1,1-Di-t-butyl Peroxide1-3

[110-05-4]  · C8H18O2  · 1,1-Di-t-butyl Peroxide  · (MW 146.23)

(radical initiator, initiates anti-Markovnikov addition of HX to alkenes (X = halogen, S, Si, P);4 initiates, by H-abstraction, the following radical reactions of compounds with an activated C-H bond: (a) dehydrodimerization;5,6 (b) intra-7 and intermolecular additions3,8,9 to alkenes, alkynes, and carbonyl compounds; (c) addition to protonated heterocycles;10,11 (d) fragmentation;12,13 mediates alcohol deoxygenation via silane reduction of esters14 and chlorohydrin formation by reaction with TiCl4 and alkene15)

Alternate Names: t-butyl peroxide; DTBP.

Physical Data: bp 109 °C/760 mmHg, 63 °C/119 mmHg; d 0.796 g cm-3.

Solubility: freely soluble in organic solvents.

Form Supplied in: clear colorless liquid.

Analysis of Reagent Purity: Kropf describes various procedures (chemical and chromatographic) for the analysis of peroxides.1b

Handling, Storage, and Precautions: explosive; harmful if exposed by inhalation or skin contact; strong oxidizer; flammable; keep away from heat. Caution: All experiments involving peroxy compounds should be carried out behind a safety shield. Use in a fume hood.

General Discussion.

Di-t-butyl peroxide is a commonly used initator for radical reactions. It undergoes facile unimolecular thermal decomposition to the t-butoxy radical, which in turn fragments to a methyl radical and acetone. The half-lives of DTBP are approximately 3 h at 140 °C and 24 h at 120 °C.2 Accordingly, radical reactions that proceed at 110-150 °C can be initiated by DTBP, since a steady concentration of the initiating radical would be available for the reactions. Alkoxy radicals are electrophilic and they initiate the reaction by abstraction of a C-H bond a to a heteroatom. The resultant radicals undergo a variety of carbon-carbon bond forming reactions, including polymerization.16 Scheme 1 shows the primary steps involved in useful C-C bond forming reactions. Use of precursors having an activated C-H bond is advantageous for this purpose, since the chain-transfer step also produces the primary adducts along with the propagating radical, which is also one of the reactants. However, because of the high bond energy associated with the C-H bond, these types of compound are poor H-atom donors. Chain lengths of these reactions are generally short; the use of a large excess of the C-H precursor and a steady supply of the initiator are important for success in many instances.

Abstractions of H adjacent to ethers and amines are important examples, the heteroatom adjacent to the site of reaction providing a favorable polar contribution to the transition state for abstraction by the electrophilic oxy radical, and providing stabilization for the product radical. Examples of the use of DTBP in this way include the study of anomeric radicals by Ingold and co-workers (eq 1),17 and a synthesis of substituted tetrahydrofurans (eq 2).18

In the first case the radicals were generated by UV photolysis of the reaction mixture in the cavity of the NMR instrument used for studying the configuration at the anomeric center. By contrast, the substitution of THF was carried out under more typical thermal conditions by heating in a sealed autoclave. In this study it was found that similar substitution of tetrahydro-2-furanone could also be carried out, although generally in modest yield.

Hydrogen atom abstraction from amino acid derivatives is especially facile, since the resulting captodative radicals are highly stabilized. Treatment of an alanine derivative with DTBP led to a mixture of an a-methylated product and a diastereomeric mixture of dimers (eq 3).19 The first product is formed as a result of radical combination between the captodative amino acid radical and a methyl radical formed by scission of a t-butoxy radical. Substitution of protected dipeptides can be carried out using this approach, by including an alkylating agent such as toluene in the reaction medium (eq 4).20 The reaction relies on the action of biacetyl (2,3-Butanedione) as a photoinitiator, hydrogen atom abstraction occurring preferentially at glycine residues.

Reactions involving phosphorus centered radicals derived from diethyl hydrogen phosphite are also initiated by DTBP under thermal conditions (eq 5).21 Under modified reaction conditions, diphosphonate products, resulting from further addition to the initially formed unsaturated phosphonate, were also observed.

Typical reactions of radicals with alkene acceptors, initiated by DTBP and used in synthesis, are listed below.

Intermolecular Additions.

The radical chain nature and the anti-Markovnikov regiochemistry of radical addition reactions were originally discovered by Kharasch in the 1930s. Since then, these reactions have been used extensively for the formation of carbon-carbon3,8 and carbon-heteroatom4 bonds. Substrates that are suitable for the former include polyhalomethanes, alcohols, ethers, esters, amides, and amines. The prototypical examples compiled in Table 1 are from reviews by Walling8 and Ghosez et al.3

Among the other notable applications are addition of the radical from diethyl malonate to alkynes and alkenes (eq 6),9 addition of a 1,3-dioxalane-derived radical to formaldehyde (eq 7),22 and addition of s-alcohols to alkenes (eq 8).23 Novel radical mediated alkylations of a dipeptide makes use of DTBP as an initator (eqs 9 and 10).20

Intramolecular Addition Reactions.

