N,N'-Dicyclohexylcarbodiimide
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2008-07-10T08:33:00Z
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{{Chembox new
| Name = Dicyclohexylcarbodiimide
| ImageFile = DCC Structure.png
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| ImageName = Dicyclohexylcarbodiimide
| ImageFile1 = DCC-3D-balls.png
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| IUPACName = N,N'-dicyclohexylcarbodiimide
| OtherNames = Cyclohexanamine, DCC
| Section1 = {{Chembox Identifiers
| SMILES = C2(CCCCC2)N=C=N<br />C1CCCCC1
| CASNo = 538-75-0
| RTECS = FF2160000
}}
| Section2 = {{Chembox Properties
| Formula = C<sub>13</sub>H<sub>22</sub>N<sub>2</sub>
| MolarMass = 206.33 g/mol
| Appearance = white crystalline powder
| Density = 1.325 g/cm<sup>3</sup>, solid
| Solubility = not soluble
| Solvent = other solvents
| SolubleOther = 0.1 g/ml
| MeltingPt = 34°C (307 K)
| BoilingPt = 122°C (395 K)
}}
| Section7 = {{Chembox Hazards
| ExternalMSDS =
| NFPA-H = 3
| NFPA-F = 1
| NFPA-R =
| FlashPt = 113°C
| RPhrases = {{R22}}, {{R24}}, {{R41}}, {{R43}}
| SPhrases = {{S24}}, {{S26}}, {{S37/39}}, {{S45}}
}}
| Section8 = {{Chembox Related
| Function = [[carbodiimide]]s
| OtherFunctn = [[Carbodiimide#DIC|N,N'-diisopropylcarbodiimide]],</br>[[Carbodiimide#EDC|1-ethyl-3-(3-dimethyl</br>aminopropyl) carbodiimide</br>hydrochloride]]
}}
}}
'''Dicyclohexylcarbodiimide''' ('''DCC''') is an [[organic compound]] with chemical formula C<sub>13</sub>H<sub>22</sub>N<sub>2</sub> whose primary use is to couple [[amino acids]] during artificial [[peptide synthesis]]. Under standard conditions, DCC 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. DCC is highly soluble in [[dichloromethane]], [[tetrahydrofuran]], [[acetonitrile]] and [[dimethylformamide]], but insoluble in [[water (molecule)|water]].
==Structure and spectroscopy==
The C-N=C=N-C core of carbodiimides is nonplanar, being related to the structure of [[allene]]. Three principal resonance structures describe carbodiimides:
:RN=C=NR ↔ RN<sup>+</sup>≡C-N<sup>-</sup>R ↔ RN<sup>-</sup>-C≡N<sup>+</sup>R
The N=C=N moiety gives characteristic IR spectroscopic signature at 2117 cm<sup>-1</sup>.<ref name = tang/> The <sup>15</sup>N NMR spectrum shows a characteristic shift of 275.0 ppm upfield of nitric acid and the <sup>13</sup>C NMR spectrum features a peak at about 139 ppm downfield from TMS.<ref>{{cite journal| author= Issa Yavari, John D. Roberts| title= Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy. Carbodiimides| journal= J. Org. Chem.|volume= 43|year= 1978 |pages= 4689–4690|doi=10.1021/jo00419a001}}
</ref>
==Syntheses of DCC==
Of the several syntheses of DCC, Pri-Bara et al. use palladium acetate, iodine, and oxygen to couple cyclohexyl amine and cyclohexyl [[isocyanide]].<ref>{{cite journal| author= Ilan Pri-Bara and Jeffrey Schwartz|title= N,N-Dialkylcarbodiimide synthesis by palladium-catalysed coupling of amines with isonitriles| journal= Chem Commun| volume= 4|year= 1997|doi= 10.1039/a606012i|pages= 347}}</ref> Yields of up to 67% have been achieved using this route:
: C<sub>6</sub>H<sub>11</sub>NC + C<sub>6</sub>H<sub>11</sub>NH<sub>2</sub> + O<sub>2</sub> → (C<sub>6</sub>H<sub>11</sub>N)<sub>2</sub>C + H<sub>2</sub>O
Tang et al. condense two isocyanates using the catalyst OP(MeNCH<sub>2</sub>CH<sub>2</sub>)<sub>3</sub>N in yields of 92%:<ref name=tang>{{cite journal| author= Jiansheng Tang, Thyagarajan Mohan, John G. Verkade| title= Selective and Efficient Syntheses of Perhydro-1 ,3,5-triazine-2,4,6-trioneasn d Carbodiimides from Isocyanates Using ZP(MeNCH2CH2)sN Catalysts | journal=J. Org. Chem.| volume= 59|year= 1994|pages= 4931–4938|doi= 10.1021/jo00096a041}}</ref>
[[Image:DCC2.gif|center|Homogenous Catalysis]]
DCC has also been prepared from the [[urea]] using [[phase transfer catalysis]] by Jaszay et al. The disubstituted, arenesulfonyl chloride, and potassium carbonate react in the presence of benzyl trimethylammonium chloride.<ref>{{cite journal| author=Zsuzsa Jaszay, Imre Petnehazy, Laszlo Toke, Bela Szajani| title= Preparation of Carbodiimides Using Phase-Transfer Catalysis| journal= Synthesis| volume= 5| year= 1987|pages= 520–523| doi=10.1055/s-1987-27992}}
</ref>
[[Image:DCC3.gif|Thumb|Phase Transfer Catalysis]]
==Reactivity of DCC==
DCC is a dehydrating agent for the preparation of [[amide]]s, [[ketone]]s, [[nitrile]]s. In these reactions, DCC hydrates to form [[dicyclohexylurea]] (DCU), a compound that is insoluble in water. DCC can also be used to [[walden inversion|invert]] [[secondary alcohol]]s.
===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 [[alcohol]]s to [[aldehyde]]s and ketones. Unlike metal-mediated [[Redox|oxidations]], the reaction conditions are sufficiently mild to avoid over-oxidation of aldehydes to [[carboxylic acid]]s. 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:
[[Image:Moffatt primary.gif|Thumb|Oxidation of a primary alcohol, secondary alcohols proceed similarly]]
===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' + (C<sub>6</sub>H<sub>11</sub>N)<sub>2</sub>C → RCH=CHR' + (C<sub>6</sub>H<sub>11</sub>NH)<sub>2</sub>CO
===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, [[formaldehyde]], 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 [[4-Dimethylaminopyridine|DMAP]].<ref>{{OrgSynth | title = Esterification of Carboxylic Acids with Dicyclohexylcarbodiimide/4-Dimethylaminopyridine: Tert-Butyl Ethyl Fumarate | author = B. Neises, W. Steiglich | collvol = 7 | collvolpages = 93 | year = 1990 | prep = cv7p0093}}</ref>
==DCC-promoted peptide coupling==
During protein synthesis (such as [[Fmoc]] [[Peptide synthesis|solid-state synthesizers]]), the [[C-terminus]] is often used as the attachement site on which the amino acid [[monomer]]s are added. To enhance the [[electrophile|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 (which is now an [[ester]] group), making [[nucleophilic substitution|nucleophilic attack]] by an amino group (on the attaching amino acid) on the former C-terminus more efficient.
==Safety==
DCC is a potent allergen and a sensitizer, often causing skin rashes.
==See also==
* [[Carbodiimide]]
==References==
<references/>
==External links==
* An excellent illustration of this mechanism can be found here: [http://chemistry2.csudh.edu/rpendarvis/AmAcSeqSyn.html].
[[Category:Organic compounds]]
[[de:Dicyclohexylcarbodiimid]]
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