p-Nitrobenzenesulfonyl-4-nitroimidazole

[81006-79-3]  · C9H6N4O6S  · p-Nitrobenzenesulfonyl-4-nitroimidazole  · (MW 298.26)

(condensing agent for the triester coupling of nucleotide fragments1)

Alternate Name: p-NBSNI.

Physical Data: mp (sealed tube) 179-185 °C (dec); UV (dioxane) 253 nm.

Solubility: sol pyridine, DMSO; slightly sol dioxane, ethyl acetate.

Form Supplied in: white needles; not available commercially; may be contaminated with p-nitrobenzenesulfonic acid.

Analysis of Reagent Purity: 1H NMR (60 MHz, DMSO-d6) d 8.45 (s, 4H); 8.55 (d, J = 2 Hz, 1H); 9.10 (d, J = 2 Hz, 1H); sulfonic acid impurities are easily detected as higher field signals.

Preparative Method: by treatment of 4-nitroimidazole (1.025 equiv) and p-nitrobenzenesulfonyl chloride (1.0 equiv) with Triethylamine (1.1 equiv) in dry dioxane at 0 °C.1

Purification: recrystallization from ethyl acetate.

Handling, Storage, and Precautions: stable to air and moisture in screw cap bottles at rt for over six months.

Condensing Agent.

p-Nitrobenzenesulfonyl-4-nitroimidazole has been used as a condensing agent in the triester synthesis of oligonucleotides. The reagent activates the phosphodiester towards attack by the incoming 5-hydroxyl through formation of a mixed phosphoric-sulfonic anhydride. Typically, the suitably protected nucleotide fragments, in pyridine solution, are treated with p-NBSNI (2.5 equiv) and stirred at rt for approximately 15 h. After workup, purification is achieved through two chromatographic separations over silica gel, affording the desired polynucleotide in 60-83% yield (eq 1).1

p-Nitrobenzenesulfonyl-4-nitroimidazole holds the advantage over older reagents, such as triisopropylbenzenesulfonyl chloride, of giving fewer side products resulting from sulfonation of the free 5-hydroxyl. The long reaction times necessary are a disadvantage and the condensing agents 2,4,6-triisopropylbenzenesulfonyl-1,2,3,4-tetrazole (TPSTe) and 1-(mesitylenesulfonyl)-3-nitro-1,2,4-triazole (MSNT) are preferable.2


1. Leach, C. A.; Tamm, C.; Waldmeier, F. HCA 1981, 64, 2515.
2. Ikehara, M.; Ohtsuka, E.; Uesugi, S.; Tanaka, T. In Chemistry of Nucleosides and Nucleotides; Townsend L. B., Ed.; Plenum: New York, 1988; Vol. 1, Chapter 3.

Matthew P. Braun & Carl R. Johnson

Wayne State University, Detroit, MI, USA



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