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Chemical Synthesis

Diazald

Diazomethane is an extremely versatile reagent for the preparation of both carbon-carbon and carbon-heteroatom bonds.1 It is one of the most common methylating reagents for the preparation of methyl esters from the corresponding carboxylic acids.2 Additionally, diazomethane has found extensive application in the alkylation of phenols, enols, and heteroatoms such as nitrogen and sulfur. Diazomethane has also been used in: cycloalkanone ring expansion,3 preparation of α-diazo ketones,4 and pyrazoline formation,5 and Pd-catalyzed cyclopropanation (Scheme 1).6


Due to its instability and toxicity, diazomethane is not amenable to storage or transport.7 Therefore, several diazomethane precursors have been developed over the past few decades. The majority of these precursors contain an N-methyl-N-nitroso group, which generates diazomethane upon treatment with base (Scheme 2).


Of the precursors used, N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitroso-p-toluenesulfonamide (Diazald®) have been the most popular. MNNG is toxic, a severe irritant, a carcinogen,8 and a potent mutagen.9 Additionally, the use of MNNG has historically been limited to small-scale production of diazomethane (ca. 1 mmol). Because of these hazard concerns, Sigma-Aldrich no longer offers MNNG for sale to our customers. While Diazald® is also considered to be a severe irritant, it has not demonstrated the acute toxicity of MNNG. Moreover, it is amenable to large-scale production (~300 mmol) of diazomethane.10

For these reasons, Sigma-Aldrich is pleased to offer Diazald® (D28000) as the preferred diazomethane precursor. We also offer a variety of specialized glassware kits for the safe and convenient production of diazomethane on scales from 1 to 300 mmol.11 For our customers who have purchased the MNNG diazomethane generator (Z411736), Diazald® can be easily substituted for MNNG.12

Product Name   Product # 
Diazald® 99% D28000

References:

  1. For thorough reviews, see: (a) Hopps, H. B. et al. Aldrichimica Acta 1970, 3, 9; (b) Black, T. H. et al. Aldrichimica Acta 1983, 16, 3.
  2. For a recent example, see: Madin, A. et al. J. Am. Chem. Soc. 2005, 127, 18054.
  3. For a recent example, see: Harmata, M. et al. Org. Lett. 2005, 7, 1881.
  4. For a recent example, see: Huang, Y. et al. Org. Lett. 2005, 7, 5841.
  5. For a recent example, see: García Ruano, J. L. et al. J. Org. Chem. 2005, 70, 8942.
  6. For a recent example, see: Mattson, R. J. et al. J. Med. Chem. 2005, 48, 6023.
    (a) Registry of Toxic Effects of Chemical Substances; NIOSH: Cincinnati, OH; PA7000000;
    (b) Lewis, C. E. et al. Occup. Med. 1964, 6, 91; (c) Schoental, R. et al. Nature 1960, 188, 420.
  7. Registry of Toxic Effects of Chemical Substances; NIOSH: Cincinnati, OH; MF4200000.
  8. Mandell, J. D. et al. J. Biochem. Biophys. Res. Commun. 1960, 3, 575; Adelberg, E. A. et al. J. Biochem. Biophys. Res. Commun. 1965, 18, 788.
  9. For proper handling of Diazald® in diazomethane preparation, please view our technical bulletin, AL-180: HERE.
  10. Our extensive collection of diazomethane glassware kits can be viewed on our website: HERE.
  11. Ngan, F. et al. J. Chromatogr. Sci. 1991, 29, 8.