Mesityloxytris(dimethylamino)phosphonium Azide

[73014-63-8]  · C15H29N6OP  · Mesityloxytris(dimethylamino)phosphonium Azide  · (MW 340.47)

(organic soluble source of azide ion1)

Physical Data: mp 110-112 °C.

Solubility: sol most organic solvents.

Form Supplied in: not commercially available from common sources.

Preparative Method: readily prepared in a 68% yield from 2,4,6-trimethylphenol by treatment with Hexamethylphosphorous Triamide then Sodium Azide (eq 1).1

Purification: precipitation from an acetone solution by the addition of diethyl ether.

Mesityloxytris(dimethylamino)phosphonium azide is an organic soluble form of azide that is reported to be a better source of azide than tetrabutylammonium azide. It has been used for the preparation of glycosyl azides (eq 2).1 The anomeric alcohol is first activated through formation of the phosphonium chloride by treatment with carbon tetrachloride and (NMe2)3P. The phosphonium salt is then reacted with the phosphonium azide, forming the glycosyl azide and regenerating (NMe2)3P.

The intermediate phosphonium chlorides are formed with a trans configuration relative to the C-2 substituent and the substitution generally occurs with inversion of configuration to give a cis-azide. Reported yields are good, mostly in the 65-80% range. Most common carbohydrate protecting groups appear to be stable to these conditions, including acetals, trityl (eq 3), benzyl (eq 4), and t-butyldiphenylsilyl. The resulting glycosyl azides are used in the synthesis of triazole nucleosides,2 and purine3 or pyrimidine4 nucleosides.

Several advantages of this method over previously reported methods are described. The major advantage is that the use of toxic silver azide is eliminated. The reagent can be prepared from readily available starting materials and is soluble in organic solvents. The phosphonium azide is crystalline and nonhygroscopic. The reaction is fast and performed at low temperatures and the resulting glycosyl azide is readily separated from the water-soluble byproducts. The major disadvantage of this method is that (NMe2)3P must be used. A later reported method which employs Azidotrimethylsilane and a Lewis acid catalyst has been reported to be a better method to carry out this transformation.5

1. Chretien, F.; Castro, B.; Gross, B. S 1979, 937.
2. Chretien, F.; Gross, B. JHC 1982, 19, 263.
3. Chretien, F.; Gross, B. T 1982, 38, 103.
4. Ralph, R. K.; Shaw, G. JCS 1956, 1877.
5. Logue, M. W.; Han, B. Y. Carbohydr. Res. 1983, 121, 287.

Valerie Vaillancourt & Michele M. Cudahy

The Upjohn Co., Kalamazoo, MI, USA

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