Carboxylic acids heteroaromatics acylation

In a direct route from carboxylic acids to acyl azides diphenyl phosphorazidate is used probably the reaction passes through a cyclic transition state (Scheme 41). With aromatic and heteroaromatic educts, yields as high as 75% may be obtained. If aliphatic acids are treated under the same conditions, the corresponding azides are, however, immediately transformed into urethanes via isocyanates. Aroyl azides can also be obtained in excellent yields by reaction of carboxylic acids with NaNa and phenyl di-chlorophosphate in the presence of tetrabutylammonium bromide or pyridine (Scheme 41). ... 

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. 

Synthetically useful ozonolyses of heteroaromatic systems include the preparation of pyridine derivatives from quinolines (eq 22), the preparation of versatile A-acyl amides by the ozono-lysis of imidazoles (eq 23), and the unmasking of a latent carboxylic acid function by theozonolysisof a furan system (eq 24). ... 

Further acylations of unsaturated fatty compounds were carried out with aromatic and heteroaromatic carboxylic acid chlorides such as benzoyl chloride and thiophene-2-carboxylic acid chloride. The benzoylation of 10-undecenoic acid [2a], induced by EtAlCl2, was already complete after a reaction time of 30 min (Scheme 6). Product [14], a phenyl allyl ketone, was obtained as a mixture of ( )/(Z)-stereoisomers in an isolated yield of 49%. The reaction occurred regioselectively at C-11 of the molecule chain. 

The alkylaluminum halide-induced Friedel-Crafts acylation is a very general and synthetically useful reaction that allows the functionalization of unsaturated fatty compounds. Acylations were carried out with different acylating agents such as acyl chlorides, dicarboxylic acid dichlorides, cyclic anhydrides, unsaturated acyl chlorides, and aromatic and heteroaromatic carboxylic acid chlorides, yielding a large... 

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... 

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