A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1964, 44, 18
DOI: 10.15227/orgsyn.044.0018
[Formic acid, azodi-, di-tert-butyl ester]
Submitted by Louis A. Carpino and Paul J. Crowley1.
Checked by Virgil Boekelheide and S. J. Cross.
1. Procedure
A. t-Butyl hydrazodiformate. A solution of 28.6 g. (0.2 mole) of t-butyl azidoformate2 and 26.4 g. (0.2 mole) of t-butyl carbazate3 in 60 ml. of pyridine (Note 1) is allowed to stand at room temperature for 1 week and is then diluted with 500 ml. of water. The snow-white microcrystalline powder that separates is removed by filtration and is washed with two 50-ml. portions of water. The yield of air-dried hydrazide, m.p. 124–126°, is 35.5–37 g. (77–80%). The product is pure enough for most applications but may be purified by recrystallization from a 1:1 mixture of benzene and ligroin (60–90°) from which it separates as small white needles, m.p. 124–125.5°. The recovery is 92%.
B. t-Butyl azodiformate. In a 500-ml. Erlenmeyer flask is placed a solution of 23.2 g. (0.1 mole) of crude t-butyl hydrazodiformate (m.p. 124–126°) in 175 ml. of methylene chloride and 7.9 g. (0.1 mole) of pyridine (Note 1). The solution is cooled by a stream of running tap water while 18.2 g. (0.102 mole) (Note 2) of N-bromosuccinimide (Note 1) is added during 6–7 minutes with swirling. The resulting solution is allowed to stand at room temperature for 5 minutes and is washed with two 100-ml. portions of water followed by one 100-ml. portion of 10% sodium hydroxide. The solution is dried for 30 minutes over magnesium sulfate, filtered into a large evaporating dish, and allowed to evaporate. The yellow-orange crystalline residue, m.p. 90–91.5°, which amounts to 20.7–21.8 g. (90–94.5%), is recrystallized by covering the dry solid with 35–40 ml. of petroleum ether (b.p. 30–60°) and adding ligroin (b.p. 60–90°) to the boiling solution until the solid dissolves. t-Butyl azodiformate, 19.8–20.0 g., m.p. 90.7–92°, separates from the cooled solution as large lemon-yellow crystals. Evaporation of the filtrate gives an additional amount of yellow solid which is recrystallized as before, yielding 0.4–0.7 g. of pure material, m.p. 90–92°. The total yield is 20.2–20.7 g. (88–90%).
2. Notes
1. The pyridine was a pure product, b.p. 113–115°, obtained from Mallinckrodt Chemical Company and used as supplied. The methylene chloride (technical grade) and N-bromosuccinimide (practical grade) were obtained from the Matheson Company and used as received.
2. Unless a 2% excess of N-bromosuccinimide is used, the azo compound is contaminated by an impurity, possibly the original hydrazo compound, which separates along with the desired product in the form of long, easily distinguished needles. The two substances cannot be separated by crystallization from ligroin.
3. Discussion
t-Butyl hydrazodiformate has been prepared by acylation of t-butyl carbazate by means of t-butyl azidoformate4 or t-butyl cyanoformate.5 t-Butyl azodiformate has been prepared only by oxidation of the hydrazo compound.6
4. Merits of the Preparation
The potassium salt of t-butyl hydrazodiformate can be easily alkylated and thus used in the synthesis of acyclic and cyclic 1,2-disubstituted hydrazines.7
Ethyl azodiformate is a well-known and useful dienophile in the Diels-Alder reaction.8 t-Butyl azodiformate behaves similarly, although it is somewhat less reactive.6 t-Butyl azodiformate does, however, provide products with ester groups that are easily cleaved. Monosubstituted hydrazines may be prepared by the addition of Grignard reagents to azoformates followed by cleavage.6

References and Notes
  1. Department of Chemistry, University of Massachusetts, Amherst, Massachusetts.
  2. L. A. Carpino, B. A. Carpino, P. J. Crowley, C. A. Giza, and P. H. Terry, this volume, p. 157, or M. A. Insalaco and D. S. Tarbell, Org. Syntheses, 50, 9 (1970). This reagent is also available from Aldrich Chemical Company, Inc.
  3. L. A. Carpino, D. Collins, S. Göwecke, J. Mayo, S. D. Thatte, and F. Tibbetts, this volume, p. 166.
  4. L. A. Carpino, J. Am. Chem. Soc., 79, 4427 (1957).
  5. L. A. Carpino, J. Am. Chem. Soc., 82, 2725 (1960).
  6. L. A. Carpino, P. H. Terry, and P. J. Crowley, J. Org. Chem., 26, 4336 (1961).
  7. L. A. Carpino, J. Am. Chem. Soc., 85, 2144 (1963).
  8. O. Diels, J. H. Blom, and W. Koll, Ann., 443, 242 (1925).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)


petroleum ether

Benzene (71-43-2)

sodium hydroxide (1310-73-2)

pyridine (110-86-1)

methylene chloride (75-09-2)

magnesium sulfate (7487-88-9)

N-bromosuccinimide (128-08-5)

Ethyl azodiformate


t-butyl carbazate (870-46-2)


Formic acid, azodi-, di-tert-butyl ester

t-butyl hydrazodiformate

t-butyl cyanoformate

potassium salt of t-butyl hydrazodiformate