Acylation of ketones, with acid anhydrides

The acylation of ketones with acid anhydrides may be effected by means of the acid reagent boron trifluoride, for example ... 

Acrolein, 446 Acrylonitrile, 916, 1022 reactions with, 914-917 Acrylic acid derivatives, 1016, 1023 Acylation of ketones, with acid anhydrides, 861 with esters, 861, 862 ... 

The third procedure illustrated by this preparation involves the reaotion of ketones with trifluoromethanesulfonic anhydride in a solvent such as pentane, methylene chloride, or carbon tetrachloride and in the presence of a base such as pyridine, lutidine, or anhydrous sodium carbonate.7-11,15 This procedure, which presumably involves either acid-catalyzed or base-catalyzed enolization of the ketone followed by acylation of the enol with the acid anhydride, has also been used to prepare other vinyl sulfonate esters such as tosylates12 or methanesulfonates.13... 

In this paper we report the use of supported heteropoly acid (silicotungstic acid) and supported phosphoric acid catalysts for the acylation of industrially relevant aromatic feedstocks with acid anhydrides in the synthesis of aromatic ketones. In particular, we describe the acylation of thioanisole 1 with iso-butyric anhydride 2 to form 4-methyl thiobutyrophenone 3. The acylation of thioanisole with acetic anhydride has been reported in which a series of zeolites were used as catalysts. Zeolite H-beta was reported to have the highest activity of the zeolites studied (41 mol % conversion, 150°C) (2). 

Acylation of olefins with acid chlorides or anhydrides catalyzed by Lewis acids. When performed in the presence of a saturated hydrocarbon, the product is the saturated ketone. 

Aldehydes can be converted to acylals by treatment with an anhydride in the presence of BF3, other Lewis acids, proton acids, or PCI3. The reaction cannot normally be applied to ketones, though an exception has been reported when the reagent is trichloroacetic anhydride, which gives acylals with ketones without a catalyst. ... 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Acylation of 179 with 2,2-difluoro-3-methyl-4-pentenoic acid anhydride yields ot-amino ketones 180 that can serve as intermediates to prepare pseudopeptides such as peptidyl ot,ot-difluoroalkylketones 181 (Scheme 7.54) or ketomethylene pseudo-peptides. ... 

In some cases, the product depends on the nature of the acylating agent. Acylation of 182 with 2,2-difluoro-4-pentenoic acid anhydride leads to acylation at C, whereas acylation with 2,2-difluoro-4-pentenoic acid choride yields the 5-acyloxyoxazole 185 as the major compound. The 5-acyloxyoxazole can be rearranged to the 5(47/)-oxazolone 183 upon treatment with 4-(dimethylamino)pyridme. Treatement of 183 with anhydrous oxalic acid promotes decarbonylation to give fluorinated a-amino ketones 184 (Scheme 7.55). Selected examples of 4-acyl-5(4//)-oxazolones are shown in Table 7.20 (Fig. 7.22). 

Triflates of boron, aluminum, and gallium were found to be efficient catalysts in Friedel-Crafts acylations.46 However, these are water-sensitive materials and were required to be used in equimolar quantities to be effective. More recently various water-tolerant and recyclable triflate salts, which were also tested in alkylation, were found to exhibit similar good characteristics in Friedel-Crafts acylations. Although benzene cannot be acylated, Sc triflate,47 48 lanthanum triflates,48-51 and Hf triflate52 usually give high yields of aryl ketones in acylation with acid anhydrides. In many cases, Li perchlorate was found to accelerate the reactions.48 52... 

C-Acylations of C,H-acidic compounds have also been realized on insoluble supports. The few examples that have been reported include the C-acylation of support-bound ester enolates with acyl halides [9], Claisen condensations of polystyrene-bound ketones with benzoic acid esters, the C-acylation of nitriles with acyl nitriles or anhydrides, and the C-acylation of phosphonates with acyl halides (Entries 5-9, Table... 

Acylations of ketone enols with anhydrides are catalysed by Lewis acids such as BF3, This process will remind you of Friedel-Crafts acylation but a better analogy is perhaps the aldol reaction where metals such as lithium hold the reagents together so that reaction can occur around a six-membered ring. 

Methylation with dimethyl sulfate in alkali gave the methyl derivatives 28 and 29. Although formaldehyde attacks at N-2, aldol condensation of 10 with benzaldehyde gave the 3a-hydroxybenzyl compound (30) which is dehydrated to the 2-acetyl-3-benzylidene compound (31) with acetic anhydride.27 With acid anhydrides the2-acyl derivatives are obtained however, with acid chlorides in pyridine or dimethylaniline the bicyclic ketone (32) is formed.31 Despite the occurrence of the bicyclic product (32) and the bicyclic intermediate (13) there is no evidence for the existence of a bicyclic tautomer of 10.37... 

Unfortunately, several important classes of a-diazo ketones cannot be prepared in good yield via these standard methods. a -Diazo derivatives of a.p-unsaturated ketones, for example, have previously proved to be particularly difficult to prepare.1113 12 The acylation of diazomethane with a.p-unsaturated acid chlorides and anhydrides is generally not a successful reaction because of the facility of dipolar cycloaddition to conjugated double bonds, which leads in this case to the formation of mixtures of isomeric pyrazolines. Also problematic are diazo transfer reactions involving base-sensitive substrates such as certain a,p-enones and heteroaryl ketones. Finally, the relatively harsh conditions and lack of regioselectivity associated with the thermodynamically controlled Claisen formylation step in the "deformylative" diazo transfer procedure limit the utility of this method when applied to the synthesis of diazo derivatives of many enones and unsymmetrical saturated ketones. 

Enol acetylation. Enol acetylation of steroidal ketones with acetic anhydride catalyzed by perchloric acid has been shown to be thermodynamically controlled (2,309). However, this acetylating reagent in the case of conjugated ketones gives complex mixtures of O-acylated and C-acylated products.1 Dienone-phenol rearrangements have been noted with A4-3-ketosteroids alkylated at C2 or C6.2... 

It is also superior to pyridine as a catalyst for C-acylation, for example in the Dakin-West reaction.3 This reaction is the conversion of a-amino acids into a-acylamino ketones by reaction with acid anhydrides catalyzed by a base (usually... 

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