[59128-90-4] · C7H6N4O2S · 1-Phenylsulfonyl-1H-tetrazole · (MW 210.24)
(coupling reagent for oligonucleotide solution synthesis using the phosphotriester method1-4)
Physical Data: mp 86-92 °C.
Solubility: insol H2O; sol pyridine, CH2Cl2; reacts slowly with H2O and protic solvents.
Form Supplied in: white crystals; not available from commercial sources.
Analysis of Reagent Purity: prior to use, the purity should be determined by mp.
Preparative Method: by reaction of Benzenesulfonyl Chloride (1 equiv) and tetrazole (1 equiv) in the presence of Triethylamine (1 equiv) in dioxane at 5 °C for 2 h. A crystalline product was obtained after dissolving the crude material in benzene, shaking with silica gel, filtering, and evaporating in vacuo to dryness.
Handling, Storage, and Precautions: the dry solid should be stored in a desiccator with drierite at 4 °C. The material decomposes completely after 20 days at 25 °C, and it should be used immediately following preparation. Cation: Avoid contact with metals and metal salts, since tetrazole may form explosive metal salts. Contact with strong oxidizers or strong heat may cause fire or explosion.
1-Phenylsulfonyl-1H-tetrazole (1) has been used as a condensing reagent in deoxyoligonucleotide solution synthesis by the phosphotriester method.1-3 It activates 5´-dimethoxytrityl (DMT) deoxynucleoside 3´-(p-chorophenyl) phosphates in anhydrous pyridine, allowing the coupling reaction with 5´-hydroxy nucleoside in 30 min at 25 °C, yielding the corresponding p-chlorophenyl phosphate dimer in 74% yield. This reaction has been extended for the preparation of oligodeoxynucleotides containing up to 12 bases with coupling times in the range of 30-120 min at 25 °C (eq 1). Couplings mediated by (1) occur more rapidly than with the corresponding 2,4,6-trimethyl and 2,4,6-triisopropyl analogs and no sulfonation at the 5´-hydroxy group has been observed.1,3
Furthermore, (1) has been used in anhydrous pyridine for 24 h at 25 °C for the preparation of a ribonucleotide dimer in 60% yield (eq 2).
Although (1) has not been used in solid-phase oligonucleotide synthesis, another more stable arylsulfonyl derivative, 1-(mesitylsulfonyl)-3-nitro-1,2,4-triazole (MSNT),5,6 is commonly used in that strategy by the phosphotriester approach.7
CID-CSIC, Barcelona, Spain
Steven A. Kates & Fernando Albericio
Millipore Corporation, Bedford, MA, USA