Acyl halides stability

There are alternatives to the addition-elimination mechanism for nucleophilic substitution of acyl chlorides. Certain acyl chlorides are known to react with alcohols by a dissociative mechanism in which acylium ions are intermediates. This mechanism is observed with aroyl halides having electron-releasing substituents. Other acyl halides show reactivity indicative of mixed or borderline mechanisms. The existence of the SnI-like dissociative mechanism reflects the relative stability of acylium ions. 

Hydrotreating has been proposed by Arbokem Inc. in Canada as a means of converting Grade Tall Oil into biofuels and fuel additives. However, this process is a hydrogenation process which produces hydrocarbons rather than biodiesel. Recently a process for making biodiesel from crude tall oil has been proposed. It relies on the use of an acid catalysts or of an acyl halide for the esterification reaction, but no information is given on the properties of this fuel, particularly concerning the oxidative stability. 

In the preceding eqnation, the primary anion-radical gives the l-chloro-2,2,2-trifluoroethyl radical. In vivo, this radical was detected by the spin-trapping method (Poyer et al. 1981). Ahr et al. (1982) had presented additional evidence for the formation of the radical as an intermediate in halo-thane metabolism and identified l-chloro-2,2-difluoroethene as a product of radical stabilization. Metabolytic transformations of l-chloro-2,2-difluoroethene lead to acyl halides, which are relevant to halothane biotoxicity (Guengerich and Macdonald 1993). 

In Friedel-Crafts acylations, an acyl halide, almost always the chloride, in the presence of a Lewis acid is employed to acylate an aromatic ring. The process is initiated by polarization of the carbon-chlorine bond of the acyl chloride, resulting in formation of a resonance-stabilized acylium ion. 

The existence of acylium ions in the reactions of acyl halides with Lewis acids has been amply demonstrated88,89, but they have not so far been directly observed in hydrolysis reactions. To achieve direct observation of an acylium ion, it must, at best, be generated into a non-reactive environment if its rate of formation is slow, or be detectable in small concentrations if it is destroyed rapidly. The limiting factors are, therefore, the rate and mechanism of heterolysis and the stability and concentration of the acylium ion formed. In this... 

Heck and Breslow (63) obtained evidence relating to Eq. (52) for the case of cobalt. They reacted a number of alkyl and acyl halides carrying functional groups with sodium cobalt tetracarbonylate under carbon monoxide. Normal acylcobalt carbonyls were readily formed except for the case of chloroacetonitrile, where a cyanomethylcobalt carbonyl was isolated. Apparently an a-nitrile group is sufficiently electronegative to stabilize the alkylcobalt carbonyl against carbonylation. 

One of the simplest classes of organohalogen compounds are the acyl halides, RCOX. We may expect these species to show some resonance stabilization beyond that of simple carbonyl compounds because of the three non-equivalent structures shown in equation 35. Since the magnitude of resonance stabilization is inherently model-dependent, it is neces-... 

Acylation can be achieved using either acyl halides or acid anhydrides. The product is a ketone. Acyl halides are more reactive than the anhydrides, but still require a Lewis acid catalyst to promote the reaction (Scheme 2.6). The attacking species is the resonance-stabilized acylium ion or the complex. 

The acylium ion (RCO ), which may be generated from an acyl halide and a Lewis acid catalyst, also achieves some stabilization from oxygen lone pairs, and the carbocation remains localized on the carbonyl group. Consequently, Friedel-Crafts acylation is not accompanied by the rearrangements that affect alkylations (Scheme 4.7). 

The pyrazole ring is resistant to most reducing agents and survives intact when other heterocycles are cleaved. An illustration is provided by the reaction of the pyrazoloimidazolidinone (1) with LAH. Here the imidazolidine unit is sensitized to nucleophilic attack by the presence of a lactam carbonyl group, and the product formed is the monocyclic pyrazole (2). The stability of pyrazoles to reduction has been exploited in a synthesis of aldehydes from acyl halides. Thus N-acylpyrazoles (3) on reduction with LAH produce complexes of the type (4) these when hydrolyzed yield aldehydes and the parent pyrazoles (5). ... 

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). 

In the first step the base (usually an alkoxide, LDA, or NaH) deprotonates the a-proton of the ester to generate an ester enolate that will serve as the nucleophile in the reaction. Next, the enolate attacks the carbonyl group of the other ester (or acyl halide or anhydride) to form a tetrahedral intermediate, which breaks down in the third step by ejecting a leaving group (alkoxide or halide). Since it is adjacent to two carbonyls, the a-proton in the product p-keto ester is more acidic than in the precursor ester. Linder the basic reaction conditions this proton is removed to give rise to a resonance stabilized anion, which is much less reactive than the ester enolate generated in the first step. Therefore, the p-keto ester product does not react further. 

Stability and reactivity have an inverse relationship, which means that tire more stable a compound, generally the less reactive - and vice versa. Since acyl halides are the least stable group listed above, it makes sense that they can be chemically changed to the other types. Since the amides are the most stable type listed above, it should logically follow that they cannot be easily changed into the other molecule types, and this is indeed the case. 

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