538-75-0

Basic information

• Product Name: Dicyclohexylcarbodiimide
• Synonyms: N,N'-DICYLOHEXYLCARBODIIMIDE;N,N-DICYCHOHEXYLCARBODIIMIDE;N,N-DICYCLOHEXYL CARBODIIMIDE;N,N'-DICYCLOHEXYLCARBODIIMIDE;1,3-DICYCLOHEXYLCARBODIIMIDE;Bis(cyclohexyl)carbodiimide;DCCI;DCC
• CAS NO: 538-75-0
• Molecular Formula: C₁₃H₂₂N₂
• Molecular Weight: 206.33
• EINECS: 208-704-1
• Product Categories: Pharmaceutical Intermediates;Amino Acid Derivatives;Starting Raw Materials & Intermediates;Miscellaneous;Organics;Coupling Reagent;Peptide Coupling Reagents;Condensing Agents (DNA / RNA Synthesis);Biochemistry;Condensation & Active Esterification;Coupling Reactions (Peptide Synthesis);Nucleosides, Nucleotides & Related Reagents;Peptide Synthesis;Protecting Agents, Phosphorylating Agents & Condensing Agents;Reagents for Oligosaccharide Synthesis;Synthetic Organic Chemistry;Peptide;Protected Amino Acids;Synthetic Reagents;CarbodiimidesSynthetic Reagents;Carbodiimides;Coupling;Peptide Synthesis;peptides;Zero-Length Crosslinker
• Mol File: 538-75-0.mol

Chemical Properties

• Melting Point: 34-35 °C(lit.)
• Boiling Point: 122-124 °C6 mm Hg(lit.)
• Flash Point: 190 °F
• Appearance: White to pale yellow/Waxy Solid or Crystalline Mass
• Density: 1.247 g/mL at 25 °C
• Vapor Pressure: 1.044-1.15Pa at 20-25℃
• Refractive Index: n20/D 1.48
• Storage Temp.: Store at RT.
• Solubility: methylene chloride: 0.1 g/mL, clear, colorless
• Water Solubility: Reaction
• Sensitive: Moisture Sensitive
• Stability: Stable, but moisture sensitive. Combustible. Incompatible with strong oxidizing agents. Avoid exposure to air or moisture.
• Merck: 14,3096
• BRN: 610662
• CAS DataBase Reference: Dicyclohexylcarbodiimide(CAS DataBase Reference)
• NIST Chemistry Reference: Dicyclohexylcarbodiimide(538-75-0)
• EPA Substance Registry System: Dicyclohexylcarbodiimide(538-75-0)

Safety Data

• Hazard Codes: T,Xn,T+
• Statements: 23/24/25-34-40-43-41-36/38-21-24-22-62-37/38-10-61-26-38-20/22
• Safety Statements: 26-36/37/39-45-41-24-37/39-24/25-36-16-53-28
• RIDADR: UN 2922 8/PG 2
• WGK Germany: 3
• RTECS: FF2160000
• F: 3-8-10-21
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 538-75-0(Hazardous Substances Data)

Usage

Chemical Description

Dicyclohexylcarbodiimide is a coupling reagent used in organic synthesis.

Chemical Description

Dicyclohexylcarbodiimide is a coupling agent that is used to activate the carboxylic acid group of the amino acid.

Chemical Description

Dicyclohexylcarbodiimide is a coupling reagent used in the synthesis of p-Nitrophenyl benzyloxycarbonyl-D-asparaginate.

Uses

Used in Pharmaceutical Industry:
Dicyclohexylcarbodiimide is used as a dehydrating condensing agent for the synthesis of amikacin and glutathione dehydrants. It is also used in the synthesis of acid anhydride, aldehyde, ketone, and isocyanate. The reaction with DCC leads to the formation of dicyclohexylurea, which has very low solubility in organic solvents, facilitating easy separation of the reaction product.
Used in Peptide Synthesis:
Dicyclohexylcarbodiimide is used as a coupling reagent in peptide chemistry, facilitating the reaction between compounds with free carboxy and amino groups to form peptides. It is particularly useful in the synthesis of peptide and nucleic acid.
Used in Research and Development:
Dicyclohexylcarbodiimide is widely used in medical, health, makeup, and biological products, as well as other synthetic fields. It is also used as a dehydrating agent for the preparation of amides, ketones, nitriles, and in the inversion and esterification of secondary alcohols.

Preparation

A stirred mixture of N,N′-dicyclohexylurea (19.7 g), phosphorus pentoxide (100 g), sand (175 g), and pyridine (700 mL) was refluxed for 2.25 h. Stirring was no longer possible after about 30 min. The mixture was filtered and the residue was extracted with pyridine (100 mL). Pyridine was removed from the combined solutions on a flash evaporator, and the residual oil was extracted with boiling petroleum ether (bp 60–80 C°) (2 × 100 mL), and then with diethyl ether (100 mL). The combined extracts were washed with iced water (3×80 mL), dried over calcium chloride, and filtered. The solvents were removed from the filtrate under reduced pressure to give 17.4 g of an oil, which on distillation yielded 13.7 g (76%) of a clear liquid; bp 143 C° (3.5 mmHg), which solidified in the receiver; mp 34–35 C°. Another method for producing DCC from dicyclohexylurea is a two-step process using phosphoryl chloride in dichloromethane at 40 C° for 4 h under non-basic conditions followed by removal of acidic components with aq. sodium hydroxide. This method, which gives an 89% yield of DCC, has been presented in a patent application.

