Carboxylic acids aromatic acylation

In the Friedel-Crafts acylation, carboxylic acid chlorides and carboxylic acid anhydrides are activated with stoichiometric amounts of A1C13 (Section 5.2.7). However, this activation is only possible in the presence of very weak nucleophiles such as aromatic compounds. Stronger nucleophiles would react with the A1C13 instead of the carboxylic acid derivative. If one wants to acylate such stronger nucleophiles—for example, alcohols or amines—with car-... 

Table 2.1 Acylation of (hetero)aromatics with carboxylic acids promoted by TFAA-phosphoric acid mixture...

Trifluoroacetic and triflic anhydrides can be utilized to promote acylation of aromatics with carboxylic acids without any metal catalyst. Thus, the trifluoroacetic anhydride (TFAA)-promoted cycloacylation of conveniently functionalized carboxylic acids prepared from Baylis-Hillman adducts... 

Cation-exchanged montmorillonites are utilized by Geneste et al. [67, 68] in the acylation of aromatics with carboxylic acids. Best results are achieved with AP -exchanged montmorillonite (60% yield of the ortho, meta, and para isomers). The influence of the chain length of different carboxylic acids on the yield of acylation appears to be similar on clays and on zeolites [35]. Indeed, acylation of toluene with CHj(CH2) COOH over Al -montmoriUonite gives 12% yield for n= 1,45% forn = 6, and 80% for = 14. 

The regioselective acylation of aromatic ethers with carboxylic acids (aromatic ether/carboxylic acid ratio =1) can be pafonned with an equimolecular mixture of trifluoroacetic anhydride adsorbed on the surface of alumina without any solvent [77]. The process can be applied, with nearly quantitative yields, to anisole and the three isomeric dimethoxybenzenes by using carboxylic acids. The authors outline that in the case of anisole, the acylation selectively occurs at the para position to the methoxy group. The reaction requires a large amount of alumina and trifluoroacetic anhydride, and consequently, it can only be appUed at the laboratory scale. The intervention of a mixed carboxyhc acidArifluoroacetic acid mixed anhydride intermediate is presumed. 

Depending on the respective reaction partner, acetic acid esters can react either as C-H acidic compounds or as acylating agents. Both are illustrated by the self-condensation of ethyl [ 1 acetate in the presence of 0.5 equivalent of sodium ethoxide or triphenymethyl sodium to give ethyl [1,3- C2]acetoacetate (Claisen condensation). In the first case, however, because of the relatively low radiochemical yields (40-45%) obtained by this procedure, it is of minor importance for the preparation of labeled ethyl acetoacetate. The deprotonation of alkyl acetates with LiHMDS followed by acylation with unlabeled or labeled acyl halides to labeled give /3-keto esters is discussed in Section 6.4. Claisen condensation of alkyl [ CJacetates with esters lacking a-hydrogens (i.e. ethyl formate, diethyl oxalate, aromatic/heteroaromatic carboxylic acid esters) proceed unidirectionally and are valuable pathways in the synthesis of ethyl [ C]formyl acetate (521. diethyl [ C]-oxaloacetate (53) and ethyl 3-oxo-3-pyrid-3-yl[2- C]acetate (54). The last example... 

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Fnedel-Crafts acylation In the presence of alumi num chloride acyl chlorides and carboxylic acid an hydrides acylate the aromatic ring of phenols... 

Acylatmg agents such as acyl chlorides and carboxylic acid anhydrides can react with phenols either at the aromatic ring (C acylation) or at the hydroxyl oxygen (O acylation)... 

Friedel-Crafts acylation (Section 12 7) An electrophilic aro matic substitution in which an aromatic compound reacts with an acyl chloride or a carboxylic acid anhydride in the presence of aluminum chlonde An acyl group becomes bonded to the nng... 

An interesting class ot covalent Inflates are vin l and ar>/ or heteroaryl Inflates Vinyl inflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyridine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

Just as an aromatic ring is alkylated by reaction with an alkyl chloride, it is acylated by reaction with a carboxylic acid chloride, RCOC1, in the presence of AICI3. That is, an acyl group (-COR pronounced a-sil) is substituted onto the aromatic ring. For example, reaction of benzene with acetyl chloride yields the ketone, acetophenone. 

Dimsyl anion 88 reacts with esters of aromatic carboxylic acids and aliphatic acids which do not have a readily transferable proton, to give /5-ketosulfoxides114,133,138-141. There are not many cases in which acyl chlorides were used142,143. However, the reaction... 

Diaryl sulfones can be formed by treatment of aromatic compounds with aryl sulfonyl chlorides and a Friedel-Crafts catalyst. This reaction is analogous to Friedel-Crafts acylation with carboxylic acid halides (11-14). In a better procedure, the aromatic compound is treated with an aryl sulfonic acid and P2O5 in polypho-sphoric acid. Still another method uses an arylsulfonic trifluoromethanesulfonic anhydride (ArS020S02CF3) (generated in situ from ArS02Br and CF3S03Ag) without a catalyst. ... 

Salts of aliphatic or aromatic carboxylic acids can be converted to the corresponding nitriles by heating with BrCN or CICN. Despite appearances, this is not a substitution reaction. When R COO was used, the label appeared in the nitrile, not in the C02, and optical activity in R was retained. The acyl isocyanate... 

The reduction of aromatic carboxylic acids to the corresponding aldehydes under aerobic conditions is of interest in biotechnology, since the oxidoreductase from Nocardia sp. is able to accept a range of substituted benzoic acids, naphthoic acids, and a few heterocyclic carboxylic acids (Li and Rosazza 1997). The reaction involves formation of an acyl-AMP intermediate by reaction of the carboxylic acid with ATP NADPH then reduces this to the aldehyde (Li and Rosazza 1998 He et al. 2004). A comparable reaction for aromatic carboxylates has been demonstrated in Neurospora crassa (Gross 1972). 

The classes of compounds that are conveniently considered together as derivatives of carboxylic acids include the acyl chlorides, carboxylic acid anhydrides, esters, and amides. In the case of simple aliphatic and aromatic acids, synthetic transformations... 

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

In method B, iV-trifluoroacetylimidazole and carboxylic acids are the acylating reagents. This method is also thought to proceed via a carboxylic trifluoroacetic anhydride. This second system is a very convenient reagent for obtaining aromatic ketones because of the use of free carboxylic acids [97]... 

A related convenient and mild method for the preparation of aliphatic and aromatic aldehydes in high yield from carboxylic acids is the reductive cleavage of l-acyl-3-methylimidazole-2-thiones by tributylstannane. 

Acylation The reagent catalyses the arylation of activated aromatic compounds by reaction with carboxylic acids. Thus methyl phenyl ether can be acylated with acetic acid in presence of trifluoroacetic anhydride in good yields. 

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