Early studies by Julia and his co-workers on the cyclization of hexenyl (eq 11) and heptenyl radicals played a key role in the development of radical synthetic methodology, and many of the earlier studies were conducted with peroxides as initiators.7 Cyclization of stabilized radicals such an malonates and cyanoesters are reversible, and the course of ring closure can be controlled by the appropriate choice of precursors and reaction conditions. Thus the cyanoacetate in eq 1224 with 2 equiv of DTBP gives the products shown, whereas under kinetic conditions, using the tin hydride method, a different product distribution is obtained (eq 13).


Radicals that are stabilized by an a-heteroatom, when produced in sufficiently high concentrations, will undergo dimerization. Use of DTBP is particularly effective for dehydrodimerizations of polyhaloalkanes,25 alcohols, ethers,5,25 amides, and esters (Table 2).5,6 Viehe, who pioneered this work, has used a-t-butylmercaptoacrylonitrile as a trapping agent for the above mentioned C-centered radicals.26 The adduct radical is stabilized by captodative effects27 and do not participate in further chain transfer chemistry. These radicals undergo ready dimerization, thereby providing a facile route to compounds with a four-carbon bridge between the original radicals (eq 14).

Fragmentation Reactions.

The tetrahydrofuranyl radical undergoes fragmentation at 140 °C to give an open-chain acyl radical. The THF radical as well as the rearranged radical are trapped by excess of alkene (eq 15).12 Benzylidene acetals undergo similar fragmentation to give a benzoate ester (eq 16).13

Homolytic Substitution Reactions.

Alkylation of electron-deficient heteroaromatic compounds developed by Minisci and co-workers is a powerful method for their functionalization.10,28 Three examples are illustrated in eqs 17, 18 and 19. The product distribution often depends on the oxidant used. For example, as shown in eq 19, DTBP gives a 1:2 mixture of two products (A and B) upon alkylation of 4-methylquinoline. t-Butyl Hydroperoxide and FeII salts give almost exclusively the dimethylaminocarbonyl radical adduct A (eq 19).11

Miscellaneous Reactions.

DTBP has been used as a hydrosilylation catalyst,4 even though catalysis29 by transition metal complexes have largely replaced the radical methods. DTBP has also been used as an oxidant for silanes.30,31 Other applications of DTBP include its use as an initiator for radical mediated deoxygenation of alcohols via the corresponding chloroformate32 or acetate ester14 (eq 20). It has also been used as an initiator for the reduction of lactones and esters to ethers using Trichlorosilane.33 In a rare example of a nonradical reaction, DTBP has been used in conjunction with Titanium(IV) Chloride for the formation of chlorohydrin from alkenes (eq 21).15

The carbonylation reaction of disulfides, catalyzed by Octacarbonyldicobalt, normally leads to the production of thioesters. However, in the presence of DTBP and in the absence of CO the reaction takes an alternative course, with benzyl disulfides undergoing clean desulfurization to give the corresponding sulfides (eq 22).34

DTBP has also been employed in palladium catalyzed carbonylation reactions. Depending on the type of catalyst used, or on the reaction conditions, the carbonylation reaction of primary amines can be used to prepare either ureas (eq 23)35 or carbamate esters (eq 24).36

Using the Palladium(II) Chloride system, the reaction involving secondary amines was found to give mixtures of carbamate ester and an oxamate ester resulting from double carbonylation.36 Analogous carbonylations of alcohols can lead to a range of products, including dialkyl carbonates, oxalates, and succinates.37