Preparation

Palladium acetate (22 mg, 0.1 mmol), iodine (50 mg, 0.2 mmol), and anhydrous sodium carbonate (320 mg, 3.0 mmol) were placed in a pressure vessel. Cyclohexylamine (0.11 mL, 1.0 mmol) and cyclohexyl isocyanide (0.1 mL, 0.8 mmol) were dissolved in acetonitrile (10 mL) and this solution was added to the reaction vessel, which was then pressurized with oxygen (40 psi) and heated to 100 C° for 3 h. The initially deep-red reaction mixture turned yellow-orange; no Pd black precipitation was observed. There was no obvious reaction rate dependence on oxygen pressure. The mixture was cooled to ambient temperature, depressurized, filtered, and analyzed by GC. DCC was isolated by evaporating the solvent and residual amine, followed by vacuum distillation. Palladium(II) complexes with a carbodiimide ligand, in which a nitrogen of the linear NbCbN moiety is bonded to the metal center, and bis(carbodiimido)palladium(II) complexes, both derived from isocyanides, have been described.

Reactivity Profile

Dicyclohexylcarbodiimide is an imide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx). Dicyclohexylcarbodiimide is incompatible with acids and oxidizing agents. Dicyclohexylcarbodiimide reacts with water.

Fire Hazard

Dicyclohexylcarbodiimide is probably combustible.

Flammability and Explosibility

Notclassified

Contact allergens

Used in peptide chemistry as a coupling reagent. It is both an irritant and a sensitizer and has caused contact dermatitis in pharmacists and chemists.

Potential Exposure

Laboratory reagent

Shipping

UN2928 Toxic solids, corrosive, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, 8- Corrosive material, Technical Name Required. UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1- Poisonous materials, Technical Name Required

Purification Methods

It is sampled as a liquid after melting in warm H2O. It is sensitive to air, and it is a potent skin irritant. It can be distilled in a vacuum and is best stored in a tightly stoppered flask in a freezer. It is very soluble in CH2Cl2 and pyridine where the reaction product with H2O, after condensation, is dicyclohexyl urea which is insoluble and can be filtered off. Alternatively dissolve it in CH2Cl2, add powdered anhydrous MgSO4, shake for 4hours, filter, evaporate and distil at 0.6mm pressure and oil bath temperature of 145o. [Bodansky et al. Biochemical Preparations 10, 122 1963, Schmidt & Seefelder Justus Liebigs Ann Chem 571 83 1951, Schmidt et al. Justus Liebigs Ann Chem 612 11 1958, Beilstein 12 IV 72.]

Incompatibilities

Dust may for explosive mixture with air. Reacts with steam and water. N,N0 - Dicyclohexylcarbodiimide is an amine/imide: contact with strong oxidizers may cause fire and explosions. Incompatible with acids, strong bases, strong reducing agents (may form flammable gasses); azo and diazo compounds (may form toxic gases); chlorinated hydrocarbons; nitro compounds. Contact with mixture of acetic acid 1 dinitrogen trioxide may cause explosion. The combustion of amide compounds generate nitrogen oxides (NOx). In the presence of moisture, may attack metals and plastics.

Waste Disposal

Whatever cannot be saved for recovery or recycling should be managed in an appropriate and approved waste facility. Although not a listed RCRA hazardous waste, this material may exhibit one or more characteristics of a hazardous waste and require appropriate analysis to determine specific disposal requirements. Processing, use or contamination of this product may change the waste management options. State and local disposal regulations may differ from federal disposal regulations. Dispose of container and unused contents in accordance with federal, state and local requirements

Synthetic route

1,3-Dicyclohexylurea (2387-23-7) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With dichloromethylenedimethyliminium chloride; triethylamine In dichloromethane at 0℃;	100%
With bis(trichloromethyl) carbonate In 1-methyl-pyrrolidin-2-one at 30 - 40℃; for 6h; Autoclave;	99.5%
With pyridine; chloroacetyl chloride In dichloromethane at 0 - 60℃; for 10h; Solvent; Temperature; Reagent/catalyst;	97.3%

1,3-dicyclohexylthiourea (1212-29-9) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With dicarbonyl(cyclopentadienyl)methyliron(II) In tetrahydrofuran at 60℃; for 24h; Reagent/catalyst; Inert atmosphere;	99%
With dicarbonyl(cyclopentadienyl)methyliron(II); Triethoxysilane In tetrahydrofuran at 60℃; for 24h; Schlenk technique; Inert atmosphere;	95%
With 1,1'-Thiocarbonyldi-2(1H)-pyridone In toluene for 8h; Heating;	94%

N,N'-Dicyclohexyl-C-chlor-formamidinium (114316-64-2) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With sodium hydroxide In water	92.4%

