Dicyclohexylcarbodiimide
General
Systematic name	N,N'-dicyclohexylcarbodiimide
Other names	Cyclohexanamine, DCC
Molecular formula	C13H22N2
SMILES	C2(CCCCC2)N=C=N C1CCCCC1
Molar mass	206.33 g/mol
Appearance	white crystalline powder
CAS number	[538-75-0]
Properties
Density and phase	1.325 g/cm3, solid
Solubility in water	not soluble
Solubility in dichloromethane	0.1 g/ml
Melting point	34°C (307 K)
Boiling point	122°C (395 K)
Hazards
MSDS	External MSDS
Main hazards	Corrosive (C), Toxic (T)
NFPA 704	Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... This article does not cite its references or sources. ... The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings. ... Molar mass is the mass of one mole of a chemical element or chemical compound. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... In physics, density is mass m per unit volume V. For the common case of a homogeneous substance, it is expressed as: where, in SI units: ρ (rho) is the density of the substance, measured in kg·m-3 m is the mass of the substance, measured in kg V is... In the physical sciences, a phase is a set of states of a macroscopic physical system that have relatively uniform chemical composition and physical properties (i. ... Solubility refers to the ability for a given substance, the solute, to dissolve in a solvent. ... “HOH” redirects here. ... Solubility refers to the ability for a given substance, the solute, to dissolve in a solvent. ... Dichloromethane or Methylene chloride is a chemical compound widely used as a solvent for organic materials. ... The melting point of a crystalline solid is the temperature at which it changes state from solid to liquid. ... The boiling point of a substance is the temperature at which it can change its state from a liquid to a gas throughout the bulk of the liquid at a given pressure. ... An example MSDS in a US format provides guidance for handling a hazardous substance and information on its composition and properties. ... The examples and perspective in this article or section may not represent a worldwide view. ... NFPA 704 is a standard maintained by the U.S. National Fire Protection Association. ... Image File history File links NFPA_704. ... 1 3 0
Flash point	113°C
R/S statement	R: R22, R24, R41, R43 S: S24, S26, S37/39, S45
RTECS number	FF2160000
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Related compounds
Related carbodiimides	N,N'-diisopropylcarbodiimide, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride
Except where noted otherwise, data are given for materials in their standard state (at 25°C, 100 kPa) Infobox disclaimer and references

Dicyclohexylcarbodiimide (DCC) is an organic compound with chemical formula C₁₃H₂₂N₂ whose primary use is to couple amino acids during artificial protein 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. The flash point of a flammable liquid is the lowest temperature at which it can form an ignitable mixture with air. ... Risk and Safety Statements, also known as R/S statements, R/S numbers, R/S phrases, and R/S sentences, is a system of hazard codes and phrases for labeling dangerous chemicals and compounds. ... R-phrases are defined in Annex III of European Union Directive 67/548/EEC: Nature of special risks attributed to dangerous substances and preparations. ... S-phrases are defined in Annex IV of European Union Directive 67/548/EEC: Safety advice concerning dangerous substances and preparations. ... RTECS, also known as Registry of Toxic Effects of Chemical Substances, is a database of toxicity information compiled from the open scientific literature that is available for charge. ... The refractive index (or index of refraction) of a medium is a measure for how much the speed of light (or other waves such as sound waves) is reduced inside the medium. ... The relative dielectric constant of a material under given conditions is a measure of the extent to which it concentrates electrostatic lines of flux. ... Ultraviolet-Visible Spectroscopy or Ultraviolet-Visible Spectrophotometry (UV/ VIS) involves the spectroscopy of photons (spectrophotometry). ... Infrared spectroscopy (IR Spectroscopy) is the subset of spectroscopy that deals with the IR region of the EM spectrum. ... Nuclear Magnetic Resonance Spectroscopy most commonly known as NMR Spectroscopy is the name given to the technique which exploits the magnetic properties of nuclei. ... Mass spectrometry (also known as mass spectroscopy (deprecated)[1] or informally, mass-spec and MS) is an analytical technique used to measure the mass-to-charge ratio of ions. ... A carbodiimide is a functional group consisting of the formula N=C=N. Carbodiimides hydrolyze to form ureas, which makes them rarely found in nature. ... A carbodiimide is a functional group consisting of the formula N=C=N. Carbodiimides hydrolyze to form ureas, which makes them rarely found in nature. ... A carbodiimide is a functional group consisting of the formula N=C=N. Carbodiimides hydrolyze to form ureas, which makes them rarely found in nature. ... In chemistry, the standard state of a material is its state at 1 bar (100 kilopascals) and 25 degrees Celsius (298. ... Benzene is the simplest of the arenes, a family of organic compounds An organic compound is any member of a large class of chemical compounds whose molecules contain carbon and hydrogen; therefore, carbides, carbonates, carbon oxides and elementary carbon are not organic (see below for more on the definition controversy... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Dichloromethane or Methylene chloride is a chemical compound widely used as a solvent for organic materials. ... For other uses of THF, see THF (disambiguation) Tetrahydrofuran is a heterocyclic organic compound. ... Acetonitrile is an organic molecule, often used as a solvent, with the chemical formula of CH3CN. Also known as methyl cyanide, it is the simplest of the organic nitriles. ... Dimethylformamide (DMF, N,N-dimethylformamide) is a clear liquid, miscible with water and majority of organic solvents. ... “HOH” redirects here. ...

