Propionyl chloride

Ethyl a-bromopropionate. This preparation illustrates the facile bromination of an acid chloride (propionyl chloride) in the presence of red phosphorus, and the subsequent conversion of the bromoacid chloride into the ethyl ester by direct interaction with ethanol. 

An improved yield is obtained by the following process. Add a mixture of 75 g. (70-5 ml.) of propionyl chloride and 90 g. (103 ml.) of sodium-dried A.R. benzene to a vigorously stirred suspension of 75 g. of finely-powdered anhydrous aluminium chloride in 100 ml, of dry carbon disulphide, Then introduce more of the aluminium chloride (about 15 g.) until no further evolution of hydrogen chloride occurs. The yield of propiophenone, b.p. 123°/25 mm., is about 90 g. 

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. 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

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. 

Propionyl chloride was purchased from Fluka AG and Aldrich Chemical Company, Inc. and was freshly distilled at 78-80°C (760 mm) prior to use. 

The checkers maintained the temperature of the reaction mixture at ca. 25°C by cooling with a water bath during the addition of propionyl chloride. 

Polyethylene glycol (molecular weight, 300-6(W) can aid in the displacement of activated halogen by fluorine. Propionyl chloride is converted to propionyl fluoride with potassium fluoride and polyethylene glycol in acetonitrile [63] Treatment of benzyl chloride with a mixture of potassium fluoride and potassium iodide for 5 h in acetonitrile containing polyethylene glycol 200 gives benzyl fluoride in 62% yield [64],... 

In their original communication on the alkylation and acylation of enamines, Stork et al. (3) had reported that the pyrrolidine enamine of cyclohexanone underwent monoacylation with acid chlorides. For example, the acylation with benzoyl chloride led to monobenzoylcyclohexanone. However, Hunig and Lendle (33) found that treatment of the morpholine enamine of cyclopentanone with 2 moles of propionyl chloride followed by acid hydrolysis gave the enol ester (56), which was proposed to have arisen from the intermediate (55). 

Lochte and Pitman (44) have reported the cyanoethylation of the pyrrolidine enamine of 3-methylcycIopentanone (84), the product being a mixture of C-2 and C-5 cyanoethylated ketones (85 and 86). Hunig and Salzwedel 20) have obtained a mixture of C2- and C5-acylated products from the reaction of morpholine enamine of 3-methylcyclopentanone with propionyl chloride. 

Bruce and Sutcliffe obtained l-acetyl-2-methyl-3-phenylindole (123) by the action of acetyl chloride on 2-methyl-3-pheiiylindole magnesium iodide in ether.These authors were able to obtain l-benzoyl-2-benzyl-3-phenylindole (124) but not l-acetyl-2-benzyl-3-phenylindole (125) from 2-benzyl-3-phenylindole magnesium iodide by analogous procedures.3-Acetyl-2-phenylindole (126) and 3-propionyl-2-pheny]indole (127) have recently been prepared in fair yield by the acylation of 2-phenylindole magnesium iodide with acetyl and propionyl chloride, respectively. Le ete obtained a mixture of l-acetyl-3-ethylindole (128) and 2-acetyl-3-ethylindole (129) by the interaction of acetyl chloride with 3-ethylindole magnesium iodide in ether. 

V. -(l-Carbobemoxy-4 -piperidyl)propionyl chloride. /3-(iV-carbo-benzyloxy-4-piporidyl)ethyl 3-indolyl ketone (208) was obtained similarly by the condensation of ]3-(A -carbobenzoxy-4-piperidyl)-propionyl chloride with indole magnesium bromide in ether. ... 

Acylation of thiosemicarbazide with propionyl chloride, interestingly, does not stop at the acylated product (124). Instead, this intermediate cyclizes to the thiadiazole, 125, under the reaction conditions. Hydrolysis then affords the heterocyclic amine, 126. Acylation by 88 followed by removal qf the acetyl group affords sulfaethidole (116) variation of thle acid chloride used in the preparation of the heterocycle leads to 117 and 118. 

Oil-soluble derivatives of testosterone itself predate those of its 19-nor congener these agents too are used to administer depot injections so as to provide in effect long-term blood levels of drug. Thus, acylation of testosterone with propionyl chloride in the presence of pyridine yields testosterone propionate (76a)acylation by means of decanoic anhydride yields testosterone decanoate (76b).Finally, reaction of 75 with 3-cyclopentylpropionyl chloride affords testosterone cypionate (76c)This last undergoes hydrolysis unusually slowly because of the presence of two substituents at the 5 position (see Newman s Rule of 6). ... 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

Condensation of prednisone, 40 with tetraethyl orthocarbonate leads to the cyelie ortho-carbonate 41 liydrolysis proceeds by protonation on the most accessible ether oxygen (that on carbon 21) to give the 17 mixed carbonate ester 42. Acylation with propionyl chloride proceeds on the remaining hydroxyl group to afford prednicarbate (43) [10],... 

FluorO-11/3-hydrOxy-16/3-methyl-170 .21-(r-ethyl-1 -ethoxy methylenedioxyipreg-na-1,4-dlene-3.20-dione Acetic Acid Propionyl Chloride... 

Bethmethasone 17-propionate (812 mg) in pyridine (10 ml) was treated with propionyl chloride (0.21 ml) at 0°C for 1 hour. Dilution with water and acidification with dilute hydrochloric acid gave the crude diester. Recrystallization from acetone-petroleum ether afforded betamethasone 17,21-dipropionate (649 mg),MP 117°C (decomposition). 

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