1. (a) Sheldon, R. A. In The Chemistry of Functional Groups, Peroxides; Patai, S., Ed.; Wiley: New York, 1983; p 161. (b) Kropf, H. MOC 1988; E13.
2. Walling, C. T 1985, 41, 3887.
3. Ghosez, A.; Giese, B.; Zipse, H. MOC 1989, EXIXa, 533.
4. Stacey, F. W.; Harris, J. F., Jr. OR 1963, 13, 150.
5. Naarmann, H.; Beaujean, M.; Merényi, R.; Viehe, H. G. Polym. Bull. 1980, 2, 363.
6. Naarmann, H.; Beaujean, M.; Merényi, R.; Viehe, H. G. Polym. Bull. 1980, 2, 417.
7. Julia, M. ACR 1971, 4, 386. See also: Beckwith, A. L. J. T 1981, 37, 3073.
8. Walling, C.; Huyser, E. S. OR 1963, 13, 91.
9. Vogel, H. S 1970, 99. For an attractive organometallic variation of several of the reactions described in this article, see Heiba, E. I.; Dessau, R. M.; Rodewald, P. G. JACS 1974, 96, 7977. See also: Fristad, W. E.; Peterson, J. R.; Ernst, A. B.; Urbi, G. B. T 1986, 42, 3429.
10. Minisci, F. S 1973, 1.
11. Arnone, A.; Cecere, M.; Galli, R.; Minisci, F.; Perchinunno, M.; Porta, O.; Gardini, G. G 1973, 103, 13.
12. Wallace, T. J.; Gritter, R. J. JOC 1962, 27, 3067.
13. Huyser, E. S.; Garcia, Z. JOC 1962, 27, 2716.
14. Sano, H.; Takeda, T.; Migata, T. CL 1988, 119. See also: Sano, H.; Ogata, M.; Migita, T. CL 1986, 77.
15. Klunder, J. M.; Caron, M.; Uchiyama, M.; Sharpless, K. B. JOC 1985, 50, 912.
16. Polymerization is favored under low concentrations of chain transfer agents. The polymer forming reactions are beyond the scope of this article and more appropriate reviews and monographs should be consulted for further information. See for example: Hodge, P. In Comprehensive Organic Chemistry; Barton, D. H. R., Ed.; Pergamon: Oxford, 1991; Vol. 5, p 833 and references cited therein.
17. (a) Malatesta, V.; McKelvey, R. D.; Babcock, B. W.; Ingold, K. U. JOC 1979, 44, 1872. (b) Malatesta, V.; Ingold, K. U. JACS 1981, 103, 609.
18. Gevorgyan, V.; Priede, E.; Liepins, E.; Gavars, M.; Lukevics, E. JOM 1990, 393, 333.
19. Burgess, V. A.; Easton, C. J.; Hay, M. P. JACS 1989, 111, 1047.
20. Schwarzberg, M.; Sperling, J.; Elad, D. JACS 1973, 95, 6418.
21. Battiste, D. R.; Haseldine, D. L. SC 1984, 14, 993.
22. Sanderson, J. R.; Lin, J. J.; Duranleau, R. G.; Yeakey, E. L.; Marquis, E. T. JOC 1988, 53, 2859.
23. Urry, W. H.; Stacey, F. W.; Huyser, E. S.; Juveland, O. O. JACS 1954, 76, 450.
24. Winkler, J.; Sridar, V. JACS 1986, 108, 1708.
25. Schwetlick, K.; Jentzsch, J.; Karl, R.; Wolter, D. JPR 1964, 25, 95.
26. Mignani, S.; Beaujean, M.; Janousek, Z.; Merényi, R.; Viehe, H. G. T (Suppl.) 1981, 37, 111.
27. Viehe, H. G.; Janousek, Z.; Merényi, R.; Stella, R. ACR 1985, 18, 148.
28. Minisci, F.; Citterio, E.; Vismara, E.; Giordano, C. T 1985, 41, 4157.
29. Fleming, I. In Comprehensive Organic Chemistry; Barton, D. H. R., Ed.; Pergamon: Oxford, 1991; Vol. 3, p. 562 and references cited therein.
30. Curtice, J.; Gilman, H.; Hammond, G. S. JACS 1957, 79, 4754.
31. Sakurai, H.; Hosomi, A.; Kumada, M. BCJ 1967, 40, 1551.
32. Billingham, N. C.; Jackson, R. A.; Malek, F. CC 1977, 344.
33. Nagata, Y.; Dohmaru, T.; Tsurugi, J. JOC 1973, 38, 795. See also: Nakao, R.; Fukumoto, T.; Tsurugi, J. JOC 1972, 37, 76 and Nakao, R.; Fukumoto, T.; Tsurugi, J. JOC 1972, 37, 4349.
34. Antebi, S.; Alper, H. TL 1985, 26, 2609.
35. Choudary, B. M.; Koteswara Rao, K.; Pirozhkov, S. D.; Lapidus, A. L. SC 1991, 1923.
36. Alper, H.; Vasapollo, G.; Hartstock, F. W.; Mlekuz, M.; Smith, D. J. H.; Morris, G. E. OM 1987, 6, 2391.
37. Morris, G. E.; Oakley, D.; Pippard, D. A.; Smith, D. J. H. CC 1987, 410.

T. V. (Babu) RajanBabu

The Ohio State University, Columbus, OH, USA

Nigel S. Simpkins

University of Nottingham, UK

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