It should be handled with caution because it is a potent allergen and a sensitizer, often causing allergic reactions, particularly skin rashes.

Structure

The structure of DCC is not a planar structure as shown in the simplified picture above. Two resonance structures are available to DCC and elucidate the structure of this molecule:

DCC resonance structures

These structures show that the central N=C=N moiety does remain linear, however, the cyclohexyl groups are not confined to a particular geometry. Also, a lack of pi bonding between the two nitrogens and the cyclohexyl groups allows them to rotate on the N-C bond axis. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ...

Synthesis 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. Yields of up to 67% have been achieved using this reaction scheme. The reaction is as follows:

Tang et al. condense two isocyanates using the catalyst OP(MeNCH₂CH₂)₃N in yields of 92%. The reaction is as follows: Image File history File links No higher resolution available. ...

Lastly, a method for the synthesis of DCC involving a phase transfer catalyst has been published by Jaszay et al. The disubstituted, arenesulfonyl chloride, and potassium carbonate react in the presence of benzyl trimethylammonium chloride. Image File history File links No higher resolution available. ...

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The N=C=N moiety gives characteristic IR spectroscopic signature at 2117 cm^-1 (Tang et al.). ¹⁵N NMR shows a characteristic shift of 275.0 ppm upfield of nitric acid. ¹³C NMR of this compound contains a peak at about 139 ppm downfield from TMS depending on solvent choice (DMSO or Chloroform).

Reactivity of DCC

DCC is a strong dehydrating agent for the preparation of amides, ketones, nitriles, and can invert secondary alcohols. During reaction, it hydrates to form dicyclohexylurea (DCU), an insoluble compound. Amide functional group In chemistry, an amide is one of two kinds of compounds: - the organic functional group characterized by a carbonyl group (C=O) linked to a nitrogen atom (N), or a compound that contains this functional group (pictured to the right); or - a particular kind of nitrogen anion. ... Ketone group A ketone(key tone) is either the functional group characterized by a carbonyl group (O=C) linked to two other carbon atoms or a chemical compound that contains this functional group. ... A nitrile is any organic compound which has a -C≡N functional group. ... In chemistry Walden inversion is the inversion of configuration of a chiral centre in a molecule in a chemical reaction. ... In general usage, alcohol (from Arabic al-khwl الكحول, or al-ghawl الغول) refers almost always to ethanol, also known as grain alcohol, and often to any beverage that contains ethanol (see alcoholic beverage). ...

Moffatt Oxidation The Pfitzner-Moffatt oxidation is a chemical reaction which describes the oxidation of primary and secondary alcohols by reaction with dicyclohexylcarbodiimide (DCC) and dimethyl sulfoxide (DMSO). ...

