Propionyl chloride Friedel-Crafts reaction

Improved method for preparation of 173 is reported by Wang and Gu (Scheme 12.29). It comprises of four-step synthesis of 179, conversion of acid into 5-2-(5-fluoropyrimidin-4-yl)propionyl chloride, Friedel-Crafts reaction to obtain ketone 180, and the reaction with 1-methyl-17/-1,2,4-triazole under basic condition. 

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. 

Tetrahydrobenzo[ ]thiophene behaves like thiophene in electrophilic substitution reactions. Thus, it is formylated with a mixture of vV-methylformanilide and phosphorus oxychloride,436 iodinated in the presence of mercuric oxide,193 and brominated by V-bromosuccinimide,193 all in the 2-position in Friedel-Crafts reactions with acetyl chloride,194-436 propionyl chloride,436 succinic... 

Preparation by Friedel-Crafts reaction of propionyl chloride with 2,4-dichloro-phenol in the presence of aluminium chloride [6391],... 

Friedel-Crafts acylation of benzo[6]thiophene and its derivatives with succinic anhydride132,439,662,663 or the ester chloride of succinic acid614, 618, 650,662 gives a y-keto acid (or ester), which is reduced to the corresponding y-(benzo[6]thienyl)butyric acid by the Huang Minion or Clemmensen method. y-(Benzo[6]thienyl)butyric acids may alternatively be prepared by the diethyl malonate synthesis on the appropriate halide,439,499 by the Arndt-Eistert reaction on the corresponding propionyl chloride,409,618 or by cyclization.347,618 The ketones (317 R = Hor OMe)347 have been prepared by cyclization... 

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. 

Also obtained by Friedel-Crafts acylation of phenol with propionyl chloride in the presence of aluminium chloride (37%) [6579] or at 125-130° for 1 h (22%) [6580,6581] according to the method [6582], N,B. This same reaction in carbon disulfide, using propionyl chloride formed in situ by action of oxalyl chloride with sodium propionate (method B), for 1 h at 70°, yield 65% [6671],... 

Preparation by reaction of propionyl chloride with 3-methy-lanisole in the presence of aluminium chloride in methylene chloride for 3 h at 0° [6976], in carbon disulfide at r.t. for 24 h (52%) [7310] or by Friedel-Crafts acylation using samarium triiodide [7318]. 

Regioselective Friedel-Crafts cyclization of a 3-(indol-3-yl)-propionyl chloride derivative was achieved using aluminum chloride. This method was used to make Uhle s ketone in high yields. A donor-acceptor complex formed in situ between aluminum chloride and chloroacetyl chloride was proposed to drive the reaction in high yields (eq 54). ... 

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