DIISOPROPYLCARBODIIMIDE (N,N'-METHANETETRAYLBIS-2-PROPANAMINE)

DIISOPROPYLCARBODIIMIDE

PRODUCT IDENTIFICATION

CAS NO.

693-13-0

DIISOPROPYLCARBODIIMIDE

EINECS NO.

211-743-7

FORMULA

(CH₃)₂CHN=C=NCH(CH₃)₂

MOL WT.

126.20

H.S. CODE

2925.19.9100

TOXICITY

SYNONYMS

N,N-Diisopropylcarbodiimide; 1,3-Diisopropylcarbodiimide;

二异丙基碳二亚胺; N,N'-Methanetetraylbis(2-propanamine); DIC; N,N'-Methanetetraylbis(1-methylethylamine);

SMILES

C(N=C=NC(C)C)(C)C

CLASSIFICATION

Coupling reagent

EXTRA NOTES

Activates carboxyl groups
Alternative to dicyclohexylcarbodiimide in peptide synthesis.
Coupling reagent for peptide syntheses

PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE

Clear liquid

MELTING POINT

BOILING POINT

145 - 148 C

SPECIFIC GRAVITY

0.80 - 0.81

SOLUBILITY IN WATER

reacts to form 1,3-Diisopropylurea

VAPOR DENSITY

log P

4.11 (octanol-water)

NFPA RATINGS

Health: 3; Flammability: 3; Reactivity: 0

REFRACTIVE INDEX

1.432 - 1.435

FLASH POINT

33 C

STABILITY

Stable under ordinary conditions. Moisture sensitive.

EXTERNAL LINKS & GENERAL DESCRIPTION

Wikipedia Linking

Google Scholar Search

Drug Information Portal (U.S. National Library of Medicine) - N,N'-Diisopropylcarbodiimide

PubChem Compound Summary - N,N'-Diisopropylcarbodiimide

http://www.ebi.ac.uk/ - N,N'-Diisopropylcarbodiimide

http://www.ncbi.nlm.nih.gov/ - N,N'-Diisopropylcarbodiimide

Material Safety Data Sheet

http://www.bgu.ac.il/
Carbodiimide reagents were designed to prevent the formation of the undesired N-acylurea and to facilitate easy separation from the by-products. The insolubility of the by-product occasionally caused problems for the synthesis of polypeptides. Since the ureas from DIC and CIC were relatively soluble in CH2Cl2, these reagents were more suitable for solid-phase peptide synthesis than DCC. The solubilities of N-cyclohexyl-N0-isopropylurea, N,N0-diisopropylurea, and N,N0-dicyclohexylurea were 30, 5.2 and 1.5 g/L in CH2Cl2, respectively. In Fmoc solid-phase peptide synthesis, the DIC/additive method was investigated in various conditions by changing the additive, base,and solvent. Carpino demonstrated that DIC/HOAt was superior to DIC/other additives.43 Further variations of the carbodiimide such as BMC, BEC, and N,N0-dicyclopentylcarbodiimide were reported (Fig. 12).44 Rapoport developed the hydrophilic side-chain-containing carbodiimide, BDDC, in 1994. BDDC in THF, DMF, or toluene gave a reasonable yield for the coupling reaction with a Bocprotected amino acid and the by-product was easily removed by an acid wash.

http://www.peptide-and-dna.com/
The formation of the amide bond together with chirality of the molecules plays a key role in the preparation of a broad range of organic compounds. It begins with the small molecules through the peptides to fully synthetic proteins. Today, the synthesis of peptide or protein based pharmaceutical drug requires up to 100 steps, the name of the game is “production cost” and the modern synthetic technologies play a central role in this battleA. thorough study of the mechanism in each method involving basic producer for logistic and technical support is a necessary term for the optimization of the coupling step of a new peptide drug and further up-scaling towards bulk manufacturing. Today, Cl-HOBt as an additive and HCTU/TCTU are excellent alternatives to the most classic methods for the large scale manufacturing of peptide and proteins.

