of finely powdered anhydrous sodium acetate prepared in the manner described below. When about half of the chloride has been added the experiment is interrupted for a short time in order to stir the pasty mass of material with a bent glass rod, the lower end of which has been flattened. The rest of the acetyl chloride is then run in at such a rate that none passes over unchanged. The anhydride is now distilled from the residual salt by mean of a luminous flame kept constantly in motion. Complete conversion of the last traces of unchanged acetyl chloride to acetic anhydride is attained by adding 3 g. of finely powdered anhydrous sodium acetate to the distillate, which is finally fractionally distilled. Boiling point of acetic anhydride 138°. Yield 55-60 g. Use for acetylation, in Perkin s synthesis (Chap. V. 8, p. 232), preparation of acetophenone (Chap. IX. 3 6, p. 346). 

Often in the Friedel-Crafts synthesis the acid chloride can be replaced by the anhydride. The preparation of acetophenone (p. 346) is an example of this modification. 

Other methods of preparing flavone include the action of ethanolic alkali on 2 -acetoxy-a,/3-dibromochalcone 7 Claisen condensation of ethyl o-ethoxybenzoate and acetophenone, and cyclization of the resulting 1,3-diketone with hydriodic acid 8 and treatment of 3-bromoflavanone with potassium hydroxide in ethanol.9 Flavone has also been prepared from ethyl phenyl-propiolate by condensation with sodium phenoxide and subsequent cyclization with phosphorus pentachloride in benzene 10 by fusing o-hydroxyacetophenone with benzoic anhydride and sodium benzoate 11 by the dehydrogenation of 2 -hydroxychal-cone with selenium dioxide 12 and by the action of alkali on flavylium chloride.13... 

This method is an improvement over the older methods for the preparation of substituted acetophenone derivatives. The yields obtained by the use of acetyl chloride in place of acetic anhydride in the preparation of -bromoacetophenone were invariably lower. 

The adduct has also been prepared by exposing solutions of maleic anhydride and acetophenone or benzophenone in benzene in tubular glass reactors to solar radiation at various altitudes [51]. The adduct was obtained in high purity. 

Benzoylacrylic acid has been prepared by the condensation of acetophenone and chloral to l,l,l-trichloro-2-hydroxy-3-benz-oylpropane, followed by hydrolysis to the corresponding acid and dehydration by the action of iodine, potassium iodide, and sodium carbonate on 7-phenylisocrotonic acid by bromination of /3-benzoylpropionic acid and subsequent dehydrohalogena-tion 1 and by the action of phenylzinc chloride on maleic anhydride. The present method is based on the work of von Pech-mann and others. ... 

The first method began with phloroacetophenone-4-methyl ether (50), which was prepared by an established route137), and by a newer method wherein phloro-acetophenone (51) was acylated with two equivalents of acetic anhydride to afford a mixture of the 2,4 and the 2,6-diacetoxyphloroacetophenones. The separated 2,6-isomer was methylated and subsequently hydrolyzed to the methyl ether (50). Monobenzylation of (50) afforded benzyl ether (52), which underwent facile Wittig reaction with carbethoxymethylenetriphenylphosphorane to give the 4-methyl-coumarin (49). 

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