Cyclohexyl isocyanate (3173-53-3) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
O=P(MeNCH2CH2)3N at 200 - 230℃; for 91h;	92%
at 20 - 230℃; for 4h; Product distribution / selectivity; Molecular sieve;	30.8%
[C5H5Fe(CO)2]2 In xylene for 24h; Heating;	27%

1,3-dicyclohexylthiourea (1212-29-9) → 2-hydroxypyridin (142-08-5) + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With di-2-pyridyl thionocarbonate; dmap In acetonitrile at 80℃; for 15h;	A n/a B 84%

1,3-Dicyclohexylurea (2387-23-7) + triphenylphosphine (603-35-0) → dicyclohexyl-carbodiimide (538-75-0) + Triphenylphosphine oxide (791-28-6)

Conditions	Yield
With aluminum oxide; LutClO4 constant current electrolysis;	A 72% B n/a
With aluminum oxide; LutClO4 In dichloromethane constant current electrolysis;	A 72% B n/a

1,3-dicyclohexylthiourea (1212-29-9) + triphenylphosphine (603-35-0) → dicyclohexyl-carbodiimide (538-75-0) + triphenylphosphine sulfide (3878-45-3)

Conditions	Yield
With aluminum oxide; LutClO4 In dichloromethane constant current electrolysis;	A 56% B n/a

1,3-dicyclohexylthiourea (1212-29-9) + triphenylphosphine (603-35-0) → dicyclohexyl-carbodiimide (538-75-0) + Triphenylphosphine oxide (791-28-6)

Conditions	Yield
With aluminum oxide; LutClO4 In dichloromethane constant current electrolysis;	A 56% B n/a

1,3-Dicyclohexylurea (2387-23-7) → Cyclohexyl isocyanide (931-53-3) + N-cyclohexylimidocarbonyl dichloride (2666-80-0) + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With sodium hydroxide; triethylamine In chloroform for 4h; Heating;	A 21% B 38% C 18%

Cyclohexyl isocyanide (931-53-3) + cyclohexylamine (108-91-8) → 1,3-Dicyclohexylurea (2387-23-7) + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With oxygen; sodium carbonate; palladium diacetate In acetonitrile at 100℃; under 2068.6 Torr; for 3h;	A 10 % Chromat. B 35%

Cyclohexyl isocyanide (931-53-3) + cyclohexylamine (108-91-8) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide In acetonitrile at 50℃; for 12h; Inert atmosphere; Electrochemical reaction;	26%
With iodine; oxygen; sodium carbonate; palladium diacetate In acetonitrile at 100℃; under 2068.6 Torr; for 3h;	67 % Chromat.
With air; gold In hexane at 20℃; for 0.166667h; Kinetics;
With Cumene hydroperoxide; iodine In tert-butyl methyl ether at 55℃; for 6h;	51 %Chromat.

Cyclohexyl isocyanate (3173-53-3) + 3-methyl-1-phenylphospholane (24901-29-9, 32721-26-9, 32721-27-0, 54932-28-4, 57664-94-5) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With xylene

1,3-Dicyclohexylurea (2387-23-7) + p-toluenesulfonyl chloride (98-59-9) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With pyridine

N-ethylmorpholine; (100-74-3) + C29H41N2O2PS2 (83599-89-7) → Dithiophosphoric acid O,O'-bis-(2,6-dimethyl-phenyl) ester; compound with 4-ethyl-morpholine + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
In dichloromethane

C29H41N2O2PS2 (83599-89-7) → C16H18O2PS2(1-) + dicyclohexyl-carbodiimide (538-75-0) + C29H41N2O2PS2*BF4(1-)*H(1+)

Conditions	Yield
In dichloromethane at 20℃; Rate constant; Product distribution; equilibrium studies, effect of addition of excess base or acid on the rate constants, effect of addition of triethylamine in various concentrations on the rate constants;

C29H41N2O2PS2 (83599-89-7) + triethylamine (121-44-8) → Dithiophosphoric acid O,O'-bis-(2,6-dimethyl-phenyl) ester; compound with triethyl-amine + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
In dichloromethane Mechanism;
In dichloromethane

C25H33N2O2PS2 (92366-10-4) → O,O-diphenyl dithiophosphate (55979-88-9) + dicyclohexyl-carbodiimide (538-75-0) + C25H33N2O2PS2*BF4(1-)*H(1+)

Conditions	Yield
In dichloromethane at 20℃; Rate constant; Product distribution; equilibrium studies, effect of addition of excess base or acid on the rate constants;

C37H57N2O2PS2 (92366-11-5) → C24H34O2PS2(1-) + dicyclohexyl-carbodiimide (538-75-0) + C37H57N2O2PS2*BF4(1-)*H(1+)

Conditions	Yield
In dichloromethane at 20℃; Rate constant; Product distribution; equilibrium studies, effect of addition of excess base or acid on the rate constants, effect of the initial substrate concentration on the rate constants;

C29H41N2O2PS2*BF4(1-)*H(1+) → C29H41N2O2PS2 (83599-89-7) + C16H18O2PS2(1-) + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; Product distribution; Rate constant; further amines, effect of base:substrate ratio on the product formation;

isothiocyanatocyclohexane (1122-82-3) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With silica gel 1.) CH2Cl2, controlled potential electrolysis, 2.) petroleum ether, ether, 200 deg C; Yield given. Multistep reaction;

