RSS-Feed abonnieren
DOI: 10.1055/s-0029-1218366
Microwave Irradiation as an Effective Means of Synthesizing Unsubstituted N-Linked 1,2,3-Triazoles from Vinyl Acetate and Azides
Publikationsverlauf
Publikationsdatum:
11. November 2009 (online)
![](https://www.thieme-connect.de/media/synlett/200920/lookinside/thumbnails/10.1055-s-0029-1218366-1.jpg)
Abstract
N-Linked 1,2,3-triazoles have been prepared by a reaction of azides with vinyl acetate under microwave irradiation. Additionally, a microwave-assisted, two-step, one-pot procedure from halides involving azide substitution in diethyl ether, followed by reaction with vinyl acetate, has effectively been employed.
Key words
1,2,3-triazole - vinyl acetate - microwave irradiation - one-pot reaction - 1,3-dipolar cycloaddition
- Supporting Information for this article is available online:
- Supporting Information
- 1
Fan W.-Q.Katritzky AR. In Comprehensive Heterocyclic Chemistry II Vol. 4:Katritzky AR.Rees CW.Scriven EFV. Pergamon Press; Oxford: 1996. p.1-126 -
2a
Micetich RG.Maiti SN.Spevak P.Hall TW.Yamabe S.Ishida N.Tanaka M.Yamazaki T.Nakai A.Ogawa K. J. Med. Chem. 1987, 30: 1469 -
2b
Maiti SN.Babu RPK.Shan R. Top. Heterocycl. Chem. 2006, 207 -
3a
Tornøe CW.Christensen C.Meldal M. J. Org. Chem. 2002, 67: 3057 -
3b
Rostovtsev VV.Green LG.Fokin VV.Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2596 - 4
Dahl RS.Finney NS. J. Am. Chem. Soc. 2004, 126: 8356 - 5
Yap AH.Weinreb WM. Tetrahedron Lett. 2006, 47: 3035 - 6
Lu L.-H.Wu J.-H.Yang C.-H. J. Chin. Chem. Soc. 2008, 55: 414 - 7
Fletcher JT.Walz SE.Keeney ME. Tetrahedron Lett. 2008, 49: 7030 - 8
Fan H.Xu G.Chen Y.Jiang Z.Zhang S.Yang Y.Ji R. Eur. J. Med. Chem. 2007, 42: 1137 - 9
Machin PJ.Hurst DN.Bradshaw RM.Blaber LC.Burden DT.Melarange RA. J. Med. Chem. 1984, 27: 503 -
10a
Reisser F. inventors; Belgian Patent 82-10558. -
10b
Tanaka M,Yamazaki T, andKajitani M. inventors; Eur. Pat. Appl. 158494. -
10c
Biagi G.Livi O.Scartoni V.Verugi E. Farmaco, Ed. Sci. 1988, 43: 597 -
10d
Biagi G.Dell’omodarme G.Ferretti M.Giorgi I.Livi O.Scartoni V. Farmaco 1990, 45: 1181 - 11
Freeze S.Norris P. Heterocycles 1999, 51: 1807 - 12
Yokoyama M.Nakao E.Sujino K.Watanabe S.Togo H. Heterocycles 1990, 31: 1669 -
13a
Microwaves in Organic Synthesis
2nd
ed.:
Loupy A. Wiley-VCH; Weinheim: 2006. -
13b
Abid M.Torok B.Huang X. Aust. J. Chem. 2009, 62: 208 - 14
Tao C.-Z.Cui X.Li J.Liu A.-X.Liu L.Guo Q.-X. Tetrahedron Lett. 2007, 48: 3525 - 15
Microwave-Assisted
Preparation of Alkyl Azides; General Procedure
Alkyl
halide (1 equiv) and NaN3 (1.1 equiv)
in DMF was mixed in a Biotage vial of 0.5-2.0 mL.
The vial was sealed, and irradiated at 100 ˚C
for 10-60 min. When the reaction was complete as monitored
by TLC analysis, the reaction mixture was diluted with Et2O
and the organic phase was washed several times with H2O
and brine and dried over MgSO4. The solvent was removed
at atmospheric pressure and room temperature (as small organic azides
do not tolerate vacuum evaporation), and the isolated alkyl azide was
sufficiently pure for the next reaction. WARNING:
organic azides are potentially explosive substances
and proper safety precautions such as a blast shield should be taken
when handling these compounds.
