Acyl halides resonance stabilization

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. 

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. 

While most of the chemistry discussed in this chapter has been developed in the past decade, several important methods have withstood the test of time and have made important contributions in areas such as natural product synthesis. Methods such as cuprate acylation and the addition of organolithiums to carboxylic acids have continued to enjoy widespread use in organic synthesis, whereas older methods including the reaction of organocadmium reagents with acid halides, once virtually the only method available for acylation, has not seen extensive utilization recently. In the following discussion, we shall be interested in cases where selective monoacylation of nonstabilized carbanion equivalents has been achieved. Especially of concern here are carbanion equivalents or more properly organometallics which possess no source of resonance stabilization other than the covalent carbon-metal bond. Other sources of carbanions that are intrinsically stabilized, such as enolates, will be covered in Chapter 3.6, Volume 2. 

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. 

The acyl halide forms a complex with the Lewis acid (AICI3), followed by the leaving of the halogen along with the Lewis acid. The resulting ion, called acylium ion, is resonance stabilized and is strongly electrophilic. This ion reacts with benzene to form an acylbenzene. 

The mechanism of Friedel-Crafts acylation (shown next) resembles that fw alkylation, except that the carbonyl group helps to stabilize the cationic intermediate. The acyl halide forms a complex with aluminum chloride loss of the tetrachloroaluminate ion ( AICI4) gives a resonance-stabilized acylium ion. The acylium ion is a strong electrophile. It reacts with benzene or an activated benzene derivative to form an acylbenzene. 

The key reactive intermediates in Friedel-Crafts acylations are acylium cations. These spedes can be formed by the reaction of acyl halides with aluminum chloride. The Lewis add initially coordinates to the carbonyl oxygen because of resonance (see Exadse 2-11). This complex is in equilibrium with an isomer in which the aluminum chloride is bound to the halogen. Dissociation then prodnces the acylium ion, which is stabilized by resonance and, unlike alkyl cations, is not prone to rearrangements. As shown in the electrostatic potential map of the acetyl cation in the margin, most of the positive charge (blue) resides on the carbonyl carbon. 

Resonance stabilization by the chlorine atom is not effective, and acyl halides are the most reactive acyl derivatives. 

Although relatively few alkyl halides react with [M(CO)s] to form straightforward RM(CO)s derivatives, almost all acyl chlorides, RCOCl, react with [M(CO)s] to form the acyl derivatives RCOM(CO)5. Approximately fifteen acyl derivatives of manganese alone have been reported. Acyl derivatives of transition metals such as these manganese compounds appear to be especially stabilized by resonance structures such as (XX), in which the metal-carbon bond has appreciable double bond character, as in the metal carbonyls themselves. The rarity and instability of acyl derivatives of nontransition metals such as tin especially emphasizes the importance of structures analogous to (XX) in stabilizing acyl derivatives of transition metals. 

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