N,N'-dicyclohexylselenourea (34656-93-4) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With oxygen; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran for 5h; Heating; Yield given;

Cyclohexyl isocyanide (931-53-3) → dicyclohexyl-carbodiimide (538-75-0) + N-benzyloxycarbonyl-alanine

Conditions	Yield
Multi-step reaction with 2 steps 1: Se, DBU / tetrahydrofuran / 1 h / Heating 2: DBU, O2 / tetrahydrofuran / 5 h / Heating View Scheme

cyclohexylamine (108-91-8) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 3-methyl-butan-1-ol 2: pyridine View Scheme

C37H37N2O5PW + diisopropyl-carbodiimide (693-13-0) → C31H29N2O5PW + dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;

C13H23ClN2*Cl2HO2P → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With triethylamine In tetrahydrofuran

Cyclohexyl isocyanate (3173-53-3) + cyclohexyl azide (19573-22-9) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
With triphenylphosphine In acetonitrile at 20℃;

carbon disulfide (75-15-0) + cyclohexylamine (108-91-8) → dicyclohexyl-carbodiimide (538-75-0)

Conditions	Yield
In water at 30℃;

O,O-dimethyl S-hydrogen phosphorothioate (1112-38-5) + dicyclohexyl-carbodiimide (538-75-0) → N-Dimethylphosphoryl-N,N'-dicyclohexylthiourea (87763-29-9)

Conditions	Yield
In diethyl ether Product distribution; Ambient temperature; other phosphoro acids investigated;	100%
In diethyl ether Ambient temperature;

bis(trifluoromethyl)trichlorophosphorane (353-77-5) + dicyclohexyl-carbodiimide (538-75-0) → C15H22Cl3F6N2P

Conditions	Yield
In tetrachloromethane Heating;	100%

tris(trifluoromethyl)phosphine dichloride (420-72-4) + dicyclohexyl-carbodiimide (538-75-0) → C16H22Cl2F9N2P

Conditions	Yield
In tetrachloromethane Heating;	100%

Trifluormethyl-phosphor-tetrachlorid (1066-48-4) + dicyclohexyl-carbodiimide (538-75-0) → C14H22Cl4F3N2P

Conditions	Yield
In tetrachloromethane Heating;	100%

2-hydroxy-2-thiono-5,5-dimethyl-1,3,2-dioxaphosphorinane (45734-11-0) + dicyclohexyl-carbodiimide (538-75-0) → 5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl 5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl-oxide (15762-04-6) + 1,3-dicyclohexylthiourea (1212-29-9)

Conditions	Yield
In acetonitrile Mechanism; Product distribution; Ambient temperature;	A 100% B 98%

3-(acetoxymethyl)-7α-chloro-Δ3-cephem-4-carboxylic acid 1,1-dioxide (126621-87-2) + dicyclohexyl-carbodiimide (538-75-0) → 3-acetoxymethyl-7α-chloro-4-spiro-<3'-(1'-cyclohexyl-4'-cyclohexylimino-2'-oxoazetidinyl)>-2-cephem 1,1-dioxide (129441-69-6, 129519-60-4, 148153-25-7)

Conditions	Yield
In dichloromethane for 0.0833333h; Product distribution; Mechanism; various cephalosporanic acid sulphones;	100%
In dichloromethane for 0.0833333h;	100%

dicyclohexyl-carbodiimide (538-75-0) → C13H22Cl5N2P

Conditions	Yield
With phosphorus pentachloride In tetrachloromethane Heating;	100%

dicyclohexyl-carbodiimide (538-75-0) + p-chlorobenzoic p-nitrophenyldiazoacetic anhydride (627892-65-3) → 4-Chloro-benzoic acid 1-cyclohexyl-4-[(Z)-cyclohexylimino]-2-(4-nitro-phenyl)-3-oxo-azetidin-2-yl ester

Conditions	Yield
dirhodium tetraacetate In benzene	100%

trans-4-oxo-2-pentenoic acid (2833-28-5) + dicyclohexyl-carbodiimide (538-75-0) → 1,3-dicyclohexyl-5-(2,2,2-trifluoro-1-trifluoromethylethyl)imidazolidine-2,4-dione

Conditions	Yield
With 2,4,6-trimethyl-pyridine In acetonitrile at 20℃;	100%

dicyclohexyl-carbodiimide (538-75-0) → (C6H11NH)2CN2C(C6H11NH)2 (53959-22-1)

Conditions	Yield
With hydrazine hydrate In tetrahydrofuran at 20℃; for 48h;	100%

morpholine (110-91-8) + dicyclohexyl-carbodiimide (538-75-0) + 4-nitrophenyl phosphate monoester bis(cyclohexylammonium) salt → 4-morpholinyl-N,N'-dicyclohexylcarboxamidinium p-nitrophenyl phosphomorpholidate

Conditions	Yield
In 2-methyl-propan-1-ol; water for 15h; Heating;	100%

Cp2Zr(N(2,6-Me2C6H3)C=N(SiMe3)N(SiMe3)) + dicyclohexyl-carbodiimide (538-75-0) → [(C5H5)2ZrN(C6H3(CH3)2)C(NC6H11)N(C6H11)]

