Carboxylic acid anhydride variation

A common synthetic method is that of equation (9), where X = MeC02,168 PhS03,169 NO3170 or C104,171 and relies on the precipitation of silver chloride. A variation of this method is the synthesis of the ring complex (5), by the reaction (10).172 In other cases, the synthesis may involve mercury(II) salts or sodium salts (equations 11 and 12).173,174 Another useful synthetic method involves reaction of alkyl- or aryl-gold(I) complexes with carboxylic acids or acid anhydrides (equations 13-15).176,177... 

Amides. Amides can be prepared in one step from a carboxylic acid and an amine by reaction with 1 (1 equiv.) and triethylamine (2 equiv.) in CH2C12 at 25°. Presumably a mixed anhydride is first formed, which reacts subsequently with the amine. A variation involves conversion of the carboxylic acid into the carboxylic anhydride by reaction with 1 (0.5 equiv.) and triethylamine subsequent addition of the amine results in the formation of the amide. Yields are generally greater than... 

The zinc procedure has been extended to CF3CCI3 to form 2 chloro-l,l,l,-trifluoro-2-alkenes (84 equation 19). and a-fluoro-a,p-unsaturated carboxylic acid methyl esters (87) with methyl dichlorofluo-roacetate (8jS equation 20). Both of these transformations are carried out with zinc and acetic anhydride. Several variations of this reaction have appeared in the literature." The mechanism appears to dramatically different from the Oshima methylenation. In this case, the reaction proceeds through the alcohol intermediate, which is converted to the acetate and reductively cleaved. 

Carbonyl dichloride can be taken similarly to form acid anhydrides (equation 31). Via a mixed anhydride and in the presence of triethylamine, it is possible to prepare symmetrical anhydrides in high yield. ° °° A variation provides ethyl chloroformate as reagent.In a first step the carboxylic acid is ethoxycarbonylated in the presence of triethylamine and then reacted with free caiiioxylic acid to form the acid anhydride (equation 32). As the intermediate can be isolated, this is a good method of forming mixed anhydrides.In addition it seems to be particularly suitable for functionalized carboxylic acids such as hydroxy acids." Polymer-bound chloroformates may be advantageous in some cases. " " ... 

Carbonylation of olefins in the presence of alcohols to give esters is called hydroesterification. Similarly, olefin carbonylation in the presence of carboxylic acids yields acid anhydrides. Both hydroesterification and acid anhydride formation by olefin carbonylation are covered in section 14.6.4. Other carbonylation variations, including the use of acetylenic substrates, thiols and amines as hydrogen sources and the carbonylation of allylic halides are not discussed. Several excellent reviews of hydrocarboxyiation and carbonylation of olefinshave appeared. 

A variation of this condensation involves reaction with aldehydes, and it is called the Perkin reaction. Condensation of an aldehyde (having no enolizable protons) with the enolate of an acid anhydride leads to an acetoxy ester such as 182.10 Internal acyl substitution by the alkoxide forms the 0-acetyl ester and liberates the carboxylate anion (183). Subsequent reaction with more acetic anhydride generates a new mixed... 

A number of variations of the Friedel-Crafts reaction conditions are possible. Acid anhydrides can serve as the acylating agent in place of acid chlorides. Also, the carboxylic acid can be used directly, particularly in combination with strong acids. For example, mixtures of carboxylic acids with polyphosphoric acid, in which a mixed anhydride is presumably formed in situ, are reactive acylating agents. Similarly, carboxylic acids dissolved in trifluoromethanesulfonic acid can carry out Friedel-Crafts acylation. The reactive electrophile under these conditions is believed to be the protonated mixed anhydride. In these procedures, the leaving group... 

Chapter 16 (Section 16.6) introduced dicarboxylic acids along with their common and lUPAC names. The common names and the lUPAC names are shown again in Table 20.1 for dicarboxylic acids of C2-C10. This chapter deals with the chemistry of carboxylic acids and their derivatives, and dicarboxylic acids have their acyl halide, ester, anhydride, and amide derivatives. The two carboxylic acid units lead to some interesting structural variations, however. 

An interesting variation of this synthesis leads to a y-lactone at C-2 and C-3. The oxopropanoate (10) reacts with formaldehyde to give the lactone of sodium 3-(2-hydroxybenzoyl)-3-hydroxymethyl-2-oxopropanoate (12) which is cyclised by acid to the chromone lactone (13) [28, 29], Acetylation of the phenolic group of an analogue (14) of the oxopropanoate (10) followed by heating with sodium acetate and acetic anhydride gives a 3-acetyl-2-carboxylic ester (15) and a smaller amount of the isomeric 2-oxoacetate (16) which loses carbon monoxide on heating with sulphuric acid. This provides a route to the little known chromone-3-carboxylic acids (17) [9]. 

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