Acetophenone: acylation

TTie true ketones, in which the >CO group is in the side chain, the most common examples being acetophenone or methyl phenyl ketone, C HjCOCH, and benzophenone or diphenyl ketone, C HjCOC(Hj. These ketones are usually prepared by a modification of the Friedel-Crafts reaction, an aromatic hydrocarbon being treated with an acyl chloride (either aliphatic or aromatic) in the presence of aluminium chloride. Thus benzene reacts with acetyl chloride... 

The preparation of benzoylacctone Is another example of the acylation of a ketone (acetophenone) by ethyl acetate to a p diketone (Claisen condensation compare preceding Section) ... 

Friedel-Crafts Acylation. The Friedel-Crafts acylation procedure is the most important method for preparing aromatic ketones and thein derivatives. Acetyl chloride (acetic anhydride) reacts with benzene ia the presence of aluminum chloride or acid catalysts to produce acetophenone [98-86-2], CgHgO (1-phenylethanone). Benzene can also be condensed with dicarboxyHc acid anhydrides to yield benzoyl derivatives of carboxyHc acids. These benzoyl derivatives are often used for constmcting polycycHc molecules (Haworth reaction). For example, benzene reacts with succinic anhydride ia the presence of aluminum chloride to produce P-benzoylpropionic acid [2051-95-8] which is converted iato a-tetralone [529-34-0] (30). 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

The course of the reaction may involve either the acylation of the ketone to a -diketonic intermediate following thereupon the pathway in Section II, C, 2, a, or alternatively the condensation of two moles of ketone to yield an intermediate dypnone which then undergoes acylation following the pathway in Section II,C, l,a. Dilthey and Fischer thought the first alternative more plausible, on the basis of reaction yields, and this lead them to explore the pathway in Section II,C,2,a. Schneider and Ross and Diels and Alder believed that the second alternative operates. Both views are plausible since acylations of methyl ketones to S-diketones are known to take place in the conditions of this reaction, and dypnone ha.s been isolated from acetophenone on treatment with Friedel-Crafts catalysts, in the absence of an acid anhydride or chloride (an excess of catalyst... 

Besides acetophenone, this reaction was also applied to p-chloro- andp-methoxyacetophenone, and even to an aliphatic ketone, acetone (although the yield was stated to be only half as large as that obtained from mesityl oxide, i.e., less than 30%, Dorofeenko and co-workers reported a 45% yield of 2,4,6-trimethylpyrylium perchlorate from acetone, acetic anhydride, and perchloric acid), and is the standard method for preparing pyrylium salts with identical substituents in positions 2 and 4. The acylating agent may be an anhydride in the presence of anhydrous or hydrated ferric chloride, or of boron fluoride, or the acid chloride with ferric chloride.Schneider and co-workers ... 

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

A compound closely related to classical adrenergic agonists in which the para hydroxy function is however replaced by an amino group has been investigated for its activity as a growth promoter in domestic animals. Acylation of the aniline derivative 26 with chloracetyl chloride will afford acetophenone 27 the amino-ketone 28 is obtained on reaction with isopropylamine. Removal of the protecting group (29) followed by reduction of the ketone affords cimaterol (30) 5J. 

Just as an aromatic ring is alkylated by reaction with an alkyl chloride, it is acylated by reaction with a carboxylic acid chloride, RCOC1, in the presence of AICI3. That is, an acyl group (-COR pronounced a-sil) is substituted onto the aromatic ring. For example, reaction of benzene with acetyl chloride yields the ketone, acetophenone. 

O-Acylated or mesylated oximes such as the ethyl carbonate of acetophenone-oxime 1772 react with TIS 17, with Beckmann rearrangement to the imidoyl iodide 1773, which adds phenylmagnesium bromide in situ to give 61% of the sec-... 

Another recent patent (22) and related patent application (31) cover incorporation and use of many active metals into Si-TUD-1. Some active materials were incorporated simultaneously (e.g., NiW, NiMo, and Ga/Zn/Sn). The various catalysts have been used for many organic reactions [TUD-1 variants are shown in brackets] Alkylation of naphthalene with 1-hexadecene [Al-Si] Friedel-Crafts benzylation of benzene [Fe-Si, Ga-Si, Sn-Si and Ti-Si, see apphcation 2 above] oligomerization of 1-decene [Al-Si] selective oxidation of ethylbenzene to acetophenone [Cr-Si, Mo-Si] and selective oxidation of cyclohexanol to cyclohexanone [Mo-Si], A dehydrogenation process (32) has been described using an immobilized pincer catalyst on a TUD-1 substrate. Previously these catalysts were homogeneous, which often caused problems in separation and recycle. Several other reactions were described, including acylation, hydrogenation, and ammoxidation. 

Electron-rich aromatic compounds such as durene, p-dimethoxybenzene, mesitylene, anisole, thiophene, and fluorene can be benzoylated or acetylated by the corresponding Af-acylimidazole in trifluoroacetic acid to give the corresponding benzophenone or acetophenone derivative in good yield (Method A). As the actual acylating agent, a mixed anhydride of trifluoroacetic acid and benzoic acid has been proposed 1973... 

A different MS-based ee-assay makes use of a proline-derived mass-tagged acylating agent.95 In the course of derivatization it is necessary that some degree of kinetic resolution comes about. The sensitivity of the method was reported to be 10% ee. It can also be applied to the reaction of a prochiral compound lacking enantiotopic groups, as in the transformation of acetophenone to phenylethanol. 

Elimination to yield alkenes can be induced thermally or by treatment with acids or bases (for one possible mechanism, see Figure 3.39) [138,206]. Less common thermal demetallations include the thermolysis of arylmethyloxy(phenyl)carbene complexes, which can lead to the formation of aryl-substituted acetophenones [276]. Further, (difluoroboroxy)carbene complexes of molybdenum, which can be prepared by treating molybdenum hexacarbonyl with an organolithium compound and then with boron trifluoride etherate at -60 °C, decompose at room temperature to yield acyl radicals [277]. 

This multi-step, one-pot process was taken further by integration of a third supported reagent for the sequential preparation of 3,5-diphenylpyrazole (Scheme 2.17). Following the previously established procedure, acetophenone was deprotonated and acylated to afford the 1,3-dicarbonyl species. This intermediate was easily separated from the spent polymers by filtration and passed without isolation into a suspension of the resin bound hydrazine salt (9), affording the desired pyrazole in 91% yield. In a subsequent publication, the authors reported that the depleted polymeric reagents from the first step of the conversion (i.e. (7) and (8)) were recovered and separated via a selective flotation procedure, enabhng them to... 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

A ketone can also be formed with a Friedel-Crafts acylation. The process requires an acid chloride and an aromatic compound. An aldehyde can t be formed by this procedure because the appropriate acid chloride, formyl chloride (HCOCl), is unstable and decomposes to carbon monoxide and hydrogen chloride. Figure 10-12 illustrates the preparation of acetophenone from benzene and acetyl chloride. 

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