Conditions	Yield
In benzene-d6 byproducts: Me3SiN=C=NSiMe3; (inert gas); an NMR tube charged with complex, 1,4-dimethoxybenzene and C6D6; carbodiimide added; not isolated, detected by NMR;	100%

2-bromophenylacetic acid (4870-65-9) + dicyclohexyl-carbodiimide (538-75-0) → 1,3-dicyclohexyl-5-phenylimidazolidine-2,4-dione

Conditions	Yield
With thymidine 5'-phosphate In dichloromethane at 20℃;	100%
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃;	98%

Trifluoromethanesulfonamide (421-85-2) + dicyclohexyl-carbodiimide (538-75-0) → N-[bis(cyclohexylamino)methylidene]-1,1,1-trifluoromethanesulfonamide (1338440-24-6)

Conditions	Yield
In dichloromethane at 20℃; for 6h;	100%
In dichloromethane for 6h;	100%
With nitromethane; copper dichloride for 2h; Milling; Green chemistry;	98%

1-benzylindole-3-carboxylic acid (27018-76-4) + dicyclohexyl-carbodiimide (538-75-0) → 2-(1-benzyl-1H-indole-3-carbonyl)-1,3-dicyclohexylisourea (1363386-89-3)

Conditions	Yield
With dmap In dichloromethane at 20℃; for 1.5h;	100%

cis-Octadecenoic acid (112-80-1) + N3,N6-di(tert-butoxycarbonyl)-3,6-diazaoctane-1,8-diol (167407-91-2) + dicyclohexyl-carbodiimide (538-75-0) → N,N'-di-tert-butylcarbonyl-N,N'-bis(2-hydroxyethyl)ethylenediamine dioleate (167951-93-1) + 1,3-Dicyclohexylurea (2387-23-7)

Conditions	Yield
dmap In n-heptane at 20 - 40℃; Product distribution / selectivity;	A n/a B 99.6%

2-Chloroaniline (95-51-2) + dicyclohexyl-carbodiimide (538-75-0) → N-o-chlorophenyl-N', N"-dicyclohexylguanidine (96405-47-9)

Conditions	Yield
With Sm[N(TMS)2]2(THF)3 at 20℃; for 0.25h; Inert atmosphere;	99.3%
Stage #1: o-chloroaniline With C76H124N6Nd2O6Si4 In neat (no solvent) for 0.166667h; Schlenk technique; Inert atmosphere; Stage #2: dicyclohexyl-carbodiimide In neat (no solvent) at 60℃; for 0.25h; Schlenk technique; Inert atmosphere;	98%
With C114H132N6O6Yb3*2C7H8 at 60℃; for 0.25h; Schlenk technique; Inert atmosphere;	98%

dicyclohexyl-carbodiimide (538-75-0) → N,N'-di-cyclohexylformamidine (2303-89-1)

Conditions	Yield
Stage #1: dicyclohexyl-carbodiimide With iron(II) tetrafluoroborate hexahydrate; phenylsilane; tris(2-diphenylphosphinoethyl)phosphine In tetrahydrofuran at 100℃; for 20h; Stage #2: With water Reagent/catalyst;	99%
With water; 5-methoxy-1,3,4-triphenyl-4,5-dihydro-1H-1,2-4-triazoline In 1,2-dimethoxyethane at 150℃; under 760.051 Torr; Inert atmosphere; Sealed tube; Microwave irradiation;	75%
With sodium tetrahydroborate In isopropyl alcohol
With hydrogen; palladium dihydroxide; barium sulfate In ethanol

carboxymethyltriphenylphosphoniumm chloride (7343-26-2) + dicyclohexyl-carbodiimide (538-75-0) → (1,3-dicyclohexylureidocarbonylmethyl)triphenylphosphonium chloride (80304-21-8)

Conditions	Yield
In dichloromethane for 0.0833333h;	99%

cyclohexylamine (108-91-8) + dicyclohexyl-carbodiimide (538-75-0) → N,N',N''-tricyclohexylguanidine (4833-41-4)

Conditions	Yield
With C24H50N5Si2Y In neat (no solvent) at 20℃; for 2h; Inert atmosphere; Schlenk technique;	99%
With zinc(II) oxide In toluene at 80℃; for 8h;	95%
In tert-butyl alcohol at 100℃; for 24h;	74%
With Zn-Al hydrotalcite In toluene at 110℃; for 12h; Sealed tube;	52%
In hexane at 90℃; for 48h; Inert atmosphere; Pressure tube;

dicyclohexyl-carbodiimide (538-75-0) + diphenylphosphane (829-85-6) → (Z)-N,N'-dicyclohexyl(diphenylphosphino)formamidine (643014-87-3, 810692-09-2)

Conditions	Yield
potassium hexamethylsilazane In tetrahydrofuran at 20℃; for 0.0833333h;	99%
With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃;	71%

cyclohexyl isoselenocyanate (4426-69-1) + dicyclohexyl-carbodiimide (538-75-0) → cyclohexyl-N-[3-cyclohexyl-4-(cyclohexylimino)-1,3-selenazetidin-2-ylidene]benzenamine

