N,N' Dicyclohexylcarbodiimide

Structure and spectroscopy

The C-N=C=N-C core of carbodiimides (N=C=N) is linear, being related to the structure of allene. Three principal resonance structures describe carbodiimides:

RN=C=NR ↔ RN⁺≡C-N⁻R ↔ RN⁻-C≡N⁺R

The N=C=N moiety gives characteristic IR spectroscopic signature at 2117 cm⁻¹. The ¹⁵N NMR spectrum shows a characteristic shift of 275.0 ppm upfield of nitric acid and the ¹³C NMR spectrum features a peak at about 139 ppm downfield from TMS.

Preparation

Of the several syntheses of DCC, Pri-Bara et al. use palladium acetate, iodine, and oxygen to couple cyclohexyl amine and cyclohexyl isocyanide. Yields of up to 67% have been achieved using this route:

C₆H₁₁NC + C₆H₁₁NH₂ + O₂ → (C₆H₁₁N)₂C + H₂O

Tang et al. condense two isocyanates using the catalyst OP(MeNCH₂CH₂)₃N in yields of 92%:

DCC has also been prepared from dicyclohexylurea using a phase transfer catalyst by Jaszay et al. The disubstituted urea, arenesulfonyl chloride, and potassium carbonate react in toluene in the presence of benzyl tetraethylammonium chloride to give DCC in 50% yield.

Reactions

DCC is a dehydrating agent for the preparation of amides, ketones, nitriles. In these reactions, DCC hydrates to form dicyclohexylurea (DCU), a compound that is nearly insoluble in most organic solvents and insoluble in water. The majority of the DCU is thus readily removed by filtration, although the last traces can be difficult to eliminate from non-polar products. DCC can also be used to invert secondary alcohols.

Peroxide formation

Reaction of an acid with hydrogen peroxide in presence of DCC leads to formation of peroxide linkage.

Moffatt oxidation

A solution of DCC and dimethyl sulfoxide (DMSO) effects the so-called Pfitzner-Moffatt oxidation. This procedure is used for the oxidation of alcohols to aldehydes and ketones. Unlike metal-mediated oxidations, the reaction conditions are sufficiently mild to avoid over-oxidation of aldehydes to carboxylic acids. Generally, three equivalents of DCC and 0.5 equivalent of proton source in DMSO are allowed to react overnight at room temperature. The reaction is quenched with acid.

Dehydration

Alcohols can also be dehydrated using DCC. This reaction proceeds by first giving the O-acylurea intermediate which is then hydrogenolyzed to produce the corresponding alkene:

RCHOHCH2R' + (C₆H₁₁N)₂C → RCH=CHR' + (C₆H₁₁NH)₂CO

Inversion of secondary alcohols

Secondary alcohols can be stereochemically inverted by formation of a formyl ester followed by saponification. The secondary alcohol is mixed directly with DCC, formic acid, and a strong base such as sodium methoxide.

Esterification

A range of alcohols, including even some tertiary alcohols, can be esterified using a carboxylic acid in the presence of DCC and a catalytic amount of DMAP.

DCC-promoted peptide coupling

During protein synthesis (such as Fmoc solid-state synthesizers), the N-terminus is often used as the attachment site on which the amino acid monomers are added. To enhance the electrophilicity of carboxylate group, the negatively charged oxygen must first be "activated" into a better leaving group. DCC is used for this purpose. The negatively charged oxygen will act as a nucleophile, attacking the central carbon in DCC. DCC is temporarily attached to the former carboxylate group forming a highly electrophilic intermediate, making nucleophilic attack by the terminal amino group on the growing peptide more efficient.

Safety

DCC is a potent allergen and a sensitizer, often causing skin rashes.