Bis(2,2,2-trichloroethyl) Azodicarboxylate

[38857-88-4]  · C6H4Cl6N2O4  · Bis(2,2,2-trichloroethyl) Azodicarboxylate  · (MW 380.83)

(a reactive dienophile,2 diene,7 and enophile8)

Physical Data: mp 110-111 °C.

Solubility: sol in a wide range of organic solvents.

Form Supplied in: slightly yellow plates.

Analysis of Reagent Purity: 1H NMR (CDCl3) displays a singlet at d 5.05.

Preparative Method: commercially available.1

Purification: recrystallize from pentane.

Handling, Storage, and Precautions: as with all azo compounds, caution should be exercised to avoid exposure of the material to heat. Store in a brown bottle.

Reaction as a Diels-Alder Dienophile.

Bis(2,2,2-trichloroethyl) azodicarboxylate (1) is most often used as a Diels-Alder dienophile.2 Its relatively high reactivity occasionally makes it preferable to the less reactive diethyl or dimethyl analogs, since the times and temperatures needed to achieve reaction are often reduced. For example, the Diels-Alder reaction illustrated (eq 1) required 5 days to reach completion when dimethyl azodicarboxylate was used, in contrast to just 1 h with (1).2

The bis(carbamate) cycloadducts are often highly viscous materials. Attempts to characterize them by 1H NMR can be difficult by virtue of the several dynamic processes which occur on the NMR timescale.3 To obtain a well-resolved spectrum requires that it be recorded at an elevated temperature.3

Most often, bis(carbamates) serve as precursors to azo compounds and the latter, in turn, to a host of theoretically interesting materials, reactive intermediates, and precursors to natural products.2,4 While hydrolytic methods can also be used, the trichloroethoxy group is most often cleaved reductively, usually with Zinc-Acetic Acid,5 or with a Zinc/Copper Couple in the presence of a proton donating solvent,2b,4 or via an electroreductive process.6 The presence of a proton donor leads to the formation of an intermediate hydrazo compound, which requires further oxidation to generate the azo linkage. Occasionally, the azo compound is initially isolated as a copper complex and then freed by making the solution basic, often by using aqueous ammonia.5 In the absence of a proton donor, the hydrazo compound is bypassed. In this case, oxidation of the intermediate dicarboxylate salt leads directly to the azo functionality.2,6 Regardless of the method, yields are sometimes variable, and experimentation is often required to achieve optimal conversion.

Reaction as a Diene.

Interestingly, (1) can also serve as a diene. Thus when irradiated (eq 2) (350 nm), a novel [4 + 2] cycloaddition occurs between (1) and a variety of glycals.7 Reaction times are quite long (e.g. 18 h to 2 weeks), but the yields are uniformly good (73-85%). Once again, the increased reactivity of (1) relative to other commonly used azodicarboxylates is apparent. For example, while the photoreaction (eq 2) requires 1.5 weeks, it fails to occur using dibenzyl azodicarboxylate. Treatment of the adducts with a catalytic amount of p-TsOH in methanol affords the corresponding methyl glycosides which, when exposed to zinc dust in acetic acid and acetone, followed by acetic anhydride/pyridine, generate 2-amino glycosides in good to excellent yields (60-97%; 75% for the case shown).

Reaction as an Enophile.

When used as an enophile, (1) provides a novel route to allylic amines.8 Ene reactions with diethyl and dimethyl azodicarboxylate have also been reported, but the yields are low. In contrast, use of the trichloroethyl derivative affords ene adducts in 60-88% yield and allows generation of both cyclic and acyclic N-acylamines under mild conditions (eq 3).

Related Reagents.

Di-t-butyl Azodicarboxylate; Diethyl Azodicarboxylate.

1. (a) Little, R. D.; Venegas, M. G. OS 1983, 61, 17. (b) Mackay, D.; Pilger, C. W.; Wong, L. L. JOC 1973, 38, 2043.
2. (a) Van Hijfte, L.; Little, R. D.; Petersen, J. L.; Moeller, K. D. JOC 1987, 52, 4647. (b) Stone, K. J.; Little, R. D. JACS 1985, 107, 2495.
3. (a) Gibbard, A. C.; Moody, C. J.; Rees, C. W. JCS(P1) 1986, 145. (b) Warrener, R. N.; Russell, R. A.; Tan, R. Y. S. AJC 1981, 34, 855.
4. Semmelhack, M. F.; Foos, J. S.; Katz, S. JACS 1973, 95, 7325.
5. Rastetter, W. H. JACS 1976, 98, 6350.
6. Little, R. D.; Carroll, G. L. JOC 1979, 44, 4720.
7. Leblanc, Y.; Fitzsimmons, B. J. TL 1989, 30, 2889.
8. Leblanc, Y.; Zamboni, R.; Bernstein, M. A. JOC 1991, 56, 1971.

R. Daniel Little & Therese M. Bregant

University of California, Santa Barbara, CA, USA

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