New Benzotriazole Reagents: Stable Isothiocyanate Equivalents and Sulfonylating Agents

Benzotriazole has been commonly employed as a leaving group and has been used extensively as a novel synthetic auxiliary.  Much of its attractiveness lies in its ability to be introduced readily and easy to remove or displace during syntheses, as well as its ability to activate other parts of the molecule.¹  The Katritzky group at the University of Florida has performed much of the pioneering work on benzotriazole-mediated synthesis, and continues to provide new methods employing the benzotriazole moiety.

N-Acylbenzotriazoles have recently been highlighted, but their utility continues to expand.  Katritzky has recently reported the use of these reagents in the preparation of a-nitro ketones,² and oxazolines and thiazolines under MW irradiation (Scheme 1).³

Katritzky has also highlighted the use of thiocarbamoylbenzotriazoles as stable isothiocyanate equivalents.  These reagents are much easier to handle than the isothiocyanates and are highly effective thioacylating reagents for preparation of thioureas and thioamides.  For example, reaction of the benzotriazole-1-carbothioic acid 2-thiazolylamide with phenethylamine proceeds smoothly to yield the asymmetrical thiourea in 95% yield (Scheme 2).⁴ 

Bis(benzotriazolyl)methanethione has been demonstrated to be an effective thiophosgene equivalent, and more robust than 1,1’-thiocarbonyldiimidazole.  As such, bis(benzotriazolyl)methanethione can be used to easily prepare numerous other thiocarbonyl products (Scheme 3).⁵ 

N-Sulfonylbenzotriazoles have been already employed by the Katritzky group as reagents to generate novel sulfonamides in good to excellent yields when the corresponding sulfonyl halide is not readily available (Scheme 4).⁶  More recently, C-sulfonylation has been demonstrated using N-sulfonylbenzotriazoles, allowing access to a variety of unique sulfones (Scheme 5).⁷

Product #	Product Name/Description	Structure	Add to Cart
557455	1-Allylbenzotriazole, 96%
596485	Benzotriazole-1-carboxamide
667536	Methyl 1H-benzotriazole-1-carboxylate, 97%
633917	Benzotriazole-1-carbonyl chloride, technical grade
589284	1-[(Trimethylsilyl)methyl]benzotriazole, 99%
660086	1,1′-Carbonylbisbenzotriazole preparation, 40 wt.% slurry in H2O
643610	Bis(1-benzotriazolyl)methanethione, 97%
642568	Tris-(1-benzotriazolyl)methane, 97%
579408	1-(Methylsulfonyl)-1H-benzotriazole, 95%
465739	1-(Phenylsulfonyl)-1H-benzotriazole, 97%
647330	1-(3-Pyridinylsulfonyl)-1H-benzotriazole, 95%
647322	1-[(1-Methyl-1H-imidazol-2-yl)sulfonyl]-1H-benzotriazole, 97%
654604	N-(Furan-2-ylmethyl)-1H-benzotriazole-1-carbothioamide, 96%
654590	N-(2-Thiazolyl)-1H-benzotriazole-1-carbothioamide, 97%
654612	N-Benzyl-1H-benzotriazole-1-carbothioamide, 97%
654620	Benzotriazol-1-ylpyrrolidin-1-ylmethanethione, 97%
654851	N-(1H-Benzotriazol-1-ylmethyl)benzamide, 97%

References:

(1) Reviews: (a) Katritzky, A. R. and Belyakov, S. A Aldrichimica Acta 1998, 31, 35. (b) Katritzky, A. R. et al. Chem. Rev. 1998, 98, 409.

(2) Katritzky, A. R. et al. J. Org. Chem. 2005, 70, 9211.

(3) Katritzky, A. R. et al. J. Org. Chem. 2004, 69, 811.

(4) Katritzky, A. R. et al. J. Org. Chem. 2004, 69, 2976.

(5) Katritzky, A. R. et al. J. Org. Chem. 2005, 70, 7866.

(6) Katritzky, A. R. et al. J. Org. Chem. 2004, 69, 1849.

(7) Katritzky, A. R. et al. J. Org. Chem. 2005, 70, 9191.