Dicyclohexylcarbodiimide reagent

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

Step 3 The resin bound C terminal ammo acid IS coupled to an N protected ammo acid by using N N dicyclohexylcarbodiimide Excess reagent and N N dicyclohexylurea are washed away from the resin after coupling is complete... 

Schemes are available, however, that start from the free carboxylic acid, plus an activator . Dicyclohexylcarbodiimide, DCC, has been extensively employed as a promoter in esterification reactions, and in protein chemistry for peptide bond formation [187]. Although the reagent is toxic, and a stoichiometric concentration or more is necessary, this procedure is very useful, especially when a new derivative is targeted. The reaction usually proceeds at room temperature, is not subject to steric hindrance, and the conditions are mild, so that several types of functional groups can be employed, including acid-sensitive unsaturated acyl groups. In combination with 4-pyrrolidinonepyridine, this reagent has been employed for the preparation of long-chain fatty esters of cellulose from carboxylic acids, as depicted in Fig. 5 [166,185,188] ...

Whereas the original Moffat-Pfitzner oxidation employs dicyclohexylcarbodiimide to convert DMSO into the reactive intermediate DMSO species 1297, which oxidizes primary or secondary alcohols via 1298 and 1299 to the carbonyl compounds and dicyclohexylurea [78-80], subsequent versions of the Moffat-Pfitzner oxidation used other reagents such as S03/pyridine [80a, 83] or oxalyl chloride [81-83] to avoid the formation of dicyclohexylurea, which is often difficult to remove. The so-called Swern oxidation, a version of the Moffat-Pfitzner oxidation employing DMSO/oxalyl chloride at -60°C in CH2CI2 and generating Me2SCl2 1277 with formation of CO/CO2, has become a standard reaction in preparative organic chemistry (Scheme 8.31). 

Fig. 6 Commonly used additives and coupling reagents. DCC dicyclohexylcarbodiimide, HOSu A-hydroxysuccinimide, HOBt 1 -hydroxybenzotriazole, HOAt 1 -hydroxy-7-azabenzotriazole...

Further evidence that carboxyl groups are important for transport activity was provided by Igarashi and Aronson [22], Friedrich et al. [23], and Kinsella et al. [24] using the carboxyl group-specific reagent, A,A -dicyclohexylcarbodiimide (DCCD). DCCD irreversibly inactivated the brush border Na /H exchanger in rabbit and... 

This carbon-carbon bond-generating reaction can be used extensively over a wide range of chemistries [11]. As the reaction is an equilibrium process, needing the removal of water to obtain high yields, chemical means have to be used to accomplish this task. 1,3-Dicyclohexylcarbodiimide (DCC) is a commonly used reagent for this purpose. Alternatively, molecular sieves find use for conventional processing, but are not so favorable for micro-reactor processing, because the sieve needs to be inserted into the micro channel (additional fabrication expenditure) and may disrupt the liquid transport if EOF is applied. 

The first version of SPPS to be developed used the t-Boc group as the amino-protecting group. f-Boc can be cleaved with relatively mild acidic treatment and TFA is usually used. The original coupling reagents utilized for SPPS were carbodiimides. In addition to dicyclohexylcarbodiimide (DCCI), N, (V -diisopropylcarbodiimide (DIPCDI) is often used. The mechanism of peptide coupling by carbodiimides was... 

On use of N,N -dicyclohexylcarbodiimide instead of sulfonyl chlorides as condensation reagent in oligonucleotide synthesis, then the pyro-, tri- and tetraphosphate stages are again involved 124). The metaphosphate 183 a is found in small amounts by 3iP-NMR spectroscopy, but again no cyclic trimetaphosphate 184 can be detected, which would also be a possible phosphorylation reagent. 

When the reagent is dicyclohexylcarbodiimide, the reaction is carried out in dichloromethane, the /V,/V -dicyclohcxylurca is removed by filtration after 15-30 minutes, the solvent is sometimes replaced by dimethylformamide, and the solution is then added to the /V-nucleophile. The /V,/V -dicyclohcxylurca is removed to help drive the coupling reaction to completion. The symmetrical anhydride is not prepared directly in the polar solvent because the latter suppresses its formation. 

Coupling the substituents to the polyacid core is a key step. The reaction must have a high yield to limit purification problems and show high selectivity between the amines and alcohols present to limit side reactions. The amidifica-tion reaction chosen is a coupling reaction used in peptide chemistry. The reaction is carried out at room temperature in the presence of a coupling reagent such as NjAT -dicyclohexylcarbodiimide, l-(3-dimethylaminopropyl)-3-ethylcar-bodiimide or l-ethoxycarbonyl-2-ethoxyl-l,2-dihydroquinoline, possibly in the presence of an activator such as hydroxybenzotriazole or N-hydroxysuccimide (Fig. 8). 

A very useful group of procedures for oxidation of alcohols to ketones have been developed which involve DMSO and any one of several electrophilic reagents, such as dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, or... 

The first studies on the sulfation of organic compounds, amino acids, and proteins have shown that pyridine/sulfur trioxide complex (pyridine/S03 or pyridine/Cl S03H),168-721 concentrated sulfuric acid,173,74 sulfuric acid//V,A -dicyclohexylcarbodiimide,175,761 and chloro-sulfonic acid177 are the most efficient reagents for the sulfation of tyrosine. More recently, alternative methods based on dimethylformamide/sulfur trioxide complex (DMF/S03),152,781 trimethylamine/sulfur trioxide (Me3N/S03),1152,1531 pyridinium acetylsulfate,137,791 and pyr-idinium trifluoroacetylsulfate1801 have been proposed to minimize side reactions which are difficult to control for the chemical sulfation of tyrosine peptides. 

Aliphatic primary and secondary alcohols have been found105 to react with N,N -dicyclohexyl-N-methylcarbodiimidium iodide (55), in tetrahydrofuran, benzene, or hexane at 35-50°, to give the corresponding iodides in high yields the reagent 55 is prepared by heating a mixture of N,N -dicyclohexylcarbodiimide and methyl iodide. The iodination reaction has been extended to steroidal alcohols, but attempts with carbohydrate substrates have not yet been reported. 

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