Benzene with propionyl chloride

Propiophenone. Propiophenone [93-55-0] (ethyl phenyl ketone) is a colorless Hquid with a flowery odor. It can be prepared by the Friedel-Crafts reaction of benzene and propionyl chloride in the presence of aluminum chloride (346), or by the catalytic reaction of benzoic acid and propionic acid in the presence of water (347). Propiophenone is commercially available (348), and is sold in Japan at 2700 Y/kg (349). It is used in the production of ephedrine, as a fragrance enhancer, and as a polymerization sensitizer. 

We can kill two birds with one stone here both problems common to the Friedel-Crafts alkylation are solved when the acylation is used instead. Firstly, the product of the acylation is a ketone the reaction introduces a deactivating, electron-withdrawing, conjugating carbonyl group to the ring, so the product is less reactive than the starting material. Reaction will stop cleanly after one acylation. Here s benzene reacting with propionyl chloride. 

Propiophenone. Prepare a solution of diphenyl-cadmium in 110 ml. of dry benzene using 4 9 g. of magnesium, 32 4 g. of bromobenzene and 19 5 g. of anhydrous cadmium chloride. Cool the solution to 10°, and add during 3 minutes a solution of 14 -8 g. of propionyl chloride (b.p. 78-79°) in 30 ml. of dry benzene use external coohng with an ice bath to prevent the temperature from rising above 40°. Stir the mixture for 2 hours at 25-35°. Work up the product as detailed above except that 6 per cent, sodium carbonate solution should replace the saturated sodium bicarbonate solution. The yield of propiophenone, b.p. 100-102°/16 mm., is 17 6 g. 

Phenylethyl Ketone. 200 g of finely powdered anhydrous aluminum chloride is suspended in 300 g of dry benzene in a flask that is cooled and equipped with a good stirring device. A mixture of 126 g of propionyl chloride and 105 g of benzene is added dropwise, with stirring, over 3 hours. After the 3 hours, the reaction mixture temp is kept at 50°. The contents of the flask are cooled and poured over crushed ice. Add 50 cc of coned HCl acid and remove the phenylethyl ketone and benzene by distillation with steam at 200-220° to yield 152 g of the ketone. 

Catalytic acylation of electron-rich aromatics is achieved with a combination of InCls and silver perchlorate (Scheme 8.114) [157]. Acetic anhydride, acetyl chloride and isopropenyl acetate serve as satisfactory acyl donors. By using an InCl3-impreg-nated Si-MCM-41 catalyst at low concentration, acylation of aromatic compounds (benzene, toluene, p-xylene, mesitylene, anisole, naphthalene, methylnaphfhalene, and methoxynaphfhalene) by acyl chlorides (benzoyl chloride, phenylacetyl chloride, propionyl chloride, or butyryl chloride) can be accomplished rapidly (3 h) at 80 °C in high yield, even in the presence of moisture in the aromatic substrate or solvent (dichloroethane) (Scheme 8.115) [158], In(OTf) j is an efficient catalyst in the sulfonylation of both activated and deactivated aromatic compounds (Scheme 8.116) [159]. 

To a filtered solution prepared from 35.6 g AICI3 (0.266 mol) and 27.2 g 3-(carbomethoxy)propionyl chloride (0.180 mol) in 150 mL dry CH2CI2 was added 27.5 g (S)-isobutyl-benzene (0.205 mol) in 70 mL dry CH2CI2 at 0°C. The mixture was stirred at 0°C for 1 h and hydrolyzed with ice and 10% HCl. Then the organic layer was dried and evaporated, and the residue was distilled to give 36.6 g 99% pure methyl (S)-3-[4-(l-methylpropyl)benzoyl]propionate in 82% yield with respect to the acyl chloride, besides 4.1 g 99% pure (S)-isobutyl-benzene. 

Obtained by reaction of propionyl chloride with catechol diethyl ether in the presence of aluminium chloride in refluxing benzene for 40 min (49%) [6850]. Also refer to [6851-6854]. 

Also obtained (by-product) by reaction of propionyl chloride with p-dimethoxy-benzene in methylene chloride in the presence of aluminium chloride at r.t. [7146,7147],... 

In the subsequent work the debenzylation of )3-benzylmercapto-a-substituted-propionyl chlorides with two moles of aluminum halide was proved to be a general and very convenient method for the preparation of optically active a-substituted-j3-thiolactones, and a series of optically pure j3-thiolactones was prepared by the debenzylation method. Debenzylation was performed at room temperature in the presence of a benzene solution of aluminum bromide. Monomers were obtained in a yield of 40—70% as shown in Table I. 

One preparative procedure for achieving this reaction involves the acylation of the magnesium enolate of diethyl malonate with an acid chloride in benzene solution (cf. Expt 5.96), and the resulting aclymalonic ester is then heated to 200 °C with an arylsulphonic acid to effect the decarbethoxylation step. An illustrative example is the preparation of ethyl 3-oxopentanoate (ethyl propionyl-acetate, Expt 5.177). 

Obtained by reaction of sodium azide with 4-[(4-propionyl-2-propyl-3-hydroxyphenyl)methoxy] benzene-acetonitrile in the presence of anunonium chloride in DMF at 105° for 20 h (32%) [7564]. 

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