Nenitzescu acylation

DARZENS - NENITZESCU Acylation Zn-Cu catalyzed Fnedel-Crafts type acylation of oleTms with acyl chlorides... 

OAKIN Oxidation 84 DAKIN WEST Acylation 84 DANHEISER Annulation 85 DANISHEFSKY Sitytoxydenes 66 DARAPSKI Ammoacid synthesis 87 DARZENS-NENITZESCU Acylation 87 DAR2fENS Epoxide synthesis 88 DAVIDSON Oxazola synthesa 89 OELEPINEAMehydeoxidalion 89 DAVIS Oxidizing reagent 90 Decker 127... 

DAKIN Oxidation 84 DAKIN - WEST Acylation 84 OANHEISER Annulation 85 DANISHEFSKY Silyloxydlenes 86 DARAPSKI Amtroaeid synthesis 87 DARZENS - NENITZESCU Acylation 87 DARZENS Epoxide synthesis 88 DAVIDSON Oxszole synthesis 89 DELEPINE Aldehyde oxidation 69 DAVIS Oxidzstg reagent 90 Decker 127... 

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. ... 

Olefins and cycloolefins give unsaturated ketones with acyl hahdes (the Nenitzescu reaction) (170). Saturated chloroketones are formed as intermediates followed by elimination of HCl. Similar products may be obtained by using acid... 

The reaction mechanism has been discussed by several earlier authors more recently, Elderfleld and King proposed that the onol form (79) of the ketone underwent acylation, whereas Balaban and Nenitzescu assumed that the )3,y-unsaturated isomer (80) of the ketone was acylated. Support for the latter view is given by the high concentration of the j8,y-unsaturated isomer (80) in equilibrium with the a,j8-isomer (78). In the case of mesityl... 

Tetramethylethylene behaves in the AlCIs-catalyzed diacetylation as 155 (Aik = iso-Pr)affording2,6-dimethyl-4-isopropylpyrylium. Although the olefin acylation had been investigated by many chemists beginning with Kondakov (cf. Nenitzescu and Balaban and Balaban and Nenitzescu ), the formation of pyrylium salts had escaped notice because they are water-soluble and had been discarded after hydrolysis of the reaction mixture. Only in the study of the ZnCla-catalyzed acetylation of diisobutene had a crystalline product been observed by Byrns and Doumani its reaction... 

Balaban, Mateescu, and Nenitzescu, diacylatcd 1,3-diphenyl-2-propanone (213, R =Ph) to 3,5-diphcnyl-4-pyrones (215), the former with acetic and polyphosphorio acids, the latter with acetyl chloride and aluminum chloride. This leaction follows the usual course of ketone acylation, and has been studied in detail several... 

Of the acylation of aliphatics, the acylation of alkenes pioneered by Nenitzescu was mainly explored, because the resulting unsaturated ketones are intermediates in synthesis. This acylation of alkenes, however, has its difficulties. First, the product unsaturated ketones, which are reactive compounds themselves, can undergo various further transformations, such as addition, elimination, and isomerization, often resulting in complex product mixtures. The acylation of alkenes, therefore, is less selective and often yields products other than expected by a simple substitution of one of the vinylic hydrogens. 

Extensions of the Nenitzescu synthesis to A-acyl- or JV-sulfonyl-quinoneimines affords 5-aminoindoles (equation 110) (58JA3291). 

Acyl cations are formed in the reversible addition of carbon monoxide to carbonium ions (Balaban and Nenitzescu, 1959 Koch and Haaf, 1958a, b 1961). The formation of the acetyl cation 193 from carbon monoxide and methane in SbF6 has been directly observed by XH n.m.r. 

Friedel-Crafts acylation of alkenes (Daizens-Nenitzescu reaction ) with unsaturated acylium ions generated from acid halides and Lewis acids constitutes a general synthesis of divinyl ketones. 

Kucklaender, U. Mechanism of the nenitzescu reaction. III. Acyl migrations. I. Tetrahedron 1975, 31,1631-1639. 

Nenitzescu indole synthesis. Hydrogenative acylation of cycloolefins with acid chlorides in the presence of aluminum chloride with five- and six-membered rings, no change in ring size occurs, but with seven-membered rings, rearrangement takes place with formation of a cyclohexane derivative. 

An unusual dependence of the structure of the reaction product on the acylating agent (catalyst and acyl group) was observed by Balaban and Nenitzescu in the diaoylation of olefins 195, where R = Me (2-methyl-2-butene ) or R = Ph (2-methylpropenyl-benzene ) strong catalysts like AICI3 or SbCls promote the formation of the 2,4,6-trisubstituted compound 197, whereas weaker... 

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