Ketones formation from acyl halide

The primary and secondary alcohol functionalities have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undeigoes most of the typical alcohol reactions, such as reaction with a free acid, acyl halide, or acid anhydride to form an ester reaction with alkali metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial application of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

Electrogenerated nickel(O) bipyridine complexes serve as catalysts for a number of syntheses (a) formation of ketones from acyl halides and either alkyl or aryl halides [319], (b) production of, )/-unsaturated esters via coupling of a -haloesters with aryl or vinyl halides [320], (c) coupling of a-chloroesters or a-chloronitriles with carbonyl... 

In spite of the impression that may have been gained from the earlier part of this chapter, reactions involving the use of aluminum halides, and especially aluminum chloride, constitute the majority of Friedel-Crafts acylation reactions. The interaction of the three components, i.e. the acyl halide, the aromatic substrate and the aluminum halide, results in the formation of hydrogen halide and a complex of the aromatic ketone with aluminum halide from which the ketone is literated after hydrolysis. There are a number of sequences in which the three components can be mixed. 

The prior formation of the reactive species, for example by mixing an acyl halide with aluminum halide, which is then allowed to react with the aromatic substrate, is known as the Perrier procedure. It is normally carried out in a solvent, such as carbon disulfide or dichloromethane, that allows the 1 1 complex to be separated from excess aluminum halide. The main advantage of this method is the solubility of the addition complex in the solvent, but it is frequently observed that the complex of the acylation product and catalyst is insoluble in carbon disulfide and may be separated from soluble by-products. The prior formation of acylium salts mentioned earlier " ° 2 and their use in the preparation of aromatic ketones can be regarded as a modification of the Perrier procedure. 

The alkylation of aromatic compounds using alkyl halides and a Lewis acid only requires a small amount of catalyst. Because Lewis acids form complexes with carbonyl compounds, the Lewis acids are effectively removed from the reagent system to the extent that product is formed. Although an equilibrium exists between the product complex and free Lewis acid, there is an apparent inhibition of formation of the acylating species. The net effect is that the amount of the ketone that is formed is normally proportional to the molar quantity of catalyst added. In reactions using acyl halides, completion occurs when slightly more than 1 mol of catalyst is used. When using a carboxylic anhydride, an excess over 2 mol of catalyst will usually be required because the other product, a carboxylic acid, will also complex with the Lewis acid. 

Ketones are formed from pyridylzinc halides on acylation with acid chlorides or anhydrides in reactions with benzoyl chloride or benzoic anhydride, pyridyl ketones (307) are formed in moderate yields. Reactions with 3-iodoquinoline gave the 3-benzoyl derivative 308. Organostannanes may be a better choice for ketone formation (see above). 

Equation 28 represents the formation of oxoalkyl phosphonic acid esters (488 R = OR) or phosphinic esters (488 R = alkyl or aryl) from phosphite or phosphonite esters and appropriate halogen-containing ketones ( > 1) or acyl halides (n = 0), and supplements the formation of the phosphonoylated or phosphinoylated alkanoic acids through reactions 21 and 22 in the previous section. 

G. Perrier [C.r. 116, 1300 (1893) Ber. 33, 815 (1900)] found that in the Friedel-Crafts reaction for the formation of ketones from hydrocarbons and acyl halides, the acyl halides and also the ketones formed in the reaction formed addition compounds with the aluminium halides which he was able to isolate ... 

This reaction was first reported by Nenitzescu in 1931. It is the formation of an a,p-unsaturated ketone directly by aluminum chloride-promoted acylation of alkenes with acyl halides. Therefore, it is known as the Darzens-Nenitzescu reaction (or Nenitzescu reductive acylation), or Nenitzescu acylation. Under such reaction conditions, Nenitzescu prepared 2-butenyl methyl ketone from acetyl chloride and 1-butene and dimethylacetylcyclohex-ene from acetyl chloride and cyclooctene. However, in the presence of benzene or hexane, the saturated ketones are often resolved, as supported by the preparation of 4-phenyl cyclohexyl methyl ketone from the reaction of cyclohexene and acetyl chloride in benzene, and the synthesis of 3- or 4-methylcyclohexyl methyl ketone by refluxing the mixture of cycloheptene and acetyl chloride in cyclohexane or isopentane. This is probably caused by the intermolecular hydrogen transfer from the solvent. In addition, owing to its intrinsic strain, cyclopropyl group reacts in a manner similar to an oleflnic functionality so that it can be readily acylated. It should be pointed out that under various reaction conditions, the Darzens-Nenitzescu reaction is often complicated by the formation of -halo ketones, 3,)/-enones, or /3-acyloxy ketones. This complication can be overcome by an aluminum chloride-promoted acylation with vinyl mercuric chloride, resulting in a high purity of stereochemistry. ... 

Finally in this Section on carbon-carbon bond formation, we report on the preparation of ketones from 5-2-pyridyl thiolates or acyl chlorides. S-2-Pyridyl thiolates react in excellent yields with diaikylcuprates to afford ketones when the reaction is carried out in a nitrogen atmosphere. However, in the presence of oxygen, esters are produced. Acyl halides, on the other hand, react with stoicheiometric amounts of organomanganous reagents to give ketones under very mild conditions and in the presence of various other potentially reactive functional groups (Scheme 31). ... 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

Acid Amides can be produced by acylating ammonia with esters, acid anhydrides, or the acids themselves (above 100 °C) an important product is formamide from methyl formate. Alternatively acid amides can be synthesized by reacting acid halides with ammonia. Catalytic hydrogenation converts the acid amides to primary amines. Ammonia and aldehydes or ketones are the basis for different stable products. With formaldehyde hexamethylenetetramine (urotropine) is obtained with acetaldehyde, ammono acetaldehyde with benzaldehyde, hydrobenzamide with ethylene and propylene oxides, aqueous ammonia reacts to form ethanol- or propanolamine. 

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