1H-Benzotriazol-1-yloxytris(dimethylamino)phosphonium Hexafluorophosphate Property

Melting point:

>130 °C (dec.)(lit.)

Flash point:

138°C

storage temp. 

2-8°C

solubility 

methanol: 25 mg/mL, clear

form 

Powder

color 

White to off-white

Water Solubility 

Soluble in methanol, acetone and dichloromethane. Insoluble in water.

Decomposition 

138 ºC

Sensitive 

Moisture & Light Sensitive

BRN 

4287025

CAS DataBase Reference

56602-33-6(CAS DataBase Reference)

Safety

Hazard Codes 

Xi,E,F

Risk Statements 

37/38-44-36/37/38-11-2

Safety Statements 

24/25-37/39-36-26-35-36/37/39

RIDADR 

UN 1325 4.1/PG 2

WGK Germany 

3

F 

8-10-21

Hazard Note 

Irritant

HazardClass 

4.1

PackingGroup 

Ⅱ

HS Code 

29339980

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H228Flammable solid

H315Causes skin irritation

H335May cause respiratory irritation

Precautionary statements

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

P240Ground/bond container and receiving equipment.

P241Use explosion-proof electrical/ventilating/lighting/…/equipment.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P302+P352IF ON SKIN: wash with plenty of soap and water.

1H-Benzotriazol-1-yloxytris(dimethylamino)phosphonium Hexafluorophosphate Chemical Properties,Usage,Production

Chemical Properties

white to off-white powder

Uses

Peptide coupling reagent which suppresses racemization.

Uses

1H-Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate is used as a reagent for peptide coupling, lactonization, selective esterification, amidation of alfa amino acids without racemization and synthesis of magnolamide for antioxidative activity and catalyst for 9-acridinecaroboxamide derivative. It is also used as a precursor for the synthesis of phenyl esters of amino acids. It acts as a substitute for (Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) reagent.

Uses

1H-Benzotriazol-1-yloxytris(dimethylamino)phosphonium Hexafluorophosphate is a peptide coupling reagent. Can be used in the preparation of phenyl esters of amino acids which have been shown to be valuable as blocked derivatives of amino acids in the field of peptide synthesis.

Preparation

To vigorously stirred HMPA (15.0 g, 83.7 mmol) at 0 C°, a solution of triphosgene (11.28 g, 38.01 mmol) in dichloromethane (15 mL) was added over a period of 40 min. The ice bath was then removed and the mixture was stirred at room temperature. At various intervals, small aliquots were removed in order to follow the disappearance of the HMPA spectroscopically. After 3 h, the solvent was removed under reduced pressure to leave a residue. This residue was redissolved in dry dichloromethane (40 mL) and solid hydroxybenzotriazole monohydrate (12.76 g, 94.4 mmol) was added with stirring. The resulting solution was cooled to about 5 C° with an acetone/ice bath, whereupon triethylamine (8.42 g, 83.4 mmol) was added over a period of 15 min and stirring was continued at -5 C for 4 h. The residue was dissolved in water (50 mL) and mixed with a filtered solution of potassium hexafluorophosphate (16.68 g, 90.6 mmol) in water (120 mL) to give benzotriazolyl-N-oxytris(dimethylamino)phosphonium hexafluorophosphate 1317 (BOP) as a crystalline solid (28.91 g, 78%).
Chloroformates 1319 and chlorides 1320 are also formed when secondary benzyl alcohols 1318 are treated with trichloromethyl chloroformate (diphosgene) in the presence of triethylamine. The distribution of products can be controlled.

Reactions of tetrahydropyranylated alcohols 1321 with N,N-dimethylphosgeniminium chloride (‘‘Viehe salt’’) 1322 give the corresponding alkyl chloride 1300 in good yields [997]. This conversion can be conveniently accomplished by adding the ‘‘Viehe salt’’ (1.05 equiv.) as a solid to a solution of the THP-protected alcohol (1 equiv.) in anhydrous dichloromethane (0.3 m) under argon at 0 C°. After completion of the reaction and aqueous work-up, the crude alkyl chlorides are purified by column chromatography.

Purification Methods

Dissolve it in CH2Cl2, dry (MgSO4), filter, concentrate it under a vacuum, then add dry Et2O and filter off the first crop. Add CH2Cl2 to the filtrate and concentrate again to obtain a second crop. The solid is washed with dry Et2O and dried in a vacuum. Also recrystallise it from dry Me2CO/Et2O and check the purity by NMR. Store it in the dark. [Castro et al. Synthesis 751 1976, Nguyen et al J Chem Soc, Perkin Trans I 1915 1987, Coste et al. Tetrahedron Lett 36 4253 1995.]