Carboxylic acids, anhydrides side chains

Carboxylic acids were introduced by the reaction of the polysilane(II) with carboxylic acid anhydrides in the presence of an amine. Table 2 shows the results. In order to examine the effect of unsaturated bonds and halides in the side chain on photolysis, double bonds or chloride groups were introduced with the carboxylic acid. Polysilanes(III) were also soluble in polar solvents and basic aqueous solution. The solubility in tetramethyl ammonium hydroxide aqueous solution(TMAH) depended strongly... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Similarly, triphenylphosphine dichloride (TPPCI2) can activate aromatic carboxylic acids in pyridine through the formation of acyloxyphosphonium salts (Scheme 2.30).313 A side reaction between tire intermediate acyloxyphosphonium species and a second carboxyl endgroup leading to the formation of anhydrides has been reported.313 This chain-limiting reaction decreases tire molar mass, while the presence of anhydride linkages in tire chains adversely affects the thermal and hydrolytic stability of the final polyester. 

E. Jacobson in 1882 fused phthalic anhydride with quinoline bases obtained from coal tar, which also contained quinaldine (136). He thus received quinophthalone (137). Quinophthalone derivatives bearing sulfonic or carboxylic acid functions represent suitable anionic dyes. Derivatives carrying basic side chains containing quarternary nitrogen, on the other hand, provide cationic dyes. The compounds are used especially as disperse dyes [1]. 

The key to a controlled molecular weight build-up, which leads to the control of product properties such as glass transition temperature and melt viscosity, is the use of a molar excess of diisopropanolamine as a chain stopper. Thus, as a first step in the synthesis process, the cyclic anhydride is dosed slowly to an excess of amine to accommodate the exothermic reaction and prevent unwanted side reactions such as double acylation of diisopropanolamine. HPLC analysis has shown that the reaction mixture after the exothermic reaction is quite complex. Although the main component is the expected acid-diol, unreacted amine and amine salts are still present and small oligomers already formed. In the absence of any catalyst, a further increase of reaction temperature to 140-180°C leads to a rapid polycondensation. The expected amount of water is distilled (under vacuum, if required) from the hot polymer melt in approximately 2-6 h depending on the anhydride used. At the end of the synthesis the concentration of carboxylic acid groups value reaches the desired low level. 

Reaction of the side chain hydroxyacetone in flumethasone (27-4) with periodic acid leads to cleavage of that function to give carboxylic acid (29-1) with the loss of the carbon atom at C-21. Further reaction of the very hindered acid group requires prior activation. Thus, acylation with diphenyl chlorophosphate leads to the mixed anhydride (29-2) this is not isolated, but treated immediately with methyl mercaptan. The product, tibecasone (29-3), is a quite effective topical anti-inflammatory agent [24]. Cleavage of the ester side chain would lead back to the inactive starting acid (29-1). 

An ester derived from prednisolone has found use as a topical ophthalmic antiinflammatory dmg. Cleavage of the side chain in prednisolone (31-1) with sodium periodate affords the corresponding carboxylic acid (30-2). Treatment of that product with propionyl chloride affords initially the ester at 17 along with some of the mixed anhydride. The anhydride is then hydrolyzed with a mild base to afford the 17-ester (31-3). Alkylation of the carboxylic acid with chloromethylchlorosufonyl chloride (from bromochloromethane and sulfonyl chloride) leads to the chloromethyl ester (31-4) and thus loteprednol [26]. 

Fig. 6.21. In situ activation of a carboxylic acid—i.e., the side chain carboxyl group of protected L-aspartic acid—as the mixed anhydride (B) and its aminolysis to a Weinreb amide. How this Weinreb amide acylates an organolithium compound is shown in Figure 6.44. The acylation of an H nucleophile by a second Weinreb amide is presented in Figure 6.42 and the acylation of a di(ketone enolate) by a third Weinreb amide in Figure 13.64. Figure 6.50 also shows how Weinreb amides of carboxylic acids can be obtained by C,C bond formation.

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