Carboxylic acids acyl substitution

Alternative methodologies for the indirect reduction of carboxylic derivatives employ as intermediates 2-substituted 1,3-benzoxathiolium tetrafluoborates (prepared from carboxylic acids, acyl chlorides, anhydrides, or esters) and dihydro-1,3-... 

Variations of this reaction have been applied over the years, typically involving the condensation of 2-aminothiophenols with substituted carboxylic acids, acyl chlorides, aldehydes, and nitriles. Initially, the reaction involves the formation of an imine that cyclizes spontaneously and then oxidation to form benzothiazole. An application of this chemistry has been showcased in the synthesis of 2-(4-aminophenyl)benzothiazoles and the evaluation of their in vitro and in vivo activities against breast cancer cell lines, with compound a exhibiting the most potent growth inhibition. Unfortunately, there are limitations due to the difficulties met during the syntheses of readily oxidizable o-aminothiophenol-bearing substituents. 

The negatively charged oxygen is a powerful electron donor to the carbonyl group. Resonance in carboxylate anions is more effective than resonance in carboxylic acids, acyl chlorides, anhydrides, esters, and amides. Carboxylate ions do not undergo nucleophilic acyl substitution. 

The result of the reaction is that the rupture of carboxylic acid acyl-oxygen bond occurs, and the hydroxy of acid is replaced by alkoxy, which is a nucleophilic substitution process of carboxylic adds. 

This is the most useful method of amide formation (equation 2). An activated carboxylic acid acylates aiiunonia, primary or secondary amines by a formal Sn2 substitution of leaving group X. The reactivity of the acylating reagent depend on the acidity of HX, and dierefore the order of reactivity is RCOHal > (RC0)20 = RCONs > RCChR > RCONH2 > RCOR. Moreover, the reaction rate increases with higher nucleophilicity of the amine as well as base or acid catalysis. 

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... 

CARBOXYLIC ACID DERIVATIVES NUCLEOPHILIC ACYL SUBSTITUTION... 

Carboxylic Acid Derivatives Nucleophilic Acyl Substitution... 

Both stages involve more than one step and these steps differ in detail among the various carboxylic acid derivatives and for different reaction conditions This chapter is organized to place the various nucleophilic acyl substitutions into a common mechanis tic framework and to point out the ways m which individual classes differ from the rest... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

---