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. Diaryl derivatives tend to convert to dimers and polymers upon standing at room temperature.
Structure and bonding
- RN=C=NR ↔ RN+≡C-N−R ↔ RN−-C≡N+R
Relevant to the significance of the polar resonance structures, no carbodiimide has been separated into its optical isomers.
The N=C=N core is nearly linear and the C-N=C angle is approximately 120″. The C=N distances are short, near 1.20 Å, characteristic of double bonds. The molecule are chiral, possessing C2-symmetry.
From thioureas and ureas
- (R(H)N)2CS + HgO → (RN)2C + HgS + H2O
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:
- (R(H)N)2CO → (RN)2C + H2O
- 2 RC=N=O → (RN)2C + CO2
Carbodiimides exhibit the reactivity characteristic of CO2, but is less electrophilic. Nucleophiles add to carbon. In this way, specialty guanidines can be prepared. As weak bases, carbodiimides bind to Lewis acids to give adducts.
- (CH3)2SO + (CyN)2C + R2CHOH → (CH3)2S + (CyNH)2CO + R2C=O
In synthetic, 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 acid 1 to give an acid anhydride 5, 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.
DCC (acronym for N,N'-dicyclohexylcarbodiimide) 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-phase peptide 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 (Coupling Reagents BOP, DCC) at : http://www.biocis.u-psud.fr/IMG/pdf/Coupling_Reagents.pdf
In contrast to DCC, DIC (acronym for N,N'-diisopropylcarbodiimide) is a liquid and its hydrolysis product N,N'-diisopropylurea, is soluble in organic solvents.
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-(2-morpholinoethyl)carbodiimide metho-p-toluene sulfonate is a carbodiimide developed for the chemical probing of RNA structure in biochemistry.
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