Synthesis of Aryl Azides via Post-Cleavage Modification of Polymer-Bound Triazenes

Frank Avemaria; Viktor Zimmermann; Stefan Bräse

doi:10.1055/s-2004-82298

LETTER

Synthesis of Aryl Azides via Post-Cleavage Modification of Polymer-Bound Triazenes

Frank Avemaria^a, Viktor Zimmermann^a, Stefan Bräse*^b
^a Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany
^b Institut für Organische Chemie, Universität Karlsruhe, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49(721)6088581; e-Mail: braese@ioc.uka.de;

Abstract

Alle Artikel dieser Rubrik

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

Volltext

Referenzen

References

<A NAME="RG20203ST-1A">1a</A> Patai S. The Chemistry of Diazonium and Diazo Groups, In The Chemistry of Functional Groups Patai S. John Wiley; Chichester: 1978.

Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., accepted (review).

<A NAME="RG20203ST-2">2</A> For example: Sharpless KB. Demko TP. Org. Lett. 2001, 3: 4091

<A NAME="RG20203ST-3">3</A> Kumar HMS. Reddy BVS. Anjaneyulu S. Yadav JS. Tetrahedron Lett. 1999, 40: 8305

<A NAME="RG20203ST-4A">4a</A> Capitosti SM. Hansen TP. Brown ML. Org. Lett. 2003, 5: 2865

<A NAME="RG20203ST-4B">4b</A> Habeeb AG. Rao PNP. Knaus EE. J. Med. Chem. 2001, 44: 3039

<A NAME="RG20203ST-5">5</A> Pinney KG. Mejia MP. Villalobos VM. Rosenquist BE. Pettit GR. Verdier-Pinard P. Hamel E. Bioorg. Med. Chem. Lett. 2000, 8: 2417

<A NAME="RG20203ST-6">6</A> Zollinger H. Diazo Chemistry Vol. 1: VCH; Weinheim: 1994.

<A NAME="RG20203ST-7">7</A> Drewry DH. Gerritz SW. Linn JA. Tetrahedron Lett. 1997, 38: 3377

<A NAME="RG20203ST-8">8</A> Schneider SE. Bishop PA. Salazar MA. Bishop OA. Anslyn EV. Tetrahedron 1998, 54: 15063

<A NAME="RG20203ST-9">9</A> Tortolani DR. Biller SA. Tetrahedron Lett. 1996, 37: 5687

<A NAME="RG20203ST-10">10</A> Lee CE. Kick EK. Ellman JA. J. Am. Chem. Soc. 1998, 120: 9735

<A NAME="RG20203ST-11A">11a</A> Le Hetet C. David M. Carreaux F. Carboni B. Sauleau A. Tetrahedron Lett. 1997, 38: 5153

<A NAME="RG20203ST-11B">11b</A> Oh HS. Hahn HG. Cheon SH. Ha DC. Tetrahedron Lett. 2000, 41: 5069

<A NAME="RG20203ST-12">12</A> Annis DA. Helluin O. Jacobsen EN. Angew. Chem. Int. Ed. 1998, 37: 1907 ; Angew. Chem. 1998, 110, 2010

<A NAME="RG20203ST-13">13</A> Hanessian S. Xie F. Tetrahedron Lett. 1998, 39: 737

<A NAME="RG20203ST-14">14</A> Nicolaou KC. Winssinger N. Vourloumis D. Ohshima T. Kim S. Pfefferkorn J. Xu JY. Li T. J. Am. Chem. Soc. 1998, 120: 10814

<A NAME="RG20203ST-15A">15a</A> Meldal M. Juliano MA. Jansson AM. Tetrahedron Lett. 1997, 38: 2531

<A NAME="RG20203ST-15B">15b</A> Long DD. Smith MD. Marquess DG. Claridge TDW. Fleet GWJ. Tetrahedron Lett. 1998, 39: 9293

<A NAME="RG20203ST-15C">15c</A> Kim JM. Bi YZ. Paikoff SJ. Schultz PG. Tetrahedron Lett. 1996, 37: 5305

<A NAME="RG20203ST-15D">15d</A> Savin KA. Woo JCG. Danishefsky SJ. J. Org. Chem. 1999, 64: 4183

<A NAME="RG20203ST-16A">16a</A> Tang ZL. Pelletier JC. Tetrahedron Lett. 1998, 39: 4773

<A NAME="RG20203ST-16B">16b</A> Tremblay MR. Poirier D. Tetrahedron Lett. 1999, 40: 1277

<A NAME="RG20203ST-16C">16c</A> Osborn NJ. Robinson JA. Tetrahedron 1993, 49: 2873

<A NAME="RG20203ST-16D">16d</A> 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

<A NAME="RG20203ST-17">17</A> Melai V. Brillante A. Zanirato P. J. Chem. Soc., Perkin Trans. 2 1998, 2447

<A NAME="RG20203ST-18A">18a</A> Freeze S. Norris P. Heterocycles 1999, 51: 1807

<A NAME="RG20203ST-18B">18b</A> Moore M. Norris P. Tetrahedron Lett. 1998, 39: 7027

<A NAME="RG20203ST-19">19</A> Gouault N. Cupif J.-F. Sauleau A. David M. Tetrahedron Lett. 2000, 41: 7293

<A NAME="RG20203ST-20">20</A> Missio A. Marchioro C. Rossi T. Panunzio M. Selva S. Seneci P. Biotechnol. Bioeng. 2000, 71: 38

<A NAME="RG20203ST-21">21</A> Butler RN. Fox A. Collier S. Burke LA. J. Chem. Soc., Perkin Trans. 2 1998, 2243

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.

<A NAME="RG20203ST-23">23</A> Nelson JC. Young JK. Moore JS. J. Org. Chem. 1996, 61: 8160

<A NAME="RG20203ST-24A">24a</A> Bräse S. Dahmen S. Chem.-Eur. J. 2000, 6: 1899

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.

<A NAME="RG20203ST-25">25</A> Bräse S. Dahmen S. Heuts J. Tetrahedron Lett. 1999, 40: 6201

<A NAME="RG20203ST-26A">26a</A> Bräse S. Schroen M. Angew. Chem. Int. Ed. 1999, 38: 1071 ; Angew. Chem. 1999, 111, 1139

<A NAME="RG20203ST-26B">26b</A> 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

<A NAME="RG20203ST-27A">27a</A> Lormann M. Dahmen S. Bräse S. Tetrahedron Lett. 2000, 41: 3813

<A NAME="RG20203ST-27B">27b</A> Bräse S. Enders D. Köbberling J. Avemaria F. Angew. Chem. Int. Ed. 1998, 37: 3413 ; Angew. Chem. 1998, 110, 3614

<A NAME="RG20203ST-28A">28a</A> Rozhkov VV. Kuvshinov AM. Shevelev SA. Org. Prep. Proced. Int. 2000, 32: 94

<A NAME="RG20203ST-28B">28b</A> Rozhkov VV. Kuvshinov AM. Gulevskaya VI. Chervin II. Shevelev SA. Synthesis 1999, 2065

<A NAME="RG20203ST-29">29</A> Clark BJ. Grayshan R. J. Chem. Res., Miniprint 1981, 3786

<A NAME="RG20203ST-30A">30a</A> Chaykovsky M. Adolph HG. J. Heterocycl. Chem. 1991, 28: 1491

<A NAME="RG20203ST-30B">30b</A> Rauhut G. Eckert F. J. Phys. Chem. 1999, 103: 9062

<A NAME="RG20203ST-30C">30c</A> Kamal MR. El-Abadelah MM. Mohammad AA. Heterocycles 1999, 50: 819

Gil, C.; Bräse, S. unpublished results.

Representative 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.

Representative 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: R_t = 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 (C_p), 56.8 (C_p), 102.9 (C_p), 121.8 (C_q), 128.6 (C_p), 135.5 (C_q), 144.6 (C_q), 152.9 (C_q). MS-DIP: m/z (%) = 208 (51), 180 (92), 152 (50), 122 (27), 106 (10), 95 (100), 92 (73), 80 (95), 77 (12), 63 (23).

Trimethyl silyl azide is a commercially available combustible liquid, which has no explosive properties.

<A NAME="RG20203ST-34B">34b</A> Groutas WC. Felker D. Synthesis 1980, 861

<A NAME="RG20203ST-35A">35a</A> Ghosh PB. Whitehouse MW. J. Med. Chem. 1968, 11: 305

<A NAME="RG20203ST-35B">35b</A> 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

Krasinski, A., Fokin, V. V., Sharpless, K. B.; Org. Lett., submitted.

<A NAME="RG20203ST-37">37</A> Scheiner P. Schomaker JH. Deming S. Libbey WJ. Nowack GP. J. Am. Chem. Soc. 1965, 87: 306

The 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[5.2.1.0^2,6]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.

<A NAME="RG20203ST-39">39</A> Lipschutz BH. Blomgren PA. Org. Lett. 2001, 3: 1869

<A NAME="RG20203ST-40">40</A> Bräse S. Chim. Oggi 2000, 18 (9): 14