Diimide1

HN=NH
(cis)

[15626-42-3]  · H2N2  · Diimide  · (MW 30.03) (trans)

[15626-43-4]

(mild, noncatalytic reducing agent for the syn reduction of C=C and C&tbond;C bonds; does not react with O-O, N-O, or other easily reduced single bonds, or with C=O, C=N, or aromatic p-bonds)

Alternate Name: diazene.

Form Supplied in: generated in situ.

Preparative Methods: the most widely used methods involve the CuI-catalyzed Oxygen or Hydrogen Peroxide oxidation of hydrazine, and the acid-catalyzed decarboxylation of Potassium Azodicarboxylate.

Introduction.

The reduction of C-C p-bonds in the presence of various N-N-containing compounds ultimately capable of producing diimide dates back to 1905;2 however, it was not until the early 1960s that the role of cis-diimide (diazene) was recognized.3-6 The results of stereochemical studies7 and theoretical calculations8 indicate that cis-diimide is the active reducing agent, and that the reduction occurs via a concerted, symmetry allowed transfer of the hydrogen atoms of cis-diimide to the C=C or C&tbond;C bond, as illustrated in eq 1. In competition with the reduction of C-C p-systems, diimide undergoes a more facile disproportionation reaction to produce nitrogen and hydrazine9 which requires the use of considerable excesses of the diimide precursor.

An important feature of the reduction of C-C p-systems is that many highly reactive functional groups can be present which would not survive under other chemical reducing or catalytic hydrogenation conditions. Such functional groups include allylic and benzylic derivatives, halides, sulfur-containing systems, O-O and N-O containing systems, and complex bioorganic molecules. Examples of the latter systems are shown in eqs 2 and 3.10,11

Relative Reactivity Toward Reduction by Diimide.

Carbon-carbon triple bonds, in general, are more reactive than double bonds toward reduction by diimide.7,12 The relative reactivity of double bonds toward reduction decreases as the degree of alkyl substitution on the double bond increases,12 and increases with increasing strain (see Table 1).12 1,3-Dienes are more reactive than monoenes, with the degree of substitution affecting the relative reactivity as observed with alkenes.13 Examples of intramolecular selectivity are illustrated in eqs 4-6.14-16

Electronegatively substituted double bonds (e.g. a,b-unsaturated carboxylic acids) are more reactive toward reduction by diimide than are alkyl- or electron donating-substituted p-systems. (The attempted reduction of a,b-unsaturated aldehydes, ketones, and esters generally results in the formation of products deriving from the reaction of the carbonyl compound with hydrazine, which is formed by the disproportionation of the diimide.)

Facial Selectivity of Reduction.

The results of experimental and theoretical studies suggest that the transition state for diimide reduction lies very early along the reaction coordinate with the cis-diimide approaching the less sterically hindered face of the p-system (eq 6).

Electronic factors also play a role in determining the chemoselectivity of reduction by diimide; this is illustrated in eq 7, in which anti-exo reduction occurs preferentially to syn-exo reduction.17

Methods of Generation of Diimide.

Numerous methods have been discovered for the generation of diimide.1a Of these, only two processes find wide use: firstly, the air (oxygen) or Hydrogen Peroxide oxidation of hydrazine in the presence of copper(I) and a catalytic amount of a carboxylic acid (eq 8) (the carboxylic acid apparently being required to catalyze the isomerization of trans- to cis-diimide); secondly, the reaction of Potassium Azodicarboxylate with a carboxylic acid in aprotic solvents (eq 9).18 The azodicarboxylate salt is formed by the reaction of Potassium Hydroxide with azodicarboxamide (commercially available). The latter procedure is especially useful for the position-specific and stereochemically controlled incorporation of deuterium or tritium into organic systems. An example is shown in eq 10, illustrating both the facial and stereoselectivity of the reaction.19


1. (a) Pasto, D. J.; Taylor, R. T. OR 1991, 40, 91. (b) Pasto, D. J. COS 1991, 8, 471. (c) Hunig, S.; Müller, H. R.; Thier, W. AG(E) 1965, 4, 271. (d) Miller, C. E. J. Chem. Educ. 1965, 42, 254.
2. Hanus, J.; Vorisek, J. CCC 1929, 1, 223.
3. Corey, E. J.; Mock, W. L.; Pasto, D. J. TL 1961, 347.
4. Hunig, S.; Muller, H.; Thier, W. TL 1961, 353.
5. van Tamelen, E. E.; Dewey, R. S.; Timmons, R. J. JACS 1961, 83, 3725.
6. Aylward, F.; Sawistowska, M. CI(L) 1962, 484.
7. Corey, E. J.; Pasto, D. J.; Mock, W. L. JACS 1961, 83, 2957.
8. Pasto, D. J.; Chipman, D. M. JACS 1979, 101, 2290.
9. Pasto, D. J.; JACS 1979, 101, 6852.
10. Adam, W.; Eggelte, H. J. JOC 1977, 42, 3987.
11. Russ, P. L.; Hegedus, L.; Kelley, J. A.; Barchi, J. J., Jr; Marquez, V. E. Nucleosides Nucleotides 1992, 11, 351.
12. Garbisch Jr., E. W.; Schildcrout, S. M.; Patterson, D. B.; Sprecher, C. M. JACS 1965, 87, 2932.
13. Siegel, S.; Foreman, M.; Fisher, R. P.; Johnson, S. E. JOC 1975, 40, 3599.
14. Mori, K.; Ohki, M.; Sato, A.; Matsui, M. T 1972, 28, 3739.
15. Rao, V. V. R.; Devaprabhakara, D. T 1978, 34, 2223.
16. Pasto, D. J.; Borchardt, J. K. TL 1973, 2517.
17. Baird, W. C., Jr.; Franzus, B.; Surridge, J. H. JACS 1967, 89, 410.
18. For specific experimental procedures see Ref. 1 and references contained therein.
19. Srinivasan, R.; Hsu, J. N. C. CC 1972, 1213.

Daniel J. Pasto

University of Notre Dame, IN, USA



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