Diethyl azodicarboxylate

Diethyl azodicarboxylate, often abbreviated DEAD, is the organic compound CH₃CH₂O₂CN=NCO₂CH₂CH₃. As indicated with this formula, the molecule consists of a central azo functional group, RN=NR, flanked by two ethyl ester groups. This red orange liquid is a valuable reagent but also quite dangerous.

Additional recommended knowledge

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Preparation

Although widely available, diethyl azodicarboxylate can be prepared in the laboratory. A two-step synthesis starts from hydrazine, first by alkylation with ethyl chloroformate. followed by treating the resulting ethyl hydrazodicarboxylate with chlorine.^[1]

2 CH₃CH₂O₂CCl + N₂H₄ → CH₃CH₂O₂CN(H)N(H)CO₂CH₂CH₃ + 2 HCl

CH₃CH₂O₂CN(H)N(H)CO₂CH₂CH₃ + Cl2 → CH₃CH₂O₂CN=NCO₂CH₂CH₃ + 2 HCl

Red fuming nitric acid can also be used in the second step.^[2]

Applications

DEAD is an efficient component in Diels-Alder reactions and in click chemistry, for example the synthesis of Bicyclo[2.1.0]pentane, which originates from Otto Diels.^[3]

DEAD is an important reagent in the Mitsunobu reaction where it forms an adduct with phosphines. In one study^[4] the compound together with triphenylphosphine and a chalcone formed a pyrazoline:

Safety

DEAD is toxic, shock sensitive, and thermally unstable. It is handled as a solution, rarely as the pure compound. This safety hazards have resulted in DEAD usage rapidly declining and being replaced with DIAD (Diisopropyl azo dicarboxylate).

References

1. ^ Rabjohn, N.. "Diethyl azodicarboxylate". Org. Synth.; Coll. Vol. 3: 375. 
2. ^ Kauer, J. C.. "Diethyl azodicarboxylate". Org. Synth.; Coll. Vol. 4: 411. 
3. ^ Gassman, P. G.;Mansfield, K. T.. "Bicyclo(2.1.0)pentane]". Org. Synth.; Coll. Vol. 5: 96. 
4. ^ A Novel Reaction of the “Huisgen Zwitterion” with Chalcones and Dienones: An Efficient Strategy for the Synthesis of Pyrazoline and Pyrazolopyridazine Derivatives Vijay Nair, Smitha C. Mathew, Akkattu T. Biju, and Eringathodi Suresh Angew. Chem. Int. Ed. 2007, 46, 2070 –2073 doi:10.1002/anie.200604025