Arylation of Sensitive 1-(Pyrrolidin-1-yl)-diazen-1-ium-diolate in Ionic Liquids

Abstract

The purpose of this research was to investigate the stability and reactivity of 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (PYRRO/NO) in dimethylformamide (DMF, as the reference solvent) and compare them to those obtained using different ionic liquids. The results of our experiments showed that PYRRO/NO is more stable (based on reactivity) in ionic liquid [EMIM][Ms] (with reaction yields up to 52%) than in DMF, that substitution products can be separated directly and quantitatively from the ionic liquid using a single flash-column separation, and that the ionic liquids can also be recovered and reused in a second iteration of the same reaction to achieve similar yields.

Keywords:

• Diazeniumdiolate
• ionic liquid
• nitric oxide donor
• nucleophilic displacement

ACKNOWLEDGMENTS

This work was supported by federal funds from the National Cancer Institute, National Institutes of Health (NIH) under contract HHSN261200800001E with SAIC–Frederick Inc. as well as by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Notes

^a Except urea.

^b Physical mixture of 2 equivalents of urea to 1 equivalent of choline chloride.

^a Average yield determined by HPLC (±standard deviation, n = 4) relative to a known concentration of pure compound 2, after 1 h of stirring at 25 °C.

^b Average yield determined by HPLC (±standard deviation, n = 4) relative to a known concentration of pure compound 2, after 24 h of stirring at 25 °C.

^c Not determined.

^d No solvent was added (neat reaction).

^a Reaction conditions: 200 mg of PYRRO/NO, 5 mL of ionic liquid, 1.25 eq. of 2,4-dinitrofluorobenzene, 1 h, 25°C.

^b Isolated yield of product 2 after quenching, extraction and flash chromatography.

^c Isolated yield of product 2 after direct purification by flash chromatography.

^d Isolated yield of product 2 after quenching, extraction, and flash chromatography using the IL recovered from method 2.

^e Not determined.