Activation of carboxylic acid

Specific biological activity of carboxylic acids peroxide derivatives in compaiison with their oxidation ability and ionization degree in aqueous solutions has been considered. Peroxyoctanoic, diperoxynonandioic and diperoxydecandioic acids give the most intense bactericidal effect among researched cai boxylic acids peroxide derivatives. The perspectives of use of the aliphatic middle-chain peracid C8-C9 as anti-infective agents have been discussed. 

In-situ activation of carboxylic acids can be also carried out by Tos - Cl/tri-ethylamine, according to Fig. 7 ... 

The Vilsmeier-Haack type adduct, formed by the reaction of oxalyl chloride with DMF can be also be employed for the activation of carboxylic acids, as shown in Fig. 8 [200]. 

Complexes Resulting from Activation of Carboxylic Acids Hydrido(carboxylato) Complexes... 

The combination of carboxyl activation by DCCI and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols. The reaction proceeds at room temperature.119... 

A great deal of work has been done on the in situ activation of carboxylic acids toward nucleophilic substitution by amines. This type of reaction is fundamental for synthesis of polypeptides (see also Section 13.3.1). Dicyclohexylcarbodiimide... 

The preparation of imidazolides by acylation of imidazole with acid chlorides is sometimes limited by the inaccessibility or instability of the required acid chlorides (e.g., formyl chloride, highly unsaturated acid chlorides, etc.) or by side-reactions in the case of multifunctional systems. For these reasons and due to the availability of an easy and convenient procedure involving very mild conditions, imidazolides today are usually prepared directly from the corresponding carboxylic acids with jV -carbonyldiimida-zole (CDI) or one of its analoga (see page 16). Use of these reagents has become more and more the preferred method for activation of carboxylic acids to azolides and their further transacylation to esters, amides, peptides, etc. (see subsequent Chapters). 

Of great preparative potential with respect to the activation of carboxylic acids to imidazolides is A -oxalyldiimidazole, which reacts with carboxylic acids or their sodium or lithium salts under release of CO and CO2 to give imidazolides in excellent yield.[23]... 

There has been a study of the mechanism of the activation of carboxylic acids to peptide formation by chloro-s -triazines in combination with tertiary amines. The first step, exemplified in Scheme 2 by the reaction of 2-chloro-4,6-disubstituted-l,3,5-triazines (18) with A -methylmorpholine, is formation of a quaternary triazinylammonium salt (20). Here there is NMR evidence for the formation at —50°C of the intermediate (19), showing that the substitution involves the two-step SnAt mechanism rather than a synchronous pathway. The subsequent reaction of (20) with a carboxylic acid yields the 2-acyloxy derivative (21), which carries an excellent leaving group for the amide-forming step. ... 

Despite continnons progress in amide bond formation, the acylation of hydroxylamine nnder carbodiimide promotion is often contaminated by Af,0-diacylation even with sub-stoichiometric amounts of acids. Appendino and colleagues have developed a practical solution to the problem by combining the in situ activation of carboxylic acids 102 with the cyclic phosphonic anhydride PPAA (103), and the generation of hydroxylamine from its corresponding hydrochloride to form 104 (Scheme 54). 

Care must be taken in the activation of carboxylic acids with alkyl chlorofor-mates, because the resulting anhydrides decompose at room temperature to yield carboxylic esters. 

Figure 13.4. Activation of carboxylic acids with carbodiimides. ...

A selection of commercially available phosphonium salts suitable for the activation of carboxylic acids in the presence of amines is sketched in Figure 13.5. Phosphonium salts such as those shown in Figure 13.5 do not react with amines, and are well suited for preparing amides on insoluble supports, with either the amine or the acid linked to the support (Table 13.5). Solutions of these reagents in dry DMF are quite stable and can be used even after standing at room temperature for several days [84]. BOP, one of the first phosphonium salts used for peptide synthesis [85], leads to the formation of mutagenic HMPA, and should therefore be replaced by the less hazardous PyBOP [86],... 

Following the corona-discharge treatment of a silicone surface and the subsequent graft polymerization of AAc, type I atelocollagen was immobilized onto the grafted surface with the use of water-soluble carbodiimide [176, 177]. As depicted in Fig. 17, the immobilization reaction involves two steps, i.e., activation of carboxylic acids and the following nucleophilic substitution with prima-... 

The combination of carboxyl activation by a carbodiimide and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols.10 The reaction proceeds at room temperature. Carbodiimides are widely applied in the synthesis of polypeptides from amino acids. The proposed mechanism for this esterification reaction involves activation of the acid via isourea 28 followed by reaction with another acid molecule to form anhydride... 

Activation of Carboxylic Acids with Sulfonic Acid Chlorides... 

Fig. 22 Schematic plot for the esterification of dextran with a-naphthylacetic acid (f), nicotinic acid (2), and naproxen (3) via in situ activation of carboxylic acids with p-toluenesulfonyl chloride (TosCl)...

Activation of Carboxylic Acids and of Carboxylic Acid Derivatives... 

Fig. 6.9. Examples of the activation of carboxylic acid derivatives in equilibrium reactions.

Fig. 6.13. Acid-free activation of carboxylic acids as carboxylic acid imidazolides.

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