N,N'-Dicyclohexylcarbodiimide

N,N'-Dicyclohexylcarbodiimide
IUPAC name N,N'-dicyclohexylcarbodiimide
Other names Cyclohexanamine, DCC
Identifiers
CAS number	538-75-0
PubChem	10868
ChemSpider	10408 Y
ChEBI	CHEBI:53090
ChEMBL	CHEMBL162598 Y
RTECS number	FF2160000
Jmol-3D images	Image 1
SMILES N(=C=N\C1CCCCC1)\C2CCCCC2
InChI InChI=1S/C13H22N2/c1-3-7-12(8-4-1)14-11-15-13-9-5-2-6-10-13/h12-13H,1-10H2 Y Key: QOSSAOTZNIDXMA-UHFFFAOYSA-N Y InChI=1/C13H22N2/c1-3-7-12(8-4-1)14-11-15-13-9-5-2-6-10-13/h12-13H,1-10H2 Key: QOSSAOTZNIDXMA-UHFFFAOYAO
Properties
Molecular formula	C13H22N2
Molar mass	206.33 g mol−1
Appearance	white crystalline powder
Density	1.325 g/cm3, solid
Melting point	34 °C, 307 K, 93 °F
Boiling point	122°C (395 K at 6 mmHg)
Solubility in water	not soluble
Hazards
R-phrases	R22 R24 R41 R43
S-phrases	S24 S26 S37/39 S45
NFPA 704	1 3 0
Flash point	113 °C
Related compounds
Related carbodiimides	N,N'-diisopropylcarbodiimide, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

For other uses, see DCC (disambiguation).

N,N'-Dicyclohexylcarbodiimide is an organic compound with chemical formula C₁₃H₂₂N₂ whose primary use is to couple amino acids during artificial peptide synthesis. Under standard conditions, it exists in the form of white crystals with a heavy, sweet odor. The low melting point of this material allows it to be melted for easy handling. It is highly soluble in dichloromethane, tetrahydrofuran, acetonitrile and dimethylformamide, but insoluble in water. The compound is often abbreviated DCC.

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.^[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.^[2]

Preparation

Of the several syntheses of DCC, Pri-Bara et al. use palladium acetate, iodine, and oxygen to couple cyclohexyl amine and cyclohexyl isocyanide.^[3] 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%:^[1]

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 triethylammonium chloride to give DCC in 50% yield.^[4]

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 insoluble in water. DCC can also be used to invert secondary alcohols.

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 and 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

Main article: Steglich 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.^[5]

DCC-promoted peptide coupling

During protein synthesis (such as Fmoc solid-state synthesizers), the N-terminus is often used as the attachement 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.

See also

• Carbodiimide

References

1. ^ ^{a b} Jiansheng Tang, Thyagarajan Mohan, John G. Verkade (1994). "Selective and Efficient Syntheses of Perhydro-1 ,3,5-triazine-2,4,6-trioneasn d Carbodiimides from Isocyanates Using ZP(MeNCH2CH2)sN Catalysts". J. Org. Chem. 59: 4931–4938. doi:10.1021/jo00096a041. 
2. ^ Issa Yavari, John D. Roberts (1978). "Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy. Carbodiimides". J. Org. Chem. 43: 4689–4690. doi:10.1021/jo00419a001. 
3. ^ Ilan Pri-Bara and Jeffrey Schwartz (1997). "N,N-Dialkylcarbodiimide synthesis by palladium-catalysed coupling of amines with isonitriles". Chem Commun 4: 347. doi:10.1039/a606012i. 
4. ^ Zsuzsa Jaszay, Imre Petnehazy, Laszlo Toke, Bela Szajani (1987). "Preparation of Carbodiimides Using Phase-Transfer Catalysis". Synthesis 5: 520–523. doi:10.1055/s-1987-27992. 
5. ^ B. Neises, W. Steglich (1990), "Esterification of Carboxylic Acids with Dicyclohexylcarbodiimide/4-Dimethylaminopyridine: Tert-Butyl Ethyl Fumarate", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv7p0093 ; Coll. Vol. 7: 93 

External links

• An excellent illustration of this mechanism can be found here: [1].