Dehydration with dicyclohexylcarbodiimide

Ketene itself is commercially prepared in this manner. Carboxylic acids have also been converted to ketenes by treatment with certain reagents, among them TsCl, dicyclohexylcarbodiimide, and l-methyl-2-chloropyridinium iodide (Mukaiya-ma s reagent) Analogously, amides can be dehydrated with P2O5, pyridine. 

The example shown above is by no means atypical. Treatment of a polycar-boxylic acid with dicyclohexylcarbodiimide (DCC) under forcing conditions effected dehydration even with a 20% DVB-polystyrene polymer. ... 

Nucleosides and nucleotides are found in places other than as part of the structure of DNA and RNA. We have seen, for example, that adenosine units are part of the structures of two important coenzymes, NADH and coenzyme A. The 5 -triphosphate of adenosine is, of course, the important energy source, ATP (Section 22. IB). The compound called 3, 5 -cyclic adenylic acid (or cyclic AMP) (Fig. 25.6) is an important regulator of hormone activity. Cells synthesize this compound from ATP through the action of an enzyme, adenylate cyclase. In the laboratory, 3, 5 -cyclic adenylic acid can be prepared through dehydration of 5 -adenylic acid with dicyclohexylcarbodiimide. 

The reaction of hydroxy-substituted carbene complexes with the dehydrating agent dicyclohexylcarbodiimide (DCC) gives the adduct XVI (Weiss et al., 1974). The reaction is thought to proceed via dehydration to give a vinylidene-carbene complex which then undergoes a [2 -I- 2] cycloaddition with DCC. 

B — dehydration of a-substituted S-mercaptopropionic acid with dicyclohexylcarbodiimide. 

A method suitable for the preparation of optically active /3-thiolactones which contain groups sensitive to acids is dehydration of -mercaptopropionic acid derivatives with dicyclohexylcarbodiimide. This method was first used by Sheehan [9] for the preparation of racemic N-carbobenzoxy- 3,i3-dimethyl-a-amino-0-thiolactone. Using the same method, Fles et al have prepared optically active A-carbobenzoxyl-, and A -tosyl-a-amino-j5-thiol-actone [10] and a-methyl-a-ethy 1-/3-thiolactone [7]. The preparation of racemic a-methyl-of-ethyl- -thiolactone was described by Sweeney and Casey [4] by condensation of a-methyl-a-ethyl-/3-bromopropionic acid with sodium sulfide. 

Another way to esterify a carboxylic acid is to treat it with an alcohol in the presence of a dehydrating agent.634 One of these is dicyclohexylcarbodiimide (DCC), which is converted... 

The synthesis of hexakis(cyclohexylsilsesquioxane) in 10% yield by the treatment of cyclohexyltrichlorosilane with water was first reported in 1965108. The X-ray structure of hexakis(cyclohexylsilsesquioxane) was determined by Molloy and coworkers in 1994109. The hexasilsesquioxanes (80) substituted by /-butyl or 1,1,2-trimethylpropyl groups are prepared by condensation of the corresponding silanetriol (78) or tetrahydroxysiloxane (79) using dicyclohexylcarbodiimide (DCC) as a dehydrating reagent in DMSO or DMF (Scheme 20)no. 

As the last example of an SN reaction at the carboxyl carbon of a carbonic acid derivative, consider the synthesis of dicyclohexylurea in Figure 6.39. In this synthesis, two equivalents of cyclohexylamine replace the two methoxy groups of dimethyl carbonate. Dicyclohexylurea can be converted into the carbodiimide dicyclohexylcarbodiimide (DCC) by treatment with tosyl chloride and triethylamine. The urea is dehydrated. The mechanism of this reaction is identical to the mechanism that is presented in Figure 8.9 for the similar preparation of a different carbodiimide. 

The standard method of preparing anhydro-5-hydroxyoxazolium hydroxides (300) is by dehydration of iV-substituted a-acylamino acids, usually with acetic anhydride (equation 154) dicyclohexylcarbodiimide and trifluoroacetic anhydride have also been used. N-Acylglycines (299 R3=H) give rise to unstable mesoionic oxazoles which tend to dimerize (see Section 4.18.3.1.5(0) if such acids are treated with trifluoroacetic anhydride, stable trifluoroacetyl derivatives (300 R3 = CF3CO) are isolated. Numerous unstable betaines (300 R1, R = alkyl or aryl, R -H) have been generated by the action of triethylamine on the corresponding hydroperchlorates, prepared by the method shown in equation (151). 

For labile multifunctional substrates, the first step in the OBO synthesis, esterification with 3-methyl-3-oxetanemethanol, can be accomplished using the carboxylic acid and a dehydrating agent such as dicyclohexylcarbodiimide (DCC) [Scheme 2.111]. ... 

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. 

More recently, an improved protocol has been reported wherein NJ "-dicyclohexylcarbodiimide (DCC) or 2-(lH-benzotrizo-l-yl)-l,l,3,3-tetra-methyluraniiunhexafluorophospate (HBTU) (Scheme 6) is used as a dehydrating agent to accelerate the intramolecular cychzation resulting in faster reaction and improved yields [27,28]. The DCC/HBTU-mediated protocol has the advantage of mild reaction conditions, a very short reaction time, and product formation in almost quantitative yields. More importantly, yields of the thiazolidinones are independent of the nature of the reactants. This modification is compatible with a solid-phase combinatorial approach to generate a library of compounds. 

Reagent for the Determination of Enantiomeric Purity of Carboxylic Acids. Amine (1) is frequently used as a derivatiz-ing reagent for determining the enantiomeric purity of carboxylic acids by HPLC, with limits of detection often as low as 1%. Most commonly used coupling methods include use of dehydrating agents such as 1,3-Dicyclohexylcarbodiimide (eq 5) and the mixed anhydride method (eq 6). ... 

Another way to esterify a carboxylic acid is to treat it with an alcohol in the presence of a dehydrating agent. One of these is dicyclohexylcarbodiimide (DCC), which is converted in the process to dicyclohexylurea (DHU). The mechanism has much in common with the nucleophilic catalysis mechanism the acid is converted to a compound with a better leaving group. However, the conversion is not by a tetrahedral mechanism (as it is in nucleophilic catalysis), since the C—O bond remains intact during this step ... 

Carbodiimides, in particular dicyclohexylcarbodiimide, have been applied in many syntheses where dehydration had to be performed under mild conditions. It is therefore no surprise that this reagent was also introduced for the synthesis of acid anhydrides from carboxylic acids." " In order to avoid N-acylation the reactions are carried out at low temperature. First 0-acylisoureas are formed, which then react further with free acid to the acid anhydride (equation 34). The reaction has been exploited in particular for the preparation of peptides." )V-alkoxycarbonyl-protected amino acids can be transformed in high yield to the corresponding anhydrides, which themselves are activated acid derivatives and may be converted to peptides. As in many other examples polymer-bound carbodiimides may prove superior sometimes, as the isolation of the products is facilitated. Easy preparation of acid anhydrides is possible in this way." ... 

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