In organic chemistry, a carbodiimide is a functional group with the formula RN=C=NR. They are exclusively synthetic. A well known carbodiimide is dicyclohexylcarbodiimide, which is used in peptide synthesis. Dialkylcarbodiimides are stable. Some diaryl derivatives tend to convert to dimers and polymers upon standing at room temperature, this mostly occurs with low melting point carbodiimides that are liquid at room temperature. Solid diaryl carbodiimides are stable, but can slowly undergo hydrolysis in the presence of water overtime.
Structure and bonding
From the perspective of bonding, carbodiimides are isoelectronic with carbon dioxide. Three principal resonance structures describe carbodiimides: Relevant to the significance of the polar resonance structures, no carbodiimide has been separated into its optical isomers. The N=C=N core is relatively linear and the C-N=C angles approach 120″. In the case of C2, the central NCN angle is 170° and the C-N=C angles are within 1° of 126°. The C=N distances are short, near 1.20 Å, characteristic of double bonds. Carbodiimides are chiral, possessing C2-symmetry. The parent compound, methanediimine, is a tautomer of cyanamide.
Synthesis
From thioureas and ureas
A classic route to carbodiimides involves dehydrosulfurization of thioureas. A typical reagent is mercuric oxide: This reaction can often be conducted as stated, even though carbodiimides react with water. In some cases, a dehydrating agent is added to the reaction mixture. The dehydration of N,N'-dialkylureas gives carbodiimides: Phosphorus pentoxide and p-Toluenesulfonyl chloride have been used as a dehydrating agents.
From isocyanates
Isocyanates convert to carbodiimides with loss of carbon dioxide: The reaction is catalyzed by phosphine oxides. This reaction is reversible.
Reactions
Compared to other heteroallenes, carbodiimides are very weak electrophiles and only react with nucleophiles in the presence of catalysts, e.g. acids. In this way, guanidines can be prepared. As weak bases, carbodiimides bind to Lewis acids to give adducts.
Carbodiimides are reagents for the Moffatt oxidation, a protocol for conversion of an alcohol to a carbonyl using dimethyl sulfoxide as the oxidizing agent: Typically the sulfoxide and diimide are used in excess. The reaction generates dimethyl sulfide and a urea as byproducts.
Coupling agents
In synthesis, compounds containing the carbodiimide functionality are used as dehydration agents. Specifically they are often used to convert carboxylic acids to amides or esters. Additives, such as N-hydroxybenzotriazole or N-hydroxysuccinimide, are often added to increase yields and decrease side reactions. Polycarbodiimides can also be used as crosslinkers for aqueous resins, such a polyurethane dispersions or acrylic dispersion. Here the polycarbodiimide reacts with carboxylic acids, which functional groups are often present in such aqueous resins, to form N-acyl urea. The result is that there have formed covalent bonds between the polymer chains, which have thus become crosslinked.
Amide formation mechanism
The formation of an amide using a carbodiimide is straightforward, but with several side reactions complicating the subject. The acid 1 will react with the carbodiimide to produce the key intermediate: the O-acylisourea 2, which can be viewed as a carboxylic ester with an activated leaving group. The O-acylisourea will react with amines to give the desired amide 3 and urea 4. The side reaction of the O-acylisourea 2 produce both desired and undesired products. The O-acylisourea 2 can react with an additional carboxylic acid1 to give an acid anhydride5, which can react further to give the desired amide 3. The main undesired reaction pathway involves the rearrangement of the O-acylisourea 2 to the stable N-acylurea 6. The use of solvents with low-dielectric constants such as dichloromethane or chloroform can minimize this side reaction.
Examples
DCC
DCC was one of the first carbodiimides developed as a reagent. It is widely used for amide and ester formation, especially for solid-phase peptide synthesis. DCC has achieved popularity mainly because of its high yielding amide coupling reactions and the fact that it is quite inexpensive. However, DCC does have some serious drawbacks, and its use is often avoided for several reasons:
The byproduct N,N'-dicyclohexylureais mostly removed by filtration, but trace impurities can be difficult to remove. It is incompatible with traditional solid-phasepeptide synthesis.
DCC is a potent allergen, repeated contact with skin increases the probability of sensitization to the compound. Clinical reports of individuals who cannot enter rooms where peptide coupling agents are used have been reported.
For alternative to DCC in coupling see at : http://www.biocis.u-psud.fr/IMG/pdf/Coupling_Reagents.pdf
DIC
In contrast to DCC, DIC is a liquid. Its hydrolysis product N,N'-diisopropylurea is soluble in organic solvents.
EDC
EDC is a water-soluble carbodiimide reagent used for a wide range of purposes. Apart from uses related to DCC and DIC, it is also used for various biochemical experiments as a crosslinker or chemical probe.
CMCT or CMC
1-cyclohexyl-carbodiimide metho-p-toluene sulfonate is a carbodiimide developed for the chemical probing of RNA structure in biochemistry.
