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DOI: 10.1055/s-2004-82298
Synthesis of Aryl Azides via Post-Cleavage Modification of Polymer-Bound Triazenes
Publication History
Publication Date:
10 May 2004 (online)
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Abstract
Starting from immobilized arenes on the triazene T1 linker resin, cleavage was achieved by trifluoroacetic acid in the presence of trimethylsilyl azide to obtain aryl azides in good yields and excellent purities. A novel cleavage protocol has been introduced and analytical and preparative applications have been presented.
Key words
aryl azides - post-cleavage modification - polymer-bound triazenes
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1a
Patai S. The Chemistry of Diazonium and Diazo Groups, In The Chemistry of Functional GroupsPatai S. John Wiley; Chichester: 1978. -
1b
Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., accepted (review).
- 2 For example:
Sharpless KB.Demko TP. Org. Lett. 2001, 3: 4091 - 3
Kumar HMS.Reddy BVS.Anjaneyulu S.Yadav JS. Tetrahedron Lett. 1999, 40: 8305 -
4a
Capitosti SM.Hansen TP.Brown ML. Org. Lett. 2003, 5: 2865 -
4b
Habeeb AG.Rao PNP.Knaus EE. J. Med. Chem. 2001, 44: 3039 - 5
Pinney KG.Mejia MP.Villalobos VM.Rosenquist BE.Pettit GR.Verdier-Pinard P.Hamel E. Bioorg. Med. Chem. Lett. 2000, 8: 2417 - 6
Zollinger H. Diazo Chemistry Vol. 1: VCH; Weinheim: 1994. - 7
Drewry DH.Gerritz SW.Linn JA. Tetrahedron Lett. 1997, 38: 3377 - 8
Schneider SE.Bishop PA.Salazar MA.Bishop OA.Anslyn EV. Tetrahedron 1998, 54: 15063 - 9
Tortolani DR.Biller SA. Tetrahedron Lett. 1996, 37: 5687 - 10
Lee CE.Kick EK.Ellman JA. J. Am. Chem. Soc. 1998, 120: 9735 -
11a
Le Hetet C.David M.Carreaux F.Carboni B.Sauleau A. Tetrahedron Lett. 1997, 38: 5153 -
11b
Oh HS.Hahn HG.Cheon SH.Ha DC. Tetrahedron Lett. 2000, 41: 5069 - 12
Annis DA.Helluin O.Jacobsen EN. Angew. Chem. Int. Ed. 1998, 37: 1907 ; Angew. Chem. 1998, 110, 2010 - 13
Hanessian S.Xie F. Tetrahedron Lett. 1998, 39: 737 - 14
Nicolaou KC.Winssinger N.Vourloumis D.Ohshima T.Kim S.Pfefferkorn J.Xu JY.Li T. J. Am. Chem. Soc. 1998, 120: 10814 -
15a
Meldal M.Juliano MA.Jansson AM. Tetrahedron Lett. 1997, 38: 2531 -
15b
Long DD.Smith MD.Marquess DG.Claridge TDW.Fleet GWJ. Tetrahedron Lett. 1998, 39: 9293 -
15c
Kim JM.Bi YZ.Paikoff SJ.Schultz PG. Tetrahedron Lett. 1996, 37: 5305 -
15d
Savin KA.Woo JCG.Danishefsky SJ. J. Org. Chem. 1999, 64: 4183 -
16a
Tang ZL.Pelletier JC. Tetrahedron Lett. 1998, 39: 4773 -
16b
Tremblay MR.Poirier D. Tetrahedron Lett. 1999, 40: 1277 -
16c
Osborn NJ.Robinson JA. Tetrahedron 1993, 49: 2873 -
16d
Liang R.Yan L.Loebach J.Ge M.Uozumi Y.Sekanina K.Horan N.Gildersleeve J.Thompson C.Smith A.Biswas K.Still WC.Kahne D. Science 1996, 274: 1520 - 17
Melai V.Brillante A.Zanirato P. J. Chem. Soc., Perkin Trans. 2 1998, 2447 -
18a
Freeze S.Norris P. Heterocycles 1999, 51: 1807 -
18b
Moore M.Norris P. Tetrahedron Lett. 1998, 39: 7027 - 19
Gouault N.Cupif J.-F.Sauleau A.David M. Tetrahedron Lett. 2000, 41: 7293 - 20
Missio A.Marchioro C.Rossi T.Panunzio M.Selva S.Seneci P. Biotechnol. Bioeng. 2000, 71: 38 - 21
Butler RN.Fox A.Collier S.Burke LA. J. Chem. Soc., Perkin Trans. 2 1998, 2243 - 23
Nelson JC.Young JK.Moore JS. J. Org. Chem. 1996, 61: 8160 -
24a
Bräse S.Dahmen S. Chem.-Eur. J. 2000, 6: 1899 -
24b
Bräse, S.; Dahmen, S.; Lormann, M. The T1 Linker: Multidirectional Cleavage for Solid Phase Organic Synthesis; Proceedings of ECSOC-3, The Third International Electronic Conference on Synthetic Organic Chemistry, 1999, see also http://www.mdpi.org/ecsoc-3.htm.
