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.