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Preparation of 5-Substituted 1H-Tetrazoles from Nitriles in Water

Zachary P. Demko and K. Barry Sharpless*

*Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037

Z. P. Demko, K. B. Sharpless, J. Org. Chem., 2001, 66, 7945-7950.

DOI: 10.1021/jo010635w

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The reaction of sodium azide with nitriles to give 1H-tetrazoles proceeds readily in water with zinc salts as catalysts. The scope of the reaction is quite broad; a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides are all viable substrates.

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An aqueous solution of 1 M zinc bromide has ca. pH 7, and when sodium azide is added (1 M), it is slightly alkaline, ca. pH 8; consequently, even at 100 C, release of hydrazoic acid is minimized. When the reactions were run at a concentration of 1 M in sodium azide and 1 M in ZnBr2, a small amount of liberated hydrazoic acid could be detected in the headspace above the refluxing solvent; when the concentration was dropped to 0.5 M, no hydrazoic acid could be detected.

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ID: J42-Y2001