Subscribe to RSS
DOI: 10.1055/s-2007-1000842
Tetramethylguanidinium Azide (TMGA) - A Versatile Azidation Agent
Publication History
Publication Date:
21 December 2007 (online)
![](https://www.thieme-connect.de/media/synlett/200802/lookinside/thumbnails/10.1055-s-2007-1000842-1.jpg)
Introduction
Organic azides have been widely used in synthesis, especially for the construction of heterocyclic systems, and as precursors of the primary amino group. [1] One method to incorporate the azide moiety into organic compounds is to use tetramethylguanidinium azide as the azidation agent. Tetramethylguanidinium azide (TMGA, TMGN3) introduced by Papa [2] is commercially available, stable, non-toxic, and safe in use. [3] TMGA is a colorless hygroscopic solid, which is soluble in organic solvents (chloroform, dichloromethane, acetonitrile, nitromethane, DMF, acetone) and water; it is insoluble in diethyl ether and THF. The standard procedure for the preparation of TMGA involves the action of hydrazoic acid (HN3) on tetramethylguanidine in ether. [2] The use of TMGA allows the introduction of the azido group under very mild non-aqueous conditions; however, it is not recommended to use halogenated solvents because explosive azidomethane species may be formed during the reaction. [3] [4] TMGA is frequently used as a source of azide, in nucleophilic addition, substitution, azidolysis of epoxides, and heterocyclic ring formation. [5] It has been successfully used for the synthesis of alkyl, [2] alkenyl, [6] propargyl, [7] heteroaryl, [8] acyl, [9] phosphinic, [10] and sulfonyl azides [11] as well as for the preparation of tert-butyl azidoformate, [12] tetrazoles, [13] β-azido alcohols, [14] α-azido ketones [15] and α-amino acid derivatives. [16]
- 1
Bräse S.Gil C.Knepper K.Zimmermann V. Angew. Chem. Int. Ed. 2005, 44: 5188 - 2
Papa AJ. J. Org. Chem. 1966, 31: 1426 -
3a
Li C.Arasappan A.Fuchs PL. Tetrahedron Lett. 1993, 34: 3535 -
3b
Li C.Shih T.-L.Jeong JU.Arasappan A.Fuchs PL. Tetrahedron Lett. 1994, 35: 2645 - 4
Dharanipragada R.VanHulle K.Bannister A.Bear S.Kennedy L.Hruby VJ. Tetrahedron 1992, 48: 4733 - 5
Enders D.Backes M. Encyclopedia of Reagents for Organic SynthesisPaquette AL. Wiley; New York: 2004. -
6a
Palacios F.Aparicio D.De los Santos JM.De Heredia IP.Rubiales G. Org. Prep. Proced. Int. 1995, 27: 171 -
6b
Fotsing JR.Banert K.Hagedorn M. Tetrahedron 2005, 61: 8904 -
6c
Fotsing JR.Banert K. Synthesis 2006, 261 - 7
Fotsing JR.Banert K. Eur. J. Org. Chem. 2005, 3704 -
8a
Abramovitch RA.Shinkai I.Cue BWJr.Ragan FA.Atwood JL. J. Heterocycl. Chem. 1976, 13: 415 -
8b
Dirlam JP.Cue BWJr.Gombatz KJ. J. Org. Chem. 1978, 43: 76 - 9
Clinch K.Marquez CJ.Parrott MJ.Ramage R. Tetrahedron 1989, 45: 239 - 10
Denmark SE.Dorow RL. Chirality 2002, 14: 241 - 11
Abramovitch AR.Azogu CI.McMaster IT.Vanderpool DP. J. Org. Chem. 1978, 43: 1218 - 12
Sakai K.Anselme J.-P. J. Org. Chem. 1971, 36: 2387 -
13a
Crimmin JM.O’Hanlon PJ.Rogers NH.Walker G. J. Chem. Soc., Perkin Trans. 1 1989, 2047 -
13b
Amer MIK.Booth BL. J. Chem. Res., Synop. 1993, 4 -
14a
Crotti P.Di Bussolo V.Favero L.Macchia F.Pineschi M. Tetrahedron Lett. 1996, 37: 1675 -
14b
Di Bussolo V.Caselli M.Romano MR.Pineschi M.Crotti P. J. Org. Chem. 2004, 69: 8702 -
14c
Di Bussolo V.Romano MR.Pineschi M.Crotti P.Favero L. J. Org. Chem. 2006, 71: 1696 - 15
Pan Y.Merriman RL.Tanzer LR.Fuchs PL. Bioorg. Med. Chem. Lett. 1992, 2: 967 -
16a
Evans DA.Britton TC.Ellman JA.Dorow RL. J. Am. Chem. Soc. 1990, 112: 4011 -
16b
Smith RJ.Bienz S. Helv. Chim. Acta 2004, 87: 1681 -
16c
Treweeke NR.Hitchcock PB.Pardoe DA.Caddick S. Chem. Commun. 2005, 1868 -
16d
Xu J.Wei L.Mathvink R.He J.Park Y.-J.He H.Leiting B.Lyons KA.Marsilio F.Patel RA.Wu JK.Thornberry NA.Weber AE. Bioorg. Med. Chem. Lett. 2005, 15: 2533 -
17a
Ying L.Gervay-Hague J. Carbohydr. Res. 2003, 338: 835 -
17b
Stolz F.Reiner M.Blume A.Reutter W.Schmidt RR. J. Org. Chem. 2004, 69: 665 - 18
Mitchinson A.Blackaby WP.Bourrain S.Carling RW.Lewis RT. Tetrahedron Lett. 2006, 47: 2257 - 19
Arnold MA.Duron SG.Gin DY. J. Am. Chem. Soc. 2005, 127: 6924 -
20a
Fan G.-T.Pan Y.-S.Lu K.-C.Cheng Y.-P.Lin W.-C.Lin S.Lin C.-H.Wong C.-H.Fang J.-M.Lin C.-C. Tetrahedron 2005, 61: 1855 -
20b
Chang C.-W.Chen Y.-N.Adak AK.Lin K.-H.Tzou D.-LM.Lin C.-C. Tetrahedron 2007, 63: 4310 -
21a
Pabba J.Vasella A. Tetrahedron Lett. 2005, 46: 3619 -
21b
Pabba J.Rempel BP.Withers SG.Vasella A. Helv. Chim. Acta 2006, 89: 635