Ketone from acyl chlorides

CO 1 0 c 1 X r Nucleophilic substitution and conjugate addition to unsaturated ketones ketones from acyl chlorides b,c... 

Scheme 8.13. Synthesis of Ketones from Acyl Chlorides and Stannanes...

O O II R 2CuLi II RCC1 — RCR Section 19.10 Preparation of ketones from acyl chlorides. 

Ketones from acyl chlorides. Either dialkylirons or lithium trialkylferrates can be employed to react with acyl chlorides to furnish ketones. These reagents are prepared in situ from FeClj by reduction to FeCh and reaction with RLi or RMgX. Actually RMgX + FeCIi (cat.) is more convenient to use. 

Ketones can also be prepared from acyl chlorides by reaction at low temperature using an excess of acyl chloride. Tetrahydrofuran is the preferred solvent.91 The reaction conditions must be carefully controlled to prevent formation of tertiary alcohol by addition of a Grignard reagent to the ketone as it is formed. 

Pyridinethiolate esters, which are easily prepared from acyl chlorides, also react with Grignard reagents to give ketones (see Entry 6 in Scheme 7.3).92 /V-Mclhoxy-/V-mclhylamides are also converted to ketones by Grignard reagents (see Entries 17 and 18). 

Symmetrical ketones are sometimes prepared from acyl chlorides by way of diketenes and /3-keto acids/ ... 

The method has been adapted to the formation of l)fs-diazoacetylalkanes from dibasic acid chlorides. Diazo ketones have been obtained from acyl chlorides containing a /Sj y-double bond, an ester group, and certain heterocyclic and aryl nuclei having alkyl, methoxyl, and nitro substituents. On the other hand, functional groups such as phenolic hydroxyl, arylamino, aldehyde, active methylene, and a,/S-unsaturated linkages may interfere. The method is ideal for application to complex molecules. 

Methyl ketonesfrom carboxylic acid chlorides (3,112). Posner e/n/. report that the synthesis of ketones from acid chlorides and organocopper reagents is applicable to acid chlorides containing iodo, cyano, acyl, and carboalkoxy groups. The reaction, however,... 

O. R. 1-9, C. R. Hauser and B. E. Hudson, Jr., The Acctoacetic Ester Condensation and Related Reactions lV-4, S. M. McElvain, The Acyloins 11-4, W. S. Johnson, The Formation of Cyclic Ketones by Intramolecular Acylation VIII-2, D. A. Shirley, The Synthesis of Ketones from Acid Chlorides and Organometallic Compounds of Magnesium, Zinc, and Cadmium. ... 

The synthesis of ketones from acid chlorides has been demonstrated with several organometallic reagents (see Sections 1.13.3,1.13.4 and 1.13.5) however, the acylation of organolithiums often leads to substantid amounts of overaddition product. Initially, acid chlorides appear to be a poor choice for... 

Another variation of this oxazole synthesis consists in the utilization of diesters of enediols (diacyl derivatives of the enol tautomer of a-hydroxy ketones). In the aliphatic series, enediol esters can directly be prepared from acyl chlorides and metallic sodium in ether containing a trace of water. When the esters react with ammonium acetate, symmetrical... 

The aromatic ketones are most conveniently prepared by means of the Friedel and Crafts reaction from acyl chlorides and aromatic hydrocarbons —... 

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. ... 

Ketones may be prepared in high yield from acyl chlorides and organomanganous iodides since these organometallic reagents attack ketones very slowly. Aldehydes are of intermediate reactivity, whereas esters are inert.The reaction of an a-monosubstituted acetyl chloride with Fe2(CO)9 is a mild general means of preparing symmetrical dialkyl ketones in fairly good yield (Scheme 8). ... 

The HCl generated in this reaction destroys one equivalent of diazomethane. This can be avoided by including a base, such as triethylamine, to neutralize the acid. " Cyclic a-diazoketones, which are not available from acyl chlorides, can be prepared by reaction of an enolate equivalent with a sulfonyl azide. This reaction is called diazo transfer Various arenesulfonyl azides and methanesulfonyl azide are used most frequently. Several types of compounds can act as the carbon nucleophile. These include the anion of the hydroxymethylene derivative of the ketone or the dialkylaminomethylene derivative of... 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

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