''N'',''N''′-Dicyclohexylcarbodiimide (DCC or DCCD) is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the chemical formula (C₆H₁₁N)₂C. It is a waxy white solid with a sweet odor. Its primary use is to couple

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

during artificial

peptide synthesis In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl ...

. The low melting point of this material allows it to be melted for easy handling. It is highly soluble in

dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible with ...

tetrahydrofuran Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is ma ...

acetonitrile Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula and structure . This colourless liquid is the simplest organic nitrile (hydrogen cyanide is a simpler nitrile, but the cyanide anion is not clas ...

and

dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the majo ...

, but insoluble in

water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...

Structure and spectroscopy

The C−N=C=N−C core of carbodiimides (N=C=N) is linear, being related to the structure of

allene In organic chemistry, allenes are organic compounds in which one carbon atom has double bonds with each of its two adjacent carbon centres (). Allenes are classified as cumulated dienes. The parent compound of this class is propadiene, which ...

. The molecule has idealized C₂ symmetry. The N=C=N moiety gives characteristic IR spectroscopic signature at 2117 cm⁻¹. The ¹⁵N

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...

spectrum shows a characteristic shift of 275 ppm upfield of

nitric acid Nitric acid is the inorganic compound with the formula . It is a highly corrosive mineral acid. The compound is colorless, but older samples tend to be yellow cast due to decomposition into oxides of nitrogen. Most commercially available nitri ...

and the ¹³C NMR spectrum features a peak at about 139 ppm downfield from TMS.

Preparation

DCC is produced by the decarboxylation of cyclohexyl

isocyanate In organic chemistry, isocyanate is the functional group with the formula . Organic compounds that contain an isocyanate group are referred to as isocyanates. An organic compound with two isocyanate groups is known as a diisocyanate. Diisocyan ...

using phosphine oxides as a catalyst: :2 C₆H₁₁NCO → (C₆H₁₁N)₂C + CO₂ Alternative catalysts for this conversion include the highly nucleophilic OP(MeNCH₂CH₂)₃N.

Other methods

Of academic interest,

palladium acetate Palladium(II) acetate is a chemical compound of palladium described by the formula d(O2CCH3)2sub>n, abbreviated d(OAc)2sub>n. It is more reactive than the analogous platinum compound. Depending on the value of n, the compound is soluble in man ...

, iodine, and oxygen can be used to couple cyclohexyl amine and cyclohexyl

isocyanide An isocyanide (also called isonitrile or carbylamine) is an organic compound with the functional group –. It is the isomer of the related nitrile (–C≡N), hence the prefix is ''isocyano''.IUPAC Goldboo''isocyanides''/ref> The organic fragme ...

. Yields of up to 67% have been achieved using this route: : C₆H₁₁NC + C₆H₁₁NH₂ + O₂ → (C₆H₁₁N)₂C + H₂O DCC has also been prepared from

dicyclohexylurea Dicyclohexylurea is an organic compound, specifically, a urea. It is the byproduct of the reaction of dicyclohexylcarbodiimide with amines or alcohols. It may be prepared by the reaction of cyclohexylamine Cyclohexylamine is an organic compound, ...

using a

phase transfer catalyst In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the transition of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic rea ...

. The disubstituted urea, arenesulfonyl chloride, and

potassium carbonate Potassium carbonate is the inorganic compound with the formula K2 CO3. It is a white salt, which is soluble in water. It is deliquescent, often appearing as a damp or wet solid. Potassium carbonate is mainly used in the production of soap and gl ...

react in toluene in the presence of benzyl triethylammonium chloride to give DCC in 50% yield. : left, Phase transfer catalysis

Reactions

Amide, peptide, and ester formation

DCC is a dehydrating agent for the preparation of

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

s, and

nitrile In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix ''cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

s. In these reactions, DCC hydrates to form dicyclohexylurea (DCU), a compound that is nearly insoluble in most organic solvents and insoluble in water. The majority of the DCU is thus readily removed by filtration, although the last traces can be difficult to eliminate from non-polar products. DCC can also be used to invert

secondary alcohol In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is ...

s. In the Steglich esterification, alcohols, including even some tertiary alcohols, can be esterified using a carboxylic acid in the presence of DCC and a catalytic amount of DMAP. In protein synthesis (such as Fmoc solid-state synthesizers), the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

is often used as the attachment site on which the amino acid

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

s are added. To enhance the

electrophilicity In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carri ...

carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...

group, the negatively charged oxygen must first be "activated" into a better

leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited ...

. DCC is used for this purpose. The negatively charged oxygen will act as a

nucleophile In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

, attacking the central carbon in DCC. DCC is temporarily attached to the former carboxylate group forming a highly electrophilic intermediate, making

nucleophilic attack In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

by the terminal amino group on the growing peptide more efficient.

Moffatt oxidation

In combination with

dimethyl sulfoxide Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds a ...

(DMSO), DCC effects the Pfitzner-Moffatt oxidation. This procedure is used for the oxidation of alcohols to

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

s and ketones. Unlike metal-mediated

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

s, such as the

Jones oxidation The Jones oxidation is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones. The reaction was an early method for the oxidation o ...

, the reaction conditions are sufficiently mild to avoid over-oxidation of aldehydes to carboxylic acids. Generally, three equivalents of DCC and 0.5 equivalents of proton source in DMSO are allowed to react overnight at room temperature. The reaction is quenched with acid.

Other reactions

*Reaction of an acid with hydrogen peroxide in presence of DCC leads to formation of peroxide linkage. *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 *Secondary alcohols can be stereochemically inverted by formation of a formyl ester followed by

saponification Saponification is a process of converting esters into soaps and alcohols by the action of aqueous alkali (for example, aqueous sodium hydroxide solutions). Soaps are salts of fatty acids, which in turn are carboxylic acids with long carbon chains. ...

. The secondary alcohol is mixed directly with DCC,

formic acid Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid, and has the chemical formula HCOOH and structure . It is an important intermediate in chemical synthesis and occurs naturally, most notably in some ants. Es ...

, and a strong base such as

sodium methoxide Sodium methoxide is the simplest sodium alkoxide. With the formula , it is a white solid, which is formed by the deprotonation of methanol. Itis a widely used reagent in industry and the laboratory. It is also a dangerously caustic base. P ...

. *In the presence of DMAP, DCC self-condenses two molecules of phenylacetic acid and its substituted derivatives to produce a bisbenzyl ketone.

Biological action

DCC is a classical inhibitor of ATP synthase. DCC inhibits ATP synthase by binding to one of the ''c'' subunits and causing steric hindrance of the rotation of the F_O subunit.

Safety

DCC is a potent allergen and a sensitizer, often causing skin rashes.

References

External links

* An excellent illustration of this mechanism can be found here

{{DEFAULTSORT:Dicyclohexylcarbodiimide, N,N'- Dehydrating agents Peptide coupling reagents Carbodiimides Biochemistry Biochemistry methods Reagents for biochemistry Allergology Sweet-smelling chemicals Cyclohexyl compounds