Carboxylic acids carbodiimides

Mechanism of amide formation by reaction of a carboxylic acid and an amine with dicyclohexyl-carbodiimide (DCC). 

Activating agents, such as trifluoroacetic anhydride 1,1 -carbonyldiimidazolc carbodiimides sulfonyl, tosyl, and picryl chlorides and a range of phosphorus derivatives can promote direct solution reactions between dicarboxylic acids and diols or diphenols in mild conditions. The activating agents are consumed during the reaction and, therefore, do not act as catalysts. These so-called direct polycondensation or activation polycondensation reactions proceed via the in situ transformation of one of the reactants, generally the carboxylic acid, into a more... 

The reaction between acyl halides and diazomethane is of wide scope and is the best way to prepare diazo ketones. Diazomethane must be present in excess or the HX produced will react with the diazo ketone (10-74). This reaction is the first step of the Amdt-Eistert synthesis (18-8). Diazo ketones can also be prepared directly from a carboxylic acid and diazomethane or diazoethane in the presence of dicyclohexyl-carbodiimide. ... 

Figure 9 A synthetic mixture of water-soluble carboxylic acids separated by anion-exchange chromatography. Column 0.3 cm x 300 cm Diaoion CA 08, 16-20 p (Mitsubishi Kasei Kogyo). Eluant 200 mM HC1. Detection reaction with Fe3-benzohy-droxamic acid-dicyclohexy carbodiimide-hydroxylamine perchlorate-triethyl amine with absorbance at 536 nm. Analytes (1) aspartate, (2) gluconate, (3) glucuronate, (4) pyroglutamate, (5) lactate, (6) acetate, (7) tartrate, (8) malate, (9) citrate, (10) succinate, (11) isocitrate, (12) w-butyrate, (13) a-ketoglutarate. (Reprinted with permission from Kasai, Y., Tanimura, T., and Tamura, Z., Anal. Chem., 49, 655, 1977. 1977 Analytical Chemistry).

Reactions of 2,3-dioxo-l,2,3,5,6,7-hexahydropyrido[l,2,3-carboxylic acids and the homologous acetic and propionic acids, prepared by basic hydrolysis of the corresponding ester, with amines, 28% NH4OH, and hydroxylamine derivatives in the presence of l-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and hydroxybenztria-zole <1995BML1527>, 1995BML1533>, and in the presence of NEt3 and A, A -bis(2-oxo-3-oxazolidinyl)phosphinic... 

Carboxylic acids may be covalently modified with adipic acid dihydrazide or carbohydrazide to yield stable imide bonds with extending terminal hydrazide groups. Hydrazide functionalities don t spontaneously react with carboxylate groups the way they do with aldehyde groups (Section 4.5, this chapter). In this case, the carboxylic acid first must be activated with another compound that makes it reactive toward nucleophiles. In organic solutions, this may be accomplished by using a water-insoluble carbodiimide (Chapter 3, Section 1.4) or by creating an intermediate active ester, such as an NHS ester (Chapter 2, Section 1.4). 

N-substituted carbodiimides can react with carboxylic acids to form highly reactive, o-acylisourea derivatives that are extremely short-lived (Reaction 11). This active species then can react with a nucleophile such as a primary amine to form an amide bond (Reaction 12)... 

Cascade Blue cadaverine and Cascade Blue ethylenediamine both contain a carboxamide-linked diamine spacer off the 8-methoxy group of the pyrene trisulfonic acid backbone. The cadaverine version contains a 5-carbon spacer, while the ethylenediamine compound has only a 2-carbon arm. Both can be coupled to carboxylic acid-containing molecules using a carbodiimide reaction (Chapter 3, Section 1). Since Cascade Blue derivatives are water-soluble, the carbodiimide EDC can be used to couple these fluorophores to proteins and other carboxylate-containing molecules in aqueous solutions at a pH range of 4.5-7.5. The reaction forms amide bond linkages (Figure 9.39). 

Biotin-hydrazide also may be used to couple with carboxylate-containing molecules. Hydrazidcs can be coupled with carboxylic acid groups by using the carbodiimide reaction (Chapter 3, Section 1.1). The carbodiimide activates a carboxylate to an o-acylisourea intermediate. Biotin-hydrazide can react with this intermediate via nucleophilic addition to form a stable covalent bond. 

Such carbonyls may be further oxidized using potassium permanganate (KMnO and perchloric acid (HCIO4) to convert all of these groups into carboxylic acids. Once functionalized in this manner, the nanotubes can be fully dispersed in aqueous systems. Kordas et al. (2006) used these derivatives to print nanotube patterns on paper or polymer surfaces to create conductive patterns for potential use in electronic circuitry. The carboxylates also may be used as conjugation sites to link other ligands or proteins to the nanotube surface using a carbodiimide reaction as previously discussed (Section 1, this chapter Chapter 2, Section 1.11 Chapter 3, Section 1). 

More recently, the fixation efficiency on cotton of Cl Reactive Red 177 (7-43) and its 4-carboxyphenylazo analogue in the presence of various carbodiimides (including 7-44 and 7.45) was investigated, as well as homogeneous reactions of selected carboxylic acids with alcohols (including acetylcellulose in acetone). The carboxylated dye reacted more effectively with cotton cellulose in the presence of cyanamide rather than dicyandiamide,... 

The general chemistry used in this approach involves the combination of a limited amount of an amine-terminated dendrimer core reagent with an excess of carboxylic acid terminated dendrimer shell reagent [31]. These two charge differentiated species are allowed to self-assemble into the electrostatically driven supramolecular core-shell tecto(dendrimer) architecture. After equilibration, covalent bond formation at these charge neutralized dendrimer contact sites is induced with carbodiimide reagents (Scheme 1). 

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