[2094-98-6]  · C14H20N4  · 1,1-Azobis-1-cyclohexanenitrile  · (MW 244.34)

(thermally stable radical initiator1)

Alternate Name: ACN.

Physical Data: mp 114-115 °C.

Solubility: sol benzene, toluene.

Form Supplied in: white solid; widely available commercially.

Purification: recrystallization from methanol.

Handling, Storage, and Precautions: stable indefinitely at rt but prolonged heating at temperatures greater than 80 °C results in rapid decomposition.

ACN has been used as a thermally stable radical initiator. The chair configuration of the cyclohexyl moiety has been given as the reason for its relative thermal stability as compared to other azo-bis(nitrile) derivatives.1

Thermal catalysis of ACN-initiated sulfonyl radical-induced addition-cyclization reactions of 1,6 dienes with p-Toluenesulfonyl Cyanide to give functionalized cyclopentane products as a mixture of stereoisomers in 57-72% yields (eq 1).2 The cis isomer predominated and no cyclohexyl adducts were detected. Photochemically induced cyclization and thermal catalysis with Dibenzoyl Peroxide gave slightly better yields, with similar stereoselectivity.

ACN has been used in the key radical cyclization-trapping step in a prostaglandin synthesis (eq 2).3 Treatment of the iodoacetal and 4 equiv of the b-stannyl enone with ACN in refluxing toluene gives the bicyclic adduct in 72% purified yield. In contrast, the use of 0.1 equiv of Azobisisobutyronitrile (AIBN) in benzene at 65 °C as an initiator gives only trace amounts of the desired product. Heating at elevated temperatures with AIBN gives the desired adduct as a mixture of anomers in 43% yield after column chromatography.

ACN has been used for the radical addition of alkyl halides to Liebeskind's tri-n-butyltin cyclobutenedione reagent to prepare intermediates in the synthesis of the novel NMDA antagonist (eq 3).4 Typically, 0.1 equiv of ACN is introduced every 12 h to 2 equiv of dione with various alkyl halides to give the addition product in 21-56% yield. Initiation with AIBN requires longer reaction times.

ACN has been used to introduce a tertiary carbon carrying an electronegative group into the 9-position of anthracene, which can lead to triptycene-type compounds in which the stable rotational isomers can be isolated at room temperature.5

Due to its high thermal stability, ACN has also been used in physical organic chemistry for kinetic investigations1,6 and in polymer chemistry.7

1. Overberger, C. G.; Biletch, H.; Finestone, A. B.; Lilker, J.; Herbert, J. JACS 1953, 75, 2078.
2. Chuang, C.-P.; Ngoi, T. H. J. J. Chin. Chem. Soc. 1992, 39, 439.
3. Keck, G. E.; Burnett, D. A. JOC 1987, 52, 2958.
4. Kinney, W. A. TL 1993, 34, 2715.
5. Mitsuhashi, T.; Otsuka, S.; Oki, M. TL 1977, 28, 2441.
6. (a) Ohno, A.; Ohnishi, Y. TL 1972, 339. (b) Barclay, L. R. C.; Balcom, B. J.; Forrest, B. J. JACS 1986, 108, 761.
7. (a) Ryoshi, H.; Kunieda, N.; Kinoshita, M. Makromol. Chem. 1986, 187, 263. (b) Lanska, B.; Makarov, G. G.; Sebenda, J. Angew. Makromol. Chem. 1990, 181, 143. (c) Deibert, S.; Bandermann, F. Makromol. Chem., Rapid Commun. 1992, 13, 351.

Steven A. Kates & Fernando Albericio

Millipore Corporation, Bedford, MA, USA

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