Carbonyl compounds Friedel-Crafts acylation

Preparation of the C-labelled compound 65 was accomplished in a manner analogous to Scheme 14. Friedel-Crafts acylation of 44 was conducted with [2- C]-chloroacetyl chloride under aluminum trichloride catalysis to give the radiolabelled intermediate 64 (48 mCi/mmol). The carbonyl group of 64 was reduced with triethylsilane and the resulting alkyl chloride was reacted with piperazine 40 to provide C-labelled ziprasidone (65). The HCI salt of 65 was formed resulting m a final compound with a specific activity of 9.6 mCi/mmol. 

In the present paper we have studied four acid catalyzed reaotions involving carbonyl compounds alkylation of benzene with formaldehyde, esterification of phenylacetic acid, Friedel-Crafts acylation by phenylpropanoyl chloride, and the cross aldolic condensation of acetophenone with benzaldehyde in the presence of three Hp zeolites with different framework Si-to-Al... 

Pd-catalyzed reactions, 9, 431 with pentaarylantimonys, 9, 430 with tetraorganylantimony(V) compounds, 9, 429 in C-heteroatom bond formations, 9, 432 in Friedel-Crafts acylation, 9, 433 Antimony donor ligands in iron carbonyls, 6, 57... 

On the other hand, rare-earth trifluoromethanesulfonates (rare earth triflate, RE(OTf)3) have been found to work efficiently as Lewis acids even in aqueous media or in the presence of amines [4], A catalytic amount of RE(OTf)3 enables several synthetically useful reactions, for example aldol, Michael, allylation, Mannich, Diels-Alder reactions, etc., to proceed. It has also been demonstrated that a small amount of RE(OTf)3 is enough to complete the reactions and that RE(OTf)3 can easily be recovered from the reaction mixture and can be reused. A key to accomplishing the catalytic processes was assumed to be the equilibrium between Lewis acids and Lewis bases, for example water, carbonyl compounds, and amines, etc. A similar equilibrium was expected between Lewis adds and aromatic ketones, and, thus, RE(OTf)3-catalyzed Friedel-Crafts acylation was investigated [5]. 

Clemmensen Reduction (Review) The Clemmensen reduction commonly converts acylbenzenes (from Friedel-Crafts acylation, Section 17-1 IB) to alkylbenzenes, but it also works with other ketones and aldehydes that are not sensitive to acid. The carbonyl compound is heated with an excess of amalgamated zinc (zinc treated with mercury) and hydrochloric acid. The actual reduction occurs by a complex mechanism on the surface of the zinc. 

Nafion is another choice of polymer support for Sc-based Lewis acids. Nafion-Sc catalyst is readily prepared by treatment of Nafion with ScCb 6H2O in acetonitrile under reflux [116]. Nafion-Sc catalyst has been found to be effective in several synthetic reactions including allylation of carbonyl compounds with tetraallyltin, Diels-Alder reaction, Friedel-Crafts acylation, and imino Diels-Alder reactions. The use of Nafion-Sc in flow systems has also been tested. 

Friedel-Crafts acylation is one of the most important methods of preparing ketones in which the carbonyl group is attached to an aromatic ring. Once formed, these ketones may be converted into secondary alcohols by reduction, into tertiary alcohols by reaction with Grignard reagents, and into many other important classes of compounds, as we shall see. 

Cyclopropanation of styrene using alkenylbismuthonium salt 300 Deprotection of 5,5-acetals to carbonyl compounds 391 Diothioacetalization of carbonyl compounds with thiols 427 Friedel-Crafts acylation with Bi(OTf>3 as catalyst 408 Glycosylation of 1-glycosyl dimethyl phosphite with alcohols 425 Oxidation of... 

This alternative to the Friedel-Crafts reaction, extensively developed by Stille and coworkers, is particularly important, since the reaction conditions are essentially neutral, and so provides a method for acylation of compounds containing an acid-sensitive functionality which would preclude the use of the Friedel-Crafts reaction. Reaction temperatures are often below 100 C, and high (1000-fold) turnovers of the catalyst have been achieved. Solvents employed include chloroform, toluene, and, on occasions, HMPA. Some reactions have been carried out under an atmosphere of carbon monoxide to prevent excessive decarbonylation of the acyl palladium intermediate. Indeed, carbonylative coupling of alkenylstannanes with allyl halides in the presence of carbon monoxide ca. 3 atm or greater 1 atm =101 kPa) offers an alternative to the Friedel-Crafts acylation, ketones being formed by the reaction of the stannane with the acyl species formed by carbon monoxide insertion into the allyl palladium intermediate. ... 

Problems have been observed when attempting to carry out reactions with either diacid chlorides or half-ester half-acid chlorides when the two carbonyl functions are separated by either two or three carbon atoms. Rearrangement reactions occur with those compounds and so Friedel-Crafts acylation reactions may yield mixtures of products. Optically active methyl 3-methylglutarate was shown to racemize easily Suggested explanations of these effects include the involvement of alkyl diacyloxonium and acyl-oxy-alkoxycarbenium ions. NMR studies have shown that the half methyl ester-half acid chloride from phthalic acid forms the acyloxy-alkoxycarbenium ion very easilyj and that the related ions derived from succinic and glutaric acids can also be generated under stable ion conditions. ... 

Polyalkylation, an advantage here, can be a nuisance with Friedel-Crafts alkylations as can the rearrangement of primary alkyl halides. Thus, the alkyl halide (8) gives a mixture of (9> and (10) with benzene and if we want to make compound (11) we must use the Friedel-Crafts acylation, which suffers from neither of these disadvantages, and then reduce the carbonyl group (see Chapter 24). 

The Friedel-Crafts reaction was one of the first to be attempted in ionic liquids (for typical examples, see Scheme 20. Friedel-Crafts acylation, which allows easy functionalization of aromatic compounds to ketones, is of significant commercial importance. The electrophilic substitution with an acylating agent is catalyzed by an acid, typically AICI3. Since this catalyst can form a stable adduct with the carbonyl of the product, an excess of AICI3 is required, which gives rise to a copious amount of inorganic waste. 

Friedel-Crafts reactions are conversions that form one additional carbon-carbon bond with an aromatic compound, catalysed by strong Lewis acids. Inportant reactions are Friedel-Crafts alkylation, Friedel-Crafts acylation and carbonylation. 

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