1,1-Carbonylbis(3-methylimidazolium) Bis(trifluoromethanesulfonate)1

[120418-31-7]  · C11H12F6N4O7S2  · 1,1-Carbonylbis(3-methylimidazolium) Bis(trifluoromethanesulfonate)  · (MW 490.36)

(versatile coupling reagent for aminoacylations2)

Alternate Name: 1,1-carbonylbis(3-methylimidazolium) bistriflate.

Physical Data: pale white solid mp 78-80 °C; 1H d (CDCl3) 8.86 (s, 2H), 7.44 (m, 2H), 7.16 (m, 2H), 4.00 (s, 6H).

Solubility: sol nitromethane, chloroform; insol ether; reacts with water.

Analysis of Reagent Purity: freshly prepared sample is treated with water: 200 mol % of N-methylimidazolium triflate is produced along with CO2.

Preparative Methods: fresh methyl triflate is added to 1,1-carbonylbisimidazole in nitromethane at 10 °C. Solvent is then removed in vacuo, or the reagent used in situ.2

Handling, Storage, and Precautions: usually prepared under anhydrous conditions and used immediately. Can be stored in dry nitromethane solution or in solid state in absence of moisture. Preparation using aged methyl triflate should be avoided, owing to possible contamination of the coupling reagent with triflic acid.2

Coupling Reactions.

When N-Cbz derived amino acids are exposed to a freshly prepared solution of carbonylbis(3-methylimidazolium) triflate in nitromethane, coupling ensues with loss of CO2 to give the derived amide and one equivalent of methylimidazolium triflate (eq 1).2

The acylated species so prepared can be coupled with alcohols to yield esters or with amines to form amides. The yields of coupled product are typically high and formation of the coupled products takes place within 15 min in the case of amides (eq 2) and within 3 h for esters.2

Of particular note is the fact that sterically hindered alcohols (e.g. menthol) couple in nearly quantitative yield (eq 3).

Racemization is not prevalent under these neutral conditions: routine analysis of the diastereomeric excess of coupled products revealed a >99.75:0.25 ratio, confirming both the mildness of the system and the near neutral conditions that persist during the coupling. The system compares most favorably against conventional coupling agents such as N,N-Carbonyldiimidazole,3,4 where sluggish O-acylations are common5 and racemization of the acyl component in the couplings has been observed.6

1. Bodanszky, M.; Bodanszky, A. The Practice of Peptide Synthesis, Springer: New York, 1984.
2. Saha, A. K.; Schultz, P.; Rapoport, H. JACS, 1989, 111, 4856.
3. Staab, H. A. LA, 1957, 609, 75.
4. For related carbonyl bis-imidazole system see: Kamijo, T.; Harada, H.; Iizuka, K. CPB, 1984, 32, 5044.
5. Staab, H. A. AG(E), 1962, 1, 351.
6. Weygand, F.; Prox, A.; Konig, W. CB, 1966, 99, 1451.

Graham B. Jones & Robert S. Huber

Clemson University, SC, USA

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