Azobisisobutyronitrile

[78-67-1]  · C8H12N4  · Azobisisobutyronitrile  · (MW 164.21)

(reagent for initiation of radical reactions)

Alternate Name: AIBN.

Physical Data: mp 103-104 °C.

Solubility: sol benzene, toluene.

Form Supplied in: commercially available as a white powder.

Preparative Method: prepared from the corresponding hydrazine by oxidation with nitrous acid.1

Purification: recrystallized from ether.

Handling, Storage, and Precautions: avoid exposure of the reagent to light and heat; store protected from light in a refrigerator or freezer. AIBN is harmful; old or incorrectly stored samples may also present an explosion risk.

Preparation.

Azobisisobutyronitrile (AIBN) and analogs can be prepared by a two-step procedure involving initial treatment of a ketone with Hydrazine in the presence of Sodium Cyanide, followed by oxidation of the so-formed hydrazine (eq 1).1,2

Use in Radical Chemistry.

AIBN is the initiator most commonly employed in radical reactions, especially those using Tri-n-butylstannane. At temperatures above about 60 °C, AIBN decomposes with evolution of nitrogen to generate isobutyronitrile radicals, which are able to initiate radical chemistry, usually by abstraction of a hydrogen atom from Bu3SnH or some other donor. The useful working temperature range of AIBN is 60-120 °C, with the half-life at 80 °C being 1 h. In many applications involving C-C bond formation, the radical chemistry is designed to proceed by a chain reaction, and so only small amounts (typically ca. 0.1 equiv) of the initiator is required. For best results, especially at more elevated temperatures, AIBN is best added in portions or as a solution by means of a syringe pump. Typical Bu3SnH-mediated radical reactions, which involve the use of AIBN as initiator, include cyclizations of alkyl and vinyl radicals (eqs 2 and 3).3,4

In eq 2, generation of an alkyl radical is achieved by attack of a tributylstannyl radical on a Barton derivative, whereas in eq 3, the vinyl radical required is generated by addition of the stannyl radical to an alkyne. This type of cyclization has been extended to many types of substrate, including those in which a carbonyl group acts as the acceptor (eq 4),5 and those in which additional types of radical rearrangement or fragmentation occur (eq 5).5,6 The latter sequence involves addition of the initially formed radical onto the adjacent carbonyl group, followed by reopening of the so-formed cyclopropanoxy radical in regioselective fashion.6 The reaction effects a one-carbon ring expansion in good chemical yield.

AIBN can also be used in combination with many other types of radical-generating systems other than those employing Bu3SnH. Examples include cyclizations using Tris(trimethylsilyl)silane,7 Thiophenol,8 Diphenylphosphine,9 and carbonylation of radicals using Ph3GeH and CO under pressure10 (eqs 6-9).

For certain types of radical reaction, AIBN may not always give optimal results. Keck and Burnett found in their synthesis of PGF2a that the introduction of the lower side chain, involving radical addition onto a b-stannyl enone, was inefficient when AIBN was used as initiator at 65 °C. By conducting the reaction in refluxing toluene (110 °C), and replacing AIBN with the related 1,1-Azobis-1-cyclohexanenitrile (ACN), a markedly better yield of the desired adduct was obtained (eq 10).11

For reactions which require temperatures above benzene reflux, ACN, which decomposes markedly slower than AIBN, may be a generally useful alternative to AIBN, although this possibility has not been examined in detail. At elevated temperatures, other alternative initiators such as dialkyl peroxides and peresters should also be considered, although the reactivity of the radicals generated from these initiators is quite different to that of the isobutyronitrile radicals generated from AIBN.


1. Thiele, J.; Heuser, K. LA 1896, 290, 1.
2. Overburger, C. G.; O'Shaughnessy, M. T.; Shalit, H. JACS 1949, 71, 2661.
3. RajanBabu, T. V. JACS 1987, 109, 609.
4. Stork, G.; Mook, Jr., R. JACS 1987, 109, 2829.
5. Nishida, A.; Takahashi, H.; Takeda, H.; Takada, N.; Yonemitsu, O. JACS 1990, 112, 902.
6. Dowd, P.; Choi, S.-C. T 1989, 45, 77.
7. Kopping, B.; Chatgilialoglu, C.; Zehnder, M.; Giese, B. JOC 1992, 57, 3994.
8. Broka, C. A.; Reichert, D. E. C. TL 1987, 28, 1503.
9. Brumwell, J. E.; Simpkins, N. S.; Terrett, N. K. TL 1993, 34, 1215.
10. Gupta, V.; Kahne, D. TL 1993, 34, 591.
11. Keck, G. E.; Burnett, D. A. JOC 1987, 52, 2958.

Nigel S. Simpkins

University of Nottingham, UK



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