56602-33-6 Usage
Description
Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate, also known as 1H-Benzotriazol-1-yloxytris(dimethylamino)phosphonium Hexafluorophosphate, is a white to off-white powder that serves as a versatile reagent in the field of organic chemistry. It is particularly useful in peptide synthesis and related applications due to its ability to facilitate various chemical reactions without causing racemization.
Uses
Used in Pharmaceutical Industry:
Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate is used as a peptide coupling reagent for the synthesis of various pharmaceutical compounds. It is particularly valuable in the preparation of phenyl esters of amino acids, which are important as blocked derivatives in peptide synthesis. This reagent helps in the formation of peptide bonds with minimal racemization, which is crucial for maintaining the biological activity of the resulting peptides.
Used in Chemical Synthesis:
In the field of chemical synthesis, Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate is used as a reagent for various applications, including lactonization, selective esterification, and amidation of α-amino acids without racemization. It is also employed in the synthesis of magnolamide, which possesses antioxidative activity, and as a catalyst for the synthesis of 9-acridinecarboxamide derivatives.
Used as a Precursor:
Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate acts as a precursor for the synthesis of phenyl esters of amino acids, which are essential intermediates in the preparation of various biologically active peptides and pharmaceutical compounds.
Overall, Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate is a valuable reagent in the fields of pharmaceuticals and chemical synthesis, playing a crucial role in the development of new drugs and the synthesis of complex organic molecules.
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.]
Check Digit Verification of cas no
The CAS Registry Mumber 56602-33-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,6,6,0 and 2 respectively; the second part has 2 digits, 3 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 56602-33:
(7*5)+(6*6)+(5*6)+(4*0)+(3*2)+(2*3)+(1*3)=116
116 % 10 = 6
So 56602-33-6 is a valid CAS Registry Number.
InChI:InChI=1/BH4OP/c1-2-3/h1,3H2
56602-33-6Relevant articles and documents
Synthesis and chemical constitution of diphenoxyphosphoryl derivatives and phosphonium salts as coupling reagents for peptide segment condensation
Hoffmann, Frank,Jaeger, Lothar,Griehl, Carola
, p. 299 - 309 (2007/10/03)
The reactions of diphenoxyphosphoryl chloride ((PhO)2P(O)Cl) and different chlorophosphonium salts ([R3PCl]X, R = (CH3)2N, pyrrolidine, X = PF6-, BF4-), respectively, with 7-aza-1-hydroxybenzotriazole (HOAt), 1-hydroxybenzotriazole (HOBt), hydroximinomalonitrile (HOxDCO), and ethyl hydroximinocyanoacetate (HOxO) are described. The structures of the new compounds, which are useful coupling reagents for epimerization-free peptide segment condensation, are discussed on the basis of their 1H, 13C, 31P NMR, and IR spectra. The reactions of (PhO)2P(O)Cl lead to mixtures of O- and N-phosphorylated isomers of varying ratios. Contrary, reactions of chlorophosphonium salts yield exclusively one isomer.