fresh in the laboratory, especially if required in pure, non-diluted form. A two-step synthesis starts from hydrazine, first by alkylation with ethyl chloroformate, followed by treating the resulting diethyl hydrazodicarboxylate with chlorine (bubbling through the solution), hypochlorous acid, concentrated nitric acid or red fuming nitric acid. The reaction is carried out in an ice bath, and the reagents are added dropwise so that the temperature does not rise above 20 °C. Diethyl hydrazodicarboxylate is a solid with melting temperature of 131–133 °C which is collected as a residue; it is significantly more stable to heating than DEAD and is conventionally dried at a temperature of about 80 °C. Applications Mitsunobu reaction DEAD is a reagent in the Mitsunobu reaction where it forms an adduct with phosphines (usually triphenylphosphine) and assists the synthesis of esters, ethers, amines and thioethers from alcohols. Reactions normally result in the inversion of molecular symmetry. DEAD was used in the original 1967 article by Oyo Mitsunobu, and his 1981 review on the use of diethyl azodicarboxylate is a top-cited chemistry article. Mitsunobu reaction has several applications in the synthesis of natural products and pharmaceuticals. In the above reaction, which is assisted either by DEAD or DIAD (diisopropyl azodicarboxylate), thymidine 1 transforms to the derivative 2. The latter easily converts to zidovudine 4 (also known as azidothymidine or AZT), an important antiviral drug, used among others in the treatment of AIDS. Another example of pharmaceutical application of DEAD-assisted Mitsunobu reaction is the synthesis of bis[(pivaloyloxy)methyl [PIVz] derivative of 2’-deoxy-5-fluorouridine 5’-monophosphate (FdUMP), which is a potent antitumor agent. Michael reaction The azo group in DEAD is a Michael acceptor. In the presence of a copper(II) catalyst, DEAD assists conversion of β-keto esters to the corresponding hydrazine derivatives. The substitution of boronic acid esters proceeds similarly: Other reactions 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. It has also been used to generate aza-Baylis-Hillman adducts with acrylates. DEAD can be used for synthesis of heterocyclic compounds. Thus, pyrazoline derivatives convert by condensation to α,β-unsaturated ketones: Another application is the use of DEAD as enophile in ene reactions: Safety DEAD is toxic, shock and light sensitive; it can violently explode when its undiluted form is heated above 100 °C. Shipment by air of pure diethyl azodicarboxylate is prohibited in the United States and is carried