Acyl halide or anhydride

Friedel-Crafts acylation reactions usually involve the interaction of an aromatic compound with an acyl halide or anhydride in the presence of a catalyst, to form a carbon-carbon bond [74, 75]. As the product of an acylation reaction is less reactive than its starting material, monoacylation usually occurs. The catalyst in the reaction is not a true catalyst, as it is often (but not always) required in stoichiometric quantities. For Friedel-Crafts acylation reactions in chloroaluminate(III) ionic liquids or molten salts, the ketone product of an acylation reaction forms a strong complex with the ionic liquid, and separation of the product from the ionic liquid can be extremely difficult. The products are usually isolated by quenching the ionic liquid in water. Current research is moving towards finding genuine catalysts for this reaction, some of which are described in this section. 

Diacyl peroxides and acyl hydroperoxides can similarly be prepared from acyl halides or anhydrides... 

Compounds containing Si—O—Pb bonds may interact explosively with oxygen at about 140°C, or with aluminium chlorides, acyl halides or anhydrides. 

Introduction of an acyl group onto an aromatic substrate by treating the substrate with an acyl halide or anhydride in the presence of a Lewis acid. 

The equilibrium limits the practical applicability of this reaction, and other methods would normally be employed if one were working with uncommon or expensive reagents that could not be used in excess. Esters are actually more conveniently prepared using the more reactive acyl halides or anhydrides, i.e. derivatives with better leaving groups. 

Esters also react smoothly with amines, which is a useful reaction if the corresponding acyl halides or anhydrides are not easily available. The reaction proceeds through the anticipated tetrahedral anionic intermediate. There are two possible leaving groups... 

Acyl halides and anhydrides are important reactants for the formation of other carbonyl compounds, but you don t need to take up valuable brain space with information about any other acyl halide or anhydride reactions at this time. 

Treatment of pyridines with acyl halides or anhydrides gives AT-acylpyridinium salts (76). They are isolable, though highly reactive, and are postulated as intermediates in acylations in pyridine solution (Scheme 72). They are rapidly hydrolyzed by moisture. The benzo analogues of pyridine behave similarly. 

The formation of amides can be accomplished by dehydration of the ammonium salts of salicylic acid. The more common method for amines is the reaction of the ester, acyl halide, or anhydride with an amine or ammonia. Each step is fast and essentially irreversible. 

Tertiary alkyl azides can be prepared by stirring tertiary alkyl chlorides with NaN3 and ZnCl2 in CS or by treating tertiary alcohols with NaN3 and CF3COOH952 or with HN3 and TiCl4953 or BF3.954 Acyl azides, which can be used in the Curtius reaction (8-15), can be similarly prepared from acyl halides or anhydrides.955... 

The intermolecular N-acylation of amides generally requires treatment of the latter with strong acylating agents, such as ketenes, acyl halides, or anhydrides, in the presence of a base. Few examples of such N-acylations have been reported (Entries 1-3, Table 13.20 see also saftey-catch linkers, Section 3.1.2.3). 

However, acyl halides and anhydrides usually hydrolyze rapidly without the aid of an acidic or basic catalyst, when in solution. It is important to recognize that an insoluble acyl halide or anhydride often reacts slowly with water. 

Enolate anions of esters, such as ethyl 3-oxobutanoate or diethyl propanedioate, react with aeyl halides or anhydrides to give acylation products. These reactions are carried out best using sodium hydride instead of sodium ethoxide for production of the enol salt, because then no alcohol is liberated to react with the acyl halide or anhydride ... 

Given the IUPAC name of a carboxylic acid, salt, ester, amide, acyl halide, or anhydride, write its structural formula, and given the structure, write the name. 

Write the equation for the reaction of a given acyl halide or anhydride with a given nucleophile (especially with water, an alcohol, or ammonia). 

Peptide synthesis requires the formation of amide bonds between the proper amino acids in the proper sequence. With simple acids and amines, we would form an amide bond simply by converting the acid to an activated derivative (such as an acyl halide or anhydride) and adding the amine. 

These ligand have already been met (Chapter 3), including the three key synthetic routes migratory insertion of o-organyl/carbonyl complexes, electrophilic attack at electron rich metals by acyl halides or anhydrides and nucleophilic attack at coordinated CO (Figure 4.12). 

Many organic compounds react with carboxylic acids, acyl halides, or anhydrides in the presence of certain metallic halides, metallic oxides, iodine, or inorganic acids to form carbonyl compounds. The reaction is generally applicable to aromatic hydrocarbons. Benzene, alkylbenzenes, biphenyl, fluorene, naphthalene, anthracene, acenaphthene, phenanthrene, higher aromatic ring systems, and many derivatives undergo the reaction. 

Only a few oxazoloquinones are known. 2-Methylnaphtho[2,3-d]oxazole-4,9-dione (207) was obtained from 2-acylamino-3-alkylamino-l,4-naphtho-quinone in the presence of concentrated sulfuric acid (69T2427). Similarly, derivatives of 208 were obtained from 2,5-bis(acetylamino)-3,6-dihydroxy-1,4-benzoquinones and acyl halide or anhydride (64ZOB3037). The five-membered ring is easily cleaved in warm dilute acid or base (64ZOB3037). 

As an alternative to using dialkyl carbonates [(R0)2C=0] for a-acylation of ketones, the reaction of ketone enolates with alkyl cyanoformates (NC-CO2R, Mander s reagent) provides P-keto esters in good yields. Reaction of lithium enolates with acyl halides or anhydrides, however, usually leads to mixtures of O- and C-acylated... 

When an aryl hydrocarbon is reacted with an acyl halide or anhydride, hydrogen chloride is liberated and the acyl group unites with the nuclear carbon ... 

The recent application of sonochemistry to the reaction of aroyl chlorides with KCN in acetonitrile is very interesting. Aromatic acyl cyanides could also be prepared by reaction of aroyl chlorides with KCN impregnated onto XAD resins. A number of patents describe the results of the two-phase interactions of alkali metal cyanides with a solution of acyl halides or anhydrides in aprotic organic solvents, which in general run in the presence of Cu salts. ... 

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. 

Friedel-Crafts acylation Synthesis of aromatic ketones using acyl halides or anhydrides. 176... 

The basic media exceptions can be easily understood if we invoke HSAB theory and realize that the kinetic and thermodynamic products are different. As L becomes a poorer donor, the partial plus on the acyl carbon increases, making it harder. Acylation on the heteroatom of the allylic source is fast for acyl halides and anhydrides where the acyl carbon is harder (greater partial plus) than the acyl carbon of esters. If the reaction is under kinetic control (allylic source added to an excess of acyl halide or anhydride), the Z-acylated product is formed however, if equilibration occurs (excess of allylic source), the product will be the C-acylated, thermodynamic product. 

For acyl halides or anhydrides which do not afford ketenes in the presence of base (such as perfiuoroacyi halides), however, the a-acylmethylenephosphoranes can be prepared directly in one step from the phosphonium salts by using two equivalents of base by the present procedure (Table I).2 Both tetrahydrofuran and methylene chloride have been used as solvents and in the case of the title compound, tetrahydrofuran provides the best results. Good yields of the phosphoranes are generally obtained when is an electron-withdrawing group such as ester or nitrile. The yields of phosphoranes obtained for the thiomethyl or phenyl cases can be... 

Very few Friedel-Crafts methods equivalent to the acylation with acyl halides or anhydrides are available to make formylation, undoubtly because halides and anhydrides of formic acids are very unstable. 

---