Acyl halides Lewis acid complexes

The formation of acyl halide-Lewis acid complexes have been observed by several methods. For example, both 1 1 and 1 2 complexes of acetyl chloride, with AICI3 can be observed by NMR spectroscopy. The existence of acylium ions has been demonstrated by X-ray diffraction studies on crystalline salts. For example, crystal structure determinations have been reported for /i-methylphenylacylium and acetylium ions as SbFg salts. There is also a good deal of evidence from NMR measurements which demonstrates that acylium ions can exist in nonnucleophilic solvents. " The positive charge on acylium ions is delocalized onto the oxygen atom. This delocalization is demonstrated in particular by the short O—C bond lengths in acylium ions, which imply a major contribution from the structure having a triple bond ... 

The Friedel-Crafts acylation of alkynes is an extremely rapid reaction, and usually leads to the formation of the f/ flni-P-chlorovinyl ketone (equation 23). Reaction temperatures can be as low as -70 °C. The reaction proceeds via reaction of the acyl halide-Lewis acid complex with the alkyne, and whilst the implied vinyl cation has not been observed directly, the reaction products can be understood in terms of reaction of such an intermediate with nucleophiles, usually halide ion. Whilst the r/-an.r-chlorovinyl ketone has been described as the sole product of the reaction by some workers, others have reported the formation of mixtures of the cis and trans forms, under conditions that did not appear to lead to isomeriza-... 

Kinetic studies of acylation reactions are somewhat limited by the insolubility of the acyl halide-Lewis acid complexes in many of the solvent systems that are used. However, useful results have been obtained and, as far as we are concerned, relative rates of reactions are of greater importance than absolute values. In any case it is not possible to distinguish between the two mechanistic extremes on the basis of the observed kinetics." Friedel-Crafts acylations are generally characterized by high substrate selectivity and frequently by high positional selectivity. Relative rate data show, as expected, that toluene is more reactive than benzene and that /n-xylene is the most reactive of the dimethylbenzenes. Values, relative to benzene, for benzoylation catalyzed by aluminum chloride were r-butylbenzene (72), toluene (1.1 X 10 ), p-xylene (1.4 x 10 ), o-xylene (1.12 x 10 ), and m-xylene (3.94 x 10- ). Competition data for the trifluoroacetylation of a number of heterocycles using trifluoroacetic anhydride at 75 "C gave the relative rates thiophene (1.0), furan (1.4 x lO ), 2-methylfuran (1.2 x 10 ) and pyrrole (5.3 x 10 ). ... 

The formation of acyl halide-Lewis acid complexes can be demonstrated readily. Acetyl chloride, for example, forms both 1 1 and 1 2 complexes with AICI3 that can be observed by NMR. Several Lewis acid complexes of acyl chlorides have been characterized by low-temperature X-ray crystallography. For example, the crystal stmctures of PhCOCl-SbCl and PhCOCl-GaClj and [PhCOCl-TiCl4]2 have been determined. In all of these complexes, the Lewis acid is bound to the carbonyl oxygen. Figure 9.11 shows two examples. 

Acyl fluoride-Lewis acid complexes, 12 176 Acyl groups, systematic names of, 17 398 Acyl halides... 

Alkenes can be acylated with an acyl halide and a Lewis acid catalyst in what is essentially a Friedel-Crafts reaction at an aliphatic carbon. ° The product can arise by two paths. The initial attack is by the acyl cation RCO (or by the acyl halide free or complexed see 11-14) at the double bond to give a carbocation ... 

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. 

This reaction involves an acylating reagent (acyl halides, carboxylic acids or anhydrides) in the presence of an activator, usually a Lewis acid. However, as a result of the complexation of this Lewis acid with the formed ketone, more than one mole of catalyst is required per mole of reagent. It cannot be reused because the ketone is isolated after hydrolysis of the complex. Such is the dilemma of Friedel-Crafts acylation (refs. 4-6) in the presence of the traditional catalyst, aluminum chloride (eqn. 2). 

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. 

Friedel-Crafts acylation usually involves the reaction of an acyl halide, a Lewis acid catalyst, and the aromatic substrate. Several species may function as the active electrophile, depending on the reactivity of the aromatic compound. For activated aromatics, the electrophile can be a discrete positively charged acylium ion or the complex formed... 

As acylating agent, a carboxylic anhydride may be used instead of the acyl halide. The reaction then yields the arylketone together with a carboxylic acid, each of which forms a complex with the Lewis acid used. The catalyst therefore has to be employed in at least twofold excess ... 