Benzyl
Azide (1a): BnCl (1.20 mL, 10.4 mmol) and NaN3 (726
mg, 11.2 mmol) in DMF (12 mL) were irradiated for 10 min
at 100 ˚C to give benzyl azide as a colorless
oil (1.17 g, 84%). ¹H NMR (CDCl3): δ = 7.40-7.31
(m, 5 H), 4.35 (s, 2 H). NMR spectral data was in accordance with
literature values, see:
Ju Y.Kumar D.Varma RS. J. Org. Chem. 2006, 71: 6697 - 16
Microwave-Assisted
1,2,3-Triazole Formation from Azides; General Procedure
Alkyl
azide (0.24-0.58 mmol) and vinyl acetate (1.50 mL) were
mixed in a Biotage vial (0.5-2.0 mL). The vial was sealed
and irradiated at 120 ˚C until full conversion
was achieved as monitored by TLC analysis. The reaction mixture
was concentrated under reduced pressure and the crude product was
purified by flash column chromatography on silica gel.
1-Benzyl-1
H
-1,2,3-triazole (2b): Benzyl azide (1b; 68 mg, 0.51 mmol) in vinyl acetate
(1.5 mL) was irradiated at 120 ˚C for 5 h. Column
chromatography (EtOAc-CH2Cl2, 1:9; R
f = 0.41) afforded
the triazole as colorless crystals (81 mg, 99%). ¹H
NMR (CDCl3): δ = 7.71 (s, 1 H), 7.47
(d, J = 0.8
Hz, 1 H), 7.40-7.32 (m, 3 H), 7.28-7.24 (m, 2
H), 5.57 (s, 2 H). NMR spectral data was in accordance with literature
values, see:
Chuprakov S.Chernyak N.Dudnik AS.Gevorgyan V. Org. Lett. 2007, 9: 2333 -
17a
Appukkuttan P.Dehaen W.Fokin VV.Van der Eycken E. Org. Lett. 2004, 6: 4223 -
17b
Feldman AK.Colasson B.Fokin VV. Org. Lett. 2004, 6: 3897 -
18a
Barral K.Moorhouse AD.Moses JE. Org. Lett. 2007, 9: 1809 -
18b
Beckmann HSG.Wittmann V. Org. Lett. 2007, 9: 1 - 19
Sreedhar B.Surendra Reddy P.Sailendra Kumar N. Tetrahedron Lett. 2006, 47: 3055
References and Notes
Microwave-Assisted
One-Pot Formation of 1,2,3-Triazole from Alkyl Halides; General
Procedure
WARNING
: Excess azide can potentially react with acetic
acid to form explosive hydrazoic acid. Thus, vinyl acetate should
not be added before the azidation reaction has run to completion,
and proper safety precautions should be taken when handling these
compounds.
Alkyl halide (1 equiv) and tetrabutylammonium
azide (1.05 equiv) were dissolved in diethyl ether (1 mL) in a sealed Biotage
vial and irradiated at 100 ˚C until TLC analysis indicated
full consumption of the starting material. Vinyl acetate (10 equiv)
was then added and the reaction mixture was irradiated at 120 ˚C
until TLC analysis showed disappearance of the intermediate azide.
The reaction mixture was then diluted with diethyl ether and the
organic phase was washed with H2O and brine then dried
over MgSO4, concentrated under reduced pressure and purified by
column chromatography on silica gel.
1-Benzyl-1
H
-1,2,3-triazole: BnCl (50 µL, 0.35 mmol)
and TBAN (104 mg, 0.36 mmol) in Et2O (1.0 mL)
was irradiated at 100 ˚C for 15 min. Vinyl acetate
(0.32 mL, 3.5 mmol) was added and the reaction mixture was irradiated
at 120 ˚C for 9 h. Flash column chromatography
(EtOAc-CH2Cl2, 1:9;
R
f
= 0.41)
afforded the triazole as colorless crystals (36 mg, 64%).