Conditions	Yield
In hexane for 12h; Heating;	99%

1,2,3,4-tetrahydroisoquinoline (91-21-4) + dicyclohexyl-carbodiimide (538-75-0) → (E)-N,N'-dicyclohexyl-3,4-dihydro-1H-isoquinoline-2-carboxamidine

Conditions	Yield
[Y((CH3)4C5Si(CH3)2N(phenyl))(trimethylsilylmethyl)(tetrahydrofuran)2] In benzene at 80℃; for 0.5h;	99%
[{Me2Si(C5Me4)(NPh)}Y(CH2SiMe3)(thf)2] In benzene at 80℃; for 0.5h;

2,6-diisopropylbenzenamine (24544-04-5) + dicyclohexyl-carbodiimide (538-75-0) → N,N"-dicyclohexyl-N'-2,6-diisopropylphenylguanidine

Conditions	Yield
[(Me3Si)2N]3Yb(μ-Cl)Li(THF)3 In tetrahydrofuran at 60℃; for 24h;	99%
With (C9H6CMe2CH2C5H4N-α)Y[N(SiHMe2)2]2 In toluene at 80℃; for 24h; Temperature; Schlenk technique; Glovebox; Inert atmosphere;	90%
With [Ph2B(tBuIm)2FeNDipp][K(18-C-6)THF2] In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	83%
With bis(tetrahydrofuran)calcium-bis[bis(trimethylsilyl)amide] In hexane at 80℃; for 2h;	55%
With [Cp*2(Me)Zr(μ-O)Zr(NMe2)2(μ-O)Zr(Me)Cp*2] In benzene-d6 at 80℃; for 7.3h; Temperature; Reagent/catalyst; Time; Inert atmosphere;

dicyclohexyl-carbodiimide (538-75-0) + 1,4-phenylenediamine (106-50-3) → 2',2'-(1,4-phenylene)bis(1,3-dicyclohexylguanidine) (5012-73-7)

Conditions	Yield
With diethylzinc In toluene at 50℃; for 2h;	99%
[(Me3Si)2N]3Yb(μ-Cl)Li(THF)3 In tetrahydrofuran at 60℃; for 4h;	96%
With [Li(THF)(DME)]3La[μ-η2η1(iPrN)2C(NC6H4p-Cl)]3 at 50℃; for 5h; Inert atmosphere;	95%

4-Isopropylaniline (99-88-7) + dicyclohexyl-carbodiimide (538-75-0) → N-(p-isopropylphenyl)-N',N''-dicyclohexylguanidine

Conditions	Yield
[(Me3Si)2N]3Yb(μ-Cl)Li(THF)3 In dichloromethane at 40℃; for 4h;	99%
With C23H40AlN In toluene at 25℃; for 1h; Inert atmosphere; Schlenk technique;	92%
With [Cp*2(Me)Zr(μ-O)Zr(NMe2)2(μ-O)Zr(Me)Cp*2] In benzene-d6 at 110℃; for 12h; Temperature; Reagent/catalyst; Time; Inert atmosphere;

1-amino-naphthalene (134-32-7) + dicyclohexyl-carbodiimide (538-75-0) → N',N''-dicyclohexyl-N-(1-naphthyl)guanidine

Conditions	Yield
With C24H34Al2N4 In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Schlenk technique;	99%
With C36H52N5O4Si2Yb In neat at 60℃; for 6h; Inert atmosphere;	97%
With [(1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene)Ga—Ga(1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene)] In benzene-d6 at 60℃; for 1.3h; Temperature; Schlenk technique; Sealed tube;	97%
[(Me3Si)2N]3Yb(μ-Cl)Li(THF)3 In tetrahydrofuran at 60℃; for 12h;	96%
Stage #1: dicyclohexyl-carbodiimide In neat (no solvent) at 80℃; for 0.166667h; Stage #2: 1-amino-naphthalene In neat (no solvent) at 80℃;	61%

aniline (62-53-3) + dicyclohexyl-carbodiimide (538-75-0) → N-phenyl-N',N-dicyclohexylguanidine (4833-42-5)

Conditions	Yield
With Sm[N(TMS)2]2(THF)3 at 20℃; for 0.166667h; Inert atmosphere;	99%
With [Li(THF)(DME)]3La[μ-η2η1(iPrN)2C(NC6H4p-Cl)]3 at 25℃; for 0.5h; Inert atmosphere;	99%
With (Me3SiNC(Ph)N(CH2)3NC(Ph)NSiMe3)Y[O2,6-(tBu)2-4-(Me)C6H2](DME) at 60℃; for 0.5h; Inert atmosphere; Schlenk technique;	99%

