Phenylacetyl chloride, acylation with

Benzyl chloromethyl ketone has been prepared by the reaction of diazomethane with phenylacetyl chloride. The method of Clibbens and Nierenstein, in which one equivalent of diazomethane is added to the acyl chloride and the chloromethyl ketone obtained directly, could not be duplicated by Bradley and Schwarzenbach or by the submitters. 

The activity of acylureas as hypnotic and anticonvulsant agents is dealt with in some detail later. This is again one of the cases in which the functionality rather than structure determines pharmacologic activity. Thus, acylation of urea with phenylacetyl chloride gives the anticonvulsant agent, phenacemide... 

Schiff s base (j ) derived by reaction of p-chloro-anil ine and borohydride followed by acylation with phenylacetyl chloride produces amide 22,. Selective hydrolysis with HBr followed by alkylation with isopropyl bromide completes the synthesis of lorcainide (20). ... 

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

Acylation of the theophylline diamine intermediate (26-6) with phenylacetyl chloride affords the corresponding amide (28-2). Base catalyzed cyclization then leads to the purine (28-3) that now includes a quite lipophilic benzyl group on the fused imidazole ring. The molecule is then provided with a side chain that incorporates basic nitrogen, arguably to improve water solubility. The anion from (28-3) is thus first alkylated with bromochloroethane to afford the chloroethyl product (28-4). The displacement of chlorine with ethanolamine affords the bronchodilator bamifylline (28-5) [28]. 

Reactions with Acyl Halides. The palladium-carbon bond in alkyl VII and acyl VIII complexes also can be broken by acyl and alkyl halides, respectively, to give ketones (55). The reaction of the benzyl complex Vila with acetyl chloride in the presence of 2,6-lutidine provided good yield of methyl benzyl ketone, XVII. In the absence of the base, lower yields (26% ) were obtained. Surprisingly, a similar reaction between the benzyl complex and an excess of phenylacetyl chloride afforded a 156% yield of dibenzyl ketone, XVIII, based on the starting benzyl complex (see bottom of p. 105). 

The facts that the phenylacetyl complex Villa also undergoes a reaction with phenylacetyl chloride under identical experimental conditions to yield dibenzyl ketone, XVIII (218% with respect to Villa), and that XVII was also obtained from the reaction of phenylacetyl chloride with dichlorobis(triphenylphosphine)palladium(0), XIX, implicate XIX in the catalytic cycle. The palladium (II) complex XIX does indeed catalyze the conversion of an acyl halide to the corresponding symmetrical ketone (123% with respect to XIX). The palladium (IV) structures are only... 

The acylation of compound (384a) with phenylacetyl chloride gives the amide (384b) which is... 

Finally, the hydrazides 3 5 are easily transformed to the corresponding enantiomerically pure a-hydrazino and a-amino acid derivatives16. In a representative example hydrazido acid 3 (R = C6H5) is esterified (CH2N2) and deprotected to 6 with trifluoroacetic acid. The resulting solution is directly hydrogenated over a Raney nickel catalyst. The unpurified amino acid is acylated with ( + )-(5 )-methoxy(trifluoromethyl)phenylacetyl chloride [( + )-MTPA-Cl], to afford the amide 7 in 99% overall yield for the three steps. 

For acylations with propionyl and phenylacetyl chlorides, see Ref. 71JCS(C)706. 4-Amino-5-phenyltriazole, refluxed with ethyl acetoacetate in toluene, gave 4-acetoacetamido-5-phenyltriazole (7 hr, 67%), which hot acetic anhydride converted to the 3-acetyl derivative. However, the reaction of 4-aminotriazole-5-carboxamide with cold acetoacetic ester gave a IV-vinyl (and not a iV-acyl) derivative (see Section III,B) [73JCS(P1)943]. 

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]. 

The surface acidity role in the acylation of anisole with acyl chlorides was analyzed. From the relative adsorption constants of phenylacetyl chloride and anisole on Y(19) and the absence of any anisole demethyla-tion and rearrangement products, it is possible to conclude that the interaction of the acid sites of the catalyst with anisole oxygen must be not very... 

Bekassy, S., Parkas, J., Agai, B., and Figueras, F. 2000. Selectivity of C-versus 0-acylation of diphenols by clay catalysts. I. Acylation of resorcinol with phenylacetyl chloride. Top. Catal. 13 287-290. 

Cycloalkenes can also be acylated with aluminum chloride or tin tetrachloride as catalyst 627,628 cycloheptene, acetyl chloride, and aluminum chloride give 70% of 1-cycloheptenyl methyl ketone.629 The yield from cyclohexene and phenylacetyl chloride is, however, below 30% but better yields are obtained with acetyl chloride and zinc chloride (60% of 1-cyclohexenyl methyl ketone630,631) or acetic anhydride and tin tetrachloride.632... 

In related work, Saito and Hiraoka (1977a) synthesized some unusual dimeric sulfenimines (221-225) by reaction of 7-aminocephem 220 with thionyl chloride and triethylamine. A major coproduct in these transformations was dimeric cephem 226. Acylation of this material with phenylacetyl chloride gave a dimeric amide identical to a substance prepared earlier by Yanagi-sawa and Nakao (1976) [vide supra). Treatment of 221 with methanol and triethylamine produced the monomethoxylated product (227) in 74% yield. Bis-methoxylation was not achieved, even under forcing conditions. In the case of disulfide 222, similar conditions led to 7a-methoxy-7-deacetoxyce-phalosporanic acid methyl ester (27%). The mode of desulfurization is unclear at this time. Related chemistry involving nitrogen-sulfiir bonds was discussed by Sankyo researchers in a subsequent paper (Saito and Hiraoka, 1977b). 

Also obtained by Friedel-Crafts acylation of 2,4-dibromo-resorcinol with phenylacetyl chloride in nitrobenzene in the presence of alumininm chloride, first at r.t. overnight, then heating on a steam bath for 4 h (44%) [5176]. 

Preparation by acylation of resorcinol with phenylacetyl chloride in boiling ethylene dichloride (84°), using a series of clay based catalysts (KSF, KSF/0, KPIO, KIO, KO, KS) (65-81%) [5252], (60%) [5253]. 

Also obtained by Friedel-Crafts acylation of hydroquinone with phenylacetyl chloride in the presence of aluminium chloride in nitrobenzene, keeping overnight, then on a water bath for 3 h [5285] or at 70-80° for 15 min [5249],... 

Preparation by Friedel-Crafts acylation of orcinol with phenylacetyl chloride in nitrobenzene in the presence of aluminium chloride [5180]. 

Preparation from 2-methoxy-5-(phenyla-cetyOphenyl phenylacetate (SM) with refluxing methanolic potassium hydroxide (91%) [5348]. SM was obtained by acylation of 2-methoxyphenyl phenylacetate with phenylacetyl chloride in the presence of stannic chloride in nitromethane for 1 h at 20 (76%, m.p. 95 ). 

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