Phenylpropionyl Chloride

A mixture of 100 g. (0.67 mole) of /3-phenylpropionic acid [Org. Syntheses Coll. Vol. 1, 311 (1941)] and 100 g. (0.84 mole) of thionyl chloride is heated carefully to reflux and maintained at this temperature for 1.5-2 hours. (Hood.) Distillation of the reaction mixture gives, after removal of the more volatile excess thionyl chloride, 110 g. (97%) of j8-phenylpropionyl chloride boiling at 121-122°/22.5 mm. 

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A. 1-Diazo-4-phenyl-2-butanone. A 1-L Erlenmeyer flask equipped with a two-inch magnetic stirring bar and a two-hole rubber stopper fitted with a 125-mL Teflon stopcock separatory funnel (Note 2 and a drying tube filled with potassium hydroxide (Note 3) is charged with a solution of 200 mmol (3.4 equiv) of diazomethane (Note 4) in 600 mL of dry ether. The solution is cooled to 0°C and stirred at high speed (Note 5). To this cooled solution, 10.0 g (59 mmol) of hydrocinnamoyl chloride (3-phenylpropionyl chloride) (Note 6) diluted to 125 mL with anhydrous ether is added dropwise over a 1 -hr period. The resulting reaction mixture is stirred cold for an additional 0.5 hr and then at room temperature for 1 hr. After this period of time the... 

Phenylpropionyl chloride Valery 1 chloride wo-Valeryl chloride 2-Methylvaleryl chloride Butyryl chloride 2-Ethylbutyryl chloride... 

Mechanism 9-6 explains that the second equivalent of diazomethane is necessary to remove one of the CH2-protons before dediazoniation and, therefore, to prevent the formation of the (chloromethyl)alkyl ketone 9.10. Scott and Minton (1977, and references given there) showed that in some cases triethylamine and other amines also can be used as proton acceptors. Their method is the basis of two Organic Syntheses procedures, i. e., l-diazo-2-phenylethan-2-one from benzoyl chloride (Bridson and Hooz, 1988) and l-diazo-4-phenylbutan-2-one from 3-phenylpropionyl chloride (Scott and Sumpter, 1993). ... 

Akaji and Kiso" reported an efficient synthesis of 1297 (Scheme 1.331) from Boc-(l )-MeCys(Bn)-OH, Boc-Thr(Bn)-NHCH3 and 3-phenylpropionyl chloride. They improved the peptide-coupling conditions for the sterically hindered a-methylcysteine and threonine analogs normally used to prepare 1187 and 1188. 

Acyl halides are intermediates of the carbonylations of alkenes and organic-halides. Decarbonylation of acyl halides as a reversible process of the carbo-nylation is possible with Pd catalyst. The decarbonylation of aliphatic acid chlorides proceeds with Pd(0) catalyst, such as Pd on carbon or PdC, at around 200 °C[109,753]. The product is a mixture of isomeric internal alkenes. For example, when decanoyl chloride is heated with PdCF at 200 C in a distillation flask, rapid evolution of CO and HCl stops after I h, during which time a mixture of nonene isomers was distilled off in a high yield. The decarbonylation of phenylpropionyl chloride (883) affords styrene (53%). In addition, l,5-diphenyl-l-penten-3-one (884) is obtained as a byproduct (10%). formed by the insertion of styrene into the acyl chloride. Formation of the latter supports the formation of acylpalladium species as an intermediate of the decarbonylation. Decarbonylation of the benzoyl chloride 885 can be carried out in good yields at 360 with Pd on carbon as a catalyst, yielding the aryl chloride 886[754]. 

On the other hand, in the preparation of hydrindone-1 from pure instead of crude jS-phenylpropionyl chloride, the reactivity was so increased that only a few minutes heating was required to bring about ring closure in markedly improved yields.67 With pure aluminum chloride, also, the cyclization was completed in a few seconds and the yielcl -still further improved to 90%.20... 

D-Phenyl propionates of methyl esters of racemic hydroxy acids were prepared by Hammarstrom and Hamberg [190] and used for the separation of enantiomers of these compounds on QF-1. The separation was successful with methyl 3-, 15-, 16- and-17-hydroxyoctadecanoates, whereas diastereoisomers of methyl 4-, 7- and 13-hydroxyocta-decanoic acids were not separated. The derivatives were prepared at room temperature reaction of the ester of the hydroxy acid with D-2-phenylpropionyl chloride in the presence of pyridine for 2 h. 

On the other hand, there are only a few reports of catalytic nonpolymeric reactions that involve the intermolecular reaction of an alkene with an acylpalladium complex. The first example was reported in 1968 while studying the decarbonylation of acyl chlorides in the presence of various palladium salts. For example, phenylpropionyl chloride gave styrene (53%) along with l,5-diphenyl-l-penten-3-one (10%) in the presence of catalytic amounts of PdCl2. The latter compound was probably formed via reaction of the acylpalladium complex, generated via oxidative addition in the acyl-chloride bond, with styrene itself formed via decarbonylation of the acylpalladium complex followed by /S-elimina-tion (Scheme 2). 

When the double bond migration of alkenes produced by the decarbonylation is impossible, other products are formed in addition to alkenes. When phenylpropionyl chloride was decarbonylated, the main product was styrene (53%), and 1,5-diphenyl-l-penten-3-one was obtained in 10% with a small amount of unidentified products. Benzyl chloride and some unidentified products were obtained from phenylacetyl chloride (Scheme 3). 

The first step of the decarbonylation of acyl halides is their oxidative addition to form acylpalladium halides, which undergo acyl-alkyl rearrangement to form aryl- or alkylpal-ladium halides. Finally, elimination of j8-hydrogen affords alkenes and HCl. When j8-phenylpropionyl chloride was heated at 200 °C with Pd catalyst, styrene was formed as the main product, accompaiued by a small amount of l,5-diphenyl-l-penten-3-one. The... 

Groves et al. found that a simple heme-iodosobenzene system mimics the enzymic reactions.127 Cyclohexane and cyclohexene are oxidized to cyclohexanol and a mixture of cyclohexene oxide and cyclohexenol respectively by this system. Using meso-tetrakis-a,/J,a,/J-(o-acylamidophenyl)por-phinatoiron(III) chloride where the acyl group is (i )-2-phenylpropionyl or (S)-2 -methoxy-carbonyl-l,T-binaphthyl-2-carbonyl, optically active styrene oxides are obtained in 51% e.e. The Fe(TPP)Cl-PhIO system can also oxygenate arenes to arene oxides.128 Based on the following observations, mechanisms involving O—Felv(Por) t as the active species have been proposed (Scheme 30).127... 

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