Ethers, aromatic, acylation preparation

Addition of tributylstannyl-lithium to crotonaldehyde and protection of the resulting alcohol with chloromethyl methyl ether gives the stannane (192), which reacts with both alkyl and aryl aldehydes RCHO to form specifically the t/rr o-hydroxy-enol ethers (193). These latter compounds have been used to prepare tra/i5-4,5-disubstituted butyrolactones by hydrolysis and subsequent oxidation. Palladium-catalysed carbonylation of RX in the presence of organotin species constitutes a useful synthesis of unsymmetrical ketones, and in the example reported this year RX is an arenediazonium salt. The reaction, which is basically an aromatic acylation, proceeds in good to excellent yield. Another Pd-catalysed reaction of aromatics, this time aryl bromides, is their reaction with acetonyltributyltin (194), prepared from methoxytributyltin and isopropenyl acetate, to give the arylacetones (195). ... 

The acetylation (with AC2O and HC104) and Vilsmeier formylation of sterically hindered phenols have been investigated. Substituted o-hydroxy-benzophenones have been prepared in 18-68% yields by treatment of the HMPT complexes of bromomagnesium phenoxides with aromatic aldehydes. " Phenolic O- vs. C-benzoylation has been studied, with particular reference to 3,4-disubstituted phenols. Previous work on the use of trifluoroacetic anhydride to promote aromatic acylation has been extended to the preparation of symmetrical and unsymmetrical benzophenones via reaction between the methyl and benzyl ethers of orcinol and the same ethers of phloroglucinolcarboxylic acid. " Other phenolic acylations include some chalcone syntheses and the acetylation and benzoylation of 2-hydroxy-4-methoxyacetophenone (peonol). ... 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

Catalytic hydrogenation is hardly ever used for this purpose since the reaction by-product - hydrogen chloride - poses some inconveniences in the experimental procedures. Most transformations of acyl chlorides to alcohols are effected by hydrides or complex hydrides. Addition of acyl chlorides to ethereal solutions of lithium aluminum hydride under gentle refluxing produced alcohols from aliphatic, aromatic and unsaturated acyl chlorides in 72-99% yields [5i]. The reaction is suitable even for the preparation of halogenated alcohols. Dichloroacetyl chloride was converted to dichloro-... 

A wide variety of substituents are tolerated. The group R can be alkyl, halogen, alkoxy, -amido, azi-domethyl, ester, aryl, aryloxy and aryloyl, and at least one ortho substituent is permissible with no loss in yield. TTie aromatic ring can also be 2-naphthyl, 9,10-dihydro-2-phenanthryl, 3-pyridyl, thiophen-2-yl or pyrrol-3-yl. The group R can be hydrogen, yl, acyl or acetic acid. Beyond Ae antiinflammatory targets, successful reaction substrates include the methyl ketones of a binaphthyl crown ether, a morphinane and a polyaromatic hydrocarbon. The preparation of ibuprofen methyl ester (38) is shown in equation (37) as a typical example. ... 

This valuable method for the conversion of an acid to its next higher homolog has been used to prepare aliphatic, aromatic, and heterocyclic acids. Excellent reviews of the reaction have been published. Diazomethane preparations are described elsewhere (method 500). The acyl chloride is added to an excess of diazomethane in ether or benzene solution. Diazoketones are usually not purified. 

The ideas for delocalization of nitrogen lone pair electron density into an aromatic or heteroaromatic system were pursued through reduction of acylated pyrazoles and imidazoles to aldehydes in high yield. 3,5-Dimethyl-A -acylpyrazoles are easy to prepare and afford 77-96% yields of aldehydes with LiAlH4 in diethyl ether at 0 Further examples of this reaction have appeared.Although these later publications commented unfavorably on the ability of LiAlH4 to reduce acyl imidazoles to aldehydes (low yields), other workers have demonstrated that yields of 60-80% could be attained at temperatures of -20 to 4-20 °C in diethyl ether.It was considered that the earlier failure may have been caused by the presence of impurities in the acyl imidazoles. The latter are easy to prepare from the parent carboxylic acid and A jV -carbonyldiimidazole. 

In the laboratory of K. Krohn, the total synthesis of phytoalexine (+)-lacinilene C methyl ether was completed. In order to prepare the core of the natural product, an intermolecular Friedel-Crafts acylation was carried out between succinic anhydride and an aromatic substrate, followed by an intramolecular acylation. After the first acylation, the 4-keto arylbutyric acid was reduced under Clemmensen reduction conditions (to activate the aromatic ring for the intramolecular acylation). 

Acylation and alkylation of aromatic compounds. Benzophenones are obtained in good yield when a mixture of a phenolic ether and an alkoxybenzoic acid is treated with PPA prepared by stirring a mixture of 8 parts by weight of P2O5 and 5 parts by volume of 90% orthophosphoric acid (dl. 75) at 85° for 30 min. (Ayers and Denney ). Thus veratrole and vanillic acid afforded4-hydroxy-3,3, 4 -trimethoxybenzophenone. 

The Friedel-Crafts acylation of aromatic ethers has attracted considerable interest in organic synthesis and in industrial chemistry because of the widespread application of the corresponding ketones as valuable intermediates in fine chemistry [39-43]. An example is the selective acetylation of 2-methoxynaphthalene at the carbon in position 6 owing to the great interest in 2-methoxy-6-acetylnaphthalene, an intermediate in the preparation of the anti-inflammatory drug (S)-Naproxen [44,45]. 

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