- 25
Bräse S.Dahmen S.Heuts J. Tetrahedron Lett. 1999, 40: 6201 -
26a
Bräse S.Schroen M. Angew. Chem. Int. Ed. 1999, 38: 1071 ; Angew. Chem. 1999, 111, 1139 -
26b
de Meijere A.Nüske H.Es-Sayed M.Labahn T.Schroen M.Bräse S. Angew. Chem. Int. Ed. 1999, 38: 3669 ; Angew. Chem. 1999, 111, 3881 -
27a
Lormann M.Dahmen S.Bräse S. Tetrahedron Lett. 2000, 41: 3813 -
27b
Bräse S.Enders D.Köbberling J.Avemaria F. Angew. Chem. Int. Ed. 1998, 37: 3413 ; Angew. Chem. 1998, 110, 3614 -
28a
Rozhkov VV.Kuvshinov AM.Shevelev SA. Org. Prep. Proced. Int. 2000, 32: 94 -
28b
Rozhkov VV.Kuvshinov AM.Gulevskaya VI.Chervin II.Shevelev SA. Synthesis 1999, 2065 - 29
Clark BJ.Grayshan R. J. Chem. Res., Miniprint 1981, 3786 -
30a
Chaykovsky M.Adolph HG. J. Heterocycl. Chem. 1991, 28: 1491 -
30b
Rauhut G.Eckert F. J. Phys. Chem. 1999, 103: 9062 -
30c
Kamal MR.El-Abadelah MM.Mohammad AA. Heterocycles 1999, 50: 819 -
34a
Trimethyl silyl azide is a commercially available combustible liquid, which has no explosive properties.
-
34b
Groutas WC.Felker D. Synthesis 1980, 861 -
35a
Ghosh PB.Whitehouse MW. J. Med. Chem. 1968, 11: 305 -
35b
Cerecetto H.Di Maio R.Gonzalez M.Risso M.Saenz P.Seoane G.Denicola A.Peluffo G.Quijano C.Olea-Azar C. J. Med. Chem. 1999, 42: 1941 - 37
Scheiner P.Schomaker JH.Deming S.Libbey WJ.Nowack GP. J. Am. Chem. Soc. 1965, 87: 306 - 39
Lipschutz BH.Blomgren PA. Org. Lett. 2001, 3: 1869 - 40
Bräse S. Chim. Oggi 2000, 18 (9): 14
References
Bräse, S.; Lormann, M.; Vogt, H. Scope and Limitation of a Tin Promoted Amidation on Solid Phase: A New Monitoring for the T1 Triazene Linker; Proceedings of ECSOC-4, The Third International Electronic Conference on Synthetic Organic Chemistry, September 1-30, 2000, see also http://www.mdpi.org/ecsoc-4.htm.
31Gil, C.; Bräse, S. unpublished results.
32Representative Procedure for Synthesis of a T1-Resin: The aniline 2n (3.68 g, 20.2 mmol) was dissolved in 100 mL of CH2Cl2 and BF3·OEt2 (4.26 g, 30.0 mmol) was added at r.t. The mixture was cooled to -15 °C and isoamyl nitrite (3.83 g, 32.7 mmol) was added dropwise with stirring for 15 min. After stirring for 4 h the mixture was cooled to -70 °C and the solid diazonium salt was filtered off, washed with precooled Et2O and suspended in MeCN at -40 °C. In a second flask, the benzylamine resin 1 (5.00 g, 4.65 mmol, loading 0.93 mmol/g) was dissolved in THF at -20 °C and pyridine (5.87 g, 74.0 mmol) was added. The cooled suspension of the diazonium salt was added to the benzylamine resin suspension and the reaction mixture was stirred slowly for 6 h. It was allowed to warm up to r.t. The resin was filtered off, washed sequentially with THF, CH2Cl2, MeOH, pentane, DMF and dried under high vacuum.
