Acyl halides to ketenes

Mercury can be used to dehalogenate acyl halides to ketenes when a halogen IS present next to the COCl group [67] (equation 35)... 

This reaction gives better yields when the complex is first prepared in the absence of water and then subsequently reacted with one-half mole of water per mole of acyl halide, ridine is preferred over the more basic triethylamine because the latter tends to effect dehydroha-logenation of aliphatic acyl halides to ketenes. Some typical examples of this method are summarized in Table II and also given in Preparation 35-2. 

Addition of halogens to ketenes 5-27 Addition of HOBr or HOC1 to triple bonds addition of chlorine acetate or other reagents to olefins 5-34 Addition of acyl halides to olefins... 

Protonation of ketene 0,N-acetals with strong acids gives rise to the formation of iminium compounds, e.g. (98 equation 57). Ketene OA -acetals are transformed by alkyl halides or acyl halides to a-sub-stituted amides via unstable iminium salts (99 equation 58).Iminium compounds of this type are isol-able if they are immediately precipitated, e.g. as perchlorate salts (100 equation 59), Heterocumulenes such as isocyanates, isothiocyanates or S02 form 1,4-dipoles with ketene OA -acetals, which can be stabilized by protonation with perchloric acid to give salts, e.g. (101 equation 60). 

Ketenes can be prepared by treatment of acyl halides with tertiary amines. The scope is broad, and most acyl halides possessing an a hydrogen give the reaction, but if at least one R is hydrogen, only the ketene dimer, not the ketene, is isolated. However, if it is desired to use a reactive ketene in a reaction with a given compound, the ketene can be generated in situ in the presence of the given compound. ... 

The (aziridin-l-ylimino)phosphoranes (57) react with ketens to give nitrile derivatives, presumably from an intermediate ketenimine by breaking the N—N bond and migration of the aziridinyl group.60 They also react with acyl halides and... 

C(R)=NR group with a nitrilium salt RCssNR .222 The acylation of the enamine can take place by the same mechanism as alkylation, but another mechanism is also possible, if the acyl halide has an a hydrogen and if a tertiary amine is present, as it often is (it is added to neutralize the HX given off). In this mechanism, the acyl halide is dehydrohalogenated by the tertiary amine, producing a ketene (7-14) which adds to the enamine to give a cyclobutanone (5-49). This compound can be cleaved in the solution to form the same acylated imine salt (27) that would form by the more direct mechanism, or it can be isolated (in the case of enamines derived from aldehydes), or it may cleave in other ways.223... 

Diazocarbonyl compounds can also be prepared by C-acylation of diazoalkanes with polystyrene-bound acyl halides (Entry 6, Table 10.19). As an alternative to diazomethane, the more stable a-(trimethylsilyl)diazomethane may be used, which is sufficiently nucleophilic to react with acyl halides. On heating, the resulting a-(trimethyl-silyl)diazo ketones undergo Wolff rearrangement to yield ketenes, and have also been used as starting materials for the preparation of oxazoles [368]. 

An important method for the preparation of /3-keto esters is by the action of alcohols on ketene dimers in the presence of acid catalysts. Diketene and alcohols give acetoacetic esters in 60-80% yields. Dimers of higher ketenes are made by dehydrohalogenation of acyl halides and are converted to /S-keto esters in one operation (cf. method 245). 

At oxidation level 3, acid chlorides occupy a key position, since they may serve as a nearly universal substrate for an isohypsic transformation into any kind of carboxylic acid derivative. Acid halides are electrophiles that are synthetically equivalent to acyl cations (RCO ). In this capacity they are used for the synthesis of such important compounds as esters, amides (and hence, nitriles), thioesters, etc. (see Scheme 2.57), and for the formation of C-C bonds in the Friedel-Crafts reaction (see above). Acid chlorides may readily lose HCl upon treatment with triethylamine. This isohypsic conversion leads to ketenes, important reagents widely employed in [2 + 2] cycloadditions, as we will see later. 

The most important method for the preparation of aryl ketones is known as Friedel-Crafts acylation. The reaction is of wide scope. Reagents other than acyl halides can be used," including carboxylic acids," anhydrides, and ketenes. Oxalyl chloride has been used to give diaryl 1,2-diketones." Carboxylic esters usually give alkylation as the predominant product (see 11-11)." A-Carbamoyl p-lactams reacted with naphthalene in the presence of trifluoromethanesulfonic acid to give the keto-amide." ... 

NaBOs and NaBr adds two bromine atoms across a triple bond. With allenes it is easy to stop the reaction after only 1 equivalent has added, to give X C CX=C. Addition of halogen to ketenes gives a-halo acyl halides, but the yields are not good. 

Ketene aminals can be transformed by various electrophilic reagents to amidinium salts, thus mineral acids, alkyl halides, A///-dialkyliminium salts, alkoxymethyleneiminium salts, formamidinium salts, acyl halides, diazonium salts, vinylogous amidinium salts,sulfonyl halides, ketene dichlorides ... 

Cinchona alkaloids such as 121 possess a nucleophilic quinuclidine structure and can act as versatile Lewis bases to react with ketenes generated in situ from acyl halides in the presence of an add scavenger. By acting as nucleophiles, the resulting ketene enolates can react intermolecularly [53] or intramolecularly [54] with electrophilic C=0 or C=N bonds to deliver formal [2 + 2]-cycloadducts, such as chiral P-lactones or [1-lactams, via aldol (or Mannich)-i intramolecular cydization sequence reactions (Scheme 8.46). The nucleophilic ammonium enolate can also read with energetic... 

The applications of cinchona-catalyzed ketene enolates can be extended to a,P-unsaturated aliphatic acyl halides. Peters et al. presented a new concept for the synthesis of a,P-unsaturated 8-lactones, which are subunits of a number of natural and unnatural products that display a wide range of biological activity. They proposed... 

Acyl halides bearing a-hydrogen atoms, and acetyl chloride in particular, have limited stability in the presence of strong Lewis acids. Elimination of proton from the acylium ion leads to the ketene. This intermediate undergoes ready Friedel-Crafts acylation, acetyl chloride eventually forming the diacetylace-tylium ion, ° which is a poor acylating agent. For this reason, excessive reaction temperatures and times should be avoided in Friedel-Crafts acetylations. 

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