Esterification carbodiimide mediated

Scheme 7.9 Carbodiimide-mediated pathways for esterification reactions.

In a related study by the same authors, the effect of microwave irradiation on carbodiimide-mediated esterifications on solid support has been investigated employing benzoic acid28. Activation of the carboxylic acid was carried out using diisopropy-lcarbodiimide (DIC) via the O-acyl isourea or the symmetrical anhydride protocol, respectively (Scheme 7.8). 

The formation of ketene intermediates facilitates the carbodiimide mediated esterification reaction with alcohols and phenols when carboxylic acids with an electron withdrawing group in the a-position are used as substrates. ... 

Phenolic esters are obtained similarly. The presence of a nitro group in the aromatic nucleus and the use of pyridine as solvent facilitates the reaction. This reaction is recommended for the characterization of phenols. 2,4,5-Trichlorophenyl-, pentachlorophenyl-, 4-nitrophenyl- and thiophenyl esters of N-acylamino acids are prepared in this manner. These aromatic esters are used in the stepwise lengthening of peptides, du Vigneaud and coworkers synthesized lysine vasopressin from a nonapeptide which they prepared stepwise using the nitrophenyl ester method. Room temperature esterification of dicarboxylic acids and diphenols are also carbodiimide mediated using the 1 1 complex derived from DMAP and p-toluenesulfonic acid as catalyst Methacrylic acid is also esterified with phenols using carbodiimides and DMPA to mediate the reaction. ... 

In view of the rapid reaction of carbodiimides with water they are often used in dehydration reactions. Major examples are the intra- and intermolecular esterification reactions of carboxylic acids, and the formation of peptides from carboxylic acids and protected amino acids. Especially, dicyclohexylcarbodiimide (DCC) or diisopropylcar-bodiimide (DIPCD) are often used in carbodiimide mediated reactions because the corresponding urea byproducts are insoluble in most organic solvents and water, and therefore are readily removed by filtration. Also, water soluble carbodiimides, such as N-ethyl-N -(3-dimethylamino)propylcarbodiimide (EDC) or its hydrochloride (EDCCl, sometimes referred to as EDAC) are often used in these reactions. EDC reacts with carboxyl groups at pH of 4.0-6.0, but loses its reactivity at lower pH. Sometimes solid phase reactions are conducted using carbodiimide terminated linear or crosslinked polymers. 

Organothiols chemisorbed on gold surfaces are especially usefiil for electrochemical and chemical studies. For example, carboxylic acid terminated monolayers are often used. An example is the attachment of cytochrome C with its side chain lysine groups to acid terminated self assembled monolayer gold electrodes. Carbodiimide mediated esterification of ferrocene-l,l -dicarboxylic acid with phenols is used to construct thermotropic liquid crystals. ... 

Polymeric carbon nanocomposites are often functionalized with matrix polymers. An example is the functionalization of SWNTs and MWNTs with poly(vinyl alcohol) using a carbodiimide mediated esterification reaction. Also, poly(ethylene-co-vinyl alcohol) is used for this purpose to produce DMSO soluble functionalized SWNTs. In a similar manner poly(m-aminobenzene sulfonic acid) is covalently bonded to SWNTs to form water soluble graft copolymers. ... 

Monobifunctional crossUnkers, synthesized in the carbodiimide mediated esterification of dicarboxylic acids in the presence of sodium N-hydroxysuccinimide-3-sulfonate, are used in the mapping of protein structures. " ... 

The carboxamide groups of asparagine and glutamine derivatives 26 are susceptible to dehydration during carbodiimide-mediated esterification at the a-carboxy groups (Scheme 4).[64] reaction probably involves formation of aspartyl- or glutamylisoimide 28 by attack... 

Several polyarylates are liquid cr stalline materials and are widely used as industrial plastics. The synthesis of polyarylates from industrially used diphenols and various diacids has been investigated by Moore and Stupp (Moore, 1990) who published a procedure based on a carbodiimide-mediated esterification in the presence of dimetliylaminopyridinium p-toluene sulfonate (DPTS). 

Because of the convincing results even in penicillin chemistry, due to the smooth reaction conditions, carbodiimides and particndarly DCC became common coupling reagents in natural compound and peptide chemistry. In combination with binucleophiles, such as N-hydroxysuccinimide or N-hydroxybenzotriazole, the method is racemization-free [1248]. Other frequent applications are in esterifications and general dehydration reactions, and, more recently, in carbodiimide-mediated multicomponent reactions [1251] (see Section 4.S.3.5). All these reactions proceed through activated intermediates 1689. Thus, compounds with a carboxylic function 1688 can be coupled with a nucleophilic compound 1690 to afford the coupled product 1691 under extremely mild conditions. The resulting by-product dicydohexylurea 1693, however, is difficult to separate because of its ambivalent solubility properties, which usually complicate the whole work-up procedure. 

The effect of microwave irradiation on carbodiimide-mediated esterifications on solid support. Tetrahedron, 57,3915. 

The most common modifications of the carboxyl group for HA derivatisation are shown in Figure 8.1. Carboxyl groups of HA are commonly modified by carbodiimide-mediated reactions, esterification and periodate oxidation. 

The esterification of ferrocene-1,1 -dicarboxylic acid with substituted phenols to produce hexacatenar substituted ferrocenes, which are thermotropic liquid crystals, is also mediated by carbodiimides. ... 

The esterification of N-protected amino acids with alcohols mediated by carbodiimide is also accomphshed in the presence of DMAP. ... 

The two reactions most commonly employed for the modification of protein carboxyl groups have been acid-catalyzed esterification (Wilcox 1967), and coupling with nucleophiles mediated by a water-soluble carbodiimide. The latter reaction has been exploited widely in the determination of the carboxyl group content of proteins as well as in studies of carboxyl group function, and would at present appear to be the reaction of choice for these purposes. 

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