Carboxylic acids, acidity alkylation with diazo

Reagents that provide UV adsorptive derivatives of carboxylic acids are fairly numerous. The preparation of the simple benzyl esters by reacting the carboxylic ion with alkyl halides or diazo compounds has been unsuccessful due to their having unacceptable toxicity. The... 

Alkylation of Carboxylic Acids With Diazo Compounds... 

Alkylation of carboxylic acids with diazo compounds... 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

Protected 6-amino-hexahydro-l,7-dioxopyrazolo[l,2-4]pyrazole-2-carboxylic acid 274 is available by a thermolytic decomposition of diazo compound 273 via the Wolff rearrangement. The starting compound is simply available by alkylation of racemic 272 with the corresponding bromoacetoacetate and subsequent diazo transfer reaction (Scheme 35) <1996TL4891>. 

Alkylation of Carboxylic Acids with Diazo Compounds Hydro,acyloxy-de-dlazo-bisubstitution... 

Alcoholysis of trihalides 0-6 Hydrolysis of ortho esters 0-20 Alcoholysis of acyl halides 0-21 Alcoholysis of anhydrides 0-22 Esterification of carboxylic acids 0-23 Transesterification 0-24 Alkylation of carboxylic acid salts 0-25 Cleavage of ethers with anhydrides 0-26 Alkylation of carboxylic acids with diazo compounds... 

Because of the special structural requirements of the resin-bound substrate, this type of cleavage reaction lacks general applicability. Some of the few examples that have been reported are listed in Table 3.19. Lactones have also been obtained by acid-catalyzed lactonization of resin-bound 4-hydroxy or 3-oxiranyl carboxylic acids [399]. Treatment of polystyrene-bound cyclic acetals with Jones reagent also leads to the release of lactones into solution (Entry 5, Table 3.19). Resin-bound benzylic aryl or alkyl carbonates have been converted into esters by treatment with acyl halides and Lewis acids (Entry 6, Table 3.19). Similarly, alcohols bound to insoluble supports as benzyl ethers can be cleaved from the support and simultaneously converted into esters by treatment with acyl halides [400]. Esters have also been prepared by treatment of carboxylic acids with an excess of polystyrene-bound triazenes here, diazo-nium salts are released into solution, which serve to O-alkylate the acid (Entry 7, Table 3.19). This strategy can also be used to prepare sulfonates [401]. 

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R =H). In alcohols and amines esters (8.60) and amides (8.61, R = H), respectively. 

You met diazonium salts in Chapter 22. Arene diazonium salts are stable compounds, but alkyl diazonium salts, which are formed by protonation of diazo compounds, are not. They decompose rapidly with loss of N2—this was how the carboxylic acid got methylated at the beginning of the chapter. Other relatives of the azo and diazo compounds are alkyl azides. Alkyl azides have three nitrogen atoms and are usually stable but azides of low molecular weight may explode on impact or heating. 

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