Local:
Carbodiimides are a group of organic compounds which have the resonance formula N=C=N. Carbodiimides is formed by dehydration of urea or from thiourea. Carbodiimides are readily reacts with various form of amines and hydroxyl functional groups. Carbodiimides are used as dehydration agents and as activating agent of carboxylic acids to form esters or amides. The disubstituted carboxyl activating agents are used for crosslinking proteins to nucleic acids and formation of immunoconjugates in peptide synthesis. N,N'-dicyclohexylcarbodiimide (DCC) is one of the most common peptide coupling agents. It is a low melting point waxy solid; insoluble in water but highly soluble in common organic solvents like acetonitrile dichloromethane, dimethylformamide, and tetrahydrofuran. DCC is a potent allergen. N,N'-diisopropylcarbodiimide (DIC) is an alternative to DCC, DIC is a liquid and is not an allergen. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is a water-soluble activating agent for amide bonding with primary amines. It also activates phosphate groups. Typically, it is utilized in the pH range 4.0-6.0 without buffers. In particular, amine and carboxylate buffers should be avoided. Carbodiimides are so active and cause racemization of the amino acid. Active esters are less reactive and less in danger of racemization. 1-Hydroxybenzotriazole (HOBt) and 1-hydroxy-7-aza-benzotriazole (HOAt) are substances that react with the O-acylurea to form active esters. HOAt is a condensation additive in peptide synthesis. It efficiently speeds up coupling process, reduces the loss of chiral integrity, and provides a visual indication (yellow to colorless) of the reaction course. Other active esters exit as non-nucleophilic anionic salts of uronium or phosphonium such as O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate(HBTU), O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), (Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP).

CARBODIIMIDES

Product	CAS RN
N,N'-Dicyclohexylcarbodiimide	538-75-0
N,N'-Diphenylcarbodiimide	622-16-2
N,N'-Di-tert-butylcarbodiimide	691-24-7
N,N'-Diisopropylcarbodiimide	693-13-0
1,3-Di-p-tolylcarbodiimide	726-42-1
Bis(3-chloro-2-methylphenyl)carbodiimide	961-63-7
Bis(trimethylsilyl)carbodiimide	1000-70-0
Bis(o-tolylcarbodiimide)	1215-57-2
1-tert-Butyl-3-ethylcarbodiimide	1433-27-8
N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide	1892-57-5
Bis(2,6-diisopropylphenyl)carbodiimide	2162-74-5
Bis(2,6-diethylphenyl)carbodiimide	2162-75-6
N-Cyclohexyl-N'-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate	2491-17-0
N-Cyclohexyl-N'-isopropylcarbodiimide	3496-83-1
N-Methyl-N'-phenylcarbodiimide	4172-91-2
1-Cyclohexyl-3-(2-(4-morpholinyl)ethyl)carbodiimide	15580-20-8
1-(3-(Dimethylamino)propyl)-3-ethylcarbodiimide methiodide	22572-40-3
N,N'-Dicyclohexyl-N-methylcarbodiimidium iodide	36049-77-1
N-(2,2,6,6-Tetramethylpiperidyl-1-oxyl) N'-(cyclohexyl)carbodiimide	42249-40-1
1-Ethyl-3-(4-azonia-4,4-dimethylpentyl)carbodiimide	45024-77-9
Bis(2,4,6-triisopropyl-3-isocyanatophenyl)carbodiimide	68083-39-6
1-Phenyl-3-trimethylaminopropyl carbodiimide	79322-24-0
N-Cyclohexyl-N'-(4-dimethylamino-alpha-naphthyl)carbodiimide	86332-16-3
N-Cyclohexyl-N'-(1-pyrenyl)carbodiimide	98540-87-5
1-Ethyl-3-(3-dimethylaminoethyl)carbodiimide	141650-20-6

SALES SPECIFICATION

APPEARANCE

clear to faint yellow liquid

ASSAY

99.0% min

BOILING POINT

145 - 148 C

TRANSPORTATION

PACKING

HAZARD CLASS

6.1 (Packing Group: I)

UN NO.

2929

SAFETY INFORMATION

HAZARD OVERVIEW

Flammable liquid and vapor. Moisture sensitive. May be fatal if inhaled. May cause allergic respiratory and skin reaction. Causes severe eye irritation and possible injury. Causes skin and respiratory tract irritation. Target Organs: Respiratory system, eyes, skin.

GHS

SIGNAL WORD

Danger

PICTOGRAMS