Acidic chloroaluminate ionic liquids have already been described as both solvents and catalysts for reactions conventionally catalyzed by AICI3, such as catalytic Friedel-Crafts alkylation [35] or stoichiometric Friedel-Crafts acylation [36], in Section 5.1. In a very similar manner, Lewis-acidic transition metal complexes can form complex anions by reaction with organic halide salts. Seddon and co-workers, for example, patented a Friedel-Crafts acylation process based on an acidic chloro-ferrate ionic liquid catalyst [37]. 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

Treatment of lithium enolate species, such as 7, with a variety of metal halide species produces enolates with different reactivities in particular, diethylaluminum(IH) and copper(I) species have been found to profoundly alter stereodifferentiation in reactions of iron acyl enolates (see Section D.1.3.4.2.5.1.). It has not been established whether complex formation or discrete ti ansmetalation occurs usually, a temperature increase from — 78 °C to — 42 °C is required for maximum effect, suggesting that cation exchange is responsible. In some cases, such additives exert an influence at —78 °C13, and this has been attributed to simple Lewis acid-type interactions with the substrate instead of transmetalation of the enolate species. For simplicity, when such additives are allowed to react with enolate species at temperatures of — 42 =C and above prior to the addition of other reagents, the process shall be referred to as transmetalation. 

In Friedel-Crafts acylation of aromatics with acid chlorides and Lewis acid metal halides the reactive electrophile is considered to be formed in the interaction of the reagent and the catalyst. First the highly polarized donor-acceptor complex 1 is formed, which can further give other complexes and ion pairs.24 The various... 

A considerable difference between Friedel-Crafts alkylation and acylation is the amount of the Lewis acid necessary to induce the reaction. Friedel-Crafts alkylation requires the use of only catalytic amounts of the catalyst. Lewis acids, however, form complexes with the aromatic ketones, the products in Friedel-Crafts acylations, and the catalyst is thus continuously removed from the system as the reaction proceeds. To achieve complete conversion, therefore, it is necessary to use an equimolar amount of Lewis acid catalyst when the acylating agent is an acyl halide. Optimum yields can be obtained using a 1.1 molar excess of the catalyst. With... 

Selection of an appropriate solvent for Friedel-Crafts acylation is an important question since solvents are known to affect regioselectivities.8,9 In many cases acylation is carried out in an excess of the reacting aromatic compound. Aromatics, however, are poor solvents for most Lewis acids and therefore, they merely serve as diluent in biphase systems. Carbon disulfide is a reasonably good solvent just as dichloromethane and dichloroethane. Although AICI3 is insoluble in chlorinated hydrocarbons, they dissolve many of the complexes formed between acyl halides and AICI3. Nitrobenzene and nitromethane are also suitable solvents. Moreover, the 1 1 addition complexes they form with AICI3 allow acylations to be performed under mild conditions often without side reactions. 

Acyl cations are now well-established chemical species. They can be prepared in quantity in solution, and several have been isolated as their crystalline salts. Recent papers have described their formation from carboxylic acids and esters under strongly acidic conditions81214, but they are most conveniently available from the reactions of acyl halides with L.ewis acids21 well-defined Lewis acid-base complexes are formed, which decompose in a second stage to the acyl cations21-23, viz. 

The electrophile, an acyl cation, is generated in a manner similar to that outlined in Figure 17.4 for the generation of the carbocation electrophile from an alkyl halide. First the Lewis acid, aluminum trichloride, complexes with the chlorine of the acyl chloride. Then A1C14 leaves, generating an acyl cation. The acyl cation is actually more stable than most other carbocations that we have encountered because it has a resonance structure that has the octet rule satisfied for all of the atoms ... 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

While the first two allow the isolation of the reaction products, the third does not. When a Lewis acid is mixed with an acyl halide, a donor-acceptor complex RCOX. .. MtX , or full ionisation by halide ion transfer, to give RCO MtX +i, or both, take place. The extent of ionisation depends mostly on the nature and strength of the Lewis acid used Thus, for example, acetyl halides react with stannic chloride and titanium tetrachloride to give mostly the coordination complex while with antimony pentachloride, pen-tafluoride and boron fluoride they give the conesponding acylium salts. Many of these... 

An efficient method for the formal abstraction of oxide from acyl ligands was developed in our laboratory 44). Oxalyl halides react directly with the pentacarbonylmetal acyl complexes of chromium, molybdenum, and tungsten to form the fra ,s-alkylidyne(halo)tetracarbonyl complexes [Eq. (5)]. Other suitable Lewis acids are COCI2, CI3COCI, CI3COCOCI, and... 

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