A solution of DCC and dimethylsulfoxide (DMSO) is used in a reaction termed the Pfitzner-Moffatt oxidation. This procedure is used for the gentle oxidation of alcohols to aldehydes and ketones. Unlike metal-mediated oxidations, the reaction conditions are sufficiently mild to halt over-oxidation of aldehydes to carboxylic acids. Generally, 1 equivalent of the alcohol to be oxidized is mixed with 3 equiv DCC and a proton source (0.5 equiv) in DMSO and left to react overnight at room temperature. The reaction is quenched by the addition of acid. Dimethyl Sulfoxide (DMSO, empirically C2H6OS), also known as methyl sulfoxide or sulfinylbismethane, is a chemical compound. ... The Pfitzner-Moffatt oxidation is a chemical reaction which describes the oxidation of primary and secondary alcohols by reaction with dicyclohexylcarbodiimide (DCC) and dimethyl sulfoxide (DMSO). ... Functional group of an alcohol molecule. ... An aldehyde. ... Ketone group A ketone(key tone) is either the functional group characterized by a carbonyl group (O=C) linked to two other carbon atoms or a chemical compound that contains this functional group. ... Illustration of a redox reaction Redox (shorthand for oxidation/reduction reaction) describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed. ... Structure of a carboxylic acid The 3D structure of the carboxyl group A space-filling model of the carboxyl group Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -C(=O)OH, usually written -COOH or -CO2H. [1] Carboxylic acids are Bronsted...

Primary alcohols:

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Secondary alcohols:

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Dehydroxylation

Alcohols can also be dehydroxylated using DCC. This reaction proceeds by first forming an O-acylurea intermediate which is then hydrogenolyzed to produce the corresponding alkane.

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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. Saponification of a lipid with potassium hydroxide. ... The chemical compound formaldehyde (also known as methanal) is a gas with a pungent smell. ... An alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. ...

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.^[1] Chemical structure of DMAP 4-Dimethylaminopyridine, abbreviated as DMAP, is an nucleophilic catalyst which catalysis a variety of reactions. ...

Mechanism of DCC-promoted peptide coupling

During artificial protein synthesis (such as Fmoc solid-state synthesizers), the C-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 (which is now an ester group), making nucleophilic attack by an amino group (on the attaching amino acid) on the former C-terminus more efficient. It has been suggested that solid phase peptide synthesis be merged into this article or section. ... The C-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free carboxyl group (COOH). ... In chemistry, a monomer (from Greek mono one and meros part) is a small molecule that may become chemically bonded to other monomers to form a polymer. ... In chemistry, an electrophile (literally electron-lover) is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile. ... Structure of a carboxylic acid Carboxylic acids, also known as alkanoic acids, are organic acids characterized by the presence of a carboxyl group and have the general chemical formula R-C(=O)-OH, also written as R-COOH, where R is a hydrogen or an alkyl group. ... A leaving group is an atom or molecule that detaches from an organic molecule, which, after detachment, is called the residual or main part. ... In chemistry, a nucleophile (literally nucleus lover) is a reagent which is attracted to centres of positive charge. ... General formula of a carboxylate ester. ... In chemistry, nucleophilic substitution is a class of substitution reaction in which an electron-rich nucleophile attacks a molecule and replaces a group or atom, called the leaving group. ...

External links

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

• Links to external chemical sources

Notes

1. ^ B. Neises, W. Steiglich, Organic Syntheses, Coll. Vol. 7, p.93 (1990); or Vol. 63, p.183 (1985).

References

1. Ilan Pri-Bara and Jeffrey Schwartz (1997). "N,N-Dialkylcarbodiimide synthesis by palladium-catalysed coupling of amines with isonitriles". Chem Commun 4. DOI:10.1039/a606012i. 
2. 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. 
3. Issa Yavari, John D. Roberts (1978). "Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy. Carbodiimides". J. Org. Chem. 43: 4689-4690. DOI:10.1021/jo00419a001. 
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. 

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

See also

• Carbodiimide