Upstream product

• 2387-23-7 1,3-Dicyclohexylurea 
• 98-59-9 p-toluenesulfonyl chloride 
• 1212-29-9 1,3-dicyclohexylthiourea 
• 100-74-3 N-ethylmorpholine; 
• 83599-89-7 C₂₉H₄₁N₂O₂PS₂ 
• 3173-53-3 Cyclohexyl isocyanate 
• 603-35-0 triphenylphosphine 
• 121-44-8 triethylamine 
• 92366-10-4 C₂₅H₃₃N₂O₂PS₂ 
• 92366-11-5 C₃₇H₅₇N₂O₂PS₂ 
• 1122-82-3 isothiocyanatocyclohexane 
• 931-53-3 Cyclohexyl isocyanide 
• 108-91-8 cyclohexylamine 
• 34656-93-4 N,N'-dicyclohexylselenourea 

Downstream Products

• 25664-08-8 4-hydroxymethyl-2-oxo-2λ⁵-[1,3,2]dioxaphospholan-2-ol 
• 93598-65-3 3-cyclohexyl-2-cyclohexylimino-6-methyl-2,3-dihydro-[1,3]oxazin-4-one 
• 100796-47-2 (4-nitro-phenyl)-phosphonic acid ethyl ester-[2]pyridylamide 
• 100517-59-7 (4-nitro-phenyl)-phosphonic acid methyl ester-[2]pyridylamide 
• 101865-05-8 N-(3,4-dimethoxyphenethyl)-2-(2-oxocyclohexyl)acetamide 
• 90275-36-8 5-phospho-α-D-ribofuranosyl-1,2-cyclic monophosphate 
• 4004-57-3 uridine 3',5'-cyclic monophosphate 
• 6453-60-7 2'-deoxythymidine 3',5'-cyclic monophosphate 
• 3080-42-0 N-cyclohexyl-N-(cyclohexylcarbamoyl)benzamide 
• 1738-93-8 N-(N-benzyloxycarbonyl-glycyl)-N,N'-dicyclohexyl-urea 
• 634-01-5 adenosine 2',3'-cyclic monophosphate 
• 25108-11-6 1-(octadecanoyl)-1,3-dicyclohexylurea 
• 638-08-4 stearic anhydride 
• 1199-01-5 2-phenylazlactone 

Relevant articles and documents

MIGRATION REVERSIBLE DE PHOSPHORYLE S-P N-P CONTROLEE PAR TRANSFERT DE PROTON, MODELE D'ACTIVATION PAR PHOSPHORYLATION

This work describes the reversible C-addition of a sterically hindered-P thiophosphoric ester to a carbodiimide, as a model of activated biotin.The formed intermediate, is found to be in equilibrium with the corresponding N-phosphorylated thiourea.The entire system is controlled by proton transfer and reversible.

Stimuli-Responsive Frustrated Lewis-Pair-Type Reactivity of a Tungsten Iminoazaphosphiridine Complex

Reactions of 3-imino-azaphosphiridine complexes 1 a,b with carbodiimides 2 a,b, isocyanates 3 a,b, and carbon dioxide are described. Whereas exchange of the carbodiimide unit occurs in the first case, an overall ring expansion takes place with phenyl isocyanate (3 a) and carbon dioxide to yield complexes 4 and 5 bearing novel 1,3,5-oxazaphospholane ligands; the isopropyl derivative 3 b did not react under these conditions. DFT calculations provide insight into the pathway of the reaction with carbon dioxide with model complex 1 c, revealing effects of initial non-covalent interactions with the substrate onto the ring bonding, thus triggering an initially masked frustrated Lewis-pair-type behavior.

Method for preparing N,N'-dicyclohexylcarbodiimide by using co-reactor

The invention discloses a method for preparing N,N'-dicyclohexylcarbodiimide by using a co-reactor. The method comprises the steps of maintaining an aqueous solution of cyclohexylamine in a strong alkaline environment in the same reactor, adding carbon disulfide into the same reactor, and adding sodium hypochlorite for oxidation to obtain N,N'-dicyclohexylcarbodiimide. According to the method, thetechnological process is simplified through the co-reactor reaction, generation of highly toxic and harmful gas is avoided, the safety risk of production is reduced, and then the purpose of environment-friendly and safe production is achieved.

Method for producing N,N'-dicyclohexyl carbodiimide

The invention discloses a preparation method of N,N'-dicyclohexyl carbodiimide. The method comprises the following steps: taking dicyclohexyl urea (DCU) and trichloromethyl carbonate (BTC) as raw materials, dissolving dicyclohexyl urea (DCU) in a solvent, uniformly stirring, cooling, adding trichloromethyl carbonate and a catalyst loaded on a molecular sieve, carrying out heat preservation reflux, cooling, adjusting the pH value to 8-9 by using alkali, filtering the reaction liquid, evaporating out the solvent, and carrying out reduced pressure distillation to obtain the product namely N,N'-dicyclohexyl carbodiimide. According to the present invention, the problems of strong odor, strong toxicity and heavy environmental pollution of the traditional process are fundamentally eliminated, and the method has characteristics of high safety coefficient, partial catalyst recycling, high catalysis efficiency, partial raw material recycling, less three wastes, high purity and high yield, and is suitable for industrial production.

