2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite Property

Boiling point:

100 °C0.5 mm Hg(lit.)

Density 

0.949 g/mL at 25 °C(lit.)

refractive index 

n20/D 1.470(lit.)

Flash point:

141 °F

storage temp. 

-20°C

solubility 

Acetonitrile (Slightly), Benzene, Chloroform (Sparingly), Methanol (Slightly)

form 

liquid

pka

6.78±0.70(Predicted)

color 

colorless

Sensitive 

moisture sensitive, store cold

BRN 

3590103

Stability:

Explodes When Heated

InChIKey

RKVHNYJPIXOHRW-UHFFFAOYSA-N

LogP

4.04 at 20℃

CAS DataBase Reference

102691-36-1(CAS DataBase Reference)

EPA Substance Registry System

Phosphorodiamidous acid, tetrakis(1-methylethyl)-, 2-cyanoethyl ester (102691-36-1)

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

5-36/37/38-42/43-36/38

Safety Statements 

3-26-36-24/25-23-45-36/37

RIDADR 

UN 1993 3/PG 3

WGK Germany 

3

F 

10-21-34

Hazard Note 

Irritant/May Explode on Heating

HazardClass 

8

PackingGroup 

I

HS Code 

29299000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H226Flammable liquid and vapour

H302Harmful if swallowed

H317May cause an allergic skin reaction

H412Harmful to aquatic life with long lasting effects

Precautionary statements

P210Keep away from heat/sparks/open flames/hot surfaces. — No smoking.

P233Keep container tightly closed.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite Chemical Properties,Usage,Production

Description

2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite is a colorless viscous liquid, which is soluble in most organic solvents. It is a widely used phosphitylating reagent for the preparation of various phosphorylated biomolecules, such as nucleoside carbohydrate conjugates, phospholipids and glycopeptides. In particular, this reagent is highly effective for automated solid-phase DNA/RNA oligonucleotide synthesis. It has shown great utility in the coupling of nucleobases or carbohydrates via their phosphotriesters in the presence of activators such as 1H-tetrazole, in moderate yields under mild conditions.This compound is cheaper and more stable than 2-cyanoethyl N,N-diisopropylchlorophosphorodiamidite (the other commonly used phosphinylating reagent)[1].

Chemical Properties

Clear to Cloudy Colourless Liquid

Uses

Reagent for synthesizing phosphitylated nucleotides.1

Uses

2-Cyanoethyl N,N,N′,N′-tetraisopropylphosphordiamidite was used:

• in preparation of prosphoramidite reagent, required for synthesis of 12-mer oligodeoxynucleotide
• as phosphorylating agent in synthesis of 1,2-diacyl-sn-glycerophosphatidylserine
• in situ preparation of deoxyribonucleoside phosphoramidites
• in preparation of 2′-deoxy-2′-fluoro-3′-O-(β-cyanoethyl-N,N-diisopropylphosphoramidic)-5′-O-(4-methoxytrityl)-4′-thio-β-D-arabinouridine and 1-(3-O-(β-cyanoethyl-N,N-diisopropylphosphoramidic)-2-deoxy-2-fluoro-5-O-(4,4′-dimethoxytrityl)-4-thio-β-D-arabinofuranosyl)-thymine
• as reagent for synthesizing phosphitylated nucleotides

Application

2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite is an important organic reagent widely used in the preparation of modified and unmodified nucleoside phosphoramidites. Nucleoside phosphoramidites are ideal reagents for polymer-supported synthesis of oligonucleotides. The diisopropylamino leaving group is readily cleaved upon contact with the azole catalyst, resulting in an efficient coupling reaction with the free hydroxyl group on the protected nucleoside.

Synthesis

3-((dichlorophosphaneyl)oxy)propanenitrile could synthesize 2-Cyanoethyl N, N, N', N'-tetraisopropylphosphorodiamidite with diisopropylamine. This method is inexpensive manner using a two-step, one-pot procedure and purified by vacuum distillation[2]. 

References

[1] Hada N, et al. Synthetic studies on glycosphingolipids from Protostomia phyla: syntheses and biological activities of amphoteric glycolipids containing a phosphocholine residue from the earthworm Pheretima hilgendorfi. Carbohydrate Research, 2008; 343: 343, 2221.
[2] Ching S, et al. Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting diguanylate cyclase. Bioorganic & Medicinal Chemistry, 2010; 18: 6657-6665.