33Representative Procedure for Cleavage of a T1-Resin: The resin 3n (0.40 g, loading 0.74 mmol/g) was suspended in 5 mL of CH2Cl2 and trifluoroacetic acid (0.30 mL, 4.0 mmol) was added dropwise at r.t. After 2-5 min, trimethylsilyl azide (0.15 mL, 1.2 mmol) was added to the resin and after few minutes (5-10) the mixture was filtered and the solvent was removed by evaporation. 1-Azido-5-methoxy-2-methyl-4-nitro-benzene (4n): 58.5 mg, 79% yield. GC: Rt = 13.99 min. IR (KBr disk): 2100 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.18 (s, 3 H), 3.99 (s, 3 H), 6.73 (s, 1 H) 7.79 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 16.2 (Cp), 56.8 (Cp), 102.9 (Cp), 121.8 (Cq), 128.6 (Cp), 135.5 (Cq), 144.6 (Cq), 152.9 (Cq). MS-DIP: m/z (%) = 208 (51), 180 (92), 152 (50), 122 (27), 106 (10), 95 (100), 92 (73), 80 (95), 77 (12), 63 (23).
36Krasinski, A., Fokin, V. V., Sharpless, K. B.; Org. Lett., submitted.
38The crude solution of the azide (4t) was washed with H2O to remove the excess of trimethyl silyl azide, and norbornene was added. After 3 d at 25 °C the solvent was evaporated and the residue was recrystallized from petroleum ether/EtOAc (1:1).
3-(2′-Bromophenyl)-3,4,5-triazatri-cyclo[5.2.1.02,6]dec-4-ene (5): >95%. IR (KBr): 3403 (w), 3068 (w), 2968 (s), 2874 (m), 2662 (w), 1921 (w), 1802 (w), 1586 (m), 1503 (m), 1469 (s), 1325 (m), 1310 (m), 1300 (m), 1260 (m), 1247 (m), 1216 (w), 1159 (w), 1124 (m), 1079 (m), 1046 (s), 1028 (m), 1012 (m), 974 (s), 952 (m), 918 (s), 888 (w), 863 (w), 846 (m), 805 (w), 754 (s), 714 (w), 700 (m), 640 (m) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.08-1.10 (complex, 2 H, 10-H), 1.20 (m, 1 H, 9-H), 1.34 (m, 1 H, 8-H), 1.44 (m, 1 H, 9-H), 1.55 (m, 1 H, 8-H), 2.06 (d, 3
J = 4.3 Hz, 1 H, 1-H), 2.70 (d, 3
J = 4.4 Hz, 1 H, 7-H), 4.25 (d, 3
J = 9.1 Hz, 1 H, 2-H), 4.61 (d, 3
J = 9.2 Hz, 1 H, 6-H), 7.07 (ddd, 3
J = 8.0 Hz, 3
J = 7.3 Hz, 4
J = 1.7 Hz, 1 H, 5′-H), 7.28 (ddd, 3
J = 8.0 Hz, 3
J = 7.3 Hz, 4
J = 1.4 Hz, 1 H, 4′-H), 7.34 (dd, 3
J = 8.0 Hz, 4
J = 1.7 Hz, 1 H, 3′-H), 7.59 (dd, 3
J = 8.0 Hz, 4
J = 1.4 Hz, 1 H, 6′-H). 13C NMR (75 MHz, CDCl3): δ = 24.9 (-, 9-CH2), 25.4 (-, 8-CH2), 31.8 (-, 10-CH2), 40.1 (+, 1-CH), 40.7 (+, 7-CH), 61.4 (+, 2-CH), 87.0 (+, 6-CH), 116.1 (q, C-2′), 125.7 (+, C-3′), 127.1 (+, C-5′), 128.0 (+, C-4′), 133.9 (+, C-6′), 139.9 (q, C-1′). MS (FAB): m/z (%) = 292/294 (100/98) [MH+], 263/265 (26/25) [C13H14NBr+], 234/236 (9/11). MS (EI): m/z (%) = 263/265 (C13H14NBr+, 20/20) [M+ - N2], 235/236 (96/100), 222/224 (5/5), 208/210 (9/8), 197/199 (22/18), 182/184 (24/33), 171/173 (30/29), 155/157 (27/26), 143 (7), 130 (15), 118 (11), 93 (90), 91 (32), 77 (32). HRMS (EI): calcd 291.0371 for M+ resp. 263.0310 for (M+ - N2), found 263.0308. Product undergoes thermal decomposition while GC and EI measurements are taken.