Microwave-assisted method for synthesizing N,N'-dicyclohexyl carbodiimide

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing N,N'-dicyclohexyl carbodiimide through a microwave-assisted method. The method comprises the following steps: dissolving N,N'-dicyclohexyl urea in a solvent under microwave radiation, adding an oxidant and a catalyst loaded on a molecular sieve, and carrying out heat preservation reflux; adding a phase transfer catalyst, adjusting the pH value, and carrying out alkaline hydrolysis reaction; filtering, separating liquid, evaporating out the solvent, and carrying out reduced pressure distillation to obtain N,N'-dicyclohexyl carbodiimide. The catalyst loaded on the molecular sieve is large in specific surface area and high in catalytic efficiency; a microwave-assisted method is adopted, and a phase transfer catalyst is added, so that the problems of difficult two-phase reaction and incomplete reaction in the traditional process are solved, the reaction conversion rate is greatly improved, the reaction time is shortened, and the product has the characteristics of high purity and yield.

Preparation method of dicyclohexylcarbodiimide

The invention relates to a method for preparing dicyclohexylcarbodiimide by using recycled dicyclohexylurea, and the method comprises the following steps: adding the recycled dicyclohexylurea into a mixed system composed of water and an organic solvent, stirring, washing, filtering, and drying; uniformly stirring the dried dicyclohexylurea and an organic solvent, adding oxalyl chloride at a certain temperature for reaction, keeping the temperature for 0.5 h after dripping is finished, dripping reaction liquid into an aqueous solution of sodium hydroxide, filtering, standing filtrate for layering to obtain an organic phase, concentrating the organic phase, and performing reduced pressure distillation to obtain the dicyclohexylcarbodiimide. According to the method, DCU generated after DCC isused is regenerated into DCC, cyclic application is achieved, the technological method has the advantages of being safe, reliable and high in recovery rate, and industrial production can be achieved.

Method for preparing dicyclohexylcarbodiimide by using vilsmeier reagent

The invention discloses a method for preparing dicyclohexylcarbodiimide by using a vilsmeier reagent. The method comprises the following steps: preparing a vilsmeier reagent by using N, N-dimethylformamide (DMF) and thionyl chloride (SOCl2), reacting the vilsmeier reagent with dicyclohexylurea (DCU), and carrying out aftertreatment to obtain the dicyclohexylcarbodiimide. According to the method, the vilsmeier reagent is adopted, the reaction can be carried out under mild conditions, the process is safe and stable, and the method is suitable for industrial large-scale production.

Electrochemical Synthesis of Carbodiimides via Metal/Oxidant-Free Oxidative Cross-Coupling of Amines and Isocyanides

This work discloses an electrochemical oxidative cross-coupling of amines with aryl and aliphatic isocyanides. In an undivided cell, the reaction proceeds without involving any transition-metal catalyst, oxidant, or toxic reagents providing carbodiimides in good yields, thereby circumventing stoichiometric chemical oxidants, with H2 as the only byproduct. Moreover, carbodiimides were in situ converted into unsymmetrical ureas in moderate to good yields using an electricity ON-OFF strategy.

Method for synthesizing N, N'-dicyclohexylcarbodiimide through hydrogen peroxide serving as oxidizing agent

The invention relates to a method for synthesizing N, N'-dicyclohexylcarbodiimide through hydrogen peroxide serving as an oxidizing agent. The method comprises the following steps: mixing N, N'-dicyclohexyl thiocarbamide and a solvent, slowly adding a catalyst, dropwise adding hydrogen peroxide at 15 to 25 DEG C to perform oxidation reaction, performing heat preservation for 1.5 h after dropwise adding is accomplished, then performing suction filtration at 15 DEG C, and performing decoloration and reduced pressure distillation, so as to obtain the N, N'-dicyclohexylcarbodiimide. The method hasthe advantages that the oxidizing agent hydrogen peroxide is adopted to ensure that reaction is more complete, the content of by-products N, N'-dicyclohexylurea and cyclohexyl isothiocyanate is controlled to be lower than 100 ppm, the product quality is improved, and the problem that effluent brine is difficult to treat is solved; a reaction system is optimized, a triethylamine catalyst is adopted to ensure that the reaction is performed in a homogeneous reaction system, the reaction yield is improved, the DCC yield is improved to greater than 93.5 percent, and the reaction is easy to control; and the material utilization is improved, the amount of waste is reduced, the investment in environmental protection is reduced, and the production cost is reduced.

Preparation method of dicyclohexylcarbodiimide

The invention belongs to the technical field of fine chemical engineering and in particular relates to a preparation method of dicyclohexylcarbodiimide. The preparation method comprises the followingsteps: dissolving chloroacetyl chloride in a solvent to obtain a solution A; stirring dicyclohexylurea, a catalyst and a solvent uniformly to obtain a solution B; dropwise adding the solution A into the solution B at a certain temperature; then carrying out an insulating reaction; after the reaction, adding a pH regulator to regulate the solution to be neutral; carrying out suction filtration on the reaction solution; distilling the filtrate at constant pressure to remove the solvent; and then carrying out distillation at a reduced pressure to obtain dicyclohexylcarbodiimide. The preparation method of dicyclohexylcarbodiimide is simple in process, the reaction stability and the product yield are improved greatly, dicyclohexylcarbodiimide can be produced industrially on a large scale, and the preparation method has the advantages of